ADMELOG

Discard the unused diluted ADEMLOG after 24 hours if refrigerated or after 4 hours if stored at room temperature. Continuous Subcutaneous Infusion (Insulin Pump) Refer to the continuous subcutaneous insulin infusion pump user manual to see if ADMELOG can be used with the insulin pump.

Use ADMELOG in accordance with the insulin pump system's instructions for use. Administer ADMELOG by continuous subcutaneous infusion in a region recommended in the instructions from the pump manufacturer. Rotate infusion sites within the same region to reduce the risk of lipodystrophy and localized cutaneous amyloidosis.

2) , Adverse Reactions (6) ] . 8) ]. 2) ] . Change ADMELOG in the pump reservoir at least every 7 days or according to the pump user manual, whichever is shorter. Change the infusion sets and the infusion set insertion site according to the manufacturer's user manual.

Do NOT dilute or mix ADMELOG when administering by continuous subcutaneous infusion. 6°F (37°C). 6) ] . 2) ] . 6) ]. 3 Dosage Recommendations Individualize and adjust the dosage of ADMELOG based on the route of administration, the patient's metabolic needs, blood glucose monitoring results, and glycemic control goal.

7) ] . 2) ]. 2) ] . 4 Dosage Adjustment for Drug Interactions Dosage modification may be needed when ADMELOG is coadministered with certain drugs [see Drug Interactions (7) ]. Do NOT mix ADMELOG with any other insulin.

3) ] . The rates of reported hypoglycemia depend on the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors. For these reasons, comparing rates of hypoglycemia in clinical trials for ADMELOG with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that will occur in clinical practice.

In the ADMELOG trials, severe hypoglycemia was defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. 4% at 26 weeks, respectively [see Clinical Studies (14) ] .

Adverse Reactions Associated with Insulin Initiation and Intensification of Glucose Control Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy.

However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy. Lipodystrophy Long-term use of insulin, including ADMELOG, can cause lipodystrophy at the site of repeated insulin injections or infusion.

2) ] . Weight Gain Weight gain can occur with insulins, including ADMELOG, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria. Peripheral Edema Insulins, including ADMELOG, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

Adverse Reactions with Continuous Subcutaneous Insulin Infusion (CSII) of ADMELOG In a randomized, open-label crossover study in adult patients with type 1 diabetes treated over two 4-week periods, the incidence of infusion set occlusions (defined as failure to correct hyperglycemia [plasma glucose ≥300 mg/dL] by insulin bolus via insulin pump) in ADMELOG-treated patients (n=25) was evaluated.

Infusion set occlusions were reported by 24% of patients. In a randomized, 16-week, open-label, parallel design study of pediatric patients with type 1 diabetes, adverse reactions related to infusion site-related reactions for another insulin lispro product, 100 units/mL, occurred in 21% of patients.

The most frequently reported infusion site-related reactions were infusion site erythema and infusion site reaction. Allergic Reactions Local Allergy As with any insulin therapy, patients taking ADMELOG may experience redness, swelling, or itching at the site of the injection.

These minor reactions usually resolve in a few days to a few weeks, but in some occasions may require discontinuation of ADMELOG. In some instances, these reactions may be related to factors other than insulin, such as irritants in a skin cleansing agent or poor injection technique.

Systemic Allergy Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with any insulin, including ADMELOG. Generalized allergy to insulin may cause whole body rash (including pruritus), dyspnea, wheezing, hypotension, tachycardia, or diaphoresis.

Localized reactions and generalized myalgias have been reported with injected metacresol, which is an excipient in ADMELOG [see Contraindications (4) ] . 2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease.

For these reasons, comparison of the incidence of antibodies to ADMELOG in the studies described below with the incidence of antibodies in other studies or to other insulin products may be misleading. , either new ADA, or increase in titer of at least 4-fold).

, either new ADA, or increase in titer of at least 4-fold). 3 Postmarketing Experience The following additional adverse reactions have been identified during post approval use of another insulin lispro product, 100 units/mL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Medication errors in which other insulins have been accidentally substituted for another insulin lispro product, 100 units/mL, have been identified during post approval use. 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.

Make any changes to a patient's insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia.

For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed. 3 Hypoglycemia Hypoglycemia is the most common adverse reaction associated with insulins, including ADMELOG. Severe hypoglycemia can cause seizures, may be life-threatening, or cause death.

, driving or operating other machinery). Hypoglycemia can happen suddenly, and symptoms may differ in each individual and change over time in the same individual. , beta-blockers) [see Drug Interactions (7) ] , or in patients who experience recurrent hypoglycemia.

Risk Factors for Hypoglycemia The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. 2) ] . , macronutrient content or timing of meals), changes in level of physical activity, or changes to co-administered medication [see Drug Interactions (7) ] .

7) ] . Risk Mitigation Strategies for Hypoglycemia Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia.

In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended. 4 Hypoglycemia Due to Medication Errors Accidental mix-ups between insulin products have been reported.

To avoid medication errors between ADMELOG and other insulins, instruct patients to always check the insulin label before each injection. 5 Hypersensitivity Reactions Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including ADMELOG.

1) ] . ADMELOG is contraindicated in patients who have had hypersensitivity reactions to insulin lispro or any of the excipients in ADMELOG [see Contraindications (4) ] . 6 Hypokalemia All insulins, including ADMELOG, 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. , patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations). 7 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 ADMELOG, 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.

8 Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction Malfunction of the insulin pump or insulin infusion set or insulin degradation can rapidly lead to hyperglycemia and ketoacidosis. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary.

Interim subcutaneous injections with ADMELOG may be required. 2) and Patient Counseling Information (17) ] .