Pronunciation:

(re pa GLI nide)

U.S. Brand Names:

Generic Available:

Canadian Brand Names:

Use:

Pregnancy Risk Factor:

Pregnancy Implications:

Lactation:

Contraindications:

Warnings/Precautions:

Adverse Reactions:

>10%:

Central nervous system: Headache (9% to 11%)

Endocrine & metabolic: Hypoglycemia (16% to 31%)

Respiratory: Upper respiratory tract infection (10% to 16%)

1% to 10%:

Cardiovascular: Chest pain (2% to 3%)

Gastrointestinal: Nausea (3% to 5%), heartburn (2% to 4%), vomiting (2% to 3%) constipation (2% to 3%), diarrhea (4% to 5%), tooth disorder (<1% to 2%)

Genitourinary: Urinary tract infection (2% to 3%)

Neuromuscular & skeletal: Arthralgia (3% to 6%), back pain (5% to 6%), paresthesia (2% to 3%)

Respiratory: Sinusitis (3% to 6%), rhinitis (3% to 7%), bronchitis (2% to 6%)

Miscellaneous: Allergy (1% to 2%)

<1%: Anaphylactoid reaction, leukopenia, liver function tests increased, thrombocytopenia

Postmarketing and/or case reports: Alopecia, hemolytic anemia, hepatic dysfunction (severe), pancreatitis, Stevens-Johnson syndrome

Overdosage/Toxicology:

Drug Interactions:

CYP2C8/9 inducers: CYP2C8/9 inducers may decrease the levels/effects of repaglinide. Example inducers include carbamazepine, phenobarbital, phenytoin, rifampin, rifapentine, and secobarbital.

CYP2C8/9 inhibitors: CYP2C8/9 inhibitors may increase the levels/effects of repaglinide. Example inhibitors include delavirdine, fluconazole, gemfibrozil, ketoconazole, nicardipine, NSAIDs, pioglitazone, and sulfonamides.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of repaglinide. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

CYP3A4 inhibitors: May increase the levels/effects of repaglinide. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.

Gemfibrozil: Gemfibrozil may increase the serum concentration of repaglinide (prolonged, severe hypoglycemia has been reported). The addition of itraconazole may augment the effects of gemfibrozil on repaglinide. Consider alternative therapy.

HMG-CoA reductase inhibitors (eg, atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin): May increase repaglinide concentrations by decreasing metabolism.

Macrolide antibiotics (limited to agents which inhibit CYP3A4 - clarithromycin, erythromycin, troleandomycin): May increase repaglinide concentrations by decreasing metabolism. Clarithromycin increases repaglinide AUC by 40%; monitor.

Oral contraceptives: Repaglinide may increase serum concentrations of contraceptives.

Estrogens (eg, estradiol, ethinyl estradiol, mestranol): May increase repaglinide concentrations.

Progestins: May increase repaglinide concentrations.

Ethanol/Nutrition/Herb Interactions:

Ethanol: Avoid ethanol (may cause hypoglycemia).

Food: When given with food, the AUC of repaglinide is decreased.

Herb/Nutraceutical: St John's wort may decrease repaglinide levels. Avoid gymnema, garlic (may cause hypoglycemia).

Stability:

Mechanism of Action:

Pharmacodynamics/Kinetics:

Onset of action: Single dose: Increased insulin levels: ~15-60 minutes

Duration: 4-6 hours

Absorption: Rapid and complete

Distribution: Vd: 31 L

Protein binding, plasma: >98%

Metabolism: Hepatic via CYP3A4 isoenzyme and glucuronidation to inactive metabolites

Bioavailability: Mean absolute: ~56%

Half-life elimination: 1 hour

Time to peak, plasma: ~1 hour

Excretion: Within 96 hours: Feces (~90%, <2% as parent drug); Urine (~8%)

Dosage:

Initial: For patients not previously treated or whose Hb A1c is <8%, the starting dose is 0.5 mg. For patients previously treated with blood glucose-lowering agents whose Hb A1c is 8%, the initial dose is 1 or 2 mg before each meal.

Dose adjustment: Determine dosing adjustments by blood glucose response, usually fasting blood glucose. Double the preprandial dose up to 4 mg until satisfactory blood glucose response is achieved. At least 1 week should elapse to assess response after each dose adjustment.

Dose range: 0.5-4 mg taken with meals. Repaglinide may be dosed preprandial 2, 3 or 4 times/day in response to changes in the patient's meal pattern. Maximum recommended daily dose: 16 mg.

Patients receiving other oral hypoglycemic agents: When repaglinide is used to replace therapy with other oral hypoglycemic agents, it may be started the day after the final dose is given. Observe patients carefully for hypoglycemia because of potential overlapping of drug effects. When transferred from longer half-life sulfonylureas (eg, chlorpropamide), close monitoring may be indicated for up to 1 week.

Combination therapy: If repaglinide monotherapy does not result in adequate glycemic control, metformin or a thiazolidinedione may be added. Or, if metformin or thiazolidinedione therapy does not provide adequate control, repaglinide may be added. The starting dose and dose adjustments for combination therapy are the same as repaglinide monotherapy. Carefully adjust the dose of each drug to determine the minimal dose required to achieve the desired pharmacologic effect. Failure to do so could result in an increase in the incidence of hypoglycemic episodes. Use appropriate monitoring of FPG and Hb A1c measurements to ensure that the patient is not subjected to excessive drug exposure or increased probability of secondary drug failure. If glucose is not achieved after a suitable trial of combination therapy, consider discontinuing these drugs and using insulin.

Dosing adjustment in renal impairment:

Clcr 40-80 mL/minute (mild to moderate renal dysfunction): Initial dosage adjustment does not appear to be necessary.

Clcr 20-40 mL/minute: Initiate 0.5 mg with meals; titrate carefully.

Dosing adjustment in hepatic impairment: Use conservative initial and maintenance doses. Use longer intervals between dosage adjustments.

Administration:

Monitoring Parameters:

Reference Range:

Fasting blood glucose: <120 mg/dL

Glycosylated hemoglobin: <7%

Dietary Considerations:

Patient Education:

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Dosage Forms:

International Brand Names: