Insulin Lispro Junior Kwikpen Drug Information

Insulin Lispro is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.

Important Administration Instructions

Always check insulin labels before administration. This product is HUMALOG (insulin lispro). Inspect Insulin Lispro visually before use.

It should appear clear and colorless. Do not use Insulin Lispro if particulate matter or coloration is seen. Use Insulin Lispro prefilled pens with caution in patients with visual impairment that may rely on audible clicks to dial their dose.

Do NOT mix Insulin Lispro with other insulins when using a continuous subcutaneous infusion pump. Do NOT perform dose conversion when using any Insulin Lispro prefilled pens. The dose window shows the number of insulin units to be delivered and no conversion is needed.

Administration Instructions for the Approved Routes of Administration Subcutaneous Injection Administer the dose of Insulin Lispro within fifteen minutes before a meal or immediately after a meal by injection into the subcutaneous tissue of the abdominal wall, thigh, upper arm, or buttocks. Rotate the injection site within the same region from one injection to the next (abdominal wall, thigh, upper arm, or buttocks) to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis.

During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring. Insulin Lispro administered by subcutaneous injection should generally be used in regimens with an intermediate- or long-acting insulin. The Insulin Lispro KwikPen dials in 1 unit increments and delivers a maximum dose of 60 units per injection.

The Insulin Lispro Junior KwikPen dials in 0.5 unit increments and delivers a maximum dose of 30 units per injection. Subcutaneous Injection: Diluted Insulin Lispro Insulin Lispro may be diluted with Sterile Diluent for Insulin Lispro for subcutaneous injection ONLY under medical supervision. Dilute one part Insulin Lispro to: Nine parts diluent to yield a concentration one-tenth that of Insulin Lispro (equivalent to U-10).

One part diluent to yield a concentration one-half that of Insulin Lispro (equivalent to U-50). Diluted Insulin Lispro for subcutaneous injection may be stored for 28 days when refrigerated at 41°F (5°C) and for 14 days at room temperature up to 86°F (30°C). Continuous Subcutaneous Infusion (Insulin Pump) This Insulin Lispro product can be used with continuous subcutaneous insulin infusion pumps labeled for use with Humalog (insulin lispro).

Refer to the insulin pump user manual to see if Humalog can be used. Use Insulin Lispro in accordance with the insulin pump system's instructions for use. Administer Insulin Lispro 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. Train patients using continuous subcutaneous insulin infusion therapy to administer insulin by injection and have alternate insulin therapy available in case of insulin pump failure. Change Insulin Lispro in the pump reservoir at least every 7 days or according to the pump user manual, whichever is shorter.

Follow the Humalog-specific information for in-use time because Humalog-specific information may differ from general pump manual instructions. Change the infusion set and the infusion set insertion site according to the manufacturer's user manual. Do NOT dilute or mix Insulin Lispro when administering by continuous subcutaneous infusion.

Do NOT expose Insulin Lispro in the pump reservoir to temperatures greater than 98.6°F (37°C). Intravenous Administration Administer Insulin Lispro intravenously ONLY under medical supervision with close monitoring of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia. Dilute Insulin Lispro to concentrations from 0.1 unit/mL to 1.0 unit/mL using 0.9% Sodium Chloride Injection, USP.

Infusion bags prepared with Insulin Lispro are stable when stored in a refrigerator (2° to 8°C ) for 48 hours and then may be used at room temperature for up to an additional 48 hours.

Dosage Recommendations Individualize and adjust the dosage of Insulin Lispro based on route of administration, the individual's metabolic needs, blood glucose monitoring results and glycemic control goal. When switching from another insulin to Insulin Lispro. a different dosage of Insulin Lispro may be needed. Dosage modifications may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness.

Dosage Modifications for Drug Interactions

Dosage modification may be needed when Insulin Lispro is used concomitantly with certain drugs.

Instructions for Mixing with Other Insulins

The table below includes administration instructions regarding mixing Insulin Lispro with other insulins. Insulin Lispro subcutaneous injection route Insulin Lispro may be mixed with NPH insulin preparations ONLY. Insulin Lispro continuous subcutaneous infusion route (Insulin Pump) Do NOT mix Insulin Lispro with any other insulin.

Clinical Trials Experience

Because clinical trials are conducted under widely varying designs, the adverse reaction rates reported in one clinical trial may not be easily compared with those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice. Common adverse reactions, excluding hypoglycemia, were defined as events that occurred in ≥5% of patients treated with Insulin Lispro or regular human insulin. The frequencies of adverse reactions during Insulin Lispro clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below.

Table 1: Adverse Reactions That Occurred in ≥5% in Patients with Type 1 Diabetes Mellitus Table 2: Adverse Reactions That Occurred in ≥5% in Patients with Type 2 Diabetes Mellitus 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. Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including Insulin Lispro.

Lipodystrophy Long-term use of insulin, including Insulin Lispro, can cause lipodystrophy at the site of repeated insulin injections or infusion. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue), and may affect insulin absorption. Weight gain Weight gain can occur with insulins, including Insulin Lispro, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.

Peripheral Edema Insulins, including Insulin Lispro, 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) In a 12-week, randomized, crossover study in adult patients with type 1 diabetes (n=39), the rates of catheter occlusions and infusion site reactions were similar for Insulin Lispro and regular human insulin treated patients ( see Table 3 ). In both groups, the most frequently reported infusion site reactions were infusion site erythema and infusion site reaction.

Allergic Reactions Local Allergy — As with any insulin, patients taking Insulin Lispro 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 Insulin Lispro. Systemic Allergy — Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with any insulin, including Insulin Lispro.

Generalized allergy to insulin may cause whole body rash (including pruritus), dyspnea, wheezing, hypotension, tachycardia, or diaphoresis. In controlled clinical trials, pruritus (with or without rash) was seen in 17 patients receiving regular human insulin (n=2969) and 30 patients receiving Insulin Lispro (n=2944). Localized reactions and generalized myalgias have been reported with injected metacresol, which is an excipient in Insulin Lispro.

Antibody Production In large clinical trials with patients with type 1 (n=509) and type 2 (n=262) diabetes mellitus, anti-insulin antibody (insulin lispro-specific antibodies, insulin-specific antibodies, cross-reactive antibodies) formation was evaluated in patients receiving both regular human insulin and Insulin Lispro (including patients previously treated with human insulin and naive patients). As expected, the largest increase in the antibody levels occurred in patients new to insulin therapy. The antibody levels peaked by 12 months and declined over the remaining years of the study.

These antibodies do not appear to cause deterioration in glycemic control or necessitate an increase in insulin dose. There was no statistically significant relationship between the change in the total daily insulin dose and the change in percent antibody binding for any of the antibody types.

Postmarketing Experience

The following additional adverse reactions have been identified during post-approval use of Insulin Lispro. 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 Insulin Lispro 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.

The table below includes clinically significant drug interactions with Insulin Lispro. Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics. Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones.

Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine. Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine.

Pregnancy Risk Summary Published studies with insulin lispro used during pregnancy have not reported an association between insulin lispro and the induction of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations). Pregnant rats and rabbits were exposed to insulin lispro in animal reproduction studies during organogenesis.

No adverse effects on embryo/fetal viability or morphology were observed in offspring of rats exposed to insulin lispro at a dose approximately 3 times the human subcutaneous dose of 1 unit insulin lispro/kg/day. No adverse effects on embryo/fetal development were observed in offspring of rabbits exposed to insulin lispro at doses up to approximately 0.2 times the human subcutaneous dose of 1 unit/kg/day (see Data). The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20-25% in women with a HbA1c >10.

The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications.

Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Data Human Data Published data from retrospective studies and meta-analyses do not report an association with insulin lispro and major birth defects, miscarriage, or adverse maternal or fetal outcomes when insulin lispro is used during pregnancy. However, these studies cannot definitely establish or exclude the absence of any risk because of methodological limitations including small sample size, selection bias, confounding by unmeasured factors, and some lacking comparator groups.

There were no adverse effects on female fertility, implantation, or fetal viability and morphology. However, fetal growth retardation was produced at the 20 units/kg/day-dose as indicated by decreased fetal weight and an increased incidence of fetal runts/litter. There were no adverse effects on fetal viability, weight, and morphology at any dose.

Pediatric Use The safety and effectiveness of Insulin Lispro to improve glycemic control have been established in pediatric patients with diabetes mellitus. Use of Insulin Lispro for this indication is supported by evidence from adequate and well-controlled studies in 831 pediatric patients with type 1 diabetes mellitus aged 3 years and older and from studies in adults with diabetes mellitus.

Insulin Lispro is contraindicated: during episodes of hypoglycemia. in patients who are hypersensitive to Insulin Lispro or to any of the excipients in Insulin Lispro. Do not use during episodes of hypoglycemia. Do not use in patients with hypersensitivity to Insulin Lispro or any of the excipients in Insulin Lispro.

Excess insulin administration may cause hypoglycemia and hypokalemia. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed.

More severe episodes with coma, seizure, or neurologic impairment may be treated with a glucagon product for emergency use or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately.