Humalog 50/50

HUMALOG Mix50/50 is indicated to improve glycemic control in adults with diabetes mellitus.

• See Full Prescribing Information for important preparation and administration instructions. (
  2.1 Important Preparation and Administration Instructions

  Preparation Instructions

  • Always check insulin labels before administration
    [see Warnings and Precautions ]
    .
  • HUMALOG Mix50/50 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 Mix50/50 visually before use. Do not use if discoloration or particulate matter is seen.

  Administration Instructions

  • After resuspension, immediately administer HUMALOG Mix50/50 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 Mix50/50 KwikPen dials in 1 unit increments.
  • Use HUMALOG Mix50/50 KwikPen with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
  • Do not administer HUMALOG Mix50/50 intravenously or by a continuous subcutaneous insulin infusion pump.
  • Do not mix HUMALOG Mix50/50 with any other insulins or diluents.
  )
• Inject HUMALOG Mix50/50 subcutaneously (within 15 minutes before a meal) in abdominal wall, thigh, upper arm, or buttocks and rotate injection sites to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. (
  2.1 Important Preparation and Administration Instructions

  Preparation Instructions

  • Always check insulin labels before administration
    [see Warnings and Precautions ]
    .
  • HUMALOG Mix50/50 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 Mix50/50 visually before use. Do not use if discoloration or particulate matter is seen.

  Administration Instructions

  • After resuspension, immediately administer HUMALOG Mix50/50 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 Mix50/50 KwikPen dials in 1 unit increments.
  • Use HUMALOG Mix50/50 KwikPen with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
  • Do not administer HUMALOG Mix50/50 intravenously or by a continuous subcutaneous insulin infusion pump.
  • Do not mix HUMALOG Mix50/50 with any other insulins or diluents.
  ,
  2.2 Dosage Recommendations

  • Individualize and adjust the dosage of HUMALOG Mix50/50 based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.
  • Inject HUMALOG Mix50/50 subcutaneously within 15 minutes before a meal.
  • HUMALOG Mix50/50 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 Mix50/50, a different dosage of HUMALOG Mix50/50 may be needed.
  • During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring
    [see Warnings and Precautions ]
    .
  )
• Individualize and adjust dosage based on metabolic needs, blood glucose monitoring results and glycemic control goal. (
  2.2 Dosage Recommendations

  • Individualize and adjust the dosage of HUMALOG Mix50/50 based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.
  • Inject HUMALOG Mix50/50 subcutaneously within 15 minutes before a meal.
  • HUMALOG Mix50/50 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 Mix50/50, a different dosage of HUMALOG Mix50/50 may be needed.
  • During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring
    [see Warnings and Precautions ]
    .
  )
• Do not administer HUMALOG Mix50/50 intravenously or by a continuous subcutaneous insulin infusion pump. (
  2.1 Important Preparation and Administration Instructions

  Preparation Instructions

  • Always check insulin labels before administration
    [see Warnings and Precautions ]
    .
  • HUMALOG Mix50/50 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 Mix50/50 visually before use. Do not use if discoloration or particulate matter is seen.

  Administration Instructions

  • After resuspension, immediately administer HUMALOG Mix50/50 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 Mix50/50 KwikPen dials in 1 unit increments.
  • Use HUMALOG Mix50/50 KwikPen with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
  • Do not administer HUMALOG Mix50/50 intravenously or by a continuous subcutaneous insulin infusion pump.
  • Do not mix HUMALOG Mix50/50 with any other insulins or diluents.
  )
• HUMALOG Mix50/50 is typically dosed twice daily (with each dose intended to cover 2 meals or a meal and a snack). (
  2.2 Dosage Recommendations

  • Individualize and adjust the dosage of HUMALOG Mix50/50 based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.
  • Inject HUMALOG Mix50/50 subcutaneously within 15 minutes before a meal.
  • HUMALOG Mix50/50 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 Mix50/50, a different dosage of HUMALOG Mix50/50 may be needed.
  • During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring
    [see Warnings and Precautions ]
    .
  )

Injectable suspension: 100 units/mL (U-100) of HUMALOG Mix50/50, 50% insulin lispro protamine and 50% insulin lispro, is a white and cloudy suspension available as:

• 10 mL multiple-dose vial
• 3 mL single-patient-use KwikPen prefilled pen

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

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

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.

• Never share
  a HUMALOG Mix50/50 KwikPen or syringe between patients, even if the needle is changed. (
  5.1 Never Share a HUMALOG Mix50/50 KwikPen or Syringe Between Patients

  HUMALOG Mix50/50 KwikPens must never be shared between patients, even if the needle is changed. Patients using HUMALOG Mix50/50 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:
  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 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:
  May be life-threatening. Increase frequency of blood glucose monitoring with changes to insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity; in patients with renal or hepatic impairment; and in patients with hypoglycemia unawareness. (
  5.3 Hypoglycemia

  Hypoglycemia is the most common adverse reaction associated with all insulins, including HUMALOG Mix50/50. 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 Mix50/50 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 can occur. Instruct patients to check insulin labels before injection. (
  5.4 Hypoglycemia Due to Medication Errors

  Accidental mix-ups between insulin products have been reported. To avoid medication errors between HUMALOG Mix50/50 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. Discontinue HUMALOG Mix50/50, monitor and treat if indicated. (
  5.5 Hypersensitivity Reactions

  Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including HUMALOG Mix50/50. If hypersensitivity reactions occur, discontinue HUMALOG Mix50/50; treat per standard of care and monitor until symptoms and signs resolve. HUMALOG Mix50/50 is contraindicated in patients who have had hypersensitivity reactions to HUMALOG Mix50/50 or any of its excipients

  [see Contraindications ]

  .
  )
• Hypokalemia:
  May be life-threatening. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated. (
  5.6 Hypokalemia

  All insulins, including HUMALOG Mix50/50, 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 Thiazolidinediones (TZDs)
  : Observe for signs and symptoms of heart failure; consider dosage reductions or discontinuation if heart failure occurs. (
  5.7 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 HUMALOG Mix50/50, 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.
  )