Dosing and uses of Prandin (repaglinide)
Adult dosage forms and strengths
tablet
- 0.5 mg
- 1 mg
- 2 mg
Type 2 Diabetes Mellitus
Initial dose 0.5 mg PO with no prior treatment, or 1-2 mg with prior treatment
Titrate by up to 4 mg; double preprandial dose until satisfactory blood glucose response attained; not to exceed 16 mg qDay
Take dose 15 minutes before meal; no more than 4 meals/day
Combination Therapy
If monotherapy does not result in adequate glycemic control may add metformin or thiazolidinedione
If thiazolidinedione and metformin does not result in adequate glycemic control, repaglinide may be added
Starting dose and dose adjustments for combination therapy are the same as repaglinide monotherapy
Renal Impairment
CrCl 40-80 mL/minute: No adjustments necessary
CrCl 20-40 mL/minute: 0.5 mg with meals; titrate slowly and monitor
CrCl < 20 mL/minute: Data not available
Hepatic Impairment
Use conservative initial and maintenance dosing; wait for longer intervals to make dosage adjustments
Other Indications & Uses
Management of type 2 diabetes mellitus adjunct to diet and exercise
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
Initial dose 0.5 mg PO with no prior treatment, or 1-2 mg with prior treatment
Titrate by up to 4 mg; double preprandial dose until satisfactory blood glucose response attained; not to exceed 16 mg qDay
Take dose 15 minutes before meal; no more than 4 meals/day
Combo therapy: Administer as in adults
Prandin (repaglinide) adverse (side) effects
>10%
Headache
Hypoglycemia (16-31%)
Upper respiratory infection (10-16%)
1-10%
Arthralgia (3-6%)
Chest pain
Constipation
Back pain
Sinusitis
Bronchitis
Diarrhea (4-5%)
Serious CV events (4%; versus 3% incidence with glyburide and glipizide)
<1%
Increased LFTs
Thrombocytopenia
Leukopenia
Hemolytic anemia
Pancreatitis
Visual disturbances
Anaphylactoid reactions
Warnings
Contraindications
Hypersensitivity to repaglinide
Diabetic ketoacidosis
Type I Dm
Coadministration of gemfibrozil results in increased repaglinide plasma concentration (8-fold increase); may result in severe hypoglycemia
Cautions
Stress due to infection, fever, trauma, or surgery, hepatic/renal insufficiency
Patients at risk of severe hypoglycemia: elderly, debilitated, or malnourished, adrenal or pituitary insufficiency
Pregnancy or lactation
Drugs that inhibit organic anion transporting protein OATP1B1 (e.g. cyclosporine) may increase plasma concentrations of repaglinide, which is a substrate for active hepatic uptake transporter OATP1B1
Pregnancy and lactation
Pregnancy category: C
Lactation: Not known if crosses into breast milk, avoid
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Prandin (repaglinide)
Mechanism of action
Increases insulin secretion by blocking ATP potassium channels on beta islet cells, which facilitates calcium entry through calcium channels. Increased intracellular calcium stimulates insulin release from pancreatic beta cells.
Pharmacokinetics
Half-Life: 1 hr
Onset: 30 min (initial effect); 60-90 min (maximum effect)
Duration: <4 hr
Bioavailability: 56%
Vd: 24-30 L
Protein Bound: >98%
Total Body Clearance: 38 L/hr
Metabolism: Extensively, in liver by CYP3A4 and CYP2C8
Metabolites: Oxidized dicarboxylic acid, aromatic amine, acyl glucuronide (inactive)
Excretion: 90% feces; 8 % urine
