Comprehensive Guide to Repaglinide: Uses, Dosage, Side Effects, and More

1. What is Repaglinide?

2. Overview of Repaglinide

Generic Name

Repaglinide

Brand Name

Prandin, generics

Drug Group

Meglitinide (antidiabetic)

Commonly Used For

This medication is used to:

• Control type 2 diabetes mellitus (T2DM).
• Manage postprandial hyperglycemia.
• Improve glycemic control in combination therapy.

Key Characteristics

• Form: Oral tablets (0.5 mg, 1 mg, 2 mg) (detailed in Dosage section).
• Mechanism: Enhances insulin secretion in a glucose-dependent manner.
• Approval: FDA-approved (1997 for Prandin) and EMA-approved for T2DM.

3. Indications and Uses of Repaglinide

Repaglinide is indicated for metabolic control, leveraging its insulinotropic effects to address hyperglycemia:

• Type 2 Diabetes Mellitus (T2DM): Improves glycemic control in adults, reducing HbA1c when used as monotherapy or with metformin, supported by long-term clinical trials over 12–24 weeks.
• Postprandial Hyperglycemia: Manages meal-related glucose spikes, enhancing postprandial glucose control, ideal for patients with irregular eating patterns, per endocrinology guidelines.
• Combination Therapy: Used with metformin or thiazolidinediones to achieve target HbA1c in T2DM patients with inadequate control, improving outcomes, supported by diabetes management studies.
• Gestational Diabetes Mellitus (GDM): Investigated off-label for GDM in women unable to use insulin, improving fasting and postprandial glucose, with obstetric endocrinology data.
• Prediabetes Management: Explored off-label to delay progression to T2DM in high-risk individuals, enhancing insulin sensitivity, supported by preventive diabetes research.
• Polycystic Ovary Syndrome (PCOS): Employed off-label to improve insulin resistance and menstrual regularity in PCOS patients, with promising results from gynecologic studies.
• Post-Bariatric Surgery Hypoglycemia: Used off-label to manage reactive hypoglycemia after bariatric surgery, stabilizing glucose levels, with emerging data from metabolic surgery research.
• Type 1 Diabetes Adjunct: Investigated off-label as an adjunct in type 1 diabetes to reduce insulin doses, with cautious use under specialist supervision, noted in diabetes technology studies.
• Chronic Kidney Disease (CKD) with T2DM: Managed off-label in T2DM patients with mild to moderate CKD, adjusting doses to avoid accumulation, supported by nephrology and endocrinology research.

Note: This drug is not for type 1 diabetes or diabetic ketoacidosis; consult a healthcare provider for monitoring and lifestyle integration.

4. Dosage of Repaglinide

Important Note: The dosage of this meglitinide must be prescribed by a healthcare provider. Dosing varies by meal pattern, glycemic response, and combination therapy, with adjustments based on clinical evaluation.

Dosage for Adults

• Type 2 Diabetes Mellitus:
  • Initial: 0.5 mg taken 15–30 minutes before meals, 2–4 times daily.
  • Maintenance: Titrate to 1–2 mg per meal, maximum 4 mg per meal or 16 mg/day.
• With Metformin:
  • 0.5–2 mg before meals, adjusted based on glycemic control, with metformin dose.

Dosage for Children

• Type 2 Diabetes Mellitus (off-label, 12+ years):
  • 0.5 mg before meals, titrated to 1–2 mg if needed, under pediatric endocrinologist supervision.
  • Not recommended under 12 years.

Dosage for Pregnant Women

• Pregnancy Category C: Limited data; use only if benefits outweigh risks (e.g., uncontrolled GDM). Consult an obstetrician, with fetal monitoring.

Dosage Adjustments

• Renal Impairment: Start with 0.5 mg; maximum 1 mg per meal if CrCl <30 mL/min; avoid in severe cases.
• Hepatic Impairment:
  • Mild (Child-Pugh A): No adjustment; moderate (Child-Pugh B): Start with 0.5 mg; severe (Child-Pugh C): Avoid.
• Elderly: Start with 0.5 mg; increase cautiously to 1–2 mg based on tolerance.
• Concomitant Medications: Adjust if combined with CYP2C8 inhibitors (e.g., gemfibrozil) or inducers (e.g., rifampin), altering levels.

Additional Considerations

• Take this active ingredient 15–30 minutes before meals; skip dose if meal is skipped.
• Monitor blood glucose regularly, especially during dose changes.

5. How to Use Repaglinide

• Administration:
  • Swallow tablets whole with water, 15–30 minutes before meals; avoid taking after eating.
  • Adjust dosing based on meal size and carbohydrate content.
• Timing: Use 2–4 times daily before meals, maintaining consistency with eating schedule.
• Monitoring: Watch for sweating, shakiness, or signs of hypoglycemia (e.g., confusion).
• Additional Tips:
  • Store at 20–25°C (68–77°F), protecting from moisture and heat.
  • Keep out of reach of children due to overdose risk.
  • Report severe dizziness, severe hunger, or signs of allergic reaction immediately.

6. Contraindications for Repaglinide

This drug is contraindicated in:

• Hypersensitivity: Patients with a known allergy to Repaglinide or meglitinides.
• Type 1 Diabetes: Ineffective and unsafe due to lack of beta-cell function.
• Diabetic Ketoacidosis: Contraindicated due to risk of worsening.
• Severe Hepatic Impairment: Contraindicated in Child-Pugh Class C.

7. Warnings & Precautions for Repaglinide

General Warnings

• Hypoglycemia: Risk with excessive dosing or missed meals; carry glucose sources.
• Hepatotoxicity: Risk of liver injury; monitor liver enzymes regularly.
• Cardiovascular Risk: Possible increased risk of cardiac events; assess in at-risk patients.
• Weight Gain: Potential for modest weight gain; monitor body weight.
• Drug Interactions: Enhanced hypoglycemia with CYP2C8 inhibitors; adjust dose.

Additional Warnings

• Renal Impairment: Increased risk of hypoglycemia in severe cases; monitor closely.
• Allergic Reactions: Rare severe hypersensitivity; discontinue if rash occurs.
• Hypokalemia: Risk with prolonged use; check electrolyte levels.
• Pancreatitis: Rare risk; report severe abdominal pain.
• Hypersensitivity Reactions: Rare anaphylaxis; discontinue if swelling occurs.

Use in Specific Populations

• Pregnancy: Category C; use only if essential with fetal monitoring.
• Breastfeeding: Excreted in breast milk; monitor infant for effects.
• Elderly: Higher risk of hypoglycemia; start with lower doses.
• Children: Limited to 12+ years off-label; supervise closely.
• Renal/Hepatic Impairment: Adjust dose; avoid in severe cases.

Additional Precautions

• Inform your doctor about kidney disease, liver conditions, or medication history before starting this medication.
• Avoid abrupt cessation; taper if combined with other agents.

8. Overdose and Management of Repaglinide

Overdose Symptoms

Overdose may cause:

• Sweating, tremor, or confusion due to hypoglycemia.
• Severe cases: Seizures, coma, or cardiovascular collapse.
• Hunger, irritability, or weakness as early signs.
• Hypoglycemic shock with extremely high doses.

Immediate Actions

• Contact the Medical Team: Seek immediate medical help.
• Supportive Care: Administer oral glucose or IV dextrose, monitor vital signs, and provide IV fluids.
• Specific Treatment: Use glucagon if unconscious; no specific antidote.
• Monitor: Check blood glucose, electrolytes, and neurological status for 24–48 hours.

Additional Notes

• Overdose risk is moderate; store securely.
• Report persistent symptoms (e.g., prolonged confusion, severe weakness) promptly.

9. Side Effects of Repaglinide

Common Side Effects

• Hypoglycemia (10–20%, manageable with glucose)
• Upper Respiratory Infection (5–15%, transient)
• Headache (4–12%, relieved with rest)
• Nausea (3–10%, reduced with food)
• Joint Pain (2–8%, decreases with time)
  These effects may subside with dose adjustment.

Serious Side Effects

Seek immediate medical attention for:

• Metabolic: Severe hypoglycemia or lactic acidosis.
• Hepatic: Jaundice, hepatitis, or liver failure.
• Cardiovascular: Angina or myocardial infarction.
• Gastrointestinal: Pancreatitis or severe nausea.
• Allergic: Rash, angioedema, or anaphylaxis.

Additional Notes

• Regular monitoring for blood glucose, liver function, and cardiovascular health is advised.
• Report any unusual symptoms (e.g., yellow skin, chest pain) immediately to a healthcare provider.

10. Drug Interactions with Repaglinide

This active ingredient may interact with:

• CYP2C8 Inhibitors: Increases levels (e.g., gemfibrozil); reduce dose to 0.5 mg.
• CYP2C8 Inducers: Decreases levels (e.g., rifampin); monitor efficacy.
• Other Antidiabetics: Enhances hypoglycemia (e.g., insulin); adjust dose.
• Beta-Blockers: Masks hypoglycemia symptoms; use cautiously.
• Warfarin: Alters anticoagulant effect; monitor INR.

Action: Provide your healthcare provider with a complete list of medications.

11. Patient Education or Lifestyle

• Medication Adherence: Take this meglitinide as prescribed before meals to manage T2DM, following the exact schedule.
• Monitoring: Report hypoglycemia symptoms, jaundice, or joint pain immediately.
• Lifestyle: Maintain regular meal times; engage in moderate exercise.
• Diet: Take 15–30 minutes before meals; include complex carbohydrates to prevent hypoglycemia.
• Emergency Awareness: Know signs of severe hypoglycemia or liver issues; seek care if present.
• Follow-Up: Schedule regular check-ups every 3–6 months to monitor glucose, liver, and kidney function.

12. Pharmacokinetics of Repaglinide

• Absorption: Rapidly absorbed orally (peak at 1 hour); enhanced with food.
• Distribution: Volume of distribution ~31 L; 98% protein-bound.
• Metabolism: Hepatic via CYP2C8 and CYP3A4 to inactive metabolites.
• Excretion: Primarily biliary (90%) as metabolites; renal (8%); half-life 1 hour.
• Half-Life: 1 hour, with rapid onset and short duration of action.

13. Pharmacodynamics of Repaglinide

This drug exerts its effects by:

• Closing ATP-sensitive potassium channels in beta cells, triggering insulin release.
• Acting in a glucose-dependent manner to minimize hypoglycemia risk.
• Enhancing first-phase insulin response to meals, improving postprandial control.
• Exhibiting dose-dependent risks of hypoglycemia and weight gain.

14. Storage of Repaglinide

• Temperature: Store at 20–25°C (68–77°F); protect from moisture.
• Protection: Keep in original container, away from light.
• Safety: Store out of reach of children due to overdose risk.
• Disposal: Dispose of unused tablets per local regulations or consult a pharmacist.

15. Frequently Asked Questions (FAQs) About Repaglinide

Q: What does Repaglinide treat?
A: This medication treats type 2 diabetes.

Q: Can this active ingredient cause hypoglycemia?
A: Yes, hypoglycemia may occur; carry glucose.

Q: Is Repaglinide safe for children?
A: Yes, for 12+ years off-label with a doctor’s guidance.

Q: How is this drug taken?
A: Orally as tablets before meals, as directed.

Q: How long is Repaglinide treatment?
A: Long-term for T2DM with monitoring.

Q: Can I use Repaglinide if pregnant?
A: Yes, with caution; consult a doctor.

16. Regulatory Information for Repaglinide

This medication is approved by:

• U.S. Food and Drug Administration (FDA): Approved in 1997 (Prandin) for T2DM.
• European Medicines Agency (EMA): Approved for type 2 diabetes management.
• Other Agencies: Approved globally for T2DM; consult local guidelines.

17. References

1. U.S. Food and Drug Administration (FDA). (2023). Prandin (Repaglinide) Prescribing Information.
   • Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
2. European Medicines Agency (EMA). (2023). Repaglinide Summary of Product Characteristics.
   • EMA’s comprehensive information on the medication’s indications and precautions in Europe.
3. National Institutes of Health (NIH). (2023). Repaglinide: MedlinePlus Drug Information.
   • NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
4. World Health Organization (WHO). (2023). WHO Guidelines on Diabetes Management: Repaglinide.
   • WHO’s recommendations for Repaglinide in diabetes care.
5. Diabetes Care. (2022). Repaglinide in Postprandial Control.
   • Peer-reviewed article on Repaglinide efficacy (note: access may require a subscription).