BASAGLAR KwikPen (Page 3 of 7)

6.2 Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity.

In a 52-week study of type 1 diabetes patients, 42% of patients who received BASAGLAR once daily were positive for anti-drug antibodies (ADA) at least once during the study, including 17% that were positive at baseline and 25% of patients who developed ADA during the study. Sixty-five percent of the ADA positive patients on BASAGLAR with antibody testing at week 52 remained ADA positive at week 52.

In a 24-week study of type 2 diabetes patients, 17% of patients who received BASAGLAR once daily were positive for ADA at least once during the study. Among the subjects who were positive, 5% had ADA at baseline and 12% developed antibodies during the study. The percent binding of patients positive at baseline on BASAGLAR did not increase significantly during the study. Fifty-one percent of the ADA positive patients on BASAGLAR with antibody testing at week 24 remained ADA positive at week 24. There was no evidence that these antibodies had an impact on efficacy and safety outcomes.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to BASAGLAR with the incidence of antibodies in other studies or to other products may be misleading.

6.3 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of another insulin glargine product, 100 units/mL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure.

Medication errors have been reported in which other insulin products, particularly rapid-acting insulins, have been accidentally administered instead of an insulin glargine product. To avoid medication errors between insulin glargine products and other insulin products, patients should be instructed to always verify the insulin label before each injection.

Localized cutaneous amyloidosis at the injection site has occurred. Hyperglycemia has been reported with repeated insulin injections into areas of localized cutaneous amyloidosis; hypoglycemia has been reported with a sudden change to an unaffected injection site.

7 DRUG INTERACTIONS

Table 6 includes clinically significant drug interactions with BASAGLAR

Table 6: Clinically Significant Drug Interactions with BASAGLAR
Drugs That May Increase the Risk of Hypoglycemia
Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics.
Intervention: Dose reductions and increased frequency of glucose monitoring may be required when BASAGLAR is co-administered with these drugs.
Drugs That May Decrease the Blood Glucose Lowering Effect of BASAGLAR
Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones
Intervention: Dose increases and increased frequency of glucose monitoring may be required when BASAGLAR is co-administered with these drugs.
Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of BASAGLAR
Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.
Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when BASAGLAR is co-administered with these drugs.
Drugs That May Blunt Signs and Symptoms of Hypoglycemia
Drugs: beta-blockers, clonidine, guanethidine, and reserpine
Intervention: Increased frequency of glucose monitoring may be required when BASAGLAR is co-administered with these drugs.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Published studies with use of insulin glargine products during pregnancy have not reported a clear

association with insulin glargine products and adverse developmental outcomes (see Data). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations). In animal reproduction studies, another insulin glargine product was administered to rats before, during and throughout pregnancy at doses up to 7 times the clinical dose of 10 units/day and to rabbits during organogenesis at doses approximately 2 times the clinical dose of 10 units/day. The effects of this other insulin glargine product did not generally differ from those observed with regular human insulin in rats or rabbits (see Data).

The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20-25% in women with a HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.

Data

Human Data

Published data do not report a clear association with insulin glargine products and major birth defects, miscarriage, or adverse maternal or fetal outcomes when insulin glargine products are used during pregnancy. However, these studies cannot definitely establish the absence of any risk because of methodological limitations including small sample size and some with no comparative group.

Animal Data

Subcutaneous reproduction and teratology studies have been performed with another insulin glargine product and with regular human insulin in rats and Himalayan rabbits. This other insulin glargine product was given to female rats before mating, during mating, and throughout pregnancy at dose up to 0.36 mg/kg/day, which is approximately 7 times the recommended human subcutaneous starting dose of 10 units/day (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 units/day (0.008 mg/kg/day), based on mg/m2 , were administered during organogenesis. The effects of this other insulin glargine product did not generally differ from those observed with regular human insulin in rats and 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.

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