Insulin Aspart + Insulin Aspart Protamine

Usage

• Insulin Aspart + Insulin Aspart Protamine is prescribed for Type 1 and Type 2 diabetes mellitus to improve glycemic control. It is particularly useful in cases where oral antidiabetic agents or other insulin regimens do not provide adequate control.
• Pharmacological Classification: Rapid-acting and intermediate-acting insulin combination, antidiabetic agent.
• Mechanism of Action: This combination mimics the physiological release of insulin. The insulin aspart component rapidly controls postprandial glucose excursions, while the insulin aspart protamine provides a sustained basal insulin level. Both components work by binding to insulin receptors, facilitating glucose uptake into cells and glycogen synthesis, thus lowering blood glucose levels.

Alternate Names

• While “Insulin Aspart + Insulin Aspart Protamine” is the generic name, regional or international variations may exist.
• Brand Name: NovoLog Mix 70/30 (70% protamine aspart, 30% aspart).

How It Works

• Pharmacodynamics: Insulin Aspart, a rapid-acting insulin analog, starts working within 10-20 minutes, peaks in 1-3 hours, and lasts for 3-5 hours. Insulin Aspart Protamine, an intermediate-acting insulin analog, starts working within 1-2 hours, with a less pronounced peak, and lasts for 14-16 hours. Together, they provide both prandial and basal insulin coverage.
• Pharmacokinetics:
  • Absorption: Subcutaneous injection. Aspart absorbs faster than regular human insulin due to amino acid modifications. Protamine delays the absorption of aspart.
  • Metabolism: Primarily in the liver, kidneys, and adipose tissues, similar to human insulin.
  • Elimination: Primarily renal and hepatic. The elimination half-life of aspart is approximately 81 minutes, and for faster-acting aspart, around 66 minutes.
• Mode of Action: Both components bind to insulin receptors, triggering intracellular signaling cascades promoting glucose uptake and glycogen synthesis.
• Receptor binding: Binds to insulin receptors on cell surfaces.
• No direct enzyme inhibition or neurotransmitter modulation.
• Elimination is through hepatic and renal pathways.

Dosage

Standard Dosage

Adults:

• Type 1 Diabetes: 0.5-1 unit/kg/day, split into twice-daily doses.
• Type 2 Diabetes: Initial dose of 6 units twice daily or 12 units once daily before the biggest meal. Adjust based on self-monitored blood glucose levels and glycemic targets.

Children (≥10 years):

• Similar to adult dosing.
• Children (6-9 years): Limited data available; use with caution.
• Pediatric Safety: Closely monitor for hypoglycemia. Dosage adjustments are essential based on growth spurts and puberty.

Special Cases:

• Elderly Patients: Start with conservative doses and adjust cautiously to prevent hypoglycemia which can be difficult to recognize in the elderly.

• Patients with Renal Impairment: Dosage adjustments may be required due to altered insulin clearance. Frequent blood glucose monitoring essential.

• Patients with Hepatic Dysfunction: Dosage adjustments may be necessary due to impaired insulin metabolism. Close monitoring is crucial.

• Patients with Comorbid Conditions: Consider the impact of co-existing conditions on glucose control and insulin requirements.

Clinical Use Cases

• Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use: Dosage adjustments may be needed depending on patient condition and nutritional status. Continuous glucose monitoring and frequent dose adjustments are important in these settings.
• Emergency Situations (e.g., Diabetic Ketoacidosis): NovoLog Mix 70/30 is NOT recommended for the treatment of diabetic ketoacidosis. Intravenous regular insulin is preferred in such cases.

Dosage Adjustments

Adjustments based on patient-specific factors, including renal/hepatic dysfunction, other illnesses, lifestyle changes, and concomitant medications. Regular blood glucose monitoring is essential to guide dosage adjustments.

Side Effects

Common Side Effects:

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

Rare but Serious Side Effects:

• Severe hypoglycemia
• Allergic reactions (rash, hives, itching, difficulty breathing, swelling of face, lips, tongue, or throat)
• Hypokalaemia (low potassium)

Long-Term Effects:

• Lipodystrophy (changes in fat tissue at injection site)

Adverse Drug Reactions (ADR):

• Severe hypoglycemia
• Anaphylaxis

Contraindications

• Hypoglycemia
• Hypersensitivity to insulin aspart or any of the components of NovoLog Mix 70/30.

Drug Interactions

• Other antidiabetic agents (oral or injectable): Increased risk of hypoglycemia.
• Medications that can affect blood glucose levels (e.g., corticosteroids, thiazides, atypical antipsychotics): May require dosage adjustments.
• Beta-blockers: Can mask symptoms of hypoglycemia.
• Alcohol: Can potentiate the hypoglycemic effects.

Pregnancy and Breastfeeding

• Pregnancy Category B: Animal studies have not shown adverse effects; however, human data are limited. Insulin is the preferred agent for managing diabetes during pregnancy. Monitor blood glucose closely.
• Breastfeeding: Insulin aspart is present in breast milk, but amounts are considered insignificant. Dosage adjustments may be required for breastfeeding mothers.

Drug Profile Summary

• Mechanism of Action: Mimics physiological insulin release, enhances glucose uptake and utilization.
• Side Effects: Hypoglycemia, injection site reactions, weight gain.
• Contraindications: Hypoglycemia, hypersensitivity.
• Drug Interactions: Other antidiabetic agents, beta-blockers, alcohol.
• Pregnancy & Breastfeeding: Can be used with monitoring; insulin is generally preferred in pregnancy.
• Dosage: Individualized, 0.5-1 unit/kg/day for Type 1, starting dose of 6 units BID or 12 units QD for Type 2, adjust based on blood glucose levels.
• Monitoring Parameters: Blood glucose, HbA1c, weight, potassium levels.

Popular Combinations

• Metformin: Often combined to improve glycemic control in Type 2 diabetes.
• Other long-acting insulins (e.g., glargine, detemir): May be added to basal-bolus regimens if NovoLog Mix 70/30 alone does not achieve target control.

Precautions

• General Precautions: Careful dose titration and monitoring are crucial, especially during illness, changes in activity levels, or diet. Education on hypoglycemia management is essential.
• Specific Populations: Monitor closely.
• Lifestyle Considerations: Diet, exercise, and alcohol intake affect blood glucose levels and may necessitate dosage adjustments.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Insulin Aspart + Insulin Aspart Protamine?

A: The dosage is individualized. For Type 1 diabetes, the total daily dose is typically 0.5-1 unit/kg/day, divided into twice-daily injections. For Type 2 diabetes, it can start with 6 units twice daily or 12 units once daily, with adjustments based on blood glucose targets.

Q2: Can Insulin Aspart + Insulin Aspart Protamine be used in children?

A: It is approved for use in children 10 years and older. Limited data is available for children 6-9 years old. It is not recommended for children under 6 years of age.

Q3: How is this combination administered?

A: It is administered subcutaneously, usually twice daily, 15 minutes before or immediately after a meal.

Q4: What are the most common side effects?

A: The most common side effect is hypoglycemia. Other side effects may include injection site reactions and weight gain.

Q5: What should patients do if they experience hypoglycemia?

A: Patients should consume a fast-acting source of glucose (e.g., glucose tablets, juice, candy) and recheck their blood glucose levels after 15 minutes. If hypoglycemia persists, they should seek medical attention.

Q6: Can Insulin Aspart + Insulin Aspart Protamine be mixed with other insulins?

A: No, it should not be mixed with any other insulin products.

Q7: What are the key drug interactions to consider?

A: Other antidiabetic medications, beta-blockers, alcohol, and certain medications affecting blood sugar levels can interact with Insulin Aspart + Insulin Aspart Protamine.

Q8: Is it safe to use Insulin Aspart + Insulin Aspart Protamine during pregnancy?

A: While animal data suggest no adverse effects, human data are limited. Insulin is the preferred agent for managing diabetes during pregnancy. Monitor blood sugar closely.

Q9. Can I use this medicine if I have kidney or liver problems?

A: You may need dosage adjustments. Close monitoring of your blood glucose is crucial. Discuss it with your physician for appropriate management.

Q10. Can I use Insulin Aspart + Insulin Aspart Protamine if I am breastfeeding?

A: Yes, you can use it while breastfeeding, but dosage adjustments may be required. Consult with your physician for personalized advice.