BASAGLAR KwikPen (Page 4 of 7)

8.2 Lactation

Risk Summary

There are no data on the presence of insulin glargine in human milk, the effects on the breastfed infant, or the effects on milk production. Endogenous insulin is present in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BASAGLAR and any potential adverse effects on the breastfed child from BASAGLAR or from the underlying maternal condition.

8.4 Pediatric Use

The safety and effectiveness of BASAGLAR have been established in pediatric patients (age 6 to 15 years) with type 1 diabetes based on an adequate and well-controlled trial of another insulin glargine product, 100 units/mL, in pediatric patients (age 6 to 15 years) with type 1 diabetes and additional data in adults with type 1 diabetes [see Clinical Studies (14.2)]. The safety and effectiveness of BASAGLAR in pediatric patients younger than 6 years of age with type 1 diabetes and pediatric patients with type 2 diabetes has not been established.

The dosage recommendation when changing to BASAGLAR in pediatric patients (age 6 to 15 years) with type 1 diabetes is the same as that described for adults [see Dosage and Administration (2.3, 2.4) and Clinical Studies (14)]. As in adults, the dosage of BASAGLAR must be individualized in pediatric patients (age 6 to 15 years) with type 1 diabetes based on metabolic needs and frequent monitoring of blood glucose.

In the pediatric clinical trial, pediatric patients (age 6 to 15 years) with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia compared to the adults in trials with type 1 diabetes [see Adverse Reactions (6.1)].

8.5 Geriatric Use

Of the total number of subjects in clinical studies of patients with type 2 diabetes who were treated with BASAGLAR or another insulin glargine product, 100 units/mL, each in combination with oral agents in a controlled clinical trial environment, 28.3% were 65 and over, while 4.5% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Nevertheless, caution should be exercised when BASAGLAR is administered to geriatric 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.

8.6 Renal Impairment

The effect of renal impairment on the pharmacokinetics of BASAGLAR has not been studied. Some studies with human insulin have shown increased circulating levels of insulin in patients with renal failure. Frequent glucose monitoring and dose adjustment may be necessary for BASAGLAR in patients with renal impairment [see Warnings and Precautions (5.3)].

8.7 Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of BASAGLAR has not been studied. However, as with all insulin products, more frequent glucose monitoring and dose adjustment may be necessary for BASAGLAR in patients with hepatic impairment [see Warnings and Precautions (5.3)].

8.8 Obesity

In controlled clinical trials, subgroup analyses based on BMI did not show differences in safety and efficacy between BASAGLAR and another insulin glargine product, 100 units/mL.

10 OVERDOSAGE

Excess insulin administration relative to food intake, energy expenditure, or both may lead to severe and sometimes prolonged and life-threatening hypoglycemia and hypokalemia [see Warnings and Precautions (5.3, 5.6)]. Mild episodes of hypoglycemia can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or physical activity level may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately.

11 DESCRIPTION

Insulin glargine injection is a long-acting insulin for subcutaneous use. Insulin glargine is a recombinant human insulin analog [see Clinical Pharmacology (12)]. BASAGLAR 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, insulin glargine is 21A -Gly-30B -a-L-Arg-30B b-L-Arg-human insulin and has the empirical formula C267 H404 N72 O78 S6 and a molecular weight of 6063. Insulin glargine has the following structural formula:

Structural Formula
(click image for full-size original)

BASAGLAR (insulin glargine injection) is a clear, colorless, sterile aqueous solution for subcutaneous use. Each milliliter of BASAGLAR (insulin glargine injection) contains 100 units of insulin glargine (3.6378 mg).

The 3 mL BASAGLAR prefilled pen presentations contain the following inactive ingredients per mL: glycerin (17 mg), metacresol (2.7 mg), zinc (30 mcg), zinc oxide content adjusted to provide 0.03 mg zinc ion, and Water for Injection, USP.

The pH is adjusted by addition of aqueous solutions of hydrochloric acid 10% and/or sodium hydroxide 10%. BASAGLAR has a pH of approximately 4.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

The pharmacodynamic profile for BASAGLAR was determined after subcutaneous administration of a single 0.5 U/kg dose in a euglycemic clamp study conducted in 91 healthy subjects. The median time to maximum effect of BASAGLAR (measured by the peak rate of glucose infusion) was approximately 12.0 hours. The pharmacodynamic profile of BASAGLAR following subcutaneous injection demonstrated sustained glucose lowering activity over 24 hours with no pronounced peak. The mean area under the glucose infusion rate curves (measure of overall pharmacodynamic effect) and maximum glucose infusion rate were 1670 mg/kg and 2.12 mg/kg/min, respectively.

A euglycemic clamp study in 20 patients with type 1 diabetes showed a similar pharmacodynamic profile with a sustained glucose lowering activity over 24 hours following a single 0.3 U/kg subcutaneous dose of BASAGLAR.

After subcutaneous injection of 0.3 units/kg of another insulin glargine product, 100 units/mL, in patients with type 1 diabetes, the duration of action after abdominal, deltoid, or thigh subcutaneous administration was similar.

The time course of action of insulins, including insulin glargine, may vary between individuals and within the same individual.

12.3 Pharmacokinetics

Absorption and Bioavailability

The pharmacokinetic profile for BASAGLAR was determined after subcutaneous administration of a single 0.5 U/kg dose in a euglycemic clamp study conducted in 91 healthy subjects. The insulin serum concentrations indicated a slow and prolonged absorption and a relatively constant concentration/time profile over 24 hours with no pronounced peak.

The median time to maximum serum insulin concentration was 12 hours after injection. On average, serum insulin concentrations declined to baseline by approximately 24 hours. The mean observed area under the serum insulin concentration-time curve from time zero to 24 hours and peak serum insulin concentration were 1720 pmol*hr/L and 103 pmol/L, respectively.

Metabolism and Elimination

After subcutaneous injection of another insulin glargine product, 100 units/mL, in diabetic patients, insulin glargine is metabolized at the carboxyl terminus of the Beta chain with formation of two active metabolites M1 (21A -Gly-insulin) and M2 (21A -Gly-des-30B -Thr-insulin). The in vitro activity of M1 and M2 were similar to that of insulin.

Specific Populations

Age, Race, and Gender: Effect of age, race, and gender on the pharmacokinetics of BASAGLAR has not been evaluated.

Obesity: Effect of BMI on the pharmacokinetics of BASAGLAR has not been evaluated.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2021. All Rights Reserved.