Insulin Lispro

FDA Drug Information • Also known as: Admelog, Humalog, Humalog Junior Kwikpen, Humalog Kwikpen, Humalog Mix50/50 Kwikpen, Humalog...

Brand Names: Admelog, Humalog, Humalog Junior Kwikpen, Humalog Kwikpen, Humalog Mix50/50 Kwikpen, Humalog Mix75/25, Humalog Mix75/25 Kwikpen, Humalog Tempo Pen, Insulin Lispro, Insulin Lispro Junior Kwikpen, Insulin Lispro Kwikpen, Insulin Lispro Protamine And Insulin Lispro Injectable Suspension Mix75/25 Kwikpen
Dosage Form: INJECTION, SUSPENSION
Product Type: DRUG FOR FURTHER PROCESSING

Description

11 DESCRIPTION Insulin lispro is a rapid-acting human insulin analog produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli . Insulin lispro differs from human insulin in that the amino acid proline at position B28 is replaced by lysine and the lysine in position B29 is replaced by proline. Chemically, it is Lys(B28), Pro(B29) human insulin analog and has the empirical formula C 257 H 383 N 65 O 77 S 6 and a molecular weight of 5.808 kDa, both identical to that of human insulin. Insulin lispro has the following primary structure: HUMALOG (insulin lispro) injection is a sterile, clear, and colorless solution for subcutaneous or intravenous use. Each mL of HUMALOG U-100 contains 100 units of insulin lispro, and the inactive ingredients: dibasic sodium phosphate (1.0 mg), glycerin (16 mg), metacresol (3.15 mg), trace amounts of phenol, zinc oxide (content adjusted to provide 0.0197 mg zinc ion), and Water for Injection, USP. Each mL of HUMALOG U-200 contains 200 units of insulin lispro, and the inactive ingredients: glycerin (16 mg), metacresol (3.15 mg), trace amounts of phenol, tromethamine (5 mg), zinc oxide (content adjusted to provide 0.046 mg zinc ion), and Water for Injection, USP. HUMALOG has a pH of 7.0 to 7.8. Hydrochloric acid 10% and/or sodium hydroxide 10% is added to adjust the pH. Primary Structure

What Is Insulin Lispro Used For?

1 INDICATIONS AND USAGE HUMALOG is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. HUMALOG is a rapid acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION See Full Prescribing Information for important administration instructions. ( 2.1 , 2.2 , 2.3 , 2.4 ) Subcutaneous injection ( 2.2 ): Administer HUMALOG ® U-100 or U-200 by subcutaneous injection into the abdominal wall, thigh, upper arm, or buttocks within 15 minutes before a meal or immediately after a meal. Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis. Continuous subcutaneous infusion (Insulin Pump) ( 2.2 ): Refer to the insulin infusion pump user manual to see if HUMALOG can be used. Use in accordance with the insulin pump instructions for use. Administer HUMALOG U-100 by continuous subcutaneous infusion using an insulin pump in a region recommended in the instructions from the pump manufacturer. Rotate infusion sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis. DO NOT administer HUMALOG U-200 by continuous subcutaneous infusion. Intravenous Infusion ( 2.2 ): Administer HUMALOG U-100 by intravenous infusion ONLY after dilution and under medical supervision. DO NOT administer HUMALOG U-200 by intravenous infusion. The dosage of HUMALOG must be individualized based on the route of administration and the individual's metabolic needs, blood glucose monitoring results and glycemic control goal. ( 2.3 ) Do not perform dose conversion when using the HUMALOG U-100 or U-200 prefilled pens. The dose window shows the number of insulin units to be delivered and no conversion is needed. ( 2.1 , 2.3 ) Do not mix HUMALOG U-200 with any other insulin. ( 2.4 ) 2.1 Important Administration Instructions Always check insulin labels before administration [see Warnings and Precautions ( 5.4 )] . Inspect HUMALOG visually before use. It should appear clear and colorless. Do not use HUMALOG if particulate matter or coloration is seen. Use HUMALOG prefilled pens with caution in patients with visual impairment that may rely on audible clicks to dial their dose. Do NOT mix HUMALOG U-100 with other insulins when using a continuous subcutaneous infusion pump. Do NOT transfer HUMALOG U-200 from the prefilled pen to a syringe for administration [see Warnings and Precautions ( 5.4 )] . Do NOT perform dose conversion when using any HUMALOG U-100 or U-200 prefilled pens. The dose window shows the number of insulin units to be delivered and no conversion is needed. 2.2 Administration Instructions for the Approved Routes of Administration Subcutaneous Injection: HUMALOG U-100 or U-200 Administer the dose of HUMALOG U-100 or HUMALOG U-200 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 [see Warnings...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere: Hypoglycemia [see Warnings and Precautions ( 5.3 )] . Hypoglycemia Due to Medication Errors [see Warnings and Precautions ( 5.4 )]. Hypersensitivity Reactions [see Warnings and Precautions ( 5.5 )]. Hypokalemia [see Warnings and Precautions ( 5.6 )] . Adverse reactions associated with HUMALOG include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 HUMALOG 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 HUMALOG (%) (n=81) Regular human insulin (%) (n=86) Flu syndrome 34.6 32.6 Pharyngitis 33.3 33.7 Rhinitis 24.7 29.1 Headache 29.6 22.1 Pain 19.8 16.3 Cough increased 17.3 17.4 Infection 13.6 20.9 Nausea 6.2 15.1 Accidental injury 8.6 11.6 Surgical procedure 6.2 14.0 Fever 6.2 11.6 Abdominal pain 7.4 8.1 Asthenia 7.4 8.1 Bronchitis 7.4 7.0 Diarrhea 8.6 5.8 Dysmenorrhea 6.2 7.0 Myalgia 7.4 5.8 Urinary tract infection 6.2 4.7 Table 2: Adverse Reactions That Occurred in ≥5% in Patients with Type 2 Diabetes Mellitus HUMALOG (%) (n=714) Regular human insulin (%) (n=709) Headache 11.6 9.3 Pain 10.8 10.0 Infection 10.1 7.6 Pharyngitis 6.6 8.2 Rhinitis 8.1 6.6 Flu syndrome 6.2 8.2 Surgical procedure 7.4 6.8 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 HUMALOG. Lipodystrophy Long-term use of insulin, including HUMALOG, 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 [see Dosage and Administration ( 2.2 )] . Weight gain Weight gain can occur with insulins, including HUMALOG, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria. Peripheral Edema Insulins, including HUMALOG, 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) — HUMALOG U-100 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 HUMALOG U-100 and regular human insulin treated patients ( see Table 3 ). Table 3: Catheter Occlusions and Infusion Site Reactions HUMALOG U-100 (n=38) Regular human insulin (n=39) Catheter occlusions/month 0.09 0.10 Infusion site reactions 2.6% (1/38) 2.6% (1/39) In a randomized, 16-week, open-label, parallel design study of pediatric patients with type 1 diabetes, adverse reactions related to infusion-site reactions were similar for insulin lispro and insulin aspart (21% of 100 patients versus 17% of 198...

Drug Interactions

7 DRUG INTERACTIONS The table below includes clinically significant drug interactions with HUMALOG. Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when HUMALOG is co-administered with these drugs. Drugs That May Decrease the Blood Glucose Lowering Effect of HUMALOG Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), 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. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when HUMALOG is co-administered with these drugs. Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of HUMALOG Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when HUMALOG is co-administered with these drugs. Drugs That May Blunt Signs and Symptoms of Hypoglycemia Drugs: Beta-blockers, clonidine, guanethidine and reserpine. Intervention: Increased frequency of glucose monitoring may be required when HUMALOG is co-administered with these drugs. 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 ( 7 ). 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 ( 7 ). Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine ( 7 ). Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine ( 7 ).

Contraindications

4 CONTRAINDICATIONS HUMALOG is contraindicated: during episodes of hypoglycemia [see Warnings and Precautions ( 5.3 )] . in patients who are hypersensitive to insulin lispro or to any of the excipients in HUMALOG [see Warnings and Precautions ( 5.5 )] . Do not use during episodes of hypoglycemia. ( 4 ) Do not use in patients with hypersensitivity to insulin lispro or any of the excipients in HUMALOG. ( 4 )

Pregnancy and Breastfeeding

8.1 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...

Overdosage

10 OVERDOSAGE 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.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied HUMALOG (insulin lispro) injection is a clear and colorless solution available as: a Tempo Pen contains a component that allows for data connectivity when used with a compatible transmitter. HUMALOG Total Volume Concentration NDC Number Package Size U-100 multiple-dose vial 10 mL 100 units/mL 0002-7510-01 1 vial U-100 multiple-dose vial 3 mL 100 units/mL 0002-7510-17 1 vial U-100 multiple-dose vial 3 mL 100 units/mL 0002-7533-01 1 vial U-100 single-patient-use cartridge 1 3 mL 100 units/mL 0002-7516-59 5 cartridges U-100 single-patient-use KwikPen 3 mL 100 units/mL 0002-8799-59 5 pens U-100 single-patient-use Tempo Pen a 3 mL 100 units/mL 0002-8213-05 5 pens U-100 single-patient-use Junior KwikPen 3 mL 100 units/mL 0002-7714-59 5 pens U-200 single-patient-use KwikPen 3 mL 200 units/mL 0002-7712-27 2 pens U-200 single-patient-use Tempo Pen a 3 mL 200 units/mL 0002-8208-27 2 pens The U-100 KwikPen, U-100 Tempo Pen, U-200 KwikPen, and U-200 Tempo Pen dial in 1-unit increments. The U-100 Junior KwikPen dials in 0.5-unit increments. Each prefilled pen, cartridge, and reusable pen compatible with Lilly 3 mL cartridges is for single-patient-use only. HUMALOG prefilled pens, cartridges, and reusable pens compatible with Lilly 3 mL cartridges must never be shared between patients, even if the needle is changed. Patients using HUMALOG vials must never share needles or syringes with another person. 16.2 Storage and Handling Dispense in the original sealed carton with the enclosed Instructions for Use. Protect from direct heat and light. Do not freeze and do not use if it has been frozen. See table below for storage information: * When stored at room temperature, HUMALOG U-100 and U-200 can only be used for a total of 28 days, including both not in-use (unopened) and in-use (opened) storage time. Not In-Use (Unopened) Room Temperature (Up to 86°F [30°C]) Not In-Use (Unopened) Refrigerated (36° to 46°F [2° to 8°C]) In-Use...

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.