Repaglinideinteractions

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 Intervention: Do not administer repaglinide to patients receiving gemfibrozil.

Clopidogrel Clinical Impact: Clopidogrel increased repaglinide exposures by 3.9 to 5.1 fold 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. Increased frequency of glucose monitoring may be required during concomitant use.

Cyclosporine Clinical Impact: Cyclosporine increased low dose repaglinide exposures by 2.5 fold 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 carbamezapine Drugs That May Increase the Risk of Hypoglycemia Intervention: Repaglinide dose reductions and increased frequency of glucose monitoring may be required when co-­administered.

Examples: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, nonsteroidal anti-inflammatory agents (NSAIDs), pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics Drugs That May Decrease the Blood Glucose Lowering Effect of Repaglinide Intervention: Repaglinide dose increases and increased frequency of glucose monitoring may be required when co-­administered.

Examples: Atypical antipsychotics (e.g., olanzapine and clozapine), calcium channel antagonists, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. Drugs That May Blunt Signs and Symptoms of Hypoglycemia Intervention: Increased frequency of glucose monitoring may be required when repaglinide is co-administered with these drugs.

Examples: beta-blockers, clonidine, guanethidine, and reserpine Clopidogrel: Avoid concomitant use; if used concomitantly initiate at 0.5 mg before each meal and limit total daily dose to 4 mg Cyclosporine: Limit daily dose of repaglinide to 6 mg and increase frequency of glucose monitoring when co-administered CYP2C8 and CYP3A4 Inhibitors and Drugs That May Increase the Risk of Hypoglycemia: Co-administration may require repaglinide dose reductions and increased frequency of glucose monitoring CYP2C8 and CYP3A4 Inducers and Drugs That May Decrease the Blood Glucose Lowering Effect of Repaglinide: Co-administration may require repaglinide dose increases and increased frequency of glucose monitoring Drugs That May Blunt Signs and Symptoms of Hypoglycemia: Increased frequency of glucose monitoring may be required when co-administered