Humalog 75/25
(insulin lispro / insulin lispro protamine, human)Dosage & Administration
By using PrescriberAI, you agree to the AI Terms of Use.
Humalog 75/25 Prescribing Information
HUMALOG Mix75/25 is indicated to improve glycemic control in adults with diabetes mellitus.
Limitations of Use:
The proportions of rapid-acting and intermediate-acting insulins in HUMALOG Mix75/25 are fixed and do not allow for basal versus prandial dose adjustments.
Important Preparation and Administration Instructions
Preparation Instructions
- Always check insulin labels before administration [see Warnings and Precautions ].
- HUMALOG Mix75/25 is a suspension that must be resuspended immediately before use. Resuspension is easier when the insulin has reached room temperature.
- To resuspend the:
- vial, carefully invert the vial at least 10 times until the suspension appears uniformly white and cloudy.
- KwikPen, gently roll the KwikPen at least 10 times and then carefully invert the KwikPen at least 10 times until the suspension appears uniformly white and cloudy.
- Inspect HUMALOG Mix75/25 visually before use. Do not use if discoloration or particulate matter is seen.
Administration Instructions
- After resuspension, immediately administer HUMALOG Mix75/25 by subcutaneous injection into the abdominal wall, thigh, upper arm, or buttocks.
- Rotate the 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 and Adverse Reactions ].
- The HUMALOG Mix75/25 KwikPen dials in 1 unit increments.
- Use HUMALOG Mix75/25 KwikPen with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
- Do not administer HUMALOG Mix75/25 intravenously or by a continuous subcutaneous insulin infusion pump.
- Do not mix HUMALOG Mix75/25 with any other insulins or diluents.
Dosage Recommendations
- Individualize and adjust the dosage of HUMALOG Mix75/25 based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.
- Inject HUMALOG Mix75/25 subcutaneously within 15 minutes before a meal.
- HUMALOG Mix75/25 is typically dosed twice-daily (with each dose intended to cover 2 meals or a meal and a snack).
- Dosage adjustments 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 and Use in Specific Populations ].
- When switching from another insulin to HUMALOG Mix75/25 a different dosage of HUMALOG Mix75/25 may be needed.
- During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions ].
Dosage Modifications for Drug Interactions
Dosage modification may be needed when HUMALOG Mix75/25 is used concomitantly with certain drugs [see Drug Interactions ].
Injectable suspension: 100 units/mL (U-100) of HUMALOG Mix75/25, 75% insulin lispro protamine and 25% insulin lispro, is a white and cloudy suspension available as:
- 10 mL multiple-dose vial
- 3 mL single-patient-use KwikPen prefilled pen
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, still birth, 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.
Animal Data
Animal reproduction studies have not been performed with HUMALOG Mix75/25. However, subcutaneous reproduction and teratology studies have been conducted with insulin lispro (a component of HUMALOG Mix75/25). In a combined fertility and embryo-fetal development study, female rats were given subcutaneous insulin lispro injections of 1, 5, and 20 units/kg/day (0.2, 0.8, and 3 times the human subcutaneous dose of 1 unit insulin lispro/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 produced 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, insulin lispro doses of 0.1, 0.25, and 0.75 unit/kg/day (0.03, 0.08, and 0.2 times the human subcutaneous dose of 1 unit insulin lispro/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.
Lactation
Risk Summary
Available data from published literature suggests that exogenous human insulin products, including HUMALOG Mix75/25, 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 HUMALOG Mix75/25, on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for insulin, any potential adverse effects on the breastfed child from HUMALOG Mix75/25 or from the underlying maternal condition.
Pediatric Use
Safety and effectiveness of HUMALOG Mix75/25 in pediatric patients have not been established.
Geriatric Use
Clinical studies of Humalog Mix75/25 did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. In patients aged 65 and over with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to reduce the risk of hypoglycemia [see Warnings and Precautions ].
Renal Impairment
The effect of renal impairment on the pharmacokinetics of HUMALOG Mix75/25 has not been studied. Patients with renal impairment may be at increased risk of hypoglycemia and may require more frequent HUMALOG Mix75/25 dose adjustment and more frequent glucose monitoring [see Warnings and Precautions ].
Hepatic Impairment
The effect of hepatic impairment on the pharmacokinetics of HUMALOG Mix75/25 has not been studied. Patients with hepatic impairment may be at increased risk of hypoglycemia and may require more frequent HUMALOG Mix75/25 dose adjustment and more frequent glucose monitoring [see Warnings and Precautions ].
HUMALOG Mix75/25 is contraindicated:
- during episodes of hypoglycemia [see Warnings and Precautions ]
- in patients who have had hypersensitivity reactions to HUMALOG Mix75/25 or to any of its excipients. [see Warnings and Precautions ]
Never Share a HUMALOG Mix75/25 KwikPen or Syringe Between Patients
HUMALOG Mix75/25 KwikPens must never be shared between patients, even if the needle is changed. Patients using HUMALOG Mix75/25 vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen
Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions ] or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions ].
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.
Hypoglycemia
Hypoglycemia is the most common adverse reaction associated with all insulins, including HUMALOG Mix75/25. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life-threatening, or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery).
Hypoglycemia can happen suddenly, and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions ], 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. As with all insulins, the glucose lowering effect time course of HUMALOG Mix75/25 may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature [see Clinical Pharmacology ]. Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to co-administered medication [see Drug Interactions ]. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations ].
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.
Hypoglycemia Due to Medication Errors
Accidental mix-ups between insulin products have been reported. To avoid medication errors between HUMALOG Mix75/25 and other insulins, instruct patients to always check the insulin label before each injection.
Hypersensitivity Reactions
Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including HUMALOG Mix75/25. If hypersensitivity reactions occur, discontinue HUMALOG Mix75/25; treat per standard of care and monitor until symptoms and signs resolve. HUMALOG Mix75/25 is contraindicated in patients who have had hypersensitivity reactions to HUMALOG Mix75/25 or any of its excipients [see Contraindications ].
Hypokalemia
All insulins, including HUMALOG Mix75/25, 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. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations).
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 HUMALOG Mix75/25, 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.