Never share an APIDRA SoloStar pen between patients, even if the needle is changed (5.1) Do not reuse or share needles or syringes between patients (5.1) Dose adjustment and monitoring: Closely monitor blood glucose in all patients treated with insulin. Change insulin regimens cautiously and only under medical supervision.(5.2) Hypoglycemia: Most common adverse reaction of insulin therapy and may be life-threatening (5.3) Allergic reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with any insulin, including APIDRA (5.4) Hypokalemia: All insulins, including APIDRA can cause hypokalemia, which if untreated, may result in respiratory paralysis, ventricular arrhythmia, and death (5.5) Renal or hepatic impairment: Like all insulins, may require a reduction in the APIDRA dose (5.6) Mixing: APIDRA for subcutaneous injection should not be mixed with insulins other than NPH insulin. Do not mix APIDRA with any insulin for intravenous administration or for use in a continuous infusion pump (5.7) Pump use: Change the APIDRA in the pump reservoir every 48 hours (5.8) Intravenous use: Frequently monitor for hypoglycemia and hypokalemia. (5.9) Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation of TZD if heart failure occurs (5.11) 5.1 Never share an APIDRA SoloStar pen or syringe or needle between patients APIDRA SoloStar pens must never be shared between patients, even if the needle is changed. Patients using APIDRA vials must never reuse or share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens. 5.2 Dosage 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 APIDRA 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. 5.3 Hypoglycemia Hypoglycemia is the most common adverse reaction of insulin therapy, including APIDRA. The risk of hypoglycemia increases with tighter glycemic control. Patients must be educated to recognize and manage hypoglycemia. Severe hypoglycemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or death. Severe hypoglycemia requiring the assistance of another person and/or parenteral glucose infusion or glucagon administration has been observed in clinical trials with insulin, including trials with APIDRA. 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. Intravenously administered insulin has a more rapid onset of action than subcutaneously administered insulin, requiring closer monitoring for hypoglycemia. 5.4 Hypersensitivity and allergic reactions Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including APIDRA [See Adverse reactions (6.1)]. 5.5 Hypokalemia All insulin products, including APIDRA, 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). Monitor glucose and potassium frequently when APIDRA is administered intravenously. 5.6 Renal or hepatic impairment Frequent glucose monitoring and insulin dose reduction may be required in patients with renal or hepatic impairment [See Clinical Pharmacology (12.4)]. 5.7 Mixing of insulins APIDRA for subcutaneous injection should not be mixed with insulin preparations other than NPH insulin. If APIDRA is mixed with NPH insulin, APIDRA should be drawn into the syringe first. Injection should occur immediately after mixing. Do not mix APIDRA with other insulins for intravenous administration or for use in a continuous subcutaneous infusion pump. APIDRA for intravenous administration should not be diluted with solutions other than 0.9% sodium chloride (normal saline). The efficacy and safety of mixing APIDRA with diluents or other insulins for use in external subcutaneous infusion pumps have not been established. 5.8 Subcutaneous insulin infusion pumps When used in an external insulin pump for subcutaneous infusion, APIDRA should not be diluted or mixed with any other insulin. APIDRA in the reservoir must be changed at least every 48 hours. APIDRA should not be exposed to temperatures greater than 98.6°F (37°C). Malfunction of the insulin pump or infusion set or handling errors or insulin degradation can rapidly lead to hyperglycemia, ketosis and diabetic ketoacidosis. Prompt identification and correction of the cause of hyperglycemia or ketosis or diabetic ketoacidosis is necessary. Interim subcutaneous injections with APIDRA 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. [See Dosage and Administration (2.3), How Supplied/Storage and Handling (16), and Patient Counseling Information (17.3)]. 5.9 Intravenous administration When APIDRA is administered intravenously, glucose and potassium levels must be closely monitored to avoid potentially fatal hypoglycemia and hypokalemia. Do not mix APIDRA with other insulins for intravenous administration. APIDRA may be diluted only in normal saline solution. 5.10 Drug interactions Some medications may alter insulin requirements and the risk for hypoglycemia or hyperglycemia [See Drug Interactions (7)]. 5.11 Fluid retention and heart failure with concomitant use of PPAR-gamma agonists Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including APIDRA and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.