Potentially serious drug interactions secondary to high-dose diltiazem used in the treatment of pulmonary hypertension.

Two patients had potentially serious drug interactions (phenytoin, digoxin) that were probably attributable to changes in pharmacokinetics and pharmacodynamics caused by high-dose calcium channel blocker therapy (diltiazem) in the treatment of pulmonary hypertension. Even in the approved normal dosages for the treatment of angina and hypertension, calcium channel blockers are known to cause significant changes in the metabolism of other drugs. Currently, no data exist on the effects of the very high dosages of these drugs, administered to patients with pulmonary hypertension, on the metabolism and clearance of other agents, although, based on our experience and literature reports, recommendations for monitoring therapy can be made.