warnings and cautions
5 WARNINGS AND PRECAUTIONS Dose adjustment and monitoring: Closely monitor blood glucose in all patients treated with insulin. Change insulin regimens cautiously and only under medical supervision. ( 5.1 ) Hypoglycemia: Most common adverse reaction of insulin therapy and may be life-threatening. ( 5.2 ) Allergic reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with any insulin, including HUMALOG. ( 5.3 ) Hypokalemia: All insulins, including HUMALOG can cause hypokalemia, which if untreated, may result in respiratory paralysis, ventricular arrhythmia, and death. ( 5.4 ) Renal or hepatic impairment: Like all insulins, may require a reduction in the HUMALOG dose. ( 5.5 ) Mixing: HUMALOG for subcutaneous injection should not be mixed with insulins other than NPH insulin. Do not mix HUMALOG with any insulin for use in a continuous infusion pump. ( 5.6 ) Pump use: Select a new infusion site at least every 3 days and replace the HUMALOG in the pump reservoir at least every 7 days. ( 5.7 ) 5.1 Dose Adjustment and Monitoring Glucose monitoring is essential for 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. Concomitant oral antidiabetic treatment may need to be adjusted. As with all insulin preparations, the time course of action for HUMALOG may vary in different individuals or at different times in the same individual and is dependent on many conditions, including the site of injection, local blood supply, or local temperature. Patients who change their level of physical activity or meal plan may require adjustment of insulin dosages. 5.2 Hypoglycemia Hypoglycemia is the most common adverse effect associated with insulins, including HUMALOG. The risk of hypoglycemia increases with tighter glycemic control. Patients must be educated to recognize and manage hypoglycemia. Hypoglycemia can happen suddenly and symptoms may be different for each person and may change from time to time. Severe hypoglycemia can cause seizures and may be life-threatening or cause death. 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), injection site, exercise, and concomitant medications may also alter the risk of hypoglycemia [see Drug Interactions ( 7 )] . 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. Rapid changes in serum glucose levels may induce symptoms similar to hypoglycemia in persons with diabetes, regardless of the glucose value. Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as longstanding diabetes, diabetic nerve disease, use of medications such as beta-blockers [see Drug Interactions ( 7 )] , or intensified diabetes control. These situations may result in severe hypoglycemia (and, possibly, loss of consciousness) prior to the patient's awareness of hypoglycemia. 5.3 Hypersensitivity and Allergic Reactions Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including HUMALOG [see Adverse Reactions ( 6.1 )] . 5.4 Hypokalemia All insulin products, including HUMALOG, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Use caution in patients who may be at risk for hypokalemia (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations). 5.5 Renal or Hepatic Impairment Frequent glucose monitoring and insulin dose reduction may be required in patients with renal or hepatic impairment [see Clinical Pharmacology ( 12.3 )] . 5.6 Mixing of Insulins HUMALOG for subcutaneous injection should not be mixed with insulin preparations other than NPH insulin. If HUMALOG is mixed with NPH insulin, HUMALOG should be drawn into the syringe first. Injection should occur immediately after mixing. Do not mix HUMALOG with other insulins for use in an external subcutaneous infusion pump. 5.7 Subcutaneous Insulin Infusion Pumps When used in an external insulin pump for subcutaneous infusion, HUMALOG should not be diluted or mixed with any other insulin. Change the HUMALOG in the reservoir at least every 7 days, change the infusion sets and the infusion set insertion site at least every 3 days. HUMALOG should not be exposed to temperatures greater than 98.6°F (37°C). Malfunction of the insulin pump or infusion set or insulin degradation can rapidly lead to hyperglycemia and ketosis. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Interim subcutaneous injections with HUMALOG may be required. Patients using continuous subcutaneous insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure [see Dosage and Administration ( 2.3 ), How Supplied/Storage and Handling ( 16 ), and Patient Counseling Information ( 17.2 )] . 5.8 Drug Interactions Some medications may alter insulin requirements and the risk for hypoglycemia or hyperglycemia [see Drug Interactions ( 7 )] .