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DRUG INTERACTIONS
Cationic Drugs
Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with metformin by competing for common renal tubular transport systems. Careful patient monitoring and dose adjustment of PrandiMet and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system [ see Clinical Pharmacology
].
CYP2C8 and CYP3A4 Inhibitors/Inducers
Repaglinide is metabolized by CYP2C8 and to a lesser extent by CYP3A4. Drugs that inhibit 2C8 (gemfibrozil, trimethoprim), inhibit 3A4 (itraconazole, ketaconazole), or induce CYP2C8/3A4 (rifampin) may alter the pharmacokinetics and pharmacodynamics of repaglinide. In vivo data from a study that evaluated the co-administration of gemfibrozil and repaglinide in healthy subjects showed a significant increase in repaglinide blood levels. Administration of PrandiMet and gemfibrozil to the same patient is not recommended [ see Warnings and Precautions and Clinical Pharmacology
].
Repaglinide exposures are increased more than 20-fold in patients taking both gemfibrozil and itraconazole [ see Contraindications (4) and Clinical Pharmacology
].
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OVERDOSAGE
PrandiMet
No data are available with regard to overdose of PrandiMet. Findings related to the individual active substances are listed below.
Repaglinide
In a clinical trial, dizziness, headache, and diarrhea were reported in subjects receiving increasing doses of repaglinide up to 80 mg a day for 14 days. Hypoglycemia did not occur when meals were given with these high doses.
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 should 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. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization. If hypoglycemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of concentrated (50%) glucose solution. This should be followed by a continuous infusion of more dilute (10%) glucose solution at a rate that will maintain the blood glucose at a level above 100 mg/dL.
Metformin HCl
Overdose of metformin HCl has occurred, including ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin HCl has been established. Lactic acidosis has been reported in approximately 32% of metformin HCl overdose cases [see Warnings and Precautions
]. Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin HCl overdosage is suspected.
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CONTRAINDICATIONS
PrandiMet is contraindicated in:
- Renal impairment (e.g., serum creatinine levels ≥1.5 mg/dL [males], ≥1.4 mg/dL [females], or abnormal creatinine clearance) [ see Warnings and Precautions
].
- Acute or chronic metabolic acidosis, including diabetic ketoacidosis. Diabetic ketoacidosis should be treated with insulin [ see Warnings and Precautions
].
-
Patients receiving gemfibrozil [ see
Warnings and Precautions
,
Drug Interactions
,
Clinical Pharmacology
].
-
Patients with known hypersensitivity to repaglinide, metformin HCl or any inactive ingredients in PrandiMet.
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