warnings and cautions
5. WARNINGS AND PRECAUTIONS Dose adjustment and monitoring: Monitor blood glucose in all patients treated with insulin. Insulin regimens should be modified cautiously and only under medical supervision ( 5.1 ) Administration: Do not dilute or mix with any other insulin or solution. Do not administer subcutaneously via an insulin pump or intravenously because severe hypoglycemia can occur ( 5.2 ) Do not share reusable or disposable insulin devices or needles between patients ( 5.2 ) Hypoglycemia: Most common adverse reaction of insulin therapy and may be life-threatening ( 5.3 , 6.1 ) Allergic reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur ( 5.4 , 6.1 ) Renal or hepatic impairment: May require a reduction in the LANTUS dose ( 5.5 , 5.6 ) 5.1 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. 5.2 Administration 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 [see Warnings and Precautions (5.3) ] . 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. 5.3 Hypoglycemia 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 (7) ]. 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 (2.3) ]. 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. 5.4 Hypersensitivity and allergic reactions Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including LANTUS. 5.5 Renal impairment 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 (12.3) ]. 5.6 Hepatic impairment 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 (12.3) ]. 5.7 Drug interactions Some medications may alter insulin requirements and subsequently increase the risk for hypoglycemia or hyperglycemia [See Drug Interactions (7) ].