Repaglinide (Prandin) is an oral short-acting anti-diabetic medicine that is used to treat patients with diabetes mellitus type 2 as an adjunct to diet and exercise. It is particularly useful in patients with kidney disease, elderly patients, thin, lean, and emaciated patients, and patients at risk of hypoglycemia.

Repaglinide Dose in Adults

Repaglinide Dose in the treatment of Diabetes Mellitus Type 2:

• Patients whose HbA is <8%:

  • Initially, 0.5 mg is given before each meal (2, 3, or 4 times/day depending on the number of meals)
  • The dose may be doubled  with each meal at intervals of ≥1 week until adequate glycemic control is achieved
  • maximum dose is 4 mg/dose or 16 mg/day.

• Patients whose HbA is ≥8%:

  • Initially, 1 or 2 mg is given before each meal (2, 3, or 4 times/day depending on the number of meals)
  • The dose may be doubled  dose with each meal at intervals of ≥1 week until adequate glycemic control is achieved
  • maximum dose is 4 mg/dose or 16 mg/day.

• Dosage adjustment for concomitant therapy:

  • Clopidogrel:

    • Avoid concomitant use.
    • If concomitant use is required, then start repaglinide at 0.5 mg before each meal;
    • The maximum dose is 4 mg/day.

  • Cyclosporine:

    • The maximum dose is 6 mg/day of repaglinide.

Repaglinide Dose in Childrens

Not recommended for use in children with type 1 diabetes mellitus.

Repaglinide pregnancy Risk Category: C

• Repaglinide was found to have low potential to cross placenta when used in an ex-vivo perfusion model.
• Very little information is available on the effects of repaglinide upon pregnancy outcomes.
• Poorly managed diabetes can lead to adverse maternal and fetal outcomes.
• This includes preeclampsia and preeclampsia, diabetic ketoacidosis and preterm births, complications during delivery, spontaneous abortions, preterm deliveries, major birth defects, stillbirths, macrosomia, and preterm delivery.
• Preventing adverse outcomes by keeping maternal blood glucose and HbA as close as possible to the target levels before conception and throughout pregnancy.
• However, it is important not to cause significant hypoglycemia.
• Other than repaglinide, agents are being used in the treatment of diabetes mellitus during pregnancy.

Use of repaglinide during breastfeeding

• It is unknown if breast milk contains repaglinide.
• The manufacturer does not recommend breastfeeding due to hypoglycemia.

Repaglinide dosage in kidney disease:

• CrCl >=40mL/minute

  • There is no need to adjust the dosage.

• CrCl 20-40 mL/minute

  • Start with 0.5 mg. Continue to titrate.

• CrCl 20mL/minute

  • The manufacturer's labeling does not contain any dosage adjustments (hasn't been studied).

• Hemodialysis

  • The manufacturer's labeling does not contain any dosage adjustments (hasn't been studied).

Repaglinide dosage in Liver disease:

• The manufacturer's labeling does not include any dosage adjustments.
• Be cautious and consider longer intervals between dose adjustments.

Common Side Effects of Repaglinide (Prandin) Include:

• Central Nervous System:

  • Headache

• Endocrine & Metabolic:

  • Hypoglycemia

• Respiratory:

  • Upper Respiratory Tract Infection

Less Common Side Effects Of Repaglinide (Prandin) Include:

• Cardiovascular:

  • Ischemia
  • Chest Pain

• Gastrointestinal:

  • Diarrhea
  • Constipation

• Genitourinary:

  • Urinary Tract Infection

• Hypersensitivity:

  • Hypersensitivity Reaction

• Neuromuscular & Skeletal:

  • Back Pain
  • Arthralgia

• Respiratory:

  • Sinusitis
  • Bronchitis

Contraindication to Repaglinide Include:

• Hypersensitivity to any part of repaglinide's formulation; concurrent gemfibrozil treatment
• Hepatic impairment severe
• Concurrent use of clopidogrel
• Diabetic ketoacidosis with or without coma
• Type 1 diabetes (insulin-dependent).

Warnings and precautions

• Hypoglycemia

  • Hypoglycemia severe can happen.
  • Changes in diet, physical activity, co-administered medications and use of other anti-diabetic agents can increase the risk.

• Bariatric surgery

  • Absorption altered:

    • Gastric bypass and Sleeve Gastrectomy can alter the absorption.

  • Hypoglycemia

    • It can increase the likelihood of hypoglycemia following gastric bypass, gastric band, or sleeve-gastrectomy.
    • These procedures can partially or fully restore insulin secretion and sensitivity (gastric bypass is the most effective, followed closely by the sleeve, and finally, the band).
    • In the days following gastric bypass or sleeve-gastrectomy, first-phase insulin secretion was significantly increased. Hepatic insulin sensitivity was also noticeably improved.
    • These procedures can have a positive effect on peripheral insulin sensitivity over the following 3- to 12 months.
    • It is best to choose antidiabetic drugs that are not hypoglycemic.

• Cardiovascular effects

  • Studies have shown that oral hypoglycemic medications may be linked to increased cardiovascular events.
  • Although repaglinide may increase the risk of cardiovascular events, there are not long-term studies to confirm this.
  • Combination with NPH Insul is not recommended. In two studies, there were 6 cases of myocardial infarction in patients receiving repaglinide plus insulin.
  • To determine if this combination is safe, further evaluations are necessary.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious; they may be more vulnerable to glucose-lowering effects.

• Renal impairment

  • Patients with severe renal impairment should be cautious; they may be more vulnerable to glucose-lowering effects.

Repaglinide: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitor:

• Monitoring fasting glucose and glycosylated HbA levels is recommended at least twice a year for patients with stable glycemic control who are meeting their treatment goals. Patients who are not meeting their treatment goals or who have made therapy changes should be monitored quarterly.
• Fasting glucose may be used during dose adjustment to determine response.

How to administer Repaglinide (Prandin)?

Oral:

• Do not give food more than 30 minutes prior to meals
• You can take it prerandially 2, 3 or 4 times per day depending on changes in your meal plan.
• Do not eat if a meal is missing. If hypoglycemia develops, decrease the dose.

Mechanism of action of Repaglinide (Prandin):

• Non-sulfonylurea hypoglycemic drug that blocks ATP-dependent potassium channel, depolarizes the membrane and facilites calcium entry through calcium canals.
• Insulin release from pancreatic beta cells is stimulated by intracellular calcium.
• Repaglinide-induced insulin production is mainly glucose-dependent.

Absorption:

• Complete

Distribution:

• V : 31 L

Protein binding, plasma:

• more than 98% to albumin

Metabolism:

• Mainly Hepatic via CYP3A4 and CYP2C8 isoenzymes and glucuronidation to inactive metabolites

Bioavailability:

• 56% ± 9%

Half-life elimination:

• almost 1 hour

Time to peak, plasma:

• 1 hour

Excretion:

• Via Feces (~90%, <2% as unchanged drug) & Urine (~8%, 0.1% as unchanged drug)

International Brands of Repaglinide:

• Prandin
• ACT Repaglinide
• APO-Repaglinide
• Auro-Repaglinide
• GlucoNorm
• JAMP Repaglinide
• SANDOZ Repaglinide
• Dexanorm
• Diarol
• Dibetix
• Enyglid
• Enyglide
• Eurepa
• Fulaidi
• Glimet
• Hipover
• Ilgaper
• Magicnorm
• Nomopil
• NovoNorm
• Novonorm
• Paglimide
• Posprand
• Prandin
• Pranstad
• Rapilin
• Reglin
• Reglinide
• Relinide
• Reodon
• Repa
• Repaglid
• Repanorm
• Ripalid
• Rosemond
• Sestrine
• Supernide
• Surepost

Repaglinide (Prandin) Brands in Pskistan: