"Miriam E. Tucker
Medscape Medical News
The U.S. Food and Drug Administration (FDA) will now require a "for single patient use only" warning on all multidose pen devices used for injectable diabetes medications.
Dosage adjustment and monitoring
Glucose monitoring is essential for all patients receiving insulin therapy. Changes to an insulin regimen should be made cautiously and only under medical supervision.
Changes in insulin strength, manufacturer, type, or method of administration may result in the need for a change in insulin dose or an adjustment in concomitant oral anti-diabetic treatment.
As with all insulin preparations, the time course of action for LANTUS may vary in different individuals or at different times in the same individual and is dependent on many conditions, including the local blood supply, local temperature, and physical activity.
Do not administer LANTUS intravenously or via an insulin pump. The intended duration of activity of LANTUS is dependent on injection into subcutaneous tissue Intravenous administration of the usual subcutaneous dose could result in severe hypoglycemia.
Do not dilute or mix LANTUS with any other insulin or solution. If LANTUS is diluted or mixed, the solution may become cloudy, and the pharmacokinetic or pharmacodynamic profile (e.g., onset of action, time to peak effect) of LANTUS and 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 a delayed 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 unknown.
Do not share disposable or reusable insulin devices or needles between patients, because doing so carries a risk for transmission of blood-borne pathogens.
Hypoglycemia is the most common adverse reaction of insulin, including LANTUS. The risk of hypoglycemia increases with intensive glycemic control. Patients must be educated to recognize and manage hypoglycemia. Severe hypoglycemia can lead to unconsciousness or convulsions and may result in temporary or permanent impairment of brain function or death. Severe hypoglycemia requiring the assistance of another person or parenteral glucose infusion or glucagon administration has been observed in clinical trials with insulin, including trials with LANTUS.
The timing of hypoglycemia usually reflects the time-action profile of the administered insulin formulations. Other factors such as changes in food intake (e.g., amount of food or timing of meals), exercise, and concomitant medications may also alter the risk of hypoglycemia [See DRUG INTERACTIONS].
The prolonged effect of subcutaneous LANTUS may delay recovery from hypoglycemia. 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].
As with all insulins, use caution in patients with hypoglycemia unawareness and in patients who may be predisposed to hypoglycemia (e.g., the pediatric population and patients who fast or have erratic food intake). The patient's ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery.
Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as longstanding diabetes, diabetic neuropathy, use of medications such as beta-blockers, or intensified glycemic control. These situations may result in severe hypoglycemia (and, possibly, loss of consciousness) prior to the patient's awareness of hypoglycemia.
Hypersensitivity and allergic reactions
Due to its long duration of action, Lantus is not recommended during periods of rapidly declining renal function because of the risk for prolonged hypoglycemia. Although studies have not been performed in patients with diabetes and renal impairment, a reduction in the LANTUS dose may be required in patients with renal impairment because of reduced insulin metabolism, similar to observations found with other insulins. [See CLINICAL PHARMACOLOGY].
Due to its long duration of action, Lantus is not recommended during periods of rapidly declining hepatic function because of the risk for prolonged hypoglycemia. Although studies have not been performed in patients with diabetes and hepatic impairment, a reduction in the LANTUS dose may be required in patients with hepatic impairment because of reduced capacity for gluconeogenesis and reduced insulin metabolism, similar to observations found with other insulins. [See CLINICAL PHARMACOLOGY].
Patient Counseling Information
Instructions for patients
Patients should be informed that changes to insulin regimens must be made cautiously and only under medical supervision.
Patients should be informed about the potential side effects of insulin therapy, including lipodystrophy (and the need to rotate injection sites within the same body region), weight gain, allergic reactions, and hypoglycemia. Patients should be informed that the ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia should be advised to use caution when driving or operating machinery.
Accidental mix-ups between LANTUS and other insulins, particularly short-acting insulins, have been reported. To avoid medication errors between LANTUS and other insulins, patients should be instructed to always check the insulin label before each injection.
LANTUS must only be used if the solution is clear and colorless with no particles visible. Patients must be advised that LANTUS must NOT be diluted or mixed with any other insulin or solution.
Patients should be advised not to share disposable or reusable insulin devices or needles with other patients, because doing so carries a risk for transmission of blood-borne pathogens.
Patients should be instructed on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia. 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, and skipped meals.
Patients with diabetes should be advised to inform their health care professional if they are pregnant or are contemplating pregnancy.
Refer patients to the LANTUS “PATIENT INFORMATION” for additional information.
See attached document at end of Full Prescribing Information.
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 was for the rat approximately 10 times and for the mouse approximately 5 times the recommended human subcutaneous starting dose of 10 Units/day (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 was approximately 7 times the recommended human subcutaneous starting dose of 10 Units/day (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 insulin.
Use In Specific Populations
Pregnancy Category C
Subcutaneous reproduction and teratology studies have been performed with insulin glargine and regular human insulin in rats and Himalayan rabbits. Insulin glargine 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 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 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 LANTUS in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 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 these patients.
It is unknown whether insulin glargine is excreted in human milk. Because many drugs, including human insulin, are excreted in human milk, caution should be exercised when LANTUS is administered to a nursing woman. Use of LANTUS is compatible with breastfeeding, but women with diabetes who are lactating may require adjustments of their insulin doses.
The safety and effectiveness of subcutaneous injections of LANTUS have been established in pediatric patients (age 6 to 15 years) with type 1 diabetes [see Clinical Studies]. LANTUS has not been studied in pediatric patients younger than 6 years of age with type 1 diabetes. LANTUS has not been studied in pediatric patients with type 2 diabetes.
Based on the results of a study in pediatric patients, the dose recommendation when switching to LANTUS is the same as that described for adults [see DOSAGE AND ADMINISTRATION and Clinical Studies]. As in adults, the dosage of LANTUS must be individualized in pediatric patients based on metabolic needs and frequent monitoring of blood glucose.
In controlled clinical studies comparing LANTUS to NPH insulin, 593 of 3890 patients (15%) with type 1 and type 2 diabetes were ≥ 65 years of age and 80 (2%) patients were ≥ 75 years of age. The only difference in safety or effectiveness in the subpopulation of patients ≥ 65 years of age compared to the entire study population was a higher incidence of cardiovascular events typically seen in an older population in both LANTUS and NPH insulin-treated patients. Nevertheless, caution should be exercised when LANTUS 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 [See WARNINGS AND PRECAUTIONS].This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 6/17/2013
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