Clinical medicine profile
Insulin Lispro
Insulin Analog [EPC]
- Route
- INTRAVENOUS, SUBCUTANEOUS
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
Contraindications
- 4 CONTRAINDICATIONS ADMELOG 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 ADMELOG [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 ADMELOG.
Precautions
- patients, even if the needle is changed.
- ( 5.1 ) Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Make changes to a patient's insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring.
- ( 5.2 ) Hypoglycemia: May be life-threatening.
- Monitor blood glucose and increase monitoring frequency with changes to insulin dosage, use of glucose lowering medications, meal pattern, physical activity
- in patients with renal or hepatic impairment
- and in patients with hypoglycemia unawareness.
- ( 5.3 , 6 , 7 , 8.6 , 8.7 ) Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products can occur.
- Instruct patients to check insulin labels before injection.
- ( 5.4 ) Hypersensitivity Reactions: May be life-threatening.
- Discontinue ADMELOG, monitor and treat if indicated.
- ( 5.5 ) Hypokalemia: May be life-threatening.
- Monitor potassium levels in patients at risk of hypokalemia and treat if indicated.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
instructions. ( 2.1 , 2.2 , 2.3 , 2.4 ) Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis. ( 2.2 ) Subcutaneous injection ( 2.2 ): Administer ADMELOG 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 ADMELOG can be used. Use in accordance with the insulin pump instructions for use. Administer ADMELOG 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 mix with other insulins or diluents in the pump. Intravenous Infusion: Administer ADMELOG by intravenous infusion ONLY after dilution and under medical supervision. ( 2.2 ) The dosage of ADMELOG must be individualized based on the route of administration and the patient's metabolic needs, blood glucose monitoring results and glycemic control goal. ( 2.3 ) 2.1 Important Preparation and Administration Instructions Always check insulin labels before administration [see Warnings and Precautions (5.4) ] . Inspect ADMELOG visually before use. It should appear clear and colorless. Do not use ADMELOG if particulate matter or coloration is seen. Use ADMELOG SoloStar prefilled pen with caution in patients with visual impairment who may rely on audible clicks to dial their dose. Do NOT mix ADMELOG with other insulins when administering using a continuous subcutaneous infusion pump. 2.2 Preparation and Administration Instructions for the Approved Routes of Administration Subcutaneous Injection Administer the dose of ADMELOG subcutaneously within fifteen minutes before a meal or immediately after a meal into the abdominal wall, thigh, upper arm, or buttocks. Rotate injection site within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions (5.2) , Adverse Reactions (6) ] . During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2) ] . ADMELOG administered by subcutaneous injection should generally be used in regimens with intermediate or long-acting insulin. The ADMELOG SoloStar prefilled pen dials in 1-unit increments. Prior to subcutaneous use, ADMELOG may be diluted with sterile 0.9% Sodium Chloride Injection. Dilute one-part ADMELOG to one-part 0.9% Sodium Chloride Injection to yield a concentration one-half that of ADMELOG (equivalent to U-50). If diluted ADMELOG is not used immediately, refrigerate at 2°C to 8°C (36°F to 46°F) for no more than 24 hours or store at room temperature up to 30°C (86°F) for 4 hours. 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. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions (5.2) , Adverse Reactions (6) ] . 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 [see Warnings and Precautions (5.8) ]. During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2) ] . 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. Do NOT expose ADMELOG in the pump reservoir to temperatures greater than 98.6°F (37°C). Intravenous Administration Administer ADMELOG intravenously ONLY under medical supervision [see Warnings and Precautions (5.3 , 5.6) ] . Dilute ADMELOG to concentrations from 0.1 unit/mL to 1 unit/mL using 0.9% Sodium Chloride Injection, USP [see How Supplied/Storage and Handling (16.2) ] . Closely monitor of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia [see Warnings and Precautions (5.3 , 5.6) ]. 2.3 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. 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 [see Warnings and Precautions (5.2 , 5.3) and Use in Specific Populations (8.6 , 8.7) ] . When switching from another insulin lispro product to ADMELOG, the dose of ADMELOG should be the same as the other insulin lispro product [see Warnings and Precautions (5.2) ]. When switching from other insulins to ADMELOG, the ADMELOG dosage may need to be adjusted [see Warnings and Precautions (5.2) ] . 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.
8.4 Pediatric Use The safety and effectiveness of ADMELOG to improve glycemic control have been established in pediatric patients with diabetes mellitus. Use of ADMELOG for this indication is supported by evidence from an adequate and well-controlled study with another insulin lispro product, 100 units/ml, in 60 pediatric patients 3 years of age and older with type 1 diabetes mellitus and studies in adult patients with diabetes mellitus [see Clinical Studies (14) ] .
Reduced insulin clearance — lower doses often needed in advanced CKD.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Impaired gluconeogenesis increases hypo risk.
Use, effects & interactions
Indications
- 1 INDICATIONS AND USAGE ADMELOG is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.
- ADMELOG is a rapid-acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.
Adverse effects
- 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 ADMELOG include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, and rash.
- ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis at 1-800-633-1610 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 conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- Adverse Reactions with Subcutaneous Injections of ADMELOG Two clinical trials with ADMELOG were conducted: one in patients with type 1 diabetes and one in patients with type 2 diabetes [see Clinical Studies (14) ] .
- The data in Table 1 reflect the exposure of 252 patients with type 1 diabetes to ADMELOG with mean exposure duration of 49 weeks.
- The type 1 diabetes population had the following characteristics: Mean age was 43 years and mean duration of diabetes was 20 years.
- Fifty-nine percent were male, 80% were White, 6% were Black or African American and 7% were Hispanic.
- At baseline, the mean eGFR was 90 mL/min/1.73 m 2 and 49% of patients had eGFR ≥90 mL/min/1.73 m 2 .
- The mean BMI was 26 kg/m 2 .
- The mean HbA1c at baseline was 8.07%.
- Two hundred fifty-three patients with type 2 diabetes were exposed to ADMELOG with mean exposure duration of 25 weeks.
- The type 2 diabetes population had the following characteristics: Mean age was 62 years and mean duration of diabetes was 17 years.
- Fifty-four percent were male, 90% were White, 6% were Black or African American and 17% were Hispanic.
- At baseline, the mean eGFR was 77 mL/min/1.73 m 2 and 27% of patients had eGFR ≥90 mL/min/1.73 m 2 .
- The mean BMI was 32 kg/m 2 .
Drug interactions
Open multi-drug checker ↗- PROMINENT FEATURES OF INSULIN LISPRO
- ||| Lispro human insulin analog differs from human regular insulin by its rapid onset of action and its shorter duration of activity.
- In Lipro the positions of the lysine and proline have been switched at the end of the -chain of the insulin molecule.
- ||| Insulin lispro with lysine at position 28 and proline at position 29 has a weaker tendency for self-association than human insulin
- ||| Insulin lispro has more precise action profile for the mealtime than human regular insulin
- ||| It is administered within 15 min before the meal in contrast to 30-40 min for human insulin.
- ||| It causes the postprandial rise of blood glucose that is smaller and the rate of hypoglycaemia is lower especially at night-time
- ||| Lispro human insulin should be stored in a refrigerator at 2-8C, but not in the freezer.
- The vial or cartridge of Lispro insulin can be kept unrefrigerated for up to 28 days, as long as it is kept at a temperature of less than 30C and away from direct heat and light.
- DRUG INTERACTIONS
- Corticosteroids antagonize effects of insulin by stimulating release of catecholamines, causing hyperglycemia
- thyroid hormone replacement therapy may increase insulin requirement
Mechanism & disposition
Insulin: ||| controls the storage and metabolism of carbohydrates, proteins, and fats.
Read complete mechanism
Insulin: ||| controls the storage and metabolism of carbohydrates, proteins, and fats. This occurs primarily in the liver, in muscle, and in adipose tissues after it binding to receptor sites on cellular plasma membranes. ||| is known to affect cell membrane transport characteristics, cellular growth, enzyme activation and inhibition, and changes in protein and fat metabolism. ||| promotes uptake of carbohydrates, proteins, and fats in most tissues. stimulates protein and free fatty acid synthesis. It inhibits release of free fatty acid from adipose cells. ||| increases active glucose transport through muscle and adipose cellular membranes ||| promotes conversion of intracellular glucose to glycogen and free fatty acid to triglyceride [storage forms] ||| increases hepatic glucose conversion to glyco-gen and suppresses hepatic glucose output. ||| stimulates growth hormonferre secretion by producing hypoglycemia, which is used to evaluate pituitary growth hormone reserve. ||| increases the intracellular shift of potassium and magnesium and decreases renal excretion of sodium. ||| decreases the synthesis of high-density lipopro-tein [HDL] cholesterol and increases the syn-thesis of very low-density lipoprotein [VLDL] cholesterol in the liver. ||| increases lipoprotein uptake and utilization in the lactating mammary gland. ||| stimulates activity of and tissue response to the sympathetic nervous system.
Minutes–hours (formulation-dependent)
Hours–>40 h (basal analogues)
INTRAVENOUS, SUBCUTANEOUS
and, consequently, the onset of activity are known to be affected by the site of injection, exercise, and other variables [see Warnings and Precautions (5.2) ] . Figure 1 Pharmacodynamics of AMELOG after Intravenous Administration The glucose lowering effect of intravenous admini...
When administered intravenously as bolus injections of 0.1 and 0.2 unit/kg dose in two separate groups of healthy subjects, the mean volume of distribution of another insulin lispro product, 100 units/mL, appeared to decrease with increase in dose (1.55 and 0.72 L/kg, respectivel...
is the primary activity of insulins and insulin analogs, including insulin lispro products. Insulins lower blood glucose by stimulating peripheral glucose uptake by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulins inhibit lipolysis and proteolysis a...
Metabolism Human
Pregnancy, lactation & diet
8.1 Pregnancy Risk Summary Published studies with another insulin lispro product 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 another insulin lispro product in animal reproduction studies during organogenesis. Fetal growth retardation was observed in offspring of rats exposed to insulin lispro at a dose approximately 3 times the human subcutaneous dose of 1.0 unit/kg/day. No adverse effects on embryo-fetal development were observed in offspring of rabbits exposed to insulin lispro at doses up to approximately 0.24 times the human subcutaneous dose of 1.0 unit/kg/day [see Data ] . The estimated background risk of major birth defects is 6%–10% in women with pregestational 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, preeclampsia, 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 another insulin lispro product 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. Animal data In a combined fertility and embryo-fetal development study with another insulin lispro product, female rats were given subcutaneous insulin lispro injections of 5 and 20 units/kg/day (0.8 and 3 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area, respectively) from 2 weeks prior to cohabitation through Gestation Day 19. There were no adverse effects on female fertility, implantation, or fetal viability and morphology. However, fetal growth retardation was observed at the 20 units/kg/day dose as indicated by decreased fetal weight and an increased incidence of fetal runts/litter. In an embryo-fetal development study in pregnant rabbits with another insulin lispro product, insulin lispro doses of 0.1, 0.25, and 0.75 unit/kg/day (0.03, 0.08, and 0.24 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area, respectively) were injected subcutaneously on Gestation Days 7 through 19. There were no adverse effects on fetal viability, weight, and morphology at any dose.
8.1 Pregnancy Risk Summary Published studies with another insulin lispro product 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 another insulin lispro product in animal reproduction studies during organogenesis. Fetal growth retardation was observed in offspring of rats exposed to insulin lispro at a dose approximately 3 times the human subcutaneous dose of 1.0 unit/kg/day. No adverse effects on embryo-fetal development were observed in offspring of rabbits exposed to insulin lispro at doses up to approximately 0.24 times the human subcutaneous dose of 1.0 unit/kg/day [see Data ] . The estimated background risk of major birth defects is 6%–10% in women with pregestational 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, preeclampsia, 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 another insulin lispro product 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. Animal data In a combined fertility and embryo-fetal development study with another insulin lispro product, female rats were given subcutaneous insulin lispro injections of 5 and 20 units/kg/day (0.8 and 3 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area, respectively) from 2 weeks prior to cohabitation through Gestation Day 19. There were no adverse effects on female fertility, implantation, or fetal viability and morphology. However, fetal growth retardation was observed at the 20 units/kg/day dose as indicated by decreased fetal weight and an increased incidence of fetal runts/litter. In an embryo-fetal development study in pregnant rabbits with another insulin lispro product, insulin lispro doses of 0.1, 0.25, and 0.75 unit/kg/day (0.03, 0.08, and 0.24 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area, respectively) were injected subcutaneously on Gestation Days 7 through 19. There were no adverse effects on fetal viability, weight, and morphology at any dose. 8.2 Lactation Risk Summary Available data from published literature suggest that exogenous human insulin products, including insulin lispro, are transferred into human milk. There are no adverse reactions reported in breastfed infants in the literature. There are no data on the effects of exogenous human insulin products, including insulin lispro, on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ADMELOG and any potential adverse effects on the breastfed child from ADMELOG or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of ADMELOG to improve glycemic control have been established in pediatric patients with diabetes mellitus. Use of ADMELOG for this indication is supported by evidence from an adequate and well-controlled study with another insulin lispro product, 100 units/ml, in 60 pediatric patients 3 years of age and older with type 1 diabetes mellitus and studies in adult patients with diabetes mellitus [see Clinical Studies (14) ] . 8.5 Geriatric Use Of the total number of patients (n=2,834) in eight clinical studies of another insulin lispro product, 100 units/mL, 12% (n=338) were 65 years of age or over. The majority of these patients had type 2 diabetes. HbA1c values and hypoglycemia rates did not differ by age. Of the total number of patients (n=1,011) in clinical studies of ADMELOG or another insulin lispro product, 100 units/mL, 26.5% (n=268) were 65 years of age or over. The majority of these patients had type 2 diabetes. HbA1c values and hypoglycemia rates did not differ by age. Pharmacokinetic/pharmacodynamic studies to assess the effect of age on the onset of ADMELOG action have not been performed. 8.6 Renal Impairment Patients with renal impairment may be at increased risk of hypoglycemia and may require more frequent ADMELOG dose adjustment and more frequent blood glucose monitoring [see Clinical Pharmacology (12.3) ] . 8.7 Hepatic Impairment Patients with hepatic impairment may be at increased risk of hypoglycemia and may require more frequent ADMELOG dose adjustment and more frequent blood glucose monitoring [see Clinical Pharmacology (12.3) ] .
Brands & loaded prices
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Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.