Diltiazem Hydrochloride

Concurrent use increases ivabradine exposure and may exacerbate bradycardia and conduction disturbances. Avoid concomitant use.

Diltiazem significantly increases buspirone AUC 5.5-fold and Cmax 4.1-fold, potentially enhancing effects and increasing toxicity; dose adjustments may be necessary.

Concomitant administration results in elevated plasma carbamazepine levels, resulting in toxicity in some cases.

Sinus bradycardia resulting in hospitalization and pacemaker insertion reported with concurrent use. Heart rate monitoring required.

Additive effects in prolonging AV conduction when used concomitantly with diltiazem hydrochloride.

Diltiazem increases midazolam AUC 3-4 fold and Cmax 2-fold, with elimination half-life increased 1.5-2.5 fold, resulting in prolonged sedation and increased clinical effects.

Additive effects in prolonging AV conduction; concomitant use usually well tolerated but may cause problems in patients with left ventricular dysfunction or cardiac conduction abnormalities.

Diltiazem increases propranolol bioavailability approximately 50%; propranolol dose adjustment may be warranted when initiating or withdrawing combination therapy.

CYP3A4 inducer can lower plasma levels of diltiazem. Avoid concomitant use when possible and consider alternative therapy.

Increased risk of myopathy and rhabdomyolysis with statins metabolized by CYP3A4. Limit simvastatin to 10 mg daily and diltiazem to 240 mg.

Depressed cardiac contractility, conductivity, and automaticity as well as vascular dilation.

Diltiazem increases triazolam AUC 3-4 fold and Cmax 2-fold, with elimination half-life increased 1.5-2.5 fold, resulting in prolonged sedation and increased clinical effects.

Cimetidine significantly increases peak diltiazem plasma levels by approximately 58% and increases AUC.

May require dosage adjustment due to competitive inhibition of metabolism. Particularly important in renal and/or hepatic impairment due to low therapeutic ratio.

Potential additive effects on cardiac conduction when administered with diltiazem. Careful monitoring recommended.

Strong or moderate CYP 3A inhibitors a Examples b : Ketoconazole, itraconazole, cimetidine Patients currently receiving diltiazem therapy should be carefully monitored for a change in pharmacological effect when initiating and discontinuing therapy with strong or moderate inhibitors of CYP3A4.

Strong or moderate CYP 3A inhibitors a Examples b : Ketoconazole, itraconazole, cimetidine Patients currently receiving diltiazem therapy should be carefully monitored for a change in pharmacological effect when initiating and discontinuing therapy with strong or moderate inhibitors of CYP3A4.

Increased exposure of benzodiazepines due to CYP3A4 inhibition by diltiazem.

Increased exposure of quinidine due to CYP3A4 inhibition; may require dose adjustment.

Increased exposure of ranolazine due to CYP3A4 inhibition. Limit ranolazine to 500 mg twice daily.

Produces smaller, nonsignificant increases in diltiazem levels.

In a ten-subject randomized, open-label, 4-way crossover study, coadministration of diltiazem (120 mg BID diltiazem SR for 2 weeks) with a single 20 mg dose of lovastatin resulted in 3- to 4-fold increase in mean lovastatin AUC and C max versus lovastatin alone. Diltiazem plasma levels were not significantly affected by lovastatin or pravastatin.

In the same study, there was no significant change in 20 mg single dose pravastatin AUC and C max during diltiazem coadministration. Diltiazem plasma levels were not significantly affected by lovastatin or pravastatin.

In a healthy volunteer crossover study (N=10), coadministration of a single 20 mg dose of simvastatin at the end of a 14-day regimen with 120 mg BID diltiazem SR resulted in a 5-fold increase in mean simvastatin AUC versus simvastatin alone. Subjects with increased average steady-state exposures of diltiazem showed a greater fold increase in simvastatin exposure. Computer-based simulations showed that at a daily dose of 480 mg of diltiazem, an 8- to 9-fold mean increase in simvastatin AUC can be expected.