Repaglinide (4 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- PRANDIMET
- PRANDIN
- REPAGLINIDE
- REPAGLINIDE AND METFORMIN HYDROCHLORIDE
Indications and Usage
Repaglinide tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitation of Use: Repaglinide tablets should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
Contraindications
Repaglinide tablets are contraindicated in patients with: Concomitant use of gemfibrozil [see Drug Interactions (7)] Known hypersensitivity to repaglinide or any inactive ingredients
Adverse Reactions
The following serious adverse reaction is also described elsewhere in the labeling: Hypoglycemia [see Warnings and Precautions (5.1)]
Drug Interactions
Clinically Important Drug Interactions with Repaglinide Table 3 includes a list of drugs with clinically important drug interactions when administered concomitantly with repaglinide and instructions for preventing or managing them. Table 3: Clinically Important Drug Interactions with Repaglinide Gemfibrozil Clinical Impact: Gemfibrozil significantly increased repaglinide exposures by 8.1 fold [see Clinical Pharmacology (12.3)] Intervention: Do not administer repaglinide to patients receiving gemfibrozil [see Contraindications (4)]. Clopidogrel Clinical Impact: Clopidogrel increased repaglinide exposures by 3.9 to 5.1 fold [see Clinical Pharmacology (12.3)] Intervention: Avoid concomitant use of repaglinide with clopidogrel. If concomitant use cannot be avoided, initiate repaglinide at 0.5 mg before each meal and do not exceed a total daily dose of 4 mg [see DOSAGE AND ADMINISTRATION (2.3)]. Increased frequency of glucose monitoring may be required during concomitant use. Cyclosporine Clinical Impact: Cyclosporine increased low dose repaglinide exposures by 2.5 fold [see Clinical Pharmacology (12.3)] Intervention: Daily maximum repaglinide dose should be limited to 6 mg, and increased frequency of glucose monitoring may be required when repaglinide is co-administered with cyclosporine. CYP2C8 and CYP3A4 Inhibitors Intervention: Repaglinide dose reductions and increased frequency of glucose monitoring may be required when co-administered. Examples: Drugs that are known to inhibit CYP3A4 include antifungal agents (ketoconazole, itraconazole) and antibacterial agents (clarithromycin, erythromycin). Drugs that are known to inhibit CYP2C8 include trimethoprim, gemfibrozil, montelukast, deferasirox, and clopidiogrel. CYP2C8 and CYP3A4 Inducers Intervention: Repaglinide dose increases and increased frequency of glucose monitoring may be required when co-administered. Examples: Drugs that induce the CYP3A4 and/or 2C8 enzyme systems include rifampin, barbiturates, and carba
Mechanism of Action
Repaglinide lowers blood glucose levels by stimulating the release of insulin from the pancreas. This action is dependent upon functioning beta (ß) cells in the pancreatic islets. Insulin release is glucose-dependent and diminishes at low glucose concentrations. Repaglinide closes ATP-dependent potassium channels in the ß-cell membrane by binding at characterizable sites. This potassium channel blockade depolarizes the ß-cell, which leads to an opening of calcium channels. The resulting increased calcium influx induces insulin secretion. The ion channel mechanism is highly tissue selective with low affinity for heart and skeletal muscle.
Overdosage
Severe hypoglycemic reactions with coma, seizure, or other neurological impairment may occur and constitute medical emergencies requiring immediate hospitalization. Hypoglycemic symptoms without loss of consciousness or neurologic findings should be treated aggressively with oral glucose and adjustments in drug dosage and/or meal patterns. Close monitoring may continue until the physician is assured that the patient is out of danger. Patients should be closely monitored for a minimum of 24 to 48 hours, since hypoglycemia may recur after apparent clinical recovery. There is no evidence that repaglinide is dialyzable using hemodialysis.