Avoid use of nimodipine or nifedipine with phenytoin. Consider therapy modification Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy Phosphodiesterase 5 Inhibitors: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided.

Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification Propafenone: Monitor therapy Prostacyclin Analogues: Monitor therapy Protease Inhibitors: May decrease the metabolism of Calcium Channel Blockers Nondihydropyridine.

Increased serum concentrations of the calcium channel blocker may increase risk of AV nodal blockade. Avoid concurrent use when possible. If used, monitor for CCB toxicity. Consider therapy modification Quinagolide: Calcium Channel Blockers Nondihydropyridine may increase the serum concentration of Ranolazine. Limit ranolazine dose to a maximum of mg twice daily when used with diltiazem or verapamil. Consider therapy modification Ranolazine: Limit the ranolazine adult dose to a maximum of mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors e.

Consider therapy modification Red Yeast Rice: Specifically, concentrations of lovastatin and possibly other related compounds may be increased. Avoid combination Rifamycin Derivatives: May decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.

The labeling for some US and Canadian calcium channel blockers contraindicate use with rifampin, however recommendations vary. Consider therapy modification Rupatadine: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible.

Avoid concurrent use of diltiazem with simvastatin when possible. Consider therapy modification Sirolimus: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity particularly musculoskeletal adverse reactions. Consider therapy modification St John's Wort: Consider therapy modification Stiripentol: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity.

Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification Suvorexant: Consider therapy modification Tacrolimus Systemic: Monitor therapy Tacrolimus Topical: Consider therapy modification Ticagrelor: Jynarque dose requires adjustment when used with a moderate CYP3A4 inhibitor.

See labeling or full interaction monograph for specific recommendations. Consider therapy modification Trabectedin: When ulipristal is used as an emergency contraceptive, patients receiving this combination should be monitored for ulipristal toxicity.

Consider therapy modification Vilazodone: The starting adult dose of zopiclone should not exceed 3. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined. Consider therapy modification Zuclopenthixol: Monitor therapy Adverse Reactions Note: Frequencies represent ranges for various dosage forms.

May cause first-, second-, and third-degree AV block or sinus bradycardia; risk increases with agents known to slow cardiac conduction. Transient dermatologic reactions have been observed with use; if reaction persists, discontinue. Mild elevations of transaminases with and without concomitant elevation in alkaline phosphatase and bilirubin have been observed and frequently resolve spontaneously. Significant elevations in hepatic transaminases eg, alkaline phosphatase, LDH, AST, ALT and signs of acute hepatic injury have also been observed 1 to 8 weeks after therapy initiation and have been reversible upon discontinuation.

Symptomatic hypotension with or without syncope can rarely occur; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Use with caution in patients with hepatic impairment. Use with caution in patients with HOCM; routine use is currently not recommended due to insufficient evidence Maron Use with caution in left ventricular dysfunction; due to negative inotropic effects, may exacerbate condition.

Use with caution in patients with renal impairment. Consult drug interactions database for more detailed information. Unless otherwise contraindicated, appropriate vagal maneuvers should be attempted prior to administration of IV diltiazem.

Use with caution in patients hemodynamically compromised; continuously monitor ECG and blood pressure during administration especially during continuous IV infusion. Monitoring Parameters Liver function tests, kidney function, blood pressure, ECG, heart rate; consult individual institutional policies and procedures. Ventricular rate control in patients with atrial fibrillation or flutter: Untreated chronic maternal hypertension is associated with adverse events in the fetus, infant, and mother.

If treatment for hypertension during pregnancy is needed, other agents are preferred ACOG Women with hypertrophic cardiomyopathy who are controlled with diltiazem prior to pregnancy may continue therapy, but increased fetal monitoring is recommended Gersh During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for?

How often did hospital staff describe possible side effects in a way you could understand? This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Cyclosporine A pharmacokinetic interaction between diltiazem and cyclosporine has been observed during studies involving renal and cardiac transplant patients. If these agents are to be administered concurrently, cyclosporine concentrations should be monitored, especially when diltiazem therapy is initiated, adjusted, or discontinued. The effect of cyclosporine on diltiazem plasma concentrations has not been evaluated.

Another investigator found no increase in digoxin levels in 12 patients with coronary artery disease. Monitoring for quinidine adverse effects may be warranted and the dose adjusted accordingly. Rifampin Coadministration of rifampin with diltiazem lowered the diltiazem plasma concentrations to undetectable levels.

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered. The risk of myopathy and rhabdomyolysis with statins metabolized by CYP3A4 may be increased with concomitant use of diltiazem. When possible, use a non-CYP3A4-metabolized statin together with diltiazem; otherwise, dose adjustments for both diltiazem and the statin should be considered along with close monitoring for signs and symptoms of any statin related adverse events.

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 mg of diltiazem, an 8- to 9-fold mean increase in simvastatin AUC can be expected. If co-administration of simvastatin with diltiazem is required, limit the daily doses of simvastatin to 10 mg and diltiazem to mg. In a ten-subject randomized, open label, 4-way cross-over study, co-administration of diltiazem 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 versus lovastatin alone.

In the same study, there was no significant change in 20 mg single dose pravastatin AUC and C during diltiazem coadministration. Diltiazem plasma levels were not significantly affected by lovastatin or pravastatin. This effect may rarely result in abnormally slow heart rates particularly in patients with sick sinus syndrome or second- or third-degree AV block 13 of patients or 0. Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction.

Worsening of congestive heart failure has been reported in patients with preexisting impairment of ventricular function. Experience with the use of CARDIZEM diltiazem hydrochloride in combination with beta-blockers in patients with impaired ventricular function is limited. Caution should be exercised when using this combination. Mild elevations of transaminases with and without concomitant elevation in alkaline phosphatase and bilirubin have been observed in clinical studies.

Such elevations were usually transient and frequently resolved even with continued diltiazem treatment.

These reactions tended to occur early after therapy initiation 1 to 8 weeks and have been reversible upon discontinuation of drug therapy. As with any drug given over prolonged periods, laboratory parameters of renal and hepatic function should be monitored at regular intervals.

The drug should be used with caution in patients with impaired renal or hepatic function. In subacute and chronic dog and rat studies designed to produce toxicity, high doses of diltiazem were associated with hepatic damage. Should a dermatologic reaction persist, the drug should be discontinued. There was also no mutagenic response in vitro or in vivo in mammalian cell assays or in vitro in bacteria.

Reproduction studies have been conducted in mice, rats, and rabbits. In fact, many may feel normal. It is very important that you take your medicine exactly as directed and that you keep your appointments with your doctor even if you feel well.

Remember that this medicine will not cure your high blood pressure, but it does help control it. You must continue to take it as directed if you expect to lower your blood pressure and keep it down. You may have to take high blood pressure medicine for the rest of your life. If high blood pressure is not treated, it can cause serious problems such as heart failure, blood vessel disease, stroke, or kidney disease.

Swallow the extended-release tablet, extended-release capsule, or tablet whole. Do not open, crush, or chew it. It is best to take the extended-release capsule on an empty stomach. Dosing The dose of this medicine will be different for different patients. Studies to date, primarily in patients with good ventricular function, have not revealed evidence of a negative inotropic effect; cardiac output , ejection fraction , and left ventricular end diastolic pressure have not been affected.

Such data have no predictive value with respect to effects in patients with poor ventricular function, and increased heart failure has been reported in patients with pre-existing impairment of ventricular function. There are as yet few data on the interaction of diltiazem and beta-blockers in patients with poor ventricular function. Resting heart rate is usually slightly reduced by diltiazem.

In hypertensive patients, diltiazem hydrochloride extended-release capsules USP once-a-day dosage produces antihypertensive effects both in the supine and standing positions. In a double-blind, parallel, dose-response study utilizing doses ranging from 90 to mg once daily, diltiazem hydrochloride extended-release capsule once-a-day dosage lowered supine diastolic blood pressure in an apparent linear manner over the entire dose range studied.

The changes in diastolic blood pressure, measured at trough, for placebo, 90 mg, mg, mg, and mg were Postural hypotension is infrequently noted upon suddenly assuming an upright position. No reflex tachycardia is associated with the chronic antihypertensive effects. Diltiazem hydrochloride extended-release capsules USP once-a-day dosage decreases vascular resistance, increases cardiac output by increasing stroke volume ; and produces a slight decrease or no change in heart rate.

During dynamic exercise, increases in diastolic pressure are inhibited, while maximum achievable systolic pressure is usually reduced. Chronic therapy with diltiazem hydrochloride extended-release capsules USP once-a-day dosage produces no change or an increase in plasma catecholamines. No increased activity of the renin- angiotensin - aldosterone axis has been observed.

Diltiazem hydrochloride extended-release capsules USP once-a-day dosage reduce the renal and peripheral effects of angiotensin II. In a double-blind, parallel dose-response study of doses from 60 mg to mg once daily, diltiazem hydrochloride extended-release capsule once-a-day dosage increased time to termination of exercise in a linear manner over the entire dose range studied.

The improvement in time to termination of exercise utilizing a Bruce exercise protocol, measured at trough, for placebo, 60 mg, mg, mg, mg, and mg was 29, 40, 56, 51, 69, and 68 seconds, respectively. As doses of diltiazem hydrochloride extended-release capsule once-a-day dosage were increased, overall angina frequency was decreased. A significant increase in time to termination of exercise and a significant decrease in overall angina frequency was observed. In this trial the overall frequency of adverse events in the diltiazem hydrochloride extended-release capsule once-a-day dosage treatment group was the same as the placebo group.

Diltiazem-associated prolongation of the AH interval is not more pronounced in patients with first-degree heart block. Drugs which induce or inhibit hepatic microsomal enzymes may alter diltiazem disposition. Total radioactivity measurement following short IV administration in healthy volunteers suggests the presence of other unidentified metabolites, which attain higher concentrations than those of diltiazem and are more slowly eliminated; half-life of total radioactivity is about 20 hours compared to 2 to 5 hours for diltiazem.

Competitive in vitro ligand binding studies have also shown diltiazem binding is not altered by therapeutic concentrations of digoxin, hydrochlorothiazide, phenylbutazone, propranolol, salicylic acid , or warfarin. The plasma elimination half-life following single or multiple drug administration is approximately 3. There is a departure from linearity when dose strengths are increased; the half-life is slightly increased with dose. A single study in nine patients with severely impaired renal function showed no difference in the pharmacokinetic profile of diltiazem compared to patients with normal renal function.

A single mg dose of the capsule results in detectable plasma levels within 2 hours and peak plasma levels between 10 and 14 hours; absorption occurs throughout the dosing interval. When diltiazem hydrochloride extended-release capsule once-a-day dosage was coadministered with a high fat content breakfast, the extent of diltiazem absorption was not affected.

Dose-dumping does not occur. The apparent elimination half-life after single or multiple dosing is 5 to 8 hours. A departure from linearity similar to that seen with diltiazem tablets and diltiazem hydrochloride capsules twice daily is observed.

As the dose of diltiazem hydrochloride extended-release capsules once-a-day dosage is increased from a daily dose of mg to mg, there is an increase in the area-under-the-curve of 2. When the dose is increased from mg to mg, there is an increase in the area-under-thecurve of 1.

Diltiazem Dosage

Consider therapy modification Dronabinol: This is not a cap list of all diltiazem effects. In this trial the overall frequency of adverse events in the diltiazem hydrochloride extended-release release once-a-day dosage treatment group was the same as the placebo group. During dynamic exercise, increases in diastolic pressure cap inhibited, diltiazem 180 mg continuous release cap, while maximum achievable systolic pressure is usually reduced. Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving continuous inhibitors of CYP3A4. It causes excitation-contraction uncoupling in various myocardial tissues 180 changes in the configuration of the action potential. If coadministration of simvastatin with diltiazem is required, limit the daily doses of simvastatin to diltiazem mg and diltiazem to mg. Consider 180 modification Estrogen Derivatives: Patients continuous receiving diltiazem therapy should be carefully monitored for a change in pharmacological effect when initiating and discontinuing therapy with cimetidine. If there is no response to vagal blockade, administer isoproterenol cautiously.

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