Insulin Lispro Protamine

Usage

Insulin Lispro Protamine, a combination of rapid-acting insulin lispro and intermediate-acting insulin lispro protamine, is prescribed to improve glycemic control in adults with both type 1 and type 2 diabetes mellitus. It belongs to the pharmacological classification of rapid-acting insulins and intermediate-acting insulins. This combination allows for faster onset of action compared to regular human insulin, while providing a longer duration of activity. The mechanism of action involves binding to insulin receptors on target cells, facilitating glucose uptake from the bloodstream into tissues like muscle and fat, and suppressing hepatic glucose production.

Alternate Names

Insulin Lispro Protamine and Insulin Lispro Mix75/25, or Humalog Mix75/25 (75% insulin lispro protamine and 25% insulin lispro). There is also a 50/50 variant: Humalog Mix50/50.

How It Works

Pharmacodynamics: Insulin Lispro Protamine exerts its glucose-lowering effect by binding to insulin receptors on the cell surface. This binding triggers a cascade of intracellular events, leading to increased glucose uptake by muscle and fat cells, as well as reduced glucose production by the liver.

Pharmacokinetics:

• Absorption: Subcutaneous administration results in a biphasic absorption profile. Insulin lispro component exhibits rapid absorption, with peak serum concentrations occurring within 30 minutes to 4 hours. Insulin lispro protamine component is absorbed more slowly, providing a prolonged effect.
• Metabolism: Insulin lispro is metabolized primarily at the injection site and in the liver, similar to human insulin.
• Elimination: A meaningful terminal half-life for Insulin Lispro Protamine cannot be determined due to the prolonged absorption of the protamine component.

Mode of Action: Insulin Lispro Protamine mimics the action of endogenous insulin by binding to specific insulin receptors on target cells. This receptor binding activates intracellular signaling pathways, resulting in increased glucose transporter translocation to the cell membrane, thus facilitating glucose entry into the cells.

Dosage

Standard Dosage

Adults:

The dosage is individualized based on metabolic needs, blood glucose monitoring results, and glycemic control goals. Typically, it is administered subcutaneously twice daily, within 15 minutes before the morning and evening meals. Each dose is intended to cover two meals or a meal and a snack. The total daily insulin requirement is typically between 0.5 and 1 unit/kg/day.

Children:

The safety and efficacy of Insulin Lispro Protamine in pediatric patients have not been established.

Special Cases:

• Elderly Patients: Initiate with conservative dosing and titrate cautiously due to the potential for age-related changes in organ function and increased risk of hypoglycemia.
• Patients with Renal Impairment: Insulin requirements may be reduced. Close monitoring and dose adjustment are necessary.
• Patients with Hepatic Dysfunction: Insulin requirements may be reduced. Careful glucose monitoring and dose adjustments are essential.
• Patients with Comorbid Conditions: Dose adjustments are necessary during illness, stress, or changes in physical activity or diet.

Clinical Use Cases

Insulin Lispro Protamine is not indicated for intravenous administration or use in continuous subcutaneous insulin infusion pumps. Therefore, dosage recommendations for intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations are not applicable.

Dosage Adjustments

Dosage modifications are necessary based on factors like changes in physical activity, meal patterns, renal or hepatic function, and intercurrent illness.

Side Effects

Common Side Effects

• Hypoglycemia (low blood sugar)
• Injection site reactions (pain, redness, swelling, itching)
• Weight gain
• Edema

Rare but Serious Side Effects

• Severe hypoglycemia
• Severe allergic reactions (anaphylaxis)
• Hypokalemia (low potassium)

Long-Term Effects

• Lipodystrophy (skin thickening or pitting at the injection site)

Adverse Drug Reactions (ADR)

Any severe allergic reaction (e.g., anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension, shock) requires immediate medical intervention.

Contraindications

• Hypersensitivity to insulin lispro, insulin lispro protamine, or any of the excipients.
• Episodes of hypoglycemia.

Drug Interactions

Numerous drugs can interact with insulin, including:

• Hypoglycemic Agents: Additive hypoglycemic effects.
• Hyperglycemic Agents: Reduced insulin effectiveness.
• Beta-blockers: May mask symptoms of hypoglycemia.
• Corticosteroids: May increase blood glucose levels.
• Thiazolidinediones: May increase risk of fluid retention and heart failure.

Pregnancy and Breastfeeding

• Pregnancy: Insulin Lispro Protamine can be used during pregnancy but requires careful glucose monitoring and dose adjustments due to changes in insulin requirements during pregnancy. Uncontrolled diabetes in pregnancy poses risks to both mother and fetus.
• Breastfeeding: Insulin lispro is present in human milk. Dose adjustment may be needed for breastfeeding mothers.

Drug Profile Summary

• Mechanism of Action: Binds to insulin receptors, enhancing glucose uptake and suppressing hepatic glucose output.
• Side Effects: Hypoglycemia, injection site reactions, weight gain, edema.
• Contraindications: Hypersensitivity, hypoglycemia.
• Drug Interactions: Numerous drugs can interact with insulin, potentially affecting glycemic control.
• Pregnancy & Breastfeeding: Can be used with careful monitoring and dose adjustments.
• Dosage: Individualized based on patient needs. Typical starting dose is twice daily within 15 minutes before meals.
• Monitoring Parameters: Blood glucose levels, HbA1c, signs and symptoms of hypoglycemia and hyperglycemia.

Popular Combinations

Insulin Lispro Protamine is sometimes combined with other long-acting insulins (e.g., insulin glargine, insulin detemir) to provide both basal and bolus insulin coverage.

Precautions

• General Precautions: Screen patients for allergies and pre-existing medical conditions that may affect insulin therapy. Monitor blood glucose levels regularly. Educate patients on hypoglycemia management. Never share injection devices.

• Specific Populations:

  • Pregnant Women: Monitor glucose levels carefully. Adjust doses as needed.
  • Breastfeeding Mothers: May require dose adjustments.
  • Children & Elderly: Safety and efficacy in children have not been established. Initiate with conservative dosing in elderly patients.

• Lifestyle Considerations: Diet, exercise, alcohol intake, and other lifestyle factors can influence insulin requirements.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Insulin Lispro Protamine?

A: Dosage is individualized. Typically, it’s given subcutaneously twice daily within 15 minutes before meals. Each dose should cover 2 meals or a meal and snack. Starting dose is usually between 0.5 and 1 unit/kg/day.

Q2: How should Insulin Lispro Protamine be administered?

A: It is administered subcutaneously using a syringe, pen device, or insulin pump (for insulin lispro, not insulin lispro protamine). Do not administer intravenously.

Q3: What are the signs and symptoms of hypoglycemia?

A: Symptoms can include sweating, trembling, dizziness, confusion, headache, hunger, blurred vision, and changes in mood or behavior.

Q4: What are the main drug interactions to consider with Insulin Lispro Protamine?

A: Interactions can occur with other hypoglycemic or hyperglycemic agents, beta-blockers, corticosteroids, thiazolidinediones, and many other medications. A thorough medication review is essential.

Q5: Can Insulin Lispro Protamine be used during pregnancy and breastfeeding?

A: Yes, it can be used but requires careful monitoring and dose adjustment due to changing insulin needs.

Q6: What are the long-term side effects of using Insulin Lispro Protamine?

A: Lipodystrophy can occur at the injection site with repeated injections.

Q7: How can I manage injection site reactions?

A: Rotate injection sites regularly. Use proper injection technique. Notify your doctor if reactions are severe or persistent.

Q8: What should I do if I experience a severe hypoglycemic episode?

A: If the patient is conscious, administer a fast-acting carbohydrate source (e.g., glucose tablets, juice). If the patient is unconscious, administer glucagon if available, or seek immediate medical assistance.

Q9: Can patients mix Insulin Lispro Protamine with other insulins in the same syringe?

A: No, Humalog Mix 75/25 should not be mixed with other insulin preparations, especially Humalog U-200.