Brand Name: Lantus
Generic Name: insulin glargine

Dosage Form: Injection (Lantus must NOT be diluted or mixed with any other insulin or solution)

Contents:

Description
Clinical Pharmacology
Indications and Usage
Contraindications
Warnings
Precautions
Adverse Reactions
Dosage and Administration
How is Supplied

Lantus, insulin glargine (rDNA origin), patient information (in plain English)

Description

Lantus® (insulin glargine [rDNA origin] injection) is a sterile solution of insulin glargine for use as an injection. Insulin glargine is a recombinant human insulin analog that is a long-acting (up to 24-hour duration of action), parenteral blood-glucose-lowering agent. (See CLINICAL PHARMACOLOGY). Lantus is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (K12) as the production organism. Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain. Chemically, it is 21A-Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin and has the empirical formula C267H404N72O78S6 and a molecular weight of 6063. It has the following structural formula:

Lantus consists of insulin glargine dissolved in a clear aqueous fluid. Each milliliter of Lantus (insulin glargine injection) contains 100 IU (3.6378 mg) insulin glargine.

Inactive ingredients for the 10 mL vial are 30 mcg zinc, 2.7 mg m-cresol, 20 mg glycerol 85%, 20 mcg polysorbate 20, and water for injection.

Inactive ingredients for the 3 mL cartridge are 30 mcg zinc, 2.7 mg m-cresol, 20 mg glycerol 85%, and water for injection.

The pH is adjusted by addition of aqueous solutions of hydrochloric acid and sodium hydroxide. Lantus has a pH of approximately 4.

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Clinical Pharmacology

Mechanism of Action

The primary activity of insulin, including insulin glargine, is regulation of glucose metabolism. Insulin and its analogs lower blood glucose levels by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis in the adipocyte, inhibits proteolysis, and enhances protein synthesis.

Pharmacodynamics

Insulin glargine is a human insulin analog that has been designed to have low aqueous solubility at neutral pH. At pH 4, as in the Lantus injection solution, it is completely soluble. After injection into the subcutaneous tissue, the acidic solution is neutralized, leading to formation of microprecipitates from which small amounts of insulin glargine are slowly released, resulting in a relatively constant concentration/time profile over 24 hours with no pronounced peak. This profile allows once-daily dosing as a patient's basal insulin.

In clinical studies, the glucose-lowering effect on a molar basis (i.e., when given at the same doses) of intravenous insulin glargine is approximately the same as human insulin. In euglycemic clamp studies in healthy subjects or in patients with type 1 diabetes, the onset of action of subcutaneous insulin glargine was slower than NPH human insulin. The effect profile of insulin glargine was relatively constant with no pronounced peak and the duration of its effect was prolonged compared to NPH human insulin. Figure 1 shows results from a study in patients with type 1 diabetes conducted for a maximum of 24 hours after the injection. The median time between injection and the end of pharmacological effect was 14.5 hours (range: 9.5 to 19.3 hours) for NPH human insulin, and 24 hours (range: 10.8 to >24.0 hours) (24 hours was the end of the observation period) for insulin glargine.

Figure 1. Activity Profile in Patients with Type 1 Diabetes†

*Determined as amount of glucose infused to maintain constant plasma glucose levels (hourly mean values); indicative of insulin activity.

†Between-patient variability (CV, coefficient of variation); insulin glargine, 84% and NPH, 78%.

The longer duration of action (up to 24 hours) of Lantus is directly related to its slower rate of absorption and supports once-daily subcutaneous administration. The time course of action of insulins, including Lantus, may vary between individuals and/or within the same individual.

Pharmacokinetics

Absorption and Bioavailability

After subcutaneous injection of insulin glargine in healthy subjects and in patients with diabetes, the insulin serum concentrations indicated a slower, more prolonged absorption and a relatively constant concentration/time profile over 24 hours with no pronounced peak in comparison to NPH human insulin. Serum insulin concentrations were thus consistent with the time profile of the pharmacodynamic activity of insulin glargine.

After subcutaneous injection of 0.3 IU/kg insulin glargine in patients with type 1 diabetes, a relatively constant concentration/time profile has been demonstrated. The duration of action after abdominal, deltoid, or thigh subcutaneous administration was similar.

Metabolism

A metabolism study in humans indicates that insulin glargine is partly metabolized at the carboxyl terminus of the B chain in the subcutaneous depot to form two active metabolites with in vitro activity similar to that of insulin, M1 (21A-Gly-insulin) and M2 (21A-Gly-des-30B-Thr-insulin). Unchanged drug and these degradation products are also present in the circulation.

Special Populations

Age, Race, and Gender

Information on the effect of age, race, and gender on the pharmacokinetics of Lantus is not available. However, in controlled clinical trials in adults (n=3890) and a controlled clinical trial in pediatric patients (n=349), subgroup analyses based on age, race, and gender did not show differences in safety and efficacy between insulin glargine and NPH human insulin.

Smoking

The effect of smoking on the pharmacokinetics/pharmacodynamics of Lantus has not been studied.

Pregnancy

The effect of pregnancy on the pharmacokinetics and pharmacodynamics of Lantus has not been studied (see PRECAUTIONS, Pregnancy).

Obesity

In controlled clinical trials, which included patients with Body Mass Index (BMI) up to and including 49.6 kg/m2, subgroup analyses based on BMI did not show any differences in safety and efficacy between insulin glargine and NPH human insulin.

Renal Impairment

The effect of renal impairment on the pharmacokinetics of Lantus has not been studied. However, some studies with human insulin have shown increased circulating levels of insulin in patients with renal failure. Careful glucose monitoring and dose adjustments of insulin, including Lantus, may be necessary in patients with renal dysfunction (see PRECAUTIONS, Renal Impairment).

Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of Lantus has not been studied. However, some studies with human insulin have shown increased circulating levels of insulin in patients with liver failure. Careful glucose monitoring and dose adjustments of insulin, including Lantus, may be necessary in patients with hepatic dysfunction (see PRECAUTIONS, Hepatic Impairment).

Clinical Studies

The safety and effectiveness of insulin glargine given once-daily at bedtime was compared to that of once-daily and twice-daily NPH human insulin in open-label, randomized, active-control, parallel studies of 2327 adult patients and 349 pediatric patients with type 1 diabetes mellitus and 1563 adult patients with type 2 diabetes mellitus (see Tables 1-3). In general, the reduction in glycated hemoglobin (HbA1c) with Lantus was similar to that with NPH human insulin. The overall rates of hypoglycemia did not differ between patients with diabetes treated to Lantus compared with NPH human insulin.

Type 1 Diabetes-Adult (see Table 1).

In two large, randomized, controlled clinical studies (Studies A and B), patients with type 1 diabetes (Study A; n=585, Study B; n=534) were randomized to basal-bolus treatment with Lantus once daily at bedtime or to NPH human insulin once or twice daily and treated for 28 weeks. Regular human insulin was administered before each meal. Lantus was administered at bedtime. NPH human insulin was administered once daily at bedtime or in the morning and at bedtime when used twice daily. In one large, randomized, controlled clinical study (Study C), patients with type 1 diabetes (n=619) were treated for 16 weeks with a basal-bolus insulin regimen where insulin lispro was used before each meal. Lantus was administered once daily at bedtime and NPH human insulin was administered once or twice daily. In these studies, Lantus and NPH human insulin had a similar effect on glycohemoglobin with a similar overall rate of hypoglycemia.

Table 1: Type 1 Diabetes Mellitus-Adult

	Study A		Study B		Study C
Treatment duration	28 weeks		28 weeks		16 weeks
Treatment in combination with	Regular insulin		Regular insulin		Insulin lispro
	Lantus	NPH	Lantus	NPH	Lantus	NPH
Number of subjects treated	292	293	264	270	310	309
HbA1c
Endstudy mean	8.13	8.07	7.55	7.49	7.53	7.60
Adj. mean change from baseline	+0.21	+0.10	-0.16	-0.21	-0.07	-0.08
Lantus - NPH	+0.11		+0.05		+0.01
95% CI for Treatment difference	(-0.03; +0.24)		(-0.08; +0.19)		(-0.11; +0.13)
Basal insulin dose
Endstudy mean	19.2	22.8	24.8	31.3	23.9	29.2
Mean change from baseline	-1.7	-0.3	-4.1	+1.8	-4.5	+0.9
Total insulin dose
Endstudy mean	46.7	51.7	50.3	54.8	47.4	50.7
Mean change from baseline	-1.1	-0.1	+0.3	+3.7	-2.9	+0.3
Fasting blood glucose (mg/dL)
Endstudy mean	146.3	150.8	147.8	154.4	144.4	161.3
Adj. mean change from baseline	-21.1	-16.0	-20.2	-16.9	-29.3	-11.9

Type 1 Diabetes-Pediatric (see Table 2).

In a randomized, controlled clinical study (Study D), pediatric patients (age range 6 to 15 years) with type 1 diabetes (n=349) were treated for 28 weeks with a basal-bolus insulin regimen where regular human insulin was used before each meal. Lantus was administered once daily at bedtime and NPH human insulin was administered once or twice daily. Similar effects on glycohemoglobin and the incidence of hypoglycemia were observed in both treatment groups.

Table 2: Type 1 Diabetes Mellitus-Pediatric

	Study D
Treatment duration	28 weeks
Treatment in combination with	Regular insulin
	Lantus	NPH
Number of subjects treated	174	175
HbA1c
Endstudy mean	8.91	9.18
Adj. mean change from baseline	+0.28	+0.27
Lantus - NPH	+0.01
95% CI for Treatment difference	(-0.24; +0.26)
Basal insulin dose
Endstudy mean	18.2	21.1
Mean change from baseline	-1.3	+2.4
Total insulin dose
Endstudy mean	45.0	46.0
Mean change from baseline	+1.9	+3.4
Fasting blood glucose (mg/dL)
Endstudy mean	171.9	182.7
Adj. mean change from baseline	-23.2	-12.2

Type 2 Diabetes-Adult (see Table 3).

In a large, randomized, controlled clinical study (Study E) (n=570), Lantus was evaluated for 52 weeks as part of a regimen of combination therapy with insulin and oral antidiabetes agents (a sulfonylurea, metformin, acarbose, or combinations of these drugs). Lantus administered once daily at bedtime was as effective as NPH human insulin administered once daily at bedtime in reducing glycohemoglobin and fasting glucose. There was a low rate of hypoglycemia that was similar in Lantus and NPH human insulin treated patients. In a large, randomized, controlled clinical study (Study F), in patients with type 2 diabetes not using oral antidiabetes agents (n=518), a basal-bolus regimen of Lantus once daily at bedtime or NPH human insulin administered once or twice daily was evaluated for 28 weeks. Regular human insulin was used before meals as needed. Lantus had similar effectiveness as either once- or twice-daily NPH human insulin in reducing glycohemoglobin and fasting glucose with a similar incidence of hypoglycemia.

Table 3: Type 2 Diabetes Mellitus-Adult

	Study E		Study F
Treatment duration	52 weeks		28 weeks
Treatment in combination with	Oral agents		Regular insulin
	Lantus	NPH	Lantus	NPH
Number of subjects treated	289	281	259	259
HbA1c
Endstudy mean	8.51	8.47	8.14	7.96
Adj. mean change from baseline	-0.46	-0.38	-0.41	-0.59
Lantus - NPH	-0.08		+0.17
95% CI for Treatment difference	(-0.28; +0.12)		(-0.00; +0.35)
Basal insulin dose
Endstudy mean	25.9	23.6	42.9	52.5
Mean change from baseline	+11.5	+9.0	-1.2	+7.0
Total insulin dose
Endstudy mean	25.9	23.6	74.3	80.0
Mean change from baseline	+11.5	+9.0	+10.0	+13.1
Fasting blood glucose (mg/dL)
Endstudy mean	126.9	129.4	141.5	144.5
Adj. mean change from baseline	-49.0	-46.3	-23.8	-21.6

Lantus Flexible Daily Dosing

The safety and efficacy of Lantus administered pre-breakfast, pre-dinner, or at bedtime were evaluated in a large, randomized, controlled clinical study, in patients with type 1 diabetes (study G, n=378). Patients were also treated with insulin lispro at mealtime. Lantus administered at different times of the day resulted in similar reductions in glycated hemoglobin compared to that with bedtime administration (see Table 4). In these patients, data are available from 8-point home glucose monitoring. The maximum mean blood glucose level was observed just prior to injection of Lantus regardless of time of administration, i.e. pre-breakfast, pre-dinner, or bedtime.

In this study, 5% of patients in the Lantus-breakfast arm discontinued treatment because of lack of efficacy. No patients in the other two arms discontinued for this reason. Routine monitoring during this trial revealed the following mean changes in systolic blood pressure: pre-breakfast group, 1.9 mm Hg; pre-dinner group, 0.7 mm Hg; pre-bedtime group, -2.0 mm Hg.

The safety and efficacy of Lantus administered pre-breakfast or at bedtime were also evaluated in a large, randomized, active-controlled clinical study (Study H, n=697) in type 2 diabetes patients no longer adequately controlled on oral agent therapy. All patients in this study also received AMARYL® (glimepiride) 3 mg daily. Lantus given before breakfast was at least as effective in lowering glycated hemoglobin A1c (HbA1c) as Lantus given at bedtime or NPH human insulin given at bedtime (see Table 4).

Table 4: Flexible Lantus Daily Dosing in Type 1 (Study G) and Type 2 (Study H) Diabetes Mellitus

	Study G			Study H
Treatmentduration	24 weeks			24 weeks
Treatment in combination with:	Insulin lispro			AMARYL® (glimepiride)
	Lantus Breakfast	Lantus Dinner	Lantus Bedtime	Lantus Breakfast	Lantus Bedtime	NPH Bedtime
*Intent to treat †Not applicable
Number of subjects treated*	112	124	128	234	226	227
HbA1c
Baseline mean	7.56	7.53	7.61	9.13	9.07	9.09
Endstudy mean	7.39	7.42	7.57	7.87	8.12	8.27
Mean change from baseline	-0.17	-0.11	-0.04	-1.26	-0.95	-0.83
Basal insulin dose (IU)
Endstudy mean	27.3	24.6	22.8	40.4	38.5	36.8
Mean change from baseline	5.0	1.8	1.5
Total insulin dose (IU)				NAâ€	NA	NA
Endstudy mean	53.3	54.7	51.5
Mean change from baseline	1.6	3.0	2.3

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Indications and Usage

Lantus is indicated for once-daily subcutaneous administration for the treatment of adult and pediatric patients with type 1 diabetes mellitus or adult patients with type 2 diabetes mellitus who require basal (long-acting) insulin for the control of hyperglycemia.

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Contraindications

Lantus is contraindicated in patients hypersensitive to insulin glargine or the excipients.

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Warnings

Hypoglycemia is the most common adverse effect of insulin, including Lantus. As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. Glucose monitoring is recommended for all patients with diabetes.

Any change of insulin should be made cautiously and only under medical supervision. Changes in insulin strength, timing of dosing, manufacturer, type (e.g., regular, NPH, or insulin analogs), species (animal, human), or method of manufacture (recombinant DNA versus animal-source insulin) may result in the need for a change in dosage. Concomitant oral antidiabetes treatment may need to be adjusted.

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Precautions

General

Lantus is not intended for intravenous administration. The prolonged duration of activity of insulin glargine is dependent on injection into subcutaneous tissue. Intravenous administration of the usual subcutaneous dose could result in severe hypoglycemia.

Lantus must NOT be diluted or mixed with any other insulin or solution. If Lantus is diluted or mixed, the solution may become cloudy, and the pharmacokinetic/pharmacodynamic profile (e.g., onset of action, time to peak effect) of Lantus and/or the mixed insulin may be altered in an unpredictable manner. When Lantus and regular human insulin were mixed immediately before injection in dogs, a delayed onset of action and time to maximum effect for regular human insulin was observed. The total bioavailability of the mixture was also slightly decreased compared to separate injections of Lantus and regular human insulin. The relevance of these observations in dogs to humans is not known.

As with all insulin preparations, the time course of Lantus action may vary in different individuals or at different times in the same individual and the rate of absorption is dependent on blood supply, temperature, and physical activity.

Insulin may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

Hypoglycemia

As with all insulin preparations, hypoglycemic reactions may be associated with the administration of Lantus. Hypoglycemia is the most common adverse effect of insulins. Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as long duration of diabetes, diabetes nerve disease, use of medications such as beta-blockers, or intensified diabetes control (see PRECAUTIONS, Drug Interactions). Such situations may result in severe hypoglycemia (and, possibly, loss of consciousness) prior to patients' awareness of hypoglycemia.

The time of occurrence of hypoglycemia depends on the action profile of the insulins used and may, therefore, change when the treatment regimen or timing of dosing is changed. Patients being switched from twice daily NPH insulin to once-daily Lantus should have their initial Lantus dose reduced by 20% from the previous total daily NPH dose to reduce the risk of hypoglycemia (see DOSAGE AND ADMINISTRATION, Changeover to Lantus).

The prolonged effect of subcutaneous Lantus may delay recovery from hypoglycemia.

In a clinical study, symptoms of hypoglycemia or counterregulatory hormone responses were similar after intravenous insulin glargine and regular human insulin both in healthy subjects and patients with type 1 diabetes.

Renal Impairment

Although studies have not been performed in patients with diabetes and renal impairment, Lantus requirements may be diminished because of reduced insulin metabolism, similar to observations found with other insulins (see CLINICAL PHARMACOLOGY, Special Populations).

Hepatic Impairment

Although studies have not been performed in patients with diabetes and hepatic impairment, Lantus requirements may be diminished due to reduced capacity for gluconeogenesis and reduced insulin metabolism, similar to observations found with other insulins (see CLINICAL PHARMACOLOGY, Special Populations).

Injection Site and Allergic Reactions

As with any insulin therapy, lipodystrophy may occur at the injection site and delay insulin absorption. Other injection site reactions with insulin therapy include redness, pain, itching, hives, swelling, and inflammation. Continuous rotation of the injection site within a given area may help to reduce or prevent these reactions. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Reports of injection site pain were more frequent with Lantus than NPH human insulin (2.7% insulin glargine versus 0.7% NPH). The reports of pain at the injection site were usually mild and did not result in discontinuation of therapy.

Immediate-type allergic reactions are rare. Such reactions to insulin (including insulin glargine) or the excipients may, for example, be associated with generalized skin reactions, angioedema, bronchospasm, hypotension, or shock and may be life threatening.

Intercurrent Conditions

Insulin requirements may be altered during intercurrent conditions such as illness, emotional disturbances, or stress.

Information for Patients

Lantus must only be used if the solution is clear and colorless with no particles visible (see DOSAGE AND ADMINISTRATION, Preparation and Handling).

Patients must be advised that Lantus must NOT be diluted or mixed with any other insulin or solution (see PRECAUTIONS, General).

Patients should be instructed on self-management procedures including glucose monitoring, proper injection technique, and hypoglycemia and hyperglycemia management. Patients must be instructed on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, or skipped meals. Refer patients to the Lantus "Patient Information" circular for additional information.

As with all patients who have diabetes, the ability to concentrate and/or react may be impaired as a result of hypoglycemia or hyperglycemia.

Patients with diabetes should be advised to inform their health care professional if they are pregnant or are contemplating pregnancy.

Drug Interactions

A number of substances affect glucose metabolism and may require insulin dose adjustment and particularly close monitoring.

The following are examples of substances that may increase the blood-glucose-lowering effect and susceptibility to hypoglycemia: oral antidiabetes products, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAO inhibitors, propoxyphene, salicylates, somatostatin analog (e.g., octreotide), sulfonamide antibiotics.

The following are examples of substances that may reduce the blood-glucose-lowering effect of insulin: corticosteroids, danazol, diuretics, sympathomimetic agents (e.g., epinephrine, albuterol, terbutaline), isoniazid, phenothiazine derivatives, somatropin, thyroid hormones, estrogens, progestogens (e.g., in oral contraceptives), protease inhibitors and atypical antipsychotic medications (e.g. olanzapine and clozapine).

Beta-blockers, clonidine, lithium salts, and alcohol may either potentiate or weaken the blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.

In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine, and reserpine, the signs of hypoglycemia may be reduced or absent.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In mice and rats, standard two-year carcinogenicity studies with insulin glargine were performed at doses up to 0.455 mg/kg, which is for the rat approximately 10 times and for the mouse approximately 5 times the recommended human subcutaneous starting dose of 10 IU (0.008 mg/kg/day), based on mg/m2. The findings in female mice were not conclusive due to excessive mortality in all dose groups during the study. Histiocytomas were found at injection sites in male rats (statistically significant) and male mice (not statistically significant) in acid vehicle containing groups. These tumors were not found in female animals, in saline control, or insulin comparator groups using a different vehicle. The relevance of these findings to humans is unknown.

Insulin glargine was not mutagenic in tests for detection of gene mutations in bacteria and mammalian cells (Ames- and HGPRT-test) and in tests for detection of chromosomal aberrations (cytogenetics in vitro in V79 cells and in vivo in Chinese hamsters).

In a combined fertility and prenatal and postnatal study in male and female rats at subcutaneous doses up to 0.36 mg/kg/day, which is approximately 7 times the recommended human subcutaneous starting dose of 10 IU (0.008 mg/kg/day), based on mg/m2, maternal toxicity due to dose-dependent hypoglycemia, including some deaths, was observed. Consequently, a reduction of the rearing rate occurred in the high-dose group only. Similar effects were observed with NPH human insulin.

Pregnancy

Teratogenic Effects

Pregnancy Category C. Subcutaneous reproduction and teratology studies have been performed with insulin glargine and regular human insulin in rats and Himalayan rabbits. The drug was given to female rats before mating, during mating, and throughout pregnancy at doses up to 0.36 mg/kg/day, which is approximately 7 times the recommended human subcutaneous starting dose of 10 IU (0.008 mg/kg/day), based on mg/m2. In rabbits, doses of 0.072 mg/kg/day, which is approximately 2 times the recommended human subcutaneous starting dose of 10 IU (0.008 mg/kg/day), based on mg/m2, were administered during organogenesis. The effects of insulin glargine did not generally differ from those observed with regular human insulin in rats or rabbits. However, in rabbits, five fetuses from two litters of the high-dose group exhibited dilation of the cerebral ventricles. Fertility and early embryonic development appeared normal.

There are no well-controlled clinical studies of the use of insulin glargine in pregnant women. It is essential for patients with diabetes or a history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy. Insulin requirements may decrease during the first trimester, generally increase during the second and third trimesters, and rapidly decline after delivery. Careful monitoring of glucose control is essential in such patients. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is unknown whether insulin glargine is excreted in significant amounts in human milk. Many drugs, including human insulin, are excreted in human milk. For this reason, caution should be exercised when Lantus is administered to a nursing woman. Lactating women may require adjustments in insulin dose and diet.

Pediatric Use

Safety and effectiveness of Lantus have been established in the age group 6 to 15 years with type 1 diabetes.

Geriatric Use

In controlled clinical studies comparing insulin glargine to NPH human insulin, 593 of 3890 patients with type 1 and type 2 diabetes were 65 years and older. The only difference in safety or effectiveness in this subpopulation compared to the entire study population was an expected higher incidence of cardiovascular events in both insulin glargine and NPH human insulin-treated patients.

In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions. Hypoglycemia may be difficult to recognize in the elderly (see PRECAUTIONS, Hypoglycemia).

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Adverse Reactions

The adverse events commonly associated with Lantus include the following:

Body as a whole: allergic reactions (see PRECAUTIONS).

Skin and appendages: injection site reaction, lipodystrophy, pruritus, rash (see PRECAUTIONS).

Other: hypoglycemia (see WARNINGS and PRECAUTIONS).

In clinical studies in adult patients, there was a higher incidence of treatment-emergent injection site pain in Lantus-treated patients (2.7%) compared to NPH insulin-treated patients (0.7%). The reports of pain at the injection site were usually mild and did not result in discontinuation of therapy. Other treatment-emergent injection site reactions occurred at similar incidences with both insulin glargine and NPH human insulin.

Retinopathy was evaluated in the clinical studies by means of retinal adverse events reported and fundus photography. The numbers of retinal adverse events reported for Lantus and NPH treatment groups were similar for patients with type 1 and type 2 diabetes. Progression of retinopathy was investigated by fundus photography using a grading protocol derived from the Early Treatment Diabetic Retinopathy Study (ETDRS). In one clinical study involving patients with type 2 diabetes, a difference in the number of subjects with ≥3-step progression in ETDRS scale over a 6-month period was noted by fundus photography (7.5% in Lantus group versus 2.7% in NPH treated group). The overall relevance of this isolated finding cannot be determined due to the small number of patients involved, the short follow-up period, and the fact that this finding was not observed in other clinical studies.

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Overdose

An excess of insulin relative to food intake, energy expenditure, or both may lead to severe and sometimes long-term and life-threatening hypoglycemia. Mild episodes of hypoglycemia can usually be treated with oral carbohydrates. Adjustments in drug dosage, meal patterns, or exercise may be needed.

More severe episodes with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid reoccurrence of hypoglycemia.

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Dosage and Administration

Lantus is a recombinant human insulin analog. Its potency is approximately the same as human insulin. It exhibits a relatively constant glucose-lowering profile over 24 hours that permits once-daily dosing.

Lantus may be administered at any time during the day. Lantus should be administered subcutaneously once a day at the same time every day. For patients adjusting timing of dosing with Lantus, see WARNINGS and PRECAUTIONS, Hypoglycemia. Lantus is not intended for intravenous administration (see PRECAUTIONS). Intravenous administration of the usual subcutaneous dose could result in severe hypoglycemia. The desired blood glucose levels as well as the doses and timing of antidiabetes medications must be determined individually. Blood glucose monitoring is recommended for all patients with diabetes. The prolonged duration of activity of Lantus is dependent on injection into subcutaneous space.

As with all insulins, injection sites within an injection area (abdomen, thigh, or deltoid) must be rotated from one injection to the next.

In clinical studies, there was no relevant difference in insulin glargine absorption after abdominal, deltoid, or thigh subcutaneous administration. As for all insulins, the rate of absorption, and consequently the onset and duration of action, may be affected by exercise and other variables.

Lantus is not the insulin of choice for the treatment of diabetes ketoacidosis. Intravenous short-acting insulin is the preferred treatment.

Pediatric Use

Lantus can be safely administered to pediatric patients ≥6 years of age. Administration to pediatric patients

Initiation of Lantus Therapy

In a clinical study with insulin naïve patients with type 2 diabetes already treated with oral antidiabetes drugs, Lantus was started at an average dose of 10 IU once daily, and subsequently adjusted according to the patient's need to a total daily dose ranging from 2 to 100 IU.

Changeover to Lantus

If changing from a treatment regimen with an intermediate- or long-acting insulin to a regimen with Lantus, the amount and timing of short-acting insulin or fast-acting insulin analog or the dose of any oral antidiabetes drug may need to be adjusted. In clinical studies, when patients were transferred from once-daily NPH human insulin or ultralente human insulin to once-daily Lantus, the initial dose was usually not changed. However, when patients were transferred from twice-daily NPH human insulin to Lantus once daily, to reduce the risk of hypoglycemia, the initial dose (IU) was usually reduced by approximately 20% (compared to total daily IU of NPH human insulin) and then adjusted based on patient response (see PRECAUTIONS, Hypoglycemia).

A program of close metabolic monitoring under medical supervision is recommended during transfer and in the initial weeks thereafter. The amount and timing of short-acting insulin or fast-acting insulin analog may need to be adjusted. This is particularly true for patients with acquired antibodies to human insulin needing high-insulin doses and occurs with all insulin analogs. Dose adjustment of Lantus and other insulins or oral antidiabetes drugs may be required; for example, if the patient's timing of dosing, weight or lifestyle changes, or other circumstances arise that increase susceptibility to hypoglycemia or hyperglycemia (see PRECAUTIONS, Hypoglycemia).

The dose may also have to be adjusted during intercurrent illness (see PRECAUTIONS, Intercurrent Conditions).

Preparation and Handling

Parenteral drug products should be inspected visually prior to administration whenever the solution and the container permit. Lantus must only be used if the solution is clear and colorless with no particles visible.

Mixing and diluting: Lantus must NOT be diluted or mixed with any other insulin or solution (see PRECAUTIONS, General).

Vial: The syringes must not contain any other medicinal product or residue.

Cartridge system: If OptiClik®, the Insulin Delivery Device for Lantus, malfunctions, Lantus may be drawn from the cartridge system into a U-100 syringe and injected.

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How is Supplied

Lantus 100 units per mL (U-100) is available in the following package size:

10 mL vials (NDC 0088-2220-33)

3 mL cartridge system¹, package of 5 (NDC 0088-2220-52)

¹Cartridge systems are for use only in OptiClik® (Insulin Delivery Device)

Storage

Unopened Vial/Cartridge system

Unopened Lantus vials and cartridge systems should be stored in a refrigerator, 36°F - 46°F (2°C - 8°C). Lantus should not be stored in the freezer and it should not be allowed to freeze.

Discard if it has been frozen.

Open (In-Use) Vial/Cartridge system

Opened vials, whether or not refrigerated, must be used within 28 days after the first use. They must be discarded if not used within 28 days. If refrigeration is not possible, the open vial can be kept unrefrigerated for up to 28 days away from direct heat and light, as long as the temperature is not greater than 86°F (30°C).

The opened (in-use) cartridge system in OptiClik® should NOT be refrigerated but should be kept at room temperature (below 86°F [30°C]) away from direct heat and light. The opened (in-use) cartridge system in OptiClik® kept at room temperature must be discarded after 28 days. Do not store OptiClik®, with or without cartridge system, in a refrigerator at any time.

Lantus should not be stored in the freezer and it should not be allowed to freeze. Discard if it has been frozen.

These storage conditions are summarized in the following table:

	Not in-use (unopened) Refrigerated	Not in-use (unopened) Room Temperature	In-use (opened) (See Temperature Below)
10 mL Vial	Until expiration date	28 days	28 days Refrigerated or room temperature
3 mL Cartridge system	Until expiration date	28 days	28 days Refrigerated or room temperature
3 mL Cartridge system inserted into OptiClik®			28 days Room temperature only (Do not refrigerate)

Manufactured for an distributed by:

sanofi-aventis U.S. LLC
Bridgewater NJ 08807

Made in Germany

www.Lantus.com

© 2006 sanofi-aventis U.S. LLC

OptiClik® is a registered trademark of sanofi-aventis U.S. LLC, Bridgewater NJ 08807

last updated 04/2006

Lantus, insulin glargine (rDNA origin), patient information (in plain English)

Detailed Info on Signs, Symptoms, Causes, Treatments of Diabetes

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The information in this monograph is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects. This information is generalized and is not intended as specific medical advice. If you have questions about the medicines you are taking or would like more information, check with your doctor, pharmacist, or nurse.

back to: Browse all Medications for Diabetes

Brand Names: Lantus, Lantus OptiClik Cartridge, Lantus Solostar Pen
Generic Name: insulin glargine

Pronounced: (IN soo lin GLAR jeen)

Lantus, OptiClik, Solostar Pen, full prescribing information

What is Lantus and why is Lantus prescribed?

Lantus (insulin glargine) is a man-made form of a natural hormone. It is a long-acting insulin that is slightly different from other forms of insulin that are not man-made and it works by lowering levels of glucose in the blood.

Lantus is used to treat type 1 (insulin-dependent) or type 2 (non insulin-dependent) diabetes.

Lantus may also be used for other purposes not listed.

Important information about Lantus

Do not use Lantus if you are allergic to insulin glargine.

Take care to keep your blood sugar from getting too low, causing hypoglycemia. Symptoms of low blood sugar may include headache, nausea, hunger, confusion, drowsiness, weakness, dizziness, blurred vision, fast heartbeat, sweating, tremor, or trouble concentrating. Carry a piece of non-dietetic hard candy or glucose tablets with you in case you have low blood sugar. Also be sure your family and close friends know how to help you in an emergency.

Also watch for signs of blood sugar that is too high (hyperglycemia). These symptoms include increased thirst, loss of appetite, increased urination, nausea, vomiting, drowsiness, dry skin, and dry mouth. Check your blood sugar levels and ask your doctor how to adjust your insulin doses if needed.

Never share an injection pen or cartridge with another person. Sharing injection pens or cartridges can allow disease such as hepatitis or HIV to pass from one person to another.

Lantus is only part of a complete program of treatment that may also include diet, exercise, weight control, foot care, eye care, dental care, and testing your blood sugar. Follow your diet, medication, and exercise routines very closely. Changing any of these factors can affect your blood sugar levels.

Before using Lantus

Do not use Lantus if you are allergic to insulin glargine.

Before using Lantus, tell your doctor if you have liver or kidney disease.

Tell your doctor about all other medications you use, including any oral (by mouth) diabetes medications.

Lantus is only part of a complete program of treatment that may also include diet, exercise, weight control, foot care, eye care, dental care, and testing your blood sugar. Follow your diet, medication, and exercise routines very closely. Changing any of these factors can affect your blood sugar levels.

Your doctor will need to check your progress on a regular basis. Do not miss any scheduled appointments.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether Lantus passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

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How should I use Lantus?

Use Lantus exactly as it was prescribed for you. Do not use it in larger amounts or for longer than recommended by your doctor. Follow the directions on your prescription label.

You should not mix Lantus with other insulins.

Lantus is given as an injection (shot) under your skin. Your doctor, nurse, or pharmacist will give you specific instructions on how and where to inject this medicine. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

Lantus should be thin, clear, and colorless. Do not use the medication if it has changed colors or has any particles in it. Call your doctor for a new prescription.

Choose a different place in your injection skin area each time you use Lantus. Do not inject into the same place two times in a row.

Use each disposable needle only one time. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

The SoloStar injection pen contains a total of 300 units of insulin. The pen is designed to deliver from 1 to 80 units with each press of the injection button. Do not press the button more than one time per injection unless your doctor has prescribed a dose greater than 80 units.

Never share an injection pen or cartridge with another person. Sharing injection pens or cartridges can allow disease such as hepatitis or HIV to pass from one person to another.

Check your blood sugar carefully during a time of stress or illness, if you travel, exercise more than usual, or skip meals. These things can affect your glucose levels and your Lantus insulin dose needs may also change.

Watch for signs of blood sugar that is too high (hyperglycemia). These symptoms include increased thirst, loss of appetite, increased urination, nausea, vomiting, drowsiness, dry skin, and dry mouth. Check your blood sugar levels and ask your doctor how to adjust your Lantus insulin doses if needed.

Ask your doctor how to adjust your Lantus dose if needed. Do not change your dose without first talking to your doctor. Carry an ID card or wear a medical alert bracelet stating that you have diabetes, in case of emergency. Any doctor, dentist, or emergency medical care provider who treats you should know that you are diabetic. Storing unopened vials, OptiClik, or SoloStar devices: Keep in the carton and store in a refrigerator, protected from light. Throw away any insulin not used before the expiration date on the medicine label. Store the injection pen with its cap on. Unopened vials, OptiClik, or SoloStar devices may also be stored at room temperature for up to 28 days, away from heat and bright light. Throw away any insulin not used within 28 days.

Storing after your first use: You may keep "in-use" vials or cartridges not yet loaded into the OptiClik in the refrigerator or at room temperature, protected from light. Use within 28 days.

Do not refrigerate an in-use OptiClik or SoloStar device, or a cartridge that has been inserted into the OptiClik. Keep it at room temperature and use within 28 days.

Do not freeze Lantus, and throw away the medication if it has become frozen.

What happens if I miss a dose?

Use the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use extra medicine to make up the missed dose. You should not use more than one dose in a 24-hour period unless your doctor tells you to.

It is important to keep Lantus on hand at all times. Get your prescription refilled before you run out of medicine completely.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine. An insulin overdose can cause life-threatening hypoglycemia.

Symptoms of severe hypoglycemia include extreme weakness, blurred vision, sweating, trouble speaking, tremors, stomach pain, confusion, seizure (convulsions), or coma.

What should I avoid while using Lantus?

Do not change the brand of insulin glargine or syringe you are using without first talking to your doctor or pharmacist. Avoid drinking alcohol. Your blood sugar may become dangerously low if you drink alcohol while using Lantus. Do not expose Lantus to high heat.

Lantus side effects

Get emergency medical help if you have any of these signs of insulin allergy: itching skin rash over the entire body, wheezing, trouble breathing, fast heart rate, sweating, or feeling like you might pass out.

Hypoglycemia, or low blood sugar, is the most common side effect of Lantus. Symptoms of low blood sugar may include headache, nausea, hunger, confusion, drowsiness, weakness, dizziness, blurred vision, fast heartbeat, sweating, tremor, trouble concentrating, confusion, or seizure (convulsions). Watch for signs of low blood sugar. Carry a piece of non-dietetic hard candy or glucose tablets with you in case you have low blood sugar.

Tell your doctor if you have itching, swelling, redness, or thickening of the skin where you inject Lantus.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Lantus?

Using certain medicines can make it harder for you to tell when you have low blood sugar. Tell your doctor if you use any of the following:

• albuterol (Proventil, Ventolin);
• clonidine (Catapres);
• reserpine;
• guanethidine (Ismelin); or
• beta-blockers such as atenolol (Tenormin), bisoprolol (Zebeta), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), timolol (Blocadren) and others.

There are many other medicines that can increase or decrease the effects of Lantus on lowering your blood sugar. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor. Keep a list with you of all the medicines you use and show this list to any doctor or other healthcare provider who treats you.

Where can I get more information?

• Your pharmacist can provide more information about Lantus.
• Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Lantus only for the indication prescribed.

Lantus, OptiClik, Solostar Pen, full prescribing information

Detailed Info on Signs, Symptoms, Causes, Treatments of Diabetes

last updated 04/2006

back to: Browse all Medications for Diabetes

Experience, Inc., the leading provider of career services to students and alumni, today announced the findings from a recent online poll of more than 400 hovering over their children, or 'helic students and recent graduates regarding the growing trend of parentsopter parents.'

While the overwhelming majority of students describe their parents as moderately involved, 25% of them responded that their parents were "overly involved to the point that their involvement was either annoying or embarrassing." Conversely, 13% of the respondents said their parents were not involved at all.

"This is a time when students are setting out on their own," said Zi Teng Wang, a freshman at Washington University in St. Louis. "For example, my father threw me a Fortune magazine with the 'Top 500' companies and told me to just send a resume to every one on the list. He called it an internship search, which was very frustrating. Parents mean well, but anxiety from being separated from their children can drive them to grab onto the steering wheel and never let go."

Thirty-eight percent of students admitted that their parents had either called into, or physically attended meetings with academic advisors, and 31% of students reported that their parents had called professors to complain about a grade. But the ties run strong on both sides: 65% of young adults still seek counsel from their parents on their academic and career paths.

Survey Methodology

Experience's "Helicopter Parents" online poll was completed on January 11, 2006. Students who visited Experience.com were invited to participate in the poll, and over 400 of them voluntarily completed the survey.

Psychotherapy is an effective treatment for anxiety disorders. Read how therapy helps anxiety disorders sufferers.

Role of Psychotherapy in Effective Treatment of Anxiety

Everyone feels anxious and under stress from time-to-time. Situations such as meeting tight deadlines, important social obligations or driving in heavy traffic, often bring about anxious feelings. Such mild anxiety may help make you alert and focused on facing threatening or challenging circumstances. On the other hand, anxiety disorders cause severe distress over a period of time and disrupt the lives of individuals suffering from them. The frequency and intensity of anxiety involved in these disorders is often debilitating. But fortunately, with proper and effective treatment, people suffering from anxiety disorders can lead normal lives.

• What are the major kinds of anxiety disorders?
• Why is it important to seek treatment for these anxiety disorders?
• Are there effective treatments available for anxiety disorders?
• How can a qualified therapist help someone suffering from an anxiety disorder?
• How long does psychological treatment take?

What are the major kinds of anxiety disorders?

There are several major types of anxiety disorders, each with its own characteristics.

• People with generalized anxiety disorder have recurring fears or worries, such as about health or finances, and they often have a persistent sense that something bad is just about to happen. The reason for the intense feelings of anxiety may be difficult to identify. But the fears and worries are very real and often keep individuals from concentrating on daily tasks.
• Panic disorder involves sudden, intense and unprovoked feelings of terror and dread. People who suffer from this disorder generally develop strong fears about when and where their next panic attack will occur, and they often restrict their activities as a result.
• A related disorder involves phobias, or intense fears, about certain objects or situations. Specific phobias may involve things such as encountering certain animals or fear of flying in airplanes, whereas social phobias involve fear of social settings or public places.
• Obsessive-compulsive disorder is characterized by persistent, uncontrollable and unwanted feelings or thoughts (obsessions) and routines or rituals in which individuals engage to try to prevent or rid themselves of these thoughts (compulsions). Examples of common compulsions include washing hands or cleaning house excessively for fear of germs, or checking over something repeatedly for errors.
• Someone who suffers severe physical or emotional trauma such as from a natural disaster or serious accident or crime may experience post-traumatic stress disorder. Thoughts, feelings and behavior patterns become seriously affected by reminders of the event, sometimes months or even years after the traumatic experience. Symptoms such as shortness of breath, racing heartbeat, trembling and dizziness often accompany certain anxiety disorders such as panic and generalized anxiety disorders. Although they may begin at any time, anxiety disorders often surface in adolescence or early adulthood. There is some evidence of a genetic or family predisposition to certain anxiety disorders.

Why is it important to seek treatment for these disorders?

If left untreated, anxiety disorders can have severe consequences. For example, some people who suffer from recurring panic attacks avoid at all costs putting themselves in a situation that they fear may trigger another panic attack. Such avoidance behavior may create problems by conflicting with job requirements, family obligations or other basic activities of daily living.

Many people who suffer from an untreated anxiety disorder are prone to other psychological disorders, such as depression, and they have a greater tendency to abuse alcohol and other drugs. Their relationships with family members, friends and coworkers may become very strained. And their job performance may falter.

Are there effective treatments available for anxiety disorders?

Absolutely. Most cases of anxiety disorder can be treated successfully by appropriately trained health and mental health care professionals.

According to the National Institute of Mental Health, research has demonstrated that both 'behavioral therapy' and 'cognitive therapy' can be highly effective in treating anxiety disorders. Behavioral therapy involves using techniques to reduce or stop the undesired behavior associated with these disorders. For example, one approach involves training patients in relaxation and deep breathing techniques to counteract the agitation and hyperventilation (rapid, shallow breathing) that accompany certain anxiety disorders.

Through cognitive therapy, patients learn to understand how their thoughts contribute to the symptoms of anxiety disorders, and how to change those thought patterns to reduce the likelihood of occurrence and the intensity of reaction. The patient's increased cognitive awareness is often combined with behavioral techniques to help the individual gradually confront and tolerate fearful situations in a controlled, safe environment.

Proper and effective anti-anxiety medications may have a role in treatment along with psychotherapy. In cases where medications are used, the patient's care may be managed collaboratively by a therapist and physician. It is important for patients to realize that there are side effects to any drugs, which must be monitored closely by the prescribing physician.

How can a qualified therapist help someone suffering from an anxiety disorder?

Licensed psychologists are highly qualified to diagnose and treat anxiety disorders. Individuals suffering from these disorders should seek a provider who is competent in cognitive and behavioral therapies. Experienced mental health professionals have the added benefit of having helped other patients recover from anxiety disorders.

Family psychotherapy and group psychotherapy (typically involving individuals who are not related to one another) offer helpful approaches to treatment for some patients with anxiety disorders. In addition, mental health clinics or other specialized treatment programs dealing with specific disorders such as panic or phobias may also be available nearby.

How long does psychological treatment take?

It is very important to understand that treatments for anxiety disorders do not work instantly. The patient should be comfortable from the outset with the general treatment being proposed and with the therapist with whom he or she is working. The patient's cooperation is crucial, and there must be a strong sense that the patient and therapist are collaborating as a team to remedy the anxiety disorder.

No one plan works well for all patients. Treatment needs to be tailored to the needs of the patient and to the type of disorder, or disorders, from which the individual suffers. A therapist and patient should work together to assess whether a treatment plan seems to be on track. Adjustments to the plan sometimes are necessary, since patients respond differently to treatment.

Many patients will begin to improve noticeably within eight to ten sessions, especially those who carefully follow the outlined treatment plan.

There is no question that the various kinds of anxiety disorders can severely impair a person's functioning in work, family and social environments. But the prospects for long-term recovery for most individuals who seek appropriate professional help are very good. Those who suffer from anxiety disorders can work with a qualified and experienced therapist such as a licensed psychologist to help them regain control of their feelings and thoughts -- and their lives.

Source: American Psychological Assoc., October 1998

next: Monoamine Oxidase Inhibitors (MAOIs) for Social Anxiety Disorder
~ anxiety-panic library articles
~ all anxiety disorders articles

If you have a broken leg, you can tell people you have a fracture in your left tibia. If you have a bad heart you can let people know you have a weak aortic valve. But what do you say if you have a mood disorder? Most of us settle for the explanation that we have a chemical imbalance, which is about as satisfactory as your mechanic handing you a bill with this one item: "Engine Imbalance."

Then there is the matter of collateral damage. We know depression can stop the brain it its tracks while mania runs it off the rails, with corresponding deficits in our ability to think and reason, but we are led to believe these are only temporary occurrences, right? Maybe not.

If only a mood disorder were just a mood disorder. A lengthy review article by Carrie Bearden PhD et al of the University of Pennsylvania published in Bipolar Disorders cites "findings of persistent neuropsychological deficits" in long-term bipolar patients, even when tested in symptom-free states. The relationship between these deficits and length of illness led the authors to suggest that "episodes of depression and mania may exact damage to learning and memory systems."

An article by FC Murphy PhD and BJ Sahakian PhD of Cambridge University in the British Journal of Psychiatry draws a similar conclusion: "The balance of evidence ... supports a hypothesis of residual cognitive impairments."

Father Time appears to be a major factor. Dr Bearden et al cite a study that found that chronic, multiple-episode patients exhibited more severe cognitive impairment than younger patients or patients who remit, and that these impairments were not restricted to their affective episodes. The same study found 40 percent of the patients were rapid-cyclers. Another study found that of 25 patients initially hospitalized with mania with no signs of cognitive impairment, one third showed significant cognitive impairment five to seven years later.

There is always the possibility that the meds are responsible. One long-term study found lithium users (one-third who had a university degree) to be in the low average range on functions of attention and memory. Nevertheless, the authors believe that while medication may cause some degree of cognitive slowing, our pills are not the main culprit.

Bearden et al's review of what could be wrong with the brain reads like a neurologist's laundry list from hell: ventricular enlargements, cortical atrophy, cerebellar vermal atrophy, white matter hypertensities (especially in the frontal cortex and basal ganglia structures), greater left temporal lobe volume, increased amygdala volume, enlarged right hippocampal volume, hypoplasmia of the medial temporal lobe, and more. Then there's the matter of those chemical imbalances, such as glucose metabolism and phospholipid metabolism.

Say all that in rap time and you have the sound of our brains breaking down, no longer capable of processing information the way it is supposed to. It is possible that these studies did not adequately account for the normal aging process, as Dr Bearden was ready to acknowledge to this writer, but she also added that it is "likely that there is an interaction between the disease process and normal aging processes, such that people affected with bipolar illness are somehow more vulnerable to the effects of aging."

Lest we cause a panic, Dr Bearden wants to remind readers that "while these brain differences are there, they are subtle. They are certainly not present in all people with bipolar illness, nor do we really know what there functional significance may be in any given individual. And most likely if a radiologist were to take a glance at a brain scan of a person with bipolar disorder, it would look normal - it's just when you actually measure things quantitatively that you find differences. I realize that sometimes these research findings can sound really horrific, and I don't want to cause anyone undue concern."

Also, it appears that our current bipolar medications actually repair and protect brain cells, which is one of the better arguments for staying compliant. Further research in this area may produce new drugs with enhanced neuroprotective properties.

One day, perhaps, brain doctors will be able to open up the hood and do a valve job. Researchers at the Salk Institute of Biological Studies isolated stem cells from the hippocampus of adult rats and modified the gene to produce glowing proteins, which were cloned and took on the properties of adult neurons as they matured, including the ability in some to make synaptic connections with other neurons. Alzheimer's and Parkinson's come most immediately to mind in the context of this type of research, but a mood application can't be far beyond that, assuming they can get the technology to work in humans, which is a very big if. In the meantime, there is hope, which we may have to suffice for the next decade or two.

next: UCLA-led Study Challenges Bipolar Depression Treatment Guidelines
~ bipolar disorder library
~ all bipolar disorder articles

USA WEEKEND Magazine and the world-famous Kinsey Institute team up for a special report to the nation. Topic: the most important things science has learned about sex. We've come a long way, baby.

A ubiquitous topic that no one likes to discuss. A highly private act that catches the public eye. Sublime. Dangerous. Compelling. Confusing. The most fundamental of human experiences, and the one responsible for the perpetuation our species. Sex.

In recent decades, America's sexual landscape has been rearranged by forces including new forms of contraception, skyrocketing divorce rates, a sea change in women's societal roles and an explosion of graphic media imagery. Even the idea of what constitutes sex -- think Bill Clinton and Monica Lewinsky -- has changed.

Today, USA WEEKEND Magazine teams up with the Kinsey Institute for Research in Sex, Gender and Reproduction to assess America's sexual health and understanding. The Indiana University-based research institute has created headlines for more than 50 years, ever since biologist Alfred Kinsey published "Sexual Behavior in the Human Male" and "Sexual Behavior in the Human Female" -- collectively known as the Kinsey reports. These landmark volumes shed the first scientific light on once-taboo topics, such as homosexuality, premarital sex and masturbation. The institute (kinseyinstitute.org) has continued to study human sexuality and has become the world's foremost repository of information about sex.

Sort through it all, says noted sex researcher and psychiatrist John Bancroft, M.D., director of the Kinsey Institute since 1995, and "the United States is in a mess, as far as sex is concerned." For instance, nearly half of all pregnancies are unintended, with 835,000 teenage pregnancies annually; they are said to cost the United States as much as $15 billion a year.

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Research into human sexuality could help improve these dismal numbers, as well as unravel significant medical and psychological mysteries, Bancroft says. Unfortunately, societal discomfort about sex marginalizes -- and sometimes condemns -- scientific sex research. As a result, he concedes, "It's difficult to think of any important aspect of the human condition about which we know less."

Nonetheless, sex researchers have made progress in psychological and physiological fields. Below is Bancroft's list of today's most important findings on sex.

Sexuality defines our lives. Sexuality is central to all of us -- even people who aren't sexually active. "It's absolutely fundamental to the organization of human society and has been from the earliest history," Bancroft says.

Studies show that sexuality plays a significant role in our self-esteem and emotional well-being. "For most people, what they think about themselves as a sexual person is a very important part of how they think about themselves as a human being," Bancroft explains. "The effect of having a good sexual relationship on one's well-being is very substantial." A 2000 Kinsey survey found that general physical and mental health were strongly correlated to sexual well-being and satisfaction. Poor health tended to increase sexual problems and decrease desire.

There's no "normal." Decades of scientific inquiry have made clear that sexuality exists on a continuum: No two people are exactly the same in their level of sexual interest, patterns of response or interests. And because of this variability, there really is no such thing as a "normal" frequency of sexual activity or a "normal" number of fantasies. "What is right for two people in a relationship is what works for them," Bancroft says.

Women and men have different needs. Kinsey was one of the first to question the assumption that female sexuality has the same basis as male sexuality; his findings showed that only a minority of women achieve orgasm through intercourse alone. Continued research has demonstrated the complexity of women's sexuality. A 2003 Kinsey study found that the quality of women's emotional interaction with their partner during sex proved more important than the physical aspects, such as orgasm, in determining sexual satisfaction.

Intimacy becomes more important with age. Although sexual interest and the ease of sexual response tend to decrease with age, the quality of the sexual relationship need not deteriorate. In an AARP survey of close to 1,400 adults over 45, two out of three of those with partners said they were extremely or somewhat satisfied with their sex lives. "Provided both partners can be open with each other, the importance of their sexual relationship may shift in emphasis from shared pleasure to shared intimacy," Bancroft says. Unfortunately, normal changes associated with aging -- especially men's inability to achieve consistent erections -- often are misinterpreted as a relationship failure.

Help has been found for male dysfunction. About 5% to 10% of men under 50 have erection problems due to a host of medical and psychological conditions, a number that increases sharply with age. Compared with some of the very unwieldy treatment methods that have evolved over the past 20 years, including penile implants and injections, the introduction of Viagra and drugs like it has been revolutionary. "Although it's not without side effects, it's available, it works for most people, and there wasn't anything like it there before," Bancroft says. Meanwhile, there's a push to find an equivalent drug for women, a search complicated by the fact that genital response is far less central to women's experience than erections are to men's. Low sexual interest is the most commonly reported sexual problem in women; researchers are trying to determine how often it is hormonally based.

Orientation isn't a choice. Research shows most people become aware of their sexual orientation around puberty and perhaps as early as age 10. Findings such as the discovery of the so-called gay gene have shown that genetics play a role in determining why a minority of people end up with a same-sex orientation, but Bancroft holds that genes are "just part of the picture. There are far more questions than answers."

Being ill -- and taking medicine -- can cause sexual problems. Many common medical conditions, such as depression and high blood pressure, can cause sexual problems. One of the downsides to modern medicine, however, is that the medications used to treat those conditions also can negatively impact sexual functioning. And although Bancroft says he was pushed aside when he tried to research this issue in the 1970s, it has been taken more seriously in the medical community recently.

The 2003 Kinsey study found that negative side effects on sex and mood were the most likely reason for women to discontinue oral contraceptives -- sexual impairment was cited by 86% of women who discontinued. "This is an important aspect of women's reproductive health that has not received the attention that it should from the medical profession and the pharmaceutical industry," Bancroft says.

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The media create sexual expectations. The publication of Kinsey's work 50 years ago generated a crush of media coverage. "There was shock sometimes, and horror sometimes, and amazement at how much people were doing [sexually]," Bancroft says. "Now there seems to be a preoccupation with how little people are doing."

Indeed, recently headlines have screamed that Americans are sex-starved. But Bancroft isn't so sure there's any scientific substance behind the hype. "We haven't got any clear evidence that this is the case, but that doesn't seem to deter [the media]." The reality of our sex lives is probably far less dramatic than the media would have us believe.

Technology transforms sex lives. When photography became widely available at the end of the 19th century, it soon was put to use to provide erotic images. More recently, the Internet has been both a boon and a menace to healthy sexuality. Although it provides access to very personalized information and can serve as a means of support and connection for those whose sexuality makes them feel isolated, others are unable to resist the lure of interactive Internet pornography, a fact Bancroft deems "quite scary."

Because an extraordinary variety of sexual stimuli is accessible in relatively private settings, he maintains that Internet erotica is potentially far more dangerous than traditional print or video sources and can interfere with relationships and work performance while emptying bank accounts. The National Council on Sex Addiction and Compulsivity estimates that a staggering 2 million Americans are addicted to cybersex.

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4 ways to improve America's sexual health

John Bancroft, M.D., director of the Kinsey Institute, provides his prescription for a healthier society.

Eradicate the sexual double standard. "Until we have achieved a society in which sexual responsibility is equally shared by men and women, from early adolescence onward, we will continue to have major social as well as personal problems associated with sex."

Teach sexual responsibility to young people. "The expectation is that young people will spend their years of maximum sexual arousability in a society that bombards them constantly with sexual messages in a state of 'suspended sexuality.' It does not help to deny information to adolescents when they are experiencing sexual feelings. It is also not possible to teach our youth to behave in a responsible manner without being open and honest about sex."

Respect all varieties of sexual expression, as long as they are handled responsibly. Sexual responsibility, Bancroft says, means protecting against disease and unwanted pregnancy, avoiding causing physical or psychological harm to ourselves and our partners, participating only in truly consensual sex and avoiding sexual exploitation of those too young to make responsible decisions.

Encourage trust. Being sexual means letting go. Feeling safe to do so with a partner has a powerful bonding effect. Conversely, many sexual problems result from not feeling safe or from being hurt while vulnerable.

Kinsey, the movie

The historic, sometimes demonized work of Alfred Kinsey is coming to the big screen. "Kinsey", starring Liam Neeson, is expected in theaters next fall.

"He's a really fascinating, complicated guy," says writer-director Bill Condon, who wrote the screenplay for the Academy Award winner "Chicago", "but the thing that makes it compelling is that the questions he raised are still relevant."

The Kinsey Institute is not formally involved in the production but made materials --including personal scrapbooks and letters -- available to the filmmakers.

Condon is "bracing for controversy" surrounding the film, but don't expect anything too heavy: "It's about sex, so it can't help but be funny."

Sex by the numbers ...

We're monogamous in marriage

Women: more than 80%

Men: 65% to 85%

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We think about sex ...

Every day:

Men, 54%;
Women, 19%

A few times a month/week:

Men, 43%;
Women, 67%

Less than once a month:

Men, 4%;
Women, 14%

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Frequency of sex

Ages 18-29: Average 112 times a year

Ages 30-39: Average 86 times a year

Ages 40-49: Average 69 times a year

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Contraception

90% of sexually active women and their partners use contraception, although not always consistently or correctly. Sexually transmitted diseases 15 million new cases a year

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Cover photograph by Simon Watson, Getty Images.

next: Guidelines for Diagnosis and Treatment of Sexual Dysfunction

When your partner has no interest in sex despite your best efforts, it's easy to become perplexed. And without guidance, partners may characterize the problem in ways that can destroy the relationship.

Sex: What Problem?

Kelly seemed to have it all. A loving mother of three and a public-relations executive in Manhattan, she had a handsome and charming partner who was a successful entrepreneur. They jetted off for vacations in the Caribbean and dined in the finest restaurants. But their relationship floundered in one intractable area.

"After a while," Kelly says, "he just stopped wanting to have sex. He'd go months without even touching me."

It's a subject that's full of shame: low sex drive. When your partner has no interest in sex despite your best efforts, it's easy to become perplexed. And without guidance, partners may characterize the problem in ways that can destroy the relationship.

In a society saturated with sexual imagery, it seems strange that some people have no desire for sex. But it is a startlingly common problem. Millions of people suffer from a condition known as hypoactive sexual desire (HSD), about 25 percent of all Americans, by one estimate, or a third of women and a fifth of men. Sex researchers and therapists now recognize it as the most common sexual problem.

In recent years, experts have turned their attention to the causes of low sexual desire, and sex therapists are working on strategies to treat it. Although there is a 50 percent positive outcome in treatment of hypoactive sexual desire, many of those who have HSD don't seek help. This is usually because they don't realize it's a problem, other issues in the relationship seem more important or they feel ashamed.

Many couples in conflict may have an underlying problem with sexual desire. When desire fades in one partner, other things start to fall apart.

How little is too little?

For Pam, happily married and in her forties, her once healthy sexual desire simply disappeared about six months ago. "I don't know what has happened to my sexual appetite," she says, "but it is like someone turned it off at the switch." She and her husband still have sex, maybe once every few weeks, but she does it out of obligation, not enthusiasm.

"I used to enjoy sex," Pam says. "Now there's a vital part of me that's missing."

Ordinary people aren't in a constant state of sexual desire. Everyday occurrences "fatigue, job stress, even the common cold" can drive away urges for lovemaking. Usually, however, spending romantic time with a partner, having sexual thoughts or seeing stimulating images can lead to arousal and the return of a healthy sex drive.

Yet for some people, desire never returns, or was never there to begin with. Frequently, even healthy sexual fantasies are virtually nonexistent in some people who suffer from HSD.

Just how little sex is too little? Sometimes, when a partner complains of not having enough sex, his problem may actually be an unusually high sex drive. Experts agree that there is no daily minimum requirement of sexual activity. In a British survey, published in the Journal of Sex and Marital Therapy, 24 percent of couples reported having no sex in the previous three months. And the classic study, Sex in America, found that one-third of couples had sex just a few times a year. Although the studies report frequency of sex, not desire, it's likely that one partner in these couples has HSD.

One tiny pill

Years ago, another sexual problem "erectile dysfunction" received a sudden burst of attention when a medical "cure" hit the shelves. Before Viagra came along, men with physically based problems suffered impotence in silence, and without much hope. Now many couples enjoy a renewed reservoir of passion.

Obviously, any pill that relieves hypoactive sexual desire would be wildly popular. Unfortunately, the causes of HSD seem to be complex and varied; some sufferers might be treated with a simple pill, but most will likely need therapy -- not chemistry.

Researchers believe that SSRIs quash the libido by flooding the bloodstream with serotonin, a chemical that signals satiety. "The more you bathe people in serotonin, the less they need to be sexual," says Joseph Marzucco, MSPAC, a sex therapist practicing in Portland, Oregon. "SSRIs can just devastate sexual desire."

Fortunately, researchers are studying antidepressants that act through other channels. Bupropion hydrochloride (Wellbutrin), which enhances the brain's production of the neurotransmitters dopamine and norepinephrine, has received extra attention as a substitute for SSRIs. Early studies suggest that it may actually increase sexual desire in test subjects. A study reported last year in the Journal of Sex and Marital Therapy found that nearly one-third of participants who took bupropion reported more desire, arousal and fantasy.

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It's all in your head

Physiological problems can also lead to a loss of sexual desire. Men with abnormal pituitary glands can overproduce the hormone prolactin, which usually turns off the sex drive. As reported in the International Journal of Impotence Research, tests of a drug that blocks prolactin found it increased the libido in healthy males.

In women, some experts believe that one cause of weak sexual desire is, ironically, low testosterone levels. Normally associated with brawny, deep-voiced men, testosterone is a hormone with a definite masculine identity. But women also make small amounts of it in their ovaries, and it plays an important role in their sexual lives. Without a healthy level of testosterone in the blood, some researchers believe, women are unable to properly respond to sexual stimuli. Furthermore, there is anecdotal evidence that testosterone supplements can restore the sex drive in women.

Rosemary Basson, M.D., of the Vancouver Hospital and Health Sciences Center in British Columbia, however, cautions that too little is known about the role testosterone plays in women. "We don't even know how much testosterone is normal," Basson says. "The tests designed for men can't pick up the levels found in women."

In one study suggesting that HSD is more psychological than physiological, Basson and her colleagues tested the effects of Viagra on women who reported arousal problems. Basson found that while the drug generally produced the physical signals of sexual arousal, many women reported that they still didn't feel turned on.

Indeed, many psychologists and sex therapists believe that most patients with HSD have sound bodies and troubled relationships. The clinical experience of Weeks has shown that two factors identified in a relationship can, over time, devastate the sex drive: chronically suppressed anger toward the partner and a lack, or loss, of control over the relationship. And once these issues threaten a healthy sex drive, lack of intimacy can aggravate the problems further. Without help, these issues can balloon until the relationship itself is seriously damaged. And, consequently, HSD becomes further entrenched.

Lacking the desire for desire

Although hypoactive sexual desire is one of the most difficult to address of all sexual problems, it can be treated successfully. The key is to find a highly qualified sex and marital therapist who has experience in dealing with it. Unfortunately, while HSD is the most common problem that sex therapists see, millions of cases go untreated.

Some people who lack desire are just too embarrassed to seek help, especially men. Others are so focused on immediate concerns -- such as a stressful job or a family crisis, that they put off dealing with the loss of a healthy libido. Still others have become so used to having no sex drive that they no longer miss it; they lack the desire for desire. These people represent the most severe cases, the hardest to treat.

Some people who don't get treatment find ways to adjust. "Thank goodness my husband is so patient and caring," Pam says. "He tries to spark interest, but when it is not ignited he'll settle for cuddling and caressing."

Other relationships can't survive the strain. After a year, Kelly and her boyfriend broke up. "I couldn't convince him that it was a problem," she says, "but it was."

Gerald Weeks, Ph.D., A.B.S., is a professor of counseling at the University of Nevada in Las Vegas and a board certified sex therapist of the American Board of Sexology. Jeffrey Winters, formerly with Discover magazine, is a science writer based in New York.

Brand Name: GlucaGen
Generic Name: Glucagon Hydrochloride

Contents:

Description
Pharmacology
Indications and Usage
Contraindications
Warnings
Precautions
Adverse Reactions
Overdose
Dosage and Administration
Stability and Storage
How Supplied
Information for Patients

GlucaGen, glucagon hydrochloride, patient information (in plain English)

Description

GlucaGen^® (glucagon [rDNA origin] for injection) manufactured by Novo Nordisk A/S is produced by expression of recombinant DNA in a Saccharomyces cerevisiae vector with subsequent purification.

The chemical structure of the glucagon in GlucaGen^® is identical to naturally occurring human glucagon and to glucagon extracted from beef and pork pancreas. Glucagon with the empirical formula of C₁₅₃H₂₂₅N₄₃O₄₉S, and a molecular weight of 3483, is a single-chain polypeptide containing 29 amino acid residues. The structure of glucagon is:

GlucaGen^® 1 mg (1 unit) is supplied as a sterile, lyophilized white powder in a 2 ml vial, alone, or accompanied by Sterile Water for Reconstitution (1 ml) also in a 2 ml vial (10 pack or diagnostic kit). It is also supplied as a HypoKit with a disposable prefilled syringe containing 1 ml Sterile Water for Reconstitution. Glucagon, as supplied at pH 2.5-3.5, is soluble in water.

Active Ingredient in each vial

Glucagon as hydrochloride 1 mg (corresponding to 1 unit).

Other Ingredients

Lactose monohydrate (107 mg)

When the glucagon powder is reconstituted with Sterile Water for Reconstitution (if supplied) or with Sterile Water for Injection, USP, it forms a solution of 1 mg (1 unit)/ml glucagon for subcutaneous (sc), intramuscular (im), or intravenous (iv) injection.

GlucaGen^® is an antihypoglycemic agent, and a gastrointestinal motility inhibitor.

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Clinical Pharmacology

Intramuscular (im) injection of GlucaGen^® resulted in a mean C_max (CV%) of 1686 pg/ml (43%) and median T_max of 12.5 minutes. The mean apparent half-life of 45 minutes after im injection probably reflects prolonged absorption from the injection site. Glucagon is degraded in the liver, kidney, and plasma.¹

Antihypoglycemic Action:

Glucagon induces liver glycogen breakdown, releasing glucose from the liver. Blood glucose concentration rises within 10 minutes of injection and maximal concentrations are attained at approximately a half hour after injection (see Figure). Hepatic stores of glycogen are necessary for glucagon to produce an antihypoglycemic effect.

Recovery from insulin induced hypoglycemia (mean blood glucose) after im injection of 1 mg GlucaGen^® in Type I diabetic men

Gastrointestinal Motility Inhibition: Extra hepatic effects of glucagon include relaxation of the smooth muscle of the stomach, duodenum, small bowel, and colon.

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Indications and Usage

For the treatment of hypoglycemia:

GlucaGen^® is used to treat severe hypoglycemic (low blood sugar) reactions which may occur in patients with diabetes treated with insulin. Because GlucaGen^® depletes glycogen stores, the patient should be given supplemental carbohydrates as soon as he/she awakens and is able to swallow, especially children or adolescents. Medical evaluation is recommended for all patients who experience severe hypoglycemia.

For use as a diagnostic aid:

GlucaGen^® is indicated for use during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract. Glucagon is as effective for this examination as are the anticholinergic drugs. However, the addition of the anticholinergic agent may result in increased side effects. Because GlucaGen^® depletes glycogen stores, the patient should be given oral carbohydrates as soon as the procedure is completed.

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Contraindications

Glucagon is contraindicated in patients with known hypersensitivity to glucagon or any constituent in GlucaGen^® and in patients with pheochromocytoma or with insulinoma.

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Warnings

GlucaGen^® should be administered cautiously to patients suspected of having pheochromocytoma or insulinoma. Secondary hypoglycemia may occur and should be countered by adequate carbohydrate intake following glucagon treatment.

Glucagon may release catecholamines from pheochromocytomas and is contraindicated in patients with this condition.

Allergic reactions may occur and include generalized rash, and in rare cases anaphylactic shock with breathing difficulties, and hypotension. The anaphylactic reactions have generally occurred in association with endoscopic examination during which patients often received other agents including contrast media and local anesthetics. The patients should be given standard treatment for anaphylaxis including an injection of epinephrine if they encounter respiratory difficulties after GlucaGen^® injection.

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Precautions

General

In order for GlucaGen^® treatment to reverse hypoglycemia, adequate amounts of glucose must be stored in the liver (as glycogen). Therefore, GlucaGen^® should be used with caution in patients with conditions such as prolonged fasting, starvation, adrenal insufficiency or chronic hypoglycemia because these conditions result in low levels of releasable glucose in the liver and an inadequate reversal of hypoglycemia by GlucaGen^® treatment. Caution should be observed when glucagon is used in diabetic patients or in elderly patients with known cardiac disease to inhibit gastrointestinal motility.

Information for Patients

Refer patients and family members to the "INFORMATION FOR PATIENTS" for instructions describing the method of preparing and injecting GlucaGen^®. Advise the patient and family members to become familiar with the technique of preparing glucagon before an emergency arises. Instruct patients to use 1 mg for adults or ½ the adult dose (0.5 mg) for children weighing less than 55 lbs (25 kg). To prevent severe hypoglycemia, patients and family members should be informed of the symptoms of mild hypoglycemia and how to treat it appropriately. Family members should be informed to arouse the patient as quickly as possible because prolonged hypoglycemia may result in damage to the central nervous system. Patients should be advised to inform their physician when hypoglycemic reactions occur so that the treatment regimen may be adjusted if necessary.

Laboratory Tests

Blood glucose measurements may be considered to monitor the patient's response.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies in animals to evaluate carcinogenic potential have not been performed. Several studies have been conducted to evaluate the mutagenic potential of glucagon. The mutagenic potential tested in the Ames and human lymphocyte assays, was borderline positive under certain conditions for both glucagon (pancreatic) and glucagon (rDNA) origin. In vivo, very high doses (100 and 200 mg/kg) of glucagon (both origins) gave a slightly higher incidence of micronucleus formation in male mice but there was no effect in females. The weight of evidence indicates that GlucaGen^® is not different from glucagon pancreatic origin and does not pose a genotoxic risk to humans.

GlucaGen^® was not tested in animal fertility studies. Studies in rats have shown that pancreatic glucagon does not cause impaired fertility.

Pregnancy - Pregnancy Category B

Reproduction studies were performed in rats and rabbits at GlucaGen^® doses of 0.4, 2.0, and 10 mg/kg. These doses represent exposures of up to 100 and 200 times the human dose based on mg/m2 for rats and rabbits, respectively, and revealed no evidence of harm to the fetus. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when GlucaGen^® is administered to a nursing woman.

No clinical studies have been performed in nursing mothers, however, GlucaGen® is a peptide and intact glucagon is not absorbed from the GI tract. Therefore, even if the infant ingested glucagon it would be unlikely to have any effect on the infant. Additionally, GlucaGen® has a short plasma half-life thus limiting amounts available to the child.

Pediatric use

For the treatment of hypoglycemia: The use of glucagon in pediatric patients has been reported to be safe and effective.

For use as a diagnostic aid: Safety and effectiveness in pediatric patients have not been established.

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Adverse Reactions

Severe side effects are very rare, although nausea and vomiting may occur occasionally especially with doses above 1 mg or with rapid injection (less than 1 minute).1 Hypotension has been reported up to 2 hours after administration in patients receiving GlucaGen^® as premedication for upper GI endoscopy procedures. Glucagon exerts positive inotropic and chronotropic effect and may, therefore, cause tachycardia and hypertension. Adverse reactions indicating toxicity of GlucaGen^® have not been reported. A transient increase in both blood pressure and pulse rate may occur following the administration of glucagon. Patients taking ß-blockers might be expected to have a greater increase in both pulse and blood pressure, an increase of which will be transient because of glucagon's short half-life. The increase in blood pressure and pulse rate may require therapy in patients with pheochromocytoma or coronary artery disease. (see OVERDOSAGE).

Allergic reactions may occur in rare cases. (see WARNINGS).

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Overdose

Signs and Symptoms

No reports of overdosage with GlucaGen^® have been reported. It is expected, if overdosage occurred, that the patient may experience nausea, vomiting, inhibition of GI tract motility, increase in blood pressure and pulse rate.1 In case of suspected overdosing, the serum potassium may decrease and should be monitored and corrected if needed.

The IV and SC LD₅₀ for GlucaGen^® in rats and mice ranges from 100 to greater than 200 mg/kg body weight.

Treatment

Standard symptomatic treatment may be undertaken if overdosage occurs. If the patient develops a dramatic increase in blood pressure, 5 to 10 mg of phentolamine mesylate has been shown to be effective in lowering blood pressure for the short time that control would be needed. It is unknown whether GlucaGen^® is dialyzable, but such a procedure is unlikely to provide any benefit given the short half-life and nature of the symptoms of overdose.

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Dosage and Administration

Directions for treatment of severe hypoglycemia:

Using the supplied prefilled syringe, carefully insert the needle through the rubber stopper of the vial containing GlucaGen^® powder and inject all the liquid from the syringe into the vial. Roll the vial gently until powder is completely dissolved and no particles remain in the fluid. The reconstituted fluid should be clear and of water-like consistency. The reconstituted GlucaGen^® gives a concentration of approximately 1 mg/ml glucagon. The reconstituted GlucaGen^® should be used immediately after reconstitution. Discard any unused portion. Inject 1 ml (adults and children, weighing more than 55 lbs) or ½ ml (children weighing less than 55 lbs) subcutaneously (s.c), intramuscularly (i.m), or intravenously (i.v). If the weight is not known: Children younger than 6 to 8 years should be given half dose (= ½ ml) and children older than 6 to 8 should be given the adult dose (1ml). Emergency assistance should be sought if the patient fails to respond within 15 minutes after subcutaneous or intramuscular injection of glucagon. The glucagon injection may be repeated while waiting for emergency assistance.1 Intravenous glucose MUST be administered if the patient fails to respond to glucagon. When the patient has responded to the treatment, give oral carbohydrate to restore the liver glycogen and prevent recurrence of hypoglycemia.

Directions for use as a diagnostic aid:

GlucaGen^® should be reconstituted with the supplied 1 ml of Sterile Water for Reconstitution (if supplied) or 1 ml Sterile Water for Injection, USP. Using a syringe, withdraw all of the Sterile Water for Reconstitution (if supplied) or 1 ml Sterile Water for Injection, USP and inject into the GlucaGen® vial. Roll the vial gently until powder is completely dissolved and no particles remain in the fluid. The reconstituted fluid should be clear and of water-like consistency. The reconstituted GlucaGen^® gives a concentration of approximately 1 mg/ml glucagon. The reconstituted GlucaGen^® should be used immediately after reconstitution. Discard any unused portion. When the diagnostic procedure is over, give oral carbohydrate to restore the liver glycogen and prevent occurrence of secondary hypoglycemia.

References for diagnostic aid use only:

Time of maximal glucose concentration	Time for GI smooth muscle relaxation
Intravenous: 5 to 20 minutes	Intravenous: 0.25 to 2 mg (IU) - 45 seconds
Intramuscular: 30 minutes Subcutaneous: 30 to 45 minutes	Intramuscular: 1 mg (IU) - 8 to 10 minutes 2 mg (IU) - 4 to 7 minutes

Duration of action -

Hyperglycemic action - 60 to 90 minutes

Smooth muscle relaxation -

Intravenous:

0.25 to 0.5 mg (IU) - 9 to 17 minutes

2 mg (IU) - 22 to 25 minutes

Intramuscular:

1 mg (IU) - 12 to 27 minutes

2 mg (IU) - 21 to 32 minutes

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Stability and Storage

Before Reconstitution:

The GlucaGen^® package may be stored up to 24 months at controlled room temperature 20^o to 25^o C (68^o to 77^o F) prior to reconstitution. Avoid freezing and protect from light. GlucaGen^® should not be used after the expiry date on the vials.

After Reconstitution:

Reconstituted GlucaGen^® should be used immediately. Discard any unused portion. If the solution shows any sign of gel formation or particles, it should be discarded.

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How Supplied

GlucaGen^® HypoKit includes:

1 vial containing 1 mg (1 unit) GlucaGen® (glucagon [rDNA origin] for injection)

1 disposable syringe containing 1 ml Sterile Water for Reconstitution

NDC 0169-7065-15

OR

GlucaGen^® Diagnostic Kit includes:

1 vial containing 1 mg (1 unit) GlucaGen^® (glucagon [rDNA origin] for injection)

1 vial containing 1ml Sterile Water for Reconstitution

NDC 55390-004-01

OR

The GlucaGen^® 10-pack includes:

10x1 vial containing 1 mg (1 unit) GlucaGen® (glucagon [rDNA origin] for injection)

NDC 55390-004-10

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Information for Patients

GlucaGen^® HypoKit

Emergency Use for Low Blood Sugar

(glucagon [rDNA origin] for injection) 1 mg.

BECOME FAMILIAR WITH THE FOLLOWING INSTRUCTIONS BEFORE AN EMERGENCY ARISES. DO NOT USE THIS PACKAGE AFTER THE EXPIRATION DATE. IF YOU HAVE QUESTIONS CONCERNING THE USE OF THIS PRODUCT, CONSULT A DOCTOR, NURSE, OR PHARMACIST.

Make sure that your relatives or close friends know that if you become unconscious, medical assistance must always be sought. GlucaGen^® may have been prescribed so that members of your household can give the injection if you become hypoglycemic (low blood sugar) and are unable to take sugar by mouth. If you are unconscious, GlucaGen^® can be given while awaiting medical assistance.

Show your family members and others where you keep this kit and how to use it. They need to know how to prepare it before you need it. They can practice giving a shot by giving you your normal insulin shots. It is important that they practice. A person who has never given a shot probably will not be able to do it in an emergency.

IMPORTANT

• Act quickly. Prolonged unconsciousness may be harmful.
• These simple instructions will help you give glucagon successfully.
• Turn patient on his/her side to prevent choking.
• The content of the syringe does not contain glucagon. You must mix the contents of the syringe with the glucagon in the accompanying bottle before giving injection. (see DIRECTIONS FOR USE)
• Do not mix GlucaGen^® until you are ready to use it.
• Discard any unused portion.
• Become familiar with the technique of preparing glucagon before an emergency arises.
• WARNING: THE PATIENT MAY BE IN A COMA FROM SEVERE HYPERGLYCEMIA (HIGH BLOOD SUGAR) RATHER THAN HYPOGLYCEMIA (LOW BLOOD SUGAR). IN SUCH A CASE, THE PATIENT WILL NOT RESPOND TO GLUCAGON AND REQUIRES IMMEDIATE MEDICAL ATTENTION.

INDICATION FOR USE

GlucaGen^® is used to treat severe hypoglycemic (low blood sugar) reactions which may occasionally occur in patients with diabetes. Symptoms of severe hypoglycemic reactions include disorientation, loss of consciousness, and seizures. You should only give GlucaGen^® injection if (1) the patient is unconscious, (2) the patient is having a seizure, or (3) the patient is disoriented and unable to eat sugar or a sugar-sweetened product. Milder cases of hypoglycemia should be treated promptly by eating sugar or a sugar-sweetened product such as a regular soft drink or fruit juice. GlucaGen^® does not work if it is taken by mouth.

DIRECTIONS FOR USE:

To Prepare GlucaGen^® For Injection:

Use the enclosed prefilled disposable syringe with the attached needle to reconstitute GlucaGen® before giving the injection.

Step 1. Take off the orange plastic cap off the vial. Pull the needle cover off the syringe. Insert the needle through the rubber stopper of the vial containing GlucaGen® and inject all the liquid from the syringe into the vial.

Step 1

Step 2. Without taking the syringe with a needle out of the vial, gently shake the vial in your hand until the powder has completely dissolved, and the solution is clear.

Step 2

Step 3. While the needle is still inside the vial, turn the vial upside down and while keeping the needle in the liquid, slowly withdraw all the liquid into the syringe. Be careful not to pull theplunger out of the syringe. This will also help minimize the leakage of the fluid around the syringe. The usual dose for adult and children weighing more than 55 lbs is 1 mg (1 ml). Therefore, withdraw the solution to 1 ml mark on the syringe. The usual dose for children weighing less than 55 lb is 0.5 mg (1/2 adult dose). Therefore, withdraw ½ of the solution from the vial (0.5 ml mark on the syringe) for these children. DISCARD UNUSED PORTION.

Step 3

To Inject GlucaGen^®

Step 4. Turn the patient on his/her side. When an unconscious person awakens, he/she may vomit. Turning the patient on his/her side will prevent him/her from choking. Without removing the needle from the vial and while keeping the needle in the liquid, remove any air bubble(s) in the syringe by flicking the syringe with your finger and squirting any air bubbles out of the needle into the vial. Continue pushing the plunger until you have the correct dose as described in Step 3. In the event the plunger is pushed below the required dose, pull back the plunger until you have the correct dose. When you have a correct amount of glucagon in the syringe, pull the syringe with a needle from the vial. Insert the needle into the loose tissue under the injection site, and inject the glucagon solution. THERE IS NO DANGER OF OVERDOSE.

Step 4

After Giving the Injection

Step 5. Withdraw the needle and press on the injection site. Used syringe and needle should be placed in sharps containers (such as red biohazard containers), hard plastic containers (such as detergent bottles), or metal containers (such as an empty coffee can). Such containers should be sealed and disposed of properly.

Step 6. FEED THE PATIENT AS SOON AS HE/SHE AWAKENS AND IS ABLE TO SWALLOW. Give the patient a fast-acting source of sugar (such as a regular soft drink or fruit juice) and a long-acting source of sugar (such as crackers and cheese or a meat sandwich). If the patient does not awaken within 15 minutes, give another dose of GlucaGen^® and INFORM A DOCTOR OR EMERGENCY SERVICES IMMEDIATELY.

Step 7. Even if the GlucaGen^® awakens the patient, his/her doctor should be promptly notified. A doctor should be notified whenever severe hypoglycemic reactions happen.

How GlucaGen^® Works

GlucaGen^® (glucagon [rDNA origin] for injection) is quickly absorbed after injection under the skin or into the muscle. Glucagon action causes glucose (sugar) to be released from the liver where it is stored as glycogen. Blood sugar levels increase within 10 minutes of injection and reach the highest amount approximately half an hour after injection. Glucagon works by promoting the release of glycogen (stored sugar in the liver).

When GlucaGen^® Should Not Be Used

Do not use GlucaGen^® if a patient is allergic to glucagon.

WARNINGS

Hypoglycemia may occur again following glucagon treatment. Tell your friends or relatives that you must be given a fast-acting source of sugar (such as regular soft drink or fruit juice), followed by a long acting source of sugar (carbohydrates) by mouth as soon as you are able to take it after you have responded to treatment - this will prevent the return of hypoglycemia (low blood sugar). Early symptoms of hypoglycemia may include:

• perspiration
• drowsiness
• dizziness
• sleep disturbances
• palpitation
• anxiety
• tremor
• blurred vision
• hunger
• slurred speech
• restlessness
• depressed mood
• tingling in the hands, feet, lips, or tongue
• irritability
• abnormal behavior
• lightheadedness
• unsteady movement
• inability to concentrate
• personality changes
• headache

Allergic reactions may occur rarely and include generalized rash, anaphylactic shock, breathing difficulties and hypotension (low blood pressure).

Keep this kit out of reach of children.

PRECAUTIONS

General - GlucaGen^® is only of benefit in hypoglycemia (low blood sugar) when the liver has sufficient glucose (in the form of glycogen) to release. For that reason GlucaGen^® has little or no effect if you are fasting, or if you are suffering from adrenal insufficiency, chronic hypoglycemia or alcohol induced hypoglycemia. Remember GlucaGen^® has the opposite effect of insulin.

If the GlucaGen solution shows any sign of gel formation or particles it should be discarded.

Your GlucaGen^® HypoKit for hypoglycemia (low blood sugar) includes:

• One vial of 1 mg GlucaGen^® (glucagon [rDNA origin] for injection)
• One prefilled disposable syringe with attached needle containing 1 ml Sterile Water for Reconstitution

The vial has a protective plastic cap. You must remove the plastic cap to inject the water and reconstitute the freeze-dried GlucaGen®. If the cap is loose or missing when you buy the package, return it to your local pharmacy.

Pregnancy - GlucaGen^® is glucagon which is a hormone that is always present in humans. GlucaGen® is intended for infrequent use during acute, severe hypoglycemic attacks, and may be used during pregnancy.

Nursing Mothers - Breast feeding following treatment with GlucaGen® for your hypoglycemic attack should not put your baby at risk. GlucaGen® does not stay very long in the body. Also, because glucagon is a protein, even if the infant ingested glucagon, it would be unlikely to have any effect on the infant because it would be digested.

POSSIBLE PROBLEMS WITH GlucaGen^® TREATMENT

Severe side effects are very rare, although nausea and vomiting may occur occasionally. Side effects indicating toxicity of GlucaGen® have not been reported.

A few people may be allergic to glucagon or to one of the inactive ingredients in GlucaGen®, or may experience rapid heart beat for a short while.

If you experience any other reactions which are likely to have been caused by GlucaGen®, please contact your doctor.

EXPIRATION DATE

Before mixing - The GlucaGen® package may be stored up to 24 months at controlled room temperature 20o to 25o C (68o to 77o F) prior to reconstitution. Avoid freezing and protect from light. Never use GlucaGen® after the expiration date printed on the package. GlucaGen^® does not contain preservatives and is for single use only.

After mixing - Reconstituted GlucaGen® should be used immediately. Discard any unused portion.

GlucaGen^® is a registered trademark of Novo Nordisk A/S

© Novo Nordisk A/S, 2005

For information contact:

Novo Nordisk Inc.

Princeton, New Jersey 08540

1-800-727-6500

www.novonordisk-us.com

Manufactured by:

Novo Nordisk^® A/S

2880 Bagsvaerd, Denmark

Last Updated: 11/05

GlucaGen, glucagon hydrochloride, patient information (in plain English)

Detailed Info on Signs, Symptoms, Causes, Treatments of Diabetes

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The information in this monograph is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects. This information is generalized and is not intended as specific medical advice. If you have questions about the medicines you are taking or would like more information, check with your doctor, pharmacist, or nurse.

back to: Browse all Medications for Diabetes

Brand Names: GlucaGen
Generic Name: Glucagon Hydrochloride

GlucaGen, glucagon hydrochloride, full prescribing information

Uses For Glucagen

Glucagon belongs to the group of medicines called hormones. It is an emergency medicine used to treat severe hypoglycemia (low blood sugar) in patients with diabetes who have passed out or cannot take some form of sugar by mouth.

Glucagon is also used during x-ray tests of the stomach and bowels to improve test results by relaxing the muscles of the stomach and bowels. This also makes the testing more comfortable for the patient.

Glucagon also may be used for other conditions as determined by your doctor.

Glucagon is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, glucagon is used in certain patients with the following medical conditions or undergoing certain medical procedures:

• Overdose of beta-adrenergic blocking medicines
• Overdose of calcium channel blocking medicines
• Removing food or an object stuck in the esophagus
• Hysterosalpingography (x-ray examination of the uterus and fallopian tubes)

Before Using Glucagen

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

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Pediatric

This medicine has been tested in children and, in effective doses, has not been shown to cause different side effects or problems than it does in adults.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of glucagon in the elderly with use in other age groups, it is not expected to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

Pregnancy Category	Explanation
All Trimesters	B	Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acenocoumarol
• Anisindione
• Dicumarol
• Phenindione
• Phenprocoumon
• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Diabetes mellitus—When glucagon is used for test or x-ray procedures in patients with diabetes that is well-controlled, a rise in blood sugar may occur; otherwise, glucagon is an important part of the management of diabetes because it is used to treat hypoglycemia (low blood sugar)
• Insulinoma (tumors of the pancreas gland that make too much insulin) (or history of)—Blood sugar concentrations may decrease
• Pheochromocytoma—Glucagon can cause high blood pressure

Proper Use of glucagon

This section provides information on the proper use of a number of products that contain glucagon. It may not be specific to Glucagen. Please read with care.

Glucagon is an emergency medicine and must be used only as directed by your doctor. Make sure that you and a member of your family or a friend understand exactly when and how to use this medicine before it is needed .

Glucagon is packaged in a kit with a vial of powder containing the medicine and a syringe filled with liquid to mix with the medicine. Directions for mixing and injecting the medicine are in the package. Read the directions carefully and ask your health care professional for additional explanation, if necessary.

Glucagon should not be mixed after the expiration date printed on the kit and on one vial. Check the date regularly and replace the medicine before it expires. The printed expiration date does not apply after mixing, when any unused portion must be discarded.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• As an emergency treatment for hypoglycemia:
  
  • Adults and children weighing 20 kilograms (kg) (44 pounds) or more: 1 milligram (mg). The dose may be repeated after fifteen minutes if necessary.
  • Children weighing up to 20 kg (44 pounds): 0.5 mg or 20 to 30 micrograms (mcg) per kg (9.1 to 13.6 mcg per pound) of body weight. The dose may be repeated after fifteen minutes if necessary.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Glucagen

Patients with diabetes should be aware of the symptoms of hypoglycemia (low blood sugar). These symptoms may develop in a very short time and may result from:

• using too much insulin ("insulin reaction") or as a side effect from oral antidiabetic medicines.
• delaying or missing a scheduled snack or meal.
• sickness (especially with vomiting or diarrhea).
• exercising more than usual.

Unless corrected, hypoglycemia will lead to unconsciousness, convulsions (seizures), and possibly death. Early symptoms of hypoglycemia include: anxious feeling, behavior change similar to being drunk, blurred vision, cold sweats, confusion, cool pale skin, difficulty in concentrating, drowsiness, excessive hunger, fast heartbeat, headache, nausea, nervousness, nightmares, restless sleep, shakiness, slurred speech, and unusual tiredness or weakness.

Symptoms of hypoglycemia can differ from person to person. It is important that you learn your own signs of low blood sugar so that you can treat it quickly. It is a good idea also to check your blood sugar to confirm that it is low.

You should know what to do if symptoms of low blood sugar occur. Eating or drinking something containing sugar when symptoms of low blood sugar first appear will usually prevent them from getting worse, and will probably make the use of glucagon unnecessary. Good sources of sugar include glucose tablets or gel, corn syrup, honey, sugar cubes or table sugar (dissolved in water), fruit juice, or nondiet soft drinks. If a meal is not scheduled soon (1 hour or less), you should also eat a light snack, such as crackers and cheese or half a sandwich or drink a glass of milk to keep your blood sugar from going down again. You should not eat hard candy or mints because the sugar will not get into your blood stream quickly enough. You also should not eat foods high in fat such as chocolate because the fat slows down the sugar entering the blood stream. After 10 to 20 minutes, check your blood sugar again to make sure it is not still too low.

Tell someone to take you to your doctor or to a hospital right away if the symptoms do not improve after eating or drinking a sweet food. Do not try to drive yourself.

If severe symptoms such as convulsions (seizures) or unconsciousness occur, the patient with diabetes should not be given anything to eat or drink. There is a chance that he or she could choke from not swallowing correctly. Glucagon should be administered and the patient's doctor should be called at once.

If it becomes necessary to inject glucagon, a family member or friend should know the following:

• After the injection, turn the patient on his or her left side. Glucagon may cause some patients to vomit and this position will reduce the possibility of choking.
• The patient should become conscious in less than 15 minutes after glucagon is injected, but if not, a second dose may be given. Get the patient to a doctor or to hospital emergency care as soon as possible because being unconscious too long can be harmful.
• When the patient is conscious and can swallow, give him or her some form of sugar. Glucagon is not effective for much longer than 1 ½ hours and is used only until the patient is able to swallow. Fruit juice, corn syrup, honey, and sugar cubes or table sugar (dissolved in water) all work quickly. Then, if a snack or meal is not scheduled for an hour or more, the patient should also eat some crackers and cheese or half a sandwich, or drink a glass of milk. This will prevent hypoglycemia from occurring again before the next meal or snack.
• The patient or caregiver should continue to monitor the patient's blood sugar. For about 3 to 4 hours after the patient regains consciousness, the blood sugar should be checked every hour.
• If nausea and vomiting prevent the patient from swallowing some form of sugar for an hour after glucagon is given, medical help should be obtained.

Keep your doctor informed of any hypoglycemic episodes or use of glucagon even if the symptoms are successfully controlled and there seem to be no continuing problems. Complete information is necessary for the doctor to provide the best possible treatment of any condition.

Replace your supply of glucagon as soon as possible, in case another hypoglycemic episode occurs.

You should wear a medical identification (I.D.) bracelet or chain at all times. In addition, you should carry an I.D. card that lists your medical condition and medicines.

Glucagen Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Less common

• Dizziness
• lightheadedness
• trouble in breathing

Symptoms of overdose

• Diarrhea
• irregular heartbeat
• loss of appetite
• muscle cramps or pain
• nausea (continuing)
• vomiting (continuing)
• weakness of arms, legs, and trunk (severe)

Check with your doctor as soon as possible if any of the following side effects occur:

Less common

• Skin rash

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common or rare

• Fast heartbeat
• nausea
• vomiting

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The information contained in the Thomson Healthcare (Micromedex) products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Healthcare does not assume any responsibility or risk for your use of the Thomson Healthcare products.

Last Updated: 11/05

GlucaGen, glucagon hydrochloride, full prescribing information

Detailed Info on Signs, Symptoms, Causes, Treatments of Diabetes

back to:Browse all Medications for Diabetes

 

Dr. Marlene Shiple is a certified sex counselor. Dr. Shiple's areas of expertise include sexual dysfunction, sexual addiction, sexual relationships, and intimacy issues.

David is the HealthyPlace.com moderator.

The people in blue are audience members.

---

David: Good Evening. I'm David Roberts. I'm the moderator for tonight's conference. I want to welcome everyone to HealthyPlace.com. Our topic tonight is "Sexual Issues and Questions". Our guest is Marlene Shiple, Ph.D., certified sex counselor. Dr. Shiple became interested in the specialization of sex therapy because she recognized how many people are fearful or nervous about their sexual interaction, when this should be a normal and enjoyable process of the human experience. She is here to give information and practical ideas on the topic of sexuality. Click here for more information about Dr. Shiple.

Good evening, Dr. Shiple. Thank you for being our guest tonight and welcome to HealthyPlace.com. Can you tell us a little more about yourself?

Dr. Shiple: Good evening, David and everyone out there who was able to join us tonight. I am certified with the American Association of Sex Educators, Counselors & Therapists (AASECT) as a Sex Counselor, and with the American Board of Sexology as a Sex Therapist. I have been interested in sexual issues for all of the twenty-four years that I have been in private practice. I found early in my practice that clients were fearful and uncomfortable with their sexual being. I was struck by how this held them back in their personal growth with sex being such an important area to our well-being.

David: Have you found that in the new millennium people are more or less comfortable talking about sex?

Dr. Shiple: Actually, no, I've not found most people more comfortable talking about sex, and that to me, is surprising. With all of the sexually transmitted diseases, which are of concern to many people, I was hoping that potential partners would become more verbal, more easily and more quickly. This does not seem to be happening.

David: Also, in this day and age of easy availability of sex sites over the internet, you would think more people would feel comfortable discussing it. What is it that keeps many people from feeling comfortable about expressing themselves about sex?

Dr. Shiple: I think it is lack of practice and the sex-is-bad ideas that still persist. I find in working with clients that we role play them being open and honest about sexual issues. It takes them some time to begin to feel at ease with this. Then, once they get going, they have so much to say that they have not said in so long, that it is hard to get them to stop.

David: Since we are a mental health site, I want to get directly to several issues. The first issue is sex after sexual abuse. How difficult is that, and can one expect to have "normal" sexual relations after being sexually abused?

Dr. Shiple: In my experience, it is possible to have satisfying sexual relations after being sexually abused. However, the beginning experiences in this direction require considerable awareness on the part of the person who was abused. What am I feeling, am I safe to go on, can I say hold it here? It requires a very sensitive partner, who is willing to listen and understand these requests, not take them personally, and respond according to what is being requested. With this, patience, and focused therapy working on releasing any abuse issues, I have found clients able to resume very satisfying personal and sexual relationships.

David: Here's an audience question on the subject:

punklil: Thank you for coming here to talk to us, Dr. Shiple. My question is how do you stop flashbacks in the middle of sex?

Dr. Shiple: First, I would ask if you had worked through the issues contained in the flashbacks. If not, that would be procedure number one. If you have worked through these issues, then I would suggest practice on focusing on the present, on what you are experiencing RIGHT NOW, on how you feel within you RIGHT NOW. I would suggest you take the time to remind yourself, "This is NOT the past, this is the present. I want to be here with this partner, enjoying one another."

David: What makes for great sex?

Dr. Shiple: So many ideas flooded my mind to answer your question. Actually, that is such a personal experience, that it is hard to create an answer that would fit for each person. Elements of great sex would include feeling a sense of harmony and oneness with one's partner. Freely expressing and hearing what each partner wants and doing one's best. As long as each party is comfortable to provide it. Taking the time to let it be good. Giving each partner focus for being pleasured and satisfied. Including the elements that each partner finds GREAT!

David: Here's an audience question:

slowdown: How do you get your partner to feel sexier about herself.

Dr. Shiple: Do not be distracted by the simplicity of this, consider it seriously. Does she WANT to feel sexier about herself? If not, there is not a way. If so, ask her what she thinks it would take for her to feel sexier about herself and listen carefully to what she tells you. Ask for clarification if anything is unclear about what she thinks would make her feel sexier. Then create a plan together, if she is willing, to begin to address whatever she has said. Compliment her on each step, or any beginning step she is able to make. Recognize that this is probably very, very difficult for her. After all, she has spent all of these years, however old she is, not feeling all that sexy. Ask her what she needs to help her feel more comfortable with this.

David: Why would someone see a sex therapist and when is it time to consider that you need to see a sex therapist?

Dr. Shiple: There are many reasons that clients see sex therapists. Some of these include sexual dissatisfaction, sexual dysfunction (the inability to attain an erection and/or have an orgasm if the person wants to), disagreements in frequency of sexual interaction, painful intercourse when all physical and medical reasons for this have been eliminated. These are just a few.

When it is time? That would be when you and your partner are dissatisfied with some aspect of what is going on between you two in your sexual relationship. Oftentimes, we find that the real issues may not be sexual. They may be in some other areas of communication, or, more often still, LACK of communication. Seeing a sex therapist can help you sort this out. Then, together with the therapist, you both create a strategy for solving the difficulties.

rtn12760: I am thirty-nine and have had one encounter with one female twelve years ago. What if a fear of sex has removed all desire for it, except for occasional pornography and masturbation?

Dr. Shiple: You would be surprised at how often a fear of sex, or some aspect of the sexual encounter, is EXACTLY what prevents someone from having satisfying sexual interaction. I would suggest that you find a good, sensitive sex therapist in your area and outline for him/her what you have said above.

The first step in dealing with this, would possibly be, to go back to that event and discover the dynamics that created the outcomes you experienced. Then, awareness of the thoughts that you have used over time, that have kept these dynamics active and present, would be in order. Having a sex therapist's guidance, in this case, would be very beneficial. I would expect that, in clearing up what was going on in the past, you would be in the position to create new sexual directions in the present. This would be the goal and focus of sex therapy.

David: Would you say that you, generally, have to feel good about yourself to have satisfying sex?

Dr. Shiple: In general, it certainly is a help! That, and knowing what you find to be satisfying and pleasing, so you CAN relate this to your partner.

Silvie: What number of women can achieve an orgasm through intercourse?

Dr. Shiple: There have been several research studies to quantify this. In general, somewhere in the fifty percent range. There is a false belief in vogue that the only satisfying sex is having orgasms together. This is not only not necessary, but it happens rather infrequently. It can be a problem to limit the ways that you are willing to "accept" or allow yourself pleasure. This can also limit the pleasure that you have

nett: Is it okay to have anal sex, and does it have any lasting ill effects? I'm in a heterosexual relationship.

Dr. Shiple: In terms of human sexual practice, anal sex is OK. In terms of some religious proscriptions, there are differing opinions. The problem with anal sex can be tearing the lining of the anus. If the man's penis is really large and you do not use ample lubrication this can happen. Why is that a problem? Because you will be using your anus for other purposes later on (when you defecate, this carries bacteria). If the lining of the anus is torn, you can get the infection in your body. So, you would want to use plenty of lubrication and if your partner is very large, get him to enter you before he is fully erect. If that is not possible, you might want to forego the experience.

jullian: I was wondering if you know about how medications affect sex life? I am on Paxil and it has changed my sexual experience. Is this common and do you know of any meds that do not have this effect?

Dr. Shiple: Oh, Jullian, you are entering touchy territory. Yes, many medications affect your sexual interaction. In my experience, Paxil is certainly one of them. One difficulty in answering the "any meds that do not" question, is that people experience different results from different medications. As a general rule, I would refer you back to your doctor. She or he better knows your history and can make recommendations. One word of encouragement: do not give up your quest. Keep working to find a medication that does not adversely affect your sexual interest and/or pleasure until you find one. Having satisfying sexual relations is worth it!

David: How do you broach your sexual "desires" with your partner. For instance, for some, the idea of asking for anal sex might be difficult to bring up?

Dr. Shiple: Timing would be important. Choose a time that you are relaxed and your partner is relaxed. Then set the stage. By this, I mean to say something like, "I have something that is important for me to ask you, but I am embarrassed (if you are) or nervous (if you are) about it." This lets your partner know to be appropriately ready. If you need your partner's encouragement at this point, ask for it by saying something like, "I would really like you to say it is all right, that you want to know, that you are listening." Then give your partner time to respond to this. If she/he does not respond appropriately to this, it probably is not time yet to go on to something more sensitive like stating that you would really enjoy experiencing having anal sex with her/him.

Questions: Hi Dr. S :) Here is a brief summary: I don't think I know how a "healthy" sexual relationship starts. Can you give me general ways of knowing when I'm ready? I know I'm either the "aggressor" or the "passive" participant. I don't feel sex as an emotional extension, but almost separate of "love". I can't "feel" sex as necessarily emotional, just physical.

Dr. Shiple: Is that OK with you? Or does it cause you problems? If what you are doing is satisfying to you, and to your partner, it may not be necessary to change it. However, let's presume that you are saying that you want to change it. First, you would want to take plenty of time to get to know your partner and not rush the physical, sexual interaction. Then, in that time, you would begin to experience other emotional responses with your partner. Emotional feelings that are not just sexual. This will get you on your way. Then be sure to ASK your partner what she wants. See if her expression of her desires, and how she feels, can spark some emotional response in you. These are beginnings.

TheArtOfBeingMe: Is it impossible to get out of the "sex is bad" frame of mind after sexual abuse as a child?

Dr. Shiple: YES. Let me repeat that because it is so important: Yes! With work. You would want to find an excellent and skilled cognitively-oriented sex therapist, because what you are dealing with, is how concepts and ideas affect your behavior. Then really dedicate yourself to WORK with this therapist.

Other issues, which would be a part of this, would be accepting and loving yourself as good and beautiful! Yes, you can!

ladyofthelake: In times of extreme stress, when I least want sex, my husband seems to need it the most. Is this a normal reaction?

Dr. Shiple: Absolutely, and it is not just a male-female thing. It is the difference in personal expressions. Sex provides incredible tension release. So, at a time of extreme stress, this element alone can make sex desirable for some people. For other people, as you so well point out, it is just the opposite. The stressful event takes center-stage in your mind, with all lights focusing on it. Who can think about having sex?

In a relationship, the difficulty with these differential ways of responding, is how you resolve the two poles. Does one of you look at what benefit the other partner might see in his/her approach, and get in the other person's shoes, as it were? Or does it become an argument as another way of diverting the stress-filled energy?

David: In terms of a relationship, where you have been with your partner for some time, is part of the "deal", whether you are a man or woman, to have sex when your partner wants it -- even though at occasional times you may not want to have sex at that moment? Or maybe a better phrasing of the question is, is that part of having a good relationship?

Dr. Shiple: Sometimes, and sometimes not. What I mean by that is, I think there have to be three modes of interacting:

1. we both want to have sex and we do
2. one of us wants to have sex and the other of us has no serious problem/objection with that. Maybe she or he is tired and not up to generating the energy herself or himself, but if the desirous partner can get the action going, the other party is amenable; and
3. it's just NOT the right time.

I would add that I think (c) needs to be used sparingly. But, by not having a (c), it sets up the circumstance in which one partner might feel forced, or create resentment. This resentment can undermine and destroy a relationship fast!!

rtn12760: I have a therapist who works with me on my pornography issues but doesn't touch on the fear of intimacy. Should I get a new therapist? This one was supposed to specialize in sexual addiction.

Dr. Shiple: Have you brought up to your current therapist that you want to work on fear of intimacy? Do you want to work on fear of intimacy (rather than to presume this from your question.)? If your current therapist feels competent to deal with intimacy fears, I would certainly stick with this therapist. It takes a considerable amount of time to build a therapeutic relationship, one of deep trust and benefit. I would not be looking to have you throw that over too quickly.

However, if you have asked to deal with your fear of intimacy, and the therapist is just not doing so, I would ask if she or he could refer me to someone capable in this area. Intimacy is such a crucial area to sexual satisfaction that I encourage you to take the steps to pursue this.

David: When I hear the term sexual dysfunction, I, maybe because I am a man, think about "inability to get an erection." What other categories does that cover?

Dr. Shiple: Sexual dysfunction for a male can also include what used to be called premature ejaculation. It can include problems with sexual desire. It can include not being able to sustain the erection long enough for mutual satisfaction and pleasure.

For a female, sexual dysfunction can also be inhibited sexual desire. It can include the condition of vaginismus -- in which the mouth of the vagina tightens up so fiercely and so strongly that it can prevent penetration. Even if penetration is possible, this condition creates incredible pain in the female partner, and, in her partner.

punklil: I have DID ( dissociative identity disorder, multiple personality disorder) and when I say "no" to my partner, he would call out another alter that would say "yes". Is this wrong, or does he have a right to do this?

Dr. Shiple: That would depend on the relationship between the alters. Is it OK with you that what you requested is not listened to? Is it a relief to you that one of the others would be able to please your partner when this is not possible for you? As I mentioned above, if a dynamic is going on that creates resentment for one of the partners, including the main personality, this will be a serious problem to the relationship. Does he have the right? I would seriously consider, outside of the sexual interaction, having the two of you define what you need from your partner and what you are willing to do about your partner requests. If this is absolutely unacceptable to you, Punklil, you would need to help your partner understand, and together, create other options to use when this situation comes up. If you cannot do this yourselves, I would advise you to seek a good relationship therapist for assistance.

Dawnie3: I have diabetes and get splits in the skin, which really hurt. Is this normal and what helps to relieve them and prevent them? I think it's caused from dryness.

Dr. Shiple: Dawnie3, I think that this is an excellent question, but it is out of my area of expertise. Have you asked your medical doctor about this? If not, I encourage you to do so. I would tend to bet that there is some medical treatment that could help you. I just do not know what it might be.

David: What is the best way of "complaining" about your partner's sexual habits or preferences? Some people have trouble communicating in general, but in sexual matters "tact is critical."

Dr. Shiple: Once again, timing is of the essence in this area. Choose a time when you and your partner are relaxed together. Then set the stage I mentioned above. You do this by saying something along the lines of, "I have something I need to talk to you about that is very important to me; yet I am concerned that you might get upset, angry, hurt (whatever fits). I absolutely do not want that result, yet I still need to talk with you about this."

Then proceed to talk in terms of I-messages: "I would feel so much more aroused if you ...", "I would be willing more often to initiate sex and be an active partner if we did more ...", "Sometimes I need a light touch and sometimes a need a harder touch. Would it work for you if I put my hand over yours to show you which I would enjoy most when?" If your partner says, "no" to this. Ask him/her what works for them. Get your partner actively involved in creating solutions that are helpful pleasing to him/her. You have great expertise between the two of you. You are an expert on yourself and your partner is an expert on his/her responses and inclinations. Don't miss out on the opportunity to use these areas of expertise for your mutual benefit. By all means, however, avoid "You always ..." kinds of messages; or, "You never ..." messages. These tend to create defensive responding, the very opposite of what you are looking for when you and your partner could be focusing on one (or several) solutions. As always, timing and "how you say what you say" are crucial.

spudrn: My question is that I was sexually abused as a child, and now, for me to have a successful orgasm, I have to hurt myself sexually to the point of bleeding to release my tension. How can I heal myself from this need of self-injury?

Dr. Shiple: Spudrn, that is a courageous question! Have you worked with a therapist on this? Let me assure you -- you are not alone! I have worked successfully with many, many clients with the "need" to hurt themselves physically (self-injury). This is a treatable condition. However, it requires some basic psychotherapy in the areas of increased positive self-esteem, learning self-love, developing ways of kindness with yourself. These are important skills to learn. Working with a skilled therapist to develop them is step number one. And let me say again, this condition is treatable. So, I encourage you to do the work to get this resolved.

David: For everyone's information, Dr. Shiple's website is: http://www.sexualtherapy.com/therapists/shiple.htm.

Thank you, Dr. Shiple, for being our guest tonight and sharing your expertise with us. And I want to thank everyone in the audience for coming and participating. I hope you have found the information helpful.

Dr. Shiple: Thank you, and good night.

Disclaimer: We are not recommending or endorsing any of the suggestions of our guest. In fact, we strongly encourage you to talk over any therapies, remedies or suggestions with your doctor BEFORE you implement them or make any changes in your treatment.