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%:

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

  Patients whose HbA is ≥8%:

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

• 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 Children

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

Repaglinide pregnancy Risk Category: C

• When repaglinide was employed in an ex vivo perfusion model, it was discovered that it had a poor propensity to pass the placenta.
• Almost nothing is known about how repaglinide affects the course of a pregnancy.
• 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 might make hypoglycemia more likely after a gastric bypass, gastric band, or sleeve gastrectomy.
    • These methods can restore insulin secretion and sensitivity either partially or completely (gastric bypass is the most effective, followed closely by the sleeve, and finally, the band).
    • First-phase insulin secretion dramatically increased in the days after gastric bypass or sleeve gastrectomy. The improvement in hepatic insulin sensitivity was also apparent.
    • 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

  • Oral hypoglycemic drugs may be associated with an increase in cardiovascular events, according to studies.
  • Although there are no long-term trials to support it, repaglinide may increase the risk of cardiovascular events.
  • NPH Insul should not be combined with. Six myocardial infarctions occurred in participants receiving repaglinide plus insulin in two investigations.
  • 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 who have significant renal impairment should exercise caution since these effects of reducing blood sugar may be more likely to occur.

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:

• For patients with stable glycemic control who are meeting the recommendations, monitoring fasting glucose and glycosylated HbA levels is advised at least twice a year.
• 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
• Depending on how your meal plan varies, you can take it orally 2, 3, or 4 times each day.
• Do not eat if a meal is missing. If hypoglycemia develops, decrease the dose.

Mechanism of action of Repaglinide (Prandin):

• A non-sulfonylurea hypoglycemic medication that depolarizes the membrane, inhibits the ATP-dependent potassium channel, and makes it easier for calcium to enter the body through calcium canals.
• Intracellular calcium stimulates the release of insulin by pancreatic beta cells.
• Insulin production caused by repaglinide is primarily 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: