Verapamil

In controlled studies, hypotension was observed in 0.6% of patients receiving any combination of trandolapril and verapamil hydrochloride extended-release. In patients with concomitant congestive heart failure, with or without associated renal insufficiency, ACE inhibitor therapy may cause excessive hypotension, which may be associated with oliguria or azotemia, and, rarely, with acute renal failure and death (see DOSAGE AND ADMINISTRATION ).

Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption. Neutropenia/Agranulocytosis Trandolapril Component Another ACE inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression rarely in patients with uncomplicated hypertension, but more frequently in patients with renal impairment, especially if they also have a collagen-vascular disease such as systemic lupus erythematosus or scleroderma.

Available data from clinical trials of trandolapril or trandolapril and verapamil hydrochloride extended-release tablets are insufficient to show that trandolapril does not cause agranulocytosis at similar rates. As with other ACE inhibitors, periodic monitoring of white blood cell counts in patients with collagen-vascular disease and/or renal disease should be considered.

Fetal Toxicity Trandolapril Component Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.

Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue trandolapril and verapamil hydrochloride extended-release tablets as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy.

Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to trandolapril and verapamil hydrochloride extended-release tablets for hypotension, oliguria, and hyperkalemia (see PRECAUTIONS - Pediatric Use ).