MONITOR: Coadministration with cimetidine may increase the plasma concentrations of calcium channel blockers that are substrates of the CYP450 3A4 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by cimetidine.MANAGEMENT: Close monitoring of clinical response and tolerance is recommended if cimetidine is used in combination with calcium channel blockers that are metabolized by CYP450 3A4 such as diltiazem, felodipine, nicardipine, nifedipine, nimodipine, nisoldipine, and verapamil. Dose reductions of 40% to 50% may be considered, if necessary. Patients should be advised to seek medical attention if they experience edema or swelling of the lower extremities; sudden, unexplained weight gain; difficulty breathing; chest pain or tightness; or hypotension as indicated by dizziness, fainting, or orthostasis. Other H2-receptor antagonists may be safer alternatives, since they have not been shown to significantly affect CYP450 3A4 metabolism. However, there have been isolated reports of interaction between ranitidine and calcium channel blockers including nifedipine and nitrendipine.
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