diltiazem (Rx)

Brand and Other Names:Cardizem, Cardizem CD, more...Cardizem LA, Cartia XT, Dilacor, Dilacor XR, Dilatrate, Diltazem, Diltazem CD, Dilt-CD, Diltia XT, Diltiaz, Diltiaz CD, Diltiaz SR, Diltiazem CD, Diltiazem SR, Dilzem, Taztia XT, Tiazac
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule/tablet, extended release

  • 120mg
  • 180mg
  • 240mg
  • 300mg
  • 360mg
  • 420mg

injectable solution

  • 5mg/mL

powder for injection

  • 100mg

tablet

  • 30mg
  • 60mg
  • 90mg
  • 120mg

Angina

Conventional: 30 mg PO q6hr; increased every 1 or 2 days until angina controlled (usually 180-360 mg/day PO divided q6-8hr); not to exceed 360 mg/day

Cardizem CD, Cartia XT, Dilt-CD: 120-180 mg/day PO; titrate over 7-14 days; maintenance range usually 120-320 mg/day; not to exceed 480 mg/day

DilacorXR, Dilt-XR: 120 mg/day PO; titrate after 7-14 days; maintenance range usually 120-320 mg/day; not to exceed 540 mg/day

Tiazac, Taztia XT: 120-180 mg/day PO; titrate after 7-14 days; maintenance range usually 120-320 mg/day; not to exceed 540 mg/day

Cardizem LA, Matzim LA: 180 mg/day PO; titrate after 14 days; maintenance range usually 120-320 mg/day; not to exceed 360 mg/day

Hypertension

Cardizem CD, Cartia XT, Dilt-CD: 180-240 mg/day PO; titrate after 14 days; maintenance range usually 180-420 mg/day; not to exceed 480 mg/day

Dilacor XR, Dilt-XR: 180-240 mg/day PO; titrate after 14 days; maintenance range usually 180-420 mg/day; not to exceed 540 mg/day

Tiazac, Taztia XT: 120-240 mg/day PO; titrate after 14 days; maintenance range usually 180-420 mg/day; not to exceed 540 mg/day

Cardizem LA, Matzim LA: 180-240 mg/day PO; titrate after 14 days; maintenance range usually 120-540 mg/day

Extended-release twice-daily dosing: 60-120 mg PO q12hr; may be adjusted after 14 days; maintenance range usually 240-360 mg/day

Paroxysmal Supraventricular Tachycardia

0.25 mg/kg (average adult dose, 20 mg) direct IV over 2 minutes; after 15 minutes, may repeat bolus by administering 0.35 mg/kg actual body weight over 2 min (average adult dose, 25 mg) direct IV if first dose tolerated but response inadequate; some clinicians suggest additional doses q15min  

Use weight-based dosing for lower-body-weight patients

Continuous infusion: 10 mg/hr IV initially; increased to no more than 15 mg/hr for up to 24 hours

Atrial Fibrillation/Flutter

0.25 mg/kg (usual adult dose, 20 mg) direct IV over 2 minutes; after 15 minutes, may repeat bolus by administering 0.35 mg/kg actual body weight over 2 min (average adult dose, 25 mg) direct IV if first dose tolerated but response inadequate; some clinicians suggest additional doses q15min  

Use weight-based dosing for lower-body-weight patients

Continuous infusion: 10 mg/hr IV initially; increased to no more than 15 mg/hr for up to 24 hours

Dose Modifications

Renal Impairment

  • Use caution; not studied

Hepatic Impairment

  • Use caution; not studied

Dosage Forms & Strengths

capsule/tablet, extended release

  • 120mg
  • 180mg
  • 240mg
  • 300mg
  • 360mg
  • 420mg

injectable solution

  • 5mg/mL

powder for injection

  • 100mg

tablet

  • 30mg
  • 60mg
  • 90mg
  • 120mg

Hypertension (Off-label)

1.5-2 mg/kg/day PO divided q8hr; not to exceed 6 mg/kg/day, up to 360 mg/day  

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Interactions

Interaction Checker

and diltiazem

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            Contraindicated (5)

            • dantrolene

              dantrolene, diltiazem. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Contraindicated. Rare incidence of cardiovascular collapse and marked hyperkalemia observed when coadministered; may be higher risk with nondihydropyridine calcium channel blockers.

            • flibanserin

              diltiazem will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of flibanserin with moderate or strong CYP3A4 inhibitors is contraindicated. Severe hypotension or syncope can occur.

            • lomitapide

              diltiazem increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increases lomitapide levels several folds.

            • lonafarnib

              diltiazem will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated.

            • pimozide

              diltiazem will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with potent CYP3A4 inhibitors may significantly increase the plasma concentrations of pimozide and may potentiate the risk of ventricular arrhythmias (eg, ventricular tachycardia, torsade de pointes, cardiac arrest, sudden death).

            Serious - Use Alternative (75)

            • abametapir

              abametapir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • amlodipine

              diltiazem will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use with amlodipine and diltiazem reported an a 60% increase in amlodipine AUC. Monitor increased effects and toxicities (eg, bradycardia, sinus arrest, decreased cardiac output) if amiodarone is concomitantly used with nondihydropyridine calcium channel blocker (ie, diltiazem).

            • apalutamide

              apalutamide will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • aprepitant

              diltiazem will increase the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Moderate CYP3A4 inhibitors may increase serum concentrations and/or toxicities of aprepitant.

            • atenolol

              diltiazem, atenolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • avapritinib

              diltiazem will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

            • betaxolol

              diltiazem, betaxolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • bisoprolol

              diltiazem, bisoprolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • bosutinib

              diltiazem increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • budesonide

              diltiazem will increase the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of CYP3A4 inhibitors and oral budesonide. If coadministration is necessary, closely monitor for signs and symptoms of corticosteroid excess.

            • clonidine

              clonidine, diltiazem. unknown mechanism. Avoid or Use Alternate Drug. Reports of sinus bradycardia resulting in hospitalization and pacemaker insertion reported with concomitant use. Possible life-threatening effect, monitor closely.

            • cobimetinib

              diltiazem will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (=14 days) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce cobimetinib dose to 20 mg. After discontinuing the moderate CYP3A inhibitor, resume cobimetinib 60 mg. In patients who are already receiving reduced cobimetinib doses due to adverse reactions, avoid moderate CYP3A4 and use alternative therapy.

            • colchicine

              diltiazem will increase the level or effect of colchicine by Other (see comment). Avoid or Use Alternate Drug. Colchicine is a P-gp and CYP3A4 substrate. Avoid use with drugs that are both P-gp and strong CYP3A4 inhibitors. If coadministration is necessary, decrease colchicine dose or frequency as recommended in prescribing information. Use of any colchicine product in conjunction with strong CYP3A4 inhibitors is contraindicated in patients with renal or hepatic impairment.

            • copanlisib

              diltiazem will increase the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Monitor patients for increased copanlisib effects/toxicities if coadministered with diltiazem. Consider reducing copanlisib dose to 45 mg.

            • dihydroergotamine

              diltiazem will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • dihydroergotamine intranasal

              diltiazem will increase the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • dronedarone

              diltiazem will increase the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Use lower starting doses of nondihydropyridine calcium channel blockers (eg,l, diltiazem). Consider increasing calcium channel blocker dose after combination is being well-tolerated.

            • eletriptan

              diltiazem will increase the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitantly use of eletriptan and moderate CYP3A4 inhibitors for 72 hours.

            • eliglustat

              diltiazem increases levels of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Moderate CYP3A4 inhibitors are not recommended with eliglustat poor or intermediate metabolizers; reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive metabolizers .

            • encorafenib

              diltiazem will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • entrectinib

              diltiazem will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • enzalutamide

              enzalutamide will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • eplerenone

              diltiazem will increase the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of eplerenone and mdoerate CYP3A4 inhibitor is not recommended. If combination is unavoidable, eplerenone dose should not exceed 25 mg/day for patients with congestive heart failure following MI.

            • erdafitinib

              erdafitinib will increase the level or effect of diltiazem by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.

            • erythromycin base

              diltiazem will increase the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              erythromycin base will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider an alternative to erythromycin in patients receiving diltiazem. If no alternative is available, monitor for the effects of diltiazem following erythromycin initiation/discontinuation.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider an alternative to erythromycin in patients receiving diltiazem. If no alternative is available, monitor for the effects of diltiazem following erythromycin initiation/discontinuation.

              diltiazem will increase the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider an alternative to erythromycin in patients receiving diltiazem. If no alternative is available, monitor for the effects of diltiazem following erythromycin initiation/discontinuation.

              diltiazem will increase the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider an alternative to erythromycin in patients receiving diltiazem. If no alternative is available, monitor for the effects of diltiazem following erythromycin initiation/discontinuation.

              diltiazem will increase the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • esmolol

              diltiazem, esmolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • fexinidazole

              fexinidazole will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • ibrutinib

              diltiazem increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

            • idelalisib

              idelalisib will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • indinavir

              indinavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • infigratinib

              diltiazem will increase the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ivabradine

              diltiazem will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.

              diltiazem, ivabradine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.

            • ivosidenib

              diltiazem will increase the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with moderate CYP3A4 inhibitors may increase ivosidenib plasma concentrations, thus increasing the risk of QTc prolongation. Monitor for increased risk of QTc interval prolongation.

              ivosidenib will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • lasmiditan

              lasmiditan increases levels of diltiazem by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • lemborexant

              diltiazem will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.

            • levobunolol

              diltiazem, levobunolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • lofexidine

              lofexidine, diltiazem. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.

            • lopinavir

              lopinavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lorlatinib

              lorlatinib will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lovastatin

              diltiazem will increase the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not exceed 20 mg/day of lovastatin

            • lurbinectedin

              diltiazem will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • metoprolol

              diltiazem, metoprolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • midazolam intranasal

              diltiazem will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of moderate CYP3A4 inhibitors with midazolam intranasal causes higher midazolam systemic exposure, which may prolong sedation.

            • midostaurin

              diltiazem will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.

            • mobocertinib

              diltiazem will increase the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use of moderate CYP3A4 inhibitor unavoidable, reduce mobocertinib dose by ~50% (eg, 160 to 80 mg); closely monitor QTc interval.

            • nadolol

              diltiazem, nadolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • naloxegol

              diltiazem will increase the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministation of naloxegol with moderate CYP3A4 inhibitors is unavoidable, reduce naloxegol dose to 12.5 mg qDay

            • nebivolol

              diltiazem, nebivolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • neratinib

              diltiazem will increase the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inhibitors.

            • olaparib

              diltiazem will increase the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A inhibitors cannot be avoided, reduce olaparib dose to 200 mg (capsule) or 150 mg (tablet) PO BID. Do not substitute tablets with capsules.

            • pemigatinib

              diltiazem will increase the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pemigatinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pemigatinib dose.

            • pexidartinib

              diltiazem will increase the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pexidartinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pexidartinib dose.

            • ponesimod

              ponesimod, diltiazem. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

            • primidone

              primidone will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • propafenone

              diltiazem will increase the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of diltiazem with pimozide may increase the serum concentration of pimozide (eg, ventricular tachycardia, torsade de pointes, cardiac arrest, sudden death).

            • propranolol

              diltiazem, propranolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • rifampin

              rifampin will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with diltiazem and strong CYP3A4 inducers However, if concomitant use is necessary, consider dosage adjustment and close monitoring of pharmacologic effects (eg, blood pressure) whenever a strong CYP3A4 inducer is added to or discontinued from therapy.

            • selumetinib

              diltiazem will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.

            • simvastatin

              diltiazem will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Benefits of combination therapy should be carefully weighed against the potential risks of combination. Limit simvastatin dose to no more than 10 mg/day and dilitazem dose to no more than 240 mg/day when used concurrently.

            • siponimod

              siponimod, diltiazem. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Because of the potential additive effects on heart rate, siponimod should generally not be initiated in patients taking QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers, or other drugs that may decrease heart rate. If treatment considered, obtain cardiology consult regarding switching to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.

              diltiazem will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • sonidegib

              diltiazem will increase the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sonidegib with moderate CYP3A4 inhibitors. If a moderate CYP3A inhibitor must be used, administer the moderate CYP3A inhibitor for <14 days and monitor closely for adverse reactions, particularly musculoskeletal adverse reactions.

            • sotalol

              diltiazem, sotalol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • sotorasib

              sotorasib will decrease the level or effect of diltiazem by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

            • St John's Wort

              St John's Wort will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tazemetostat

              diltiazem will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of tazemetostat with moderate CYP3A4 inhibitors. If coadministration is unavoidable, reduce tazemetostat current dose (see drug monograph Dosage Modifications).

            • tepotinib

              tepotinib will increase the level or effect of diltiazem by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

            • timolol

              diltiazem, timolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • tolvaptan

              diltiazem will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. In patients taking concomitant moderate CYP3A inhibitors, reduce tolvaptan dose (see Prescribing Information). Consider further reductions if patients cannot tolerate the reduced dose. Interrupt tolvaptan temporarily for short term therapy with moderate CYP3A inhibitors if the recommended reduced doses are not available.

            • tucatinib

              tucatinib will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • venetoclax

              diltiazem will increase the level or effect of venetoclax by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a moderate CYP3A inhibitor must be used, reduce the venetoclax dose by at least 50%. Monitor more closely for signs of venetoclax toxicities.

            • vilazodone

              diltiazem increases levels of vilazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If intolerable adverse effects occur when coadministered with moderate CYP3A4 inhibitors, reduce daily dose to 20 mg.

            • voxelotor

              voxelotor will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            Monitor Closely (259)

            • acalabrutinib

              diltiazem will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.

            • acebutolol

              acebutolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • aldesleukin

              aldesleukin increases effects of diltiazem by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • alfentanil

              diltiazem will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. In patients receiving both diltiazem and alfentanil, monitor for alfentanil toxicity (sedation, somnolence, confusion, impaired coordination, diminished reflexes, coma). Doses of alfentanil may need to be reduced.

            • alfuzosin

              diltiazem will increase the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased exposure to alfuzosin may be expected when alfuzosin is concomitantly used with diltiazem. Monitor pulse and blood pressure.

            • alprazolam

              diltiazem will increase the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for increased alprazolam side effects including drowsiness or fatigue, nausea, vomiting, diarrhea or constipation.

            • amifostine

              amifostine, diltiazem. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

            • amiodarone

              diltiazem will increase the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor increased effects and toxicities (eg, bradycardia, sinus arrest, decreased cardiac output) if amiodarone is concomitantly used with nondihydropyridine calcium channel blocker (ie, diltiazem).

            • amitriptyline

              diltiazem will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use with amitriptyline may alter blood pressure control.

            • amlodipine

              amlodipine and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • amobarbital

              amobarbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • apixaban

              diltiazem increases levels of apixaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Patients with renal impairment receiving apixaban with drugs that are combined P-gp and weak or moderate CYP3A4 inhibitors may have significant increases in exposure compared with patients with normal renal function and no inhibitor use, since both pathways of apixaban elimination are affected. Since these increases may increase bleeding risk, use apixaban in this situation only if the potential benefit justifies the potential risk.

            • aprepitant

              aprepitant will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • aripiprazole

              diltiazem will increase the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Closely monitor when aripiprazole is used with a moderate CYP3A4 inhibitor, due to potential risks for increased aripiprazole systemic exposure and effects. Refer to drug monograph for specific dosing modifications are dependent on indication, genotype, and drug formulation.

            • armodafinil

              diltiazem will increase the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              armodafinil will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • artemether/lumefantrine

              artemether/lumefantrine will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              diltiazem will increase the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with artemether/lumefantrine may increase artemether/lumefantrine levels and toxicities (eg, cardiac arrhythmias).

            • asenapine

              asenapine and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • atazanavir

              atazanavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of atazanavir with diltiazem may increase diltiazem levels and toxicities (eg, hypotension, AV block). Consider reducing diltiazem dose by 50%. Monitor blood pressure and ECG.

            • atenolol

              atenolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • atorvastatin

              diltiazem will increase the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concurrent therapy is required, monitor for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness, or discolored urine). If myopathy or rhabdomyolysis is diagnosed or suspected, monitor creatine kinase (CK) levels and discontinue use if CK levels show a marked increase.

            • avanafil

              diltiazem will increase the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Moderate CYP3A4 inhibitors may reduce avanafil clearance increasing systemic exposure to avanafil; increased levels may result in increased associated adverse events; maximum recommended dose of avanafil is 50 mg over 24 hours for patients taking concomitant moderate CYP3A4 inhibitors.

            • axitinib

              diltiazem increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration with moderate CYP3A4 inhibitors, monitor closely and reduce dose if necessary .

            • bazedoxifene/conjugated estrogens

              diltiazem will increase the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • belzutifan

              belzutifan will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • benzphetamine

              benzphetamine will decrease the level or effect of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor. Amphetamines may diminish antihypertensive effects of diltiazem. Monitor BP.

            • berotralstat

              berotralstat will increase the level or effect of diltiazem by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • betaxolol

              betaxolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • bisoprolol

              bisoprolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • bortezomib

              diltiazem will increase the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use with bortezomib may potentiate the risk of hypotension. Monitor BP.

            • bosentan

              diltiazem will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              bosentan will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • bretylium

              diltiazem, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

            • brexpiprazole

              diltiazem will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

            • buprenorphine subdermal implant

              diltiazem will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

            • buprenorphine, long-acting injection

              diltiazem will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • buspirone

              diltiazem will increase the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of buspirone with diltiazem may increase plasma concentrations and/or toxicities of buspirone. Dose adjustments may be necessary.

            • butabarbital

              butabarbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • butalbital

              butalbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cabazitaxel

              diltiazem will increase the level or effect of cabazitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cabozantinib

              diltiazem will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • calcium acetate

              calcium acetate decreases effects of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor.

            • calcium carbonate

              calcium carbonate decreases effects of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor.

            • calcium chloride

              calcium chloride decreases effects of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor.

            • calcium citrate

              calcium citrate decreases effects of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor.

            • calcium gluconate

              calcium gluconate decreases effects of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor.

            • cannabidiol

              diltiazem will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor increased cannabidol effects and toxicities if coadministered with moderate CYP3A4 inhibitors. Reduce cannabidiol dose if necessary.

            • carbamazepine

              carbamazepine will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • carvedilol

              carvedilol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • celiprolol

              celiprolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • cenobamate

              cenobamate will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • cilostazol

              diltiazem will increase the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing cilostazol dose to 50 mg PO BID when administered with diltiazem.

            • cimetidine

              cimetidine will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider alternatives to cimetidine in patients receiving diltiazem. If no alternative is available, monitor for the effects of diltiazem following cimetidine initiation/discontinuation.

              cimetidine will increase the level or effect of diltiazem by basic (cationic) drug competition for renal tubular clearance. Modify Therapy/Monitor Closely. Exercise caution when concomitantly using diltiazem with atazanavir. Consider reducing the diltiazem dose by 50%. ECG monitoring is recommended.

            • cinacalcet

              diltiazem will increase the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clarithromycin

              clarithromycin will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased effect of calcium channel blockers may lead to hypotension, edema, decreased HR, and acute kidney injury due to reduced renal blood flow

            • clevidipine

              clevidipine and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • clopidogrel

              diltiazem will decrease the level or effect of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of clopidogrel and a calcium channel blocking agent may decrease the effect of clopidogrel on platelet inhibition, possibly increasing the risk of atherothrombotic events. Clopidogrel requires hepatic biotransformation to an active metabolite, mediated by the 3A4 enzyme. Diltiazem is a 3A4 inhibitor and may decrease the hepatic metabolism of clopidogrel to its active metabolite.

            • clozapine

              diltiazem will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant treatment with clozapine and CYP2D6 or CYP3A4 inhibitors can increase clozapine levels and lead to adverse reactions. Use caution and monitor patients closely when using such inhibitors. Consider reducing clozapine dose.

            • cobicistat

              cobicistat will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conivaptan

              conivaptan will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conjugated estrogens

              diltiazem will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conjugated estrogens, vaginal

              diltiazem will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cortisone

              diltiazem will increase the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • crizotinib

              crizotinib increases levels of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              diltiazem increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

            • cyclosporine

              diltiazem will increase the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor serum cyclosporine concentrations if diltiazem or verapamil are initiated/ discontinued. During coadministration of cyclosporine and diltiazem, monitor for decreases in blood pressure.

            • dabrafenib

              dabrafenib will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • darifenacin

              diltiazem will increase the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • darunavir

              darunavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              diltiazem will increase the level or effect of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Consider avoiding the concomitant use of protease inhibitors and nondihydropyridine calcium channel blockers (CCB). Monitor for toxicities of the CCB if a protease inhibitor is initiated/dose increased.

            • dasatinib

              diltiazem will increase the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • deferasirox

              deferasirox will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • deflazacort

              diltiazem will increase the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease deflazacort dose to one-third of the recommended dose if coadministered with moderate or strong CYP3A4 inhibitors.

            • desipramine

              diltiazem will increase the level or effect of desipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dexamethasone

              diltiazem will increase the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • diazepam

              diltiazem will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • diazepam intranasal

              diltiazem will increase the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

            • disopyramide

              diltiazem will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • docetaxel

              diltiazem will increase the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • donepezil

              diltiazem will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • doxazosin

              doxazosin and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • doxorubicin

              diltiazem will increase the level or effect of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • doxorubicin liposomal

              diltiazem will increase the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dronedarone

              dronedarone will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Calcium channel blockers with depressant effects on sinus and AV nodes could potentiate dronedarone's effects on conduction. Initiate calcium channel blockers at a lower dose and titrate up only after ECG verification of tolerability.

            • duvelisib

              duvelisib will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

            • efavirenz

              efavirenz will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • elagolix

              elagolix will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Exercise caution and monitor upon coadministration of calcium channel blockers with elvitegravir/cobicistat/emtricitabine/tenofovir DF.

            • encorafenib

              encorafenib, diltiazem. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • ergotamine

              diltiazem will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erlotinib

              diltiazem will increase the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • esmolol

              esmolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • estradiol

              diltiazem will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estrogens conjugated synthetic

              diltiazem will increase the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estrogens esterified

              diltiazem will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estropipate

              diltiazem will increase the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • etravirine

              diltiazem will increase the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              etravirine will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • everolimus

              diltiazem will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Dose adjustment is based on indication. In breast cancer, PNET, renal cell cancer, or renal angiomyolipoma w/ TSC patents, decrease everolimus dose to 2.5-5 mg/day; decrease everolimus dose 50% and monitor levels in SEGA patients.

            • fedratinib

              fedratinib will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • felodipine

              diltiazem will increase the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              diltiazem and felodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • fentanyl

              diltiazem will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fentanyl intranasal

              diltiazem will increase the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fentanyl transdermal

              diltiazem will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fentanyl transmucosal

              diltiazem will increase the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fesoterodine

              diltiazem will increase the level or effect of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • finerenone

              diltiazem will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • fingolimod

              diltiazem increases effects of fingolimod by pharmacodynamic synergism. Use Caution/Monitor. Both medications decrease heart rate. Monitor patients on concomitant therapy, particularly in the first 6 hours after fingolimod is initiated or after a treatment interruption of at least two weeks, for bradycardia and atrioventricular block. To identify underlying risk factors of bradycardia and AV block, obtain a new or recent ECG in patients using calcium channel blockers prior to starting fingolimod.

            • fluconazole

              fluconazole will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fludrocortisone

              diltiazem will increase the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fluvoxamine

              fluvoxamine will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fosamprenavir

              diltiazem will increase the level or effect of fosamprenavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Protease Inhibitors may decrease metabolism of diltiazem. Increased serum concentrations of diltiazem may increase risk of AV nodal blockade.

              fosamprenavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              diltiazem will increase the level or effect of fosphenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for phenytoin toxicity if diltiazem is initiated/dose increased, or decreased phenytoin effects if diltiazem is discontinued/dose decreased. Monitor for reduced diltiazem therapeutic effects with concomitant fosphenytoin.

            • fostamatinib

              fostamatinib will increase the level or effect of diltiazem by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of P-gp substrates. Monitor for toxicities of the P-gp substrate drug that may require dosage reduction when given concurrently with fostamatinib.

            • glecaprevir/pibrentasvir

              glecaprevir/pibrentasvir will increase the level or effect of diltiazem by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • grapefruit

              grapefruit will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • griseofulvin

              griseofulvin will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • guanfacine

              diltiazem will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce guanfacine ER dose by 50% when initiating concomitant therapy with a moderate CYP3A4 inhibitor. When discontinuing moderate CYP3A4 inhibitor, increase guanfacine dose to recommended dose range. Monitor for excessive guanfacine response (eg, hypotension, bradycardia, CNS depression).

            • hawthorn

              hawthorn increases effects of diltiazem by pharmacodynamic synergism. Use Caution/Monitor.

            • hydrocortisone

              diltiazem will increase the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ifosfamide

              diltiazem will decrease the level or effect of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of a CYP3A4 inhibitor may decrease metabolism of ifosfamide, potentially reducing ifosfamide therapeutic effects.

            • iloperidone

              iloperidone increases levels of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4. Coadministration with iloperidone may increase the risk for QT prolongation and patients should be carefully monitor.

            • imatinib

              diltiazem will increase the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • imipramine

              diltiazem will increase the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • indinavir

              diltiazem will increase the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • irinotecan

              diltiazem will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • irinotecan liposomal

              diltiazem will increase the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isradipine

              diltiazem will increase the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              diltiazem and isradipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • istradefylline

              istradefylline will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

              istradefylline will increase the level or effect of diltiazem by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

            • itraconazole

              diltiazem will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of diltiazem and itraconazole may increase both drug levels, toxities, and additive negative inotropic effects.

              itraconazole will increase the level or effect of diltiazem by Other (see comment). Modify Therapy/Monitor Closely. CCBs elicit negative inotropic effects which may be additive to those of itraconazole; additionally, itraconazole can inhibit the metabolism of calcium channel blockers. Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

            • ivacaftor

              diltiazem will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • ixabepilone

              diltiazem will increase the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ketoconazole

              diltiazem will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of diltiazem and ketoconazole may increase both drug levels, toxities, and additive negative inotropic effects.

              ketoconazole will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • labetalol

              labetalol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • lapatinib

              diltiazem will increase the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lasmiditan

              diltiazem increases effects of lasmiditan by pharmacodynamic synergism. Use Caution/Monitor. Lasmiditan has been associated with a lowering of heart rate (HR). In a drug interaction study, addition of a single 200-mg dose of lasmiditan to propranolol decreased HR by an additional 5 bpm compared to propranolol alone, for a mean maximum of 19 bpm.

            • lefamulin

              diltiazem will increase the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for adverse effects if lefamulin is coadministered with moderate CYP3A inhibitors.

            • letermovir

              diltiazem will increase the level or effect of letermovir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levamlodipine

              diltiazem will increase the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate and strong CYP3A inhibitors results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment.

            • levodopa

              levodopa increases effects of diltiazem by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

            • lithium

              diltiazem increases toxicity of lithium by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of neurotoxicity.

            • lopinavir

              diltiazem will increase the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lumefantrine

              diltiazem will increase the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              lumefantrine will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lurasidone

              diltiazem increases levels of lurasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease starting dose of lurasidone to 20 mg/day and maximum daily dose of lurasidone 80 mg when coadministered with moderate CYP3A4 inhibitors. Concurrent use may increase risk of lurasidone-related adverse reactions.

            • magnesium supplement

              magnesium supplement, diltiazem. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Calcium channel blockers may increase toxic effects of magnesium; magnesium may increase hypotensive effects of calcium channel blockers.

            • maraviroc

              diltiazem will increase the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • marijuana

              diltiazem will increase the level or effect of marijuana by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mefloquine

              mefloquine increases levels of diltiazem by decreasing metabolism. Use Caution/Monitor. Risk of arrhythmia.

              diltiazem will increase the level or effect of mefloquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • metformin

              diltiazem decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

            • methadone

              diltiazem will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • methamphetamine

              methamphetamine will decrease the level or effect of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor. Amphetamines may diminish antihypertensive effects of diltiazem. Monitor BP.

            • methylphenidate

              methylphenidate will decrease the level or effect of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor. Methylphenidate may diminish antihypertensive effects. Monitor BP.

            • methylprednisolone

              diltiazem will increase the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • metoprolol

              metoprolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • midazolam

              diltiazem will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Midazolam dose adjustments may be necessary in patients receiving concomitant diltiazem and midazolam. Monitor for signs of midazolam toxicity (eg, sedation, somnolence, confusion, impaired coordination, diminished reflexes, coma).

            • mifepristone

              diltiazem will increase the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of mifepristone, CYP3A4 inhibitor with diltiazem, CYP3A4 substrate may increase plasma concentrations of diltiazem. Discontinuation or dose reduction of diltiazem may be necessary with mifepristone coadministration.

              mifepristone will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mitotane

              mitotane decreases levels of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • modafinil

              modafinil will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • moxisylyte

              moxisylyte and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • nadolol

              nadolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • nafcillin

              nafcillin will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • naldemedine

              diltiazem increases levels of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with strong or moderate CYP3A4 inhibitors.

            • nebivolol

              nebivolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • nefazodone

              nefazodone will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • nelfinavir

              diltiazem will increase the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor potential serious and/or life threatening reactions such as cardiac arrhythmias.

              nelfinavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nevirapine

              nevirapine will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nicardipine

              diltiazem will increase the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Nondihydropyridine calcium channel blockers (CCB) may increase the serum concentration of dihydropyridine CCB. Monitor for toxicities of dihydropyridine CCB if diltiazem are initiated/dose increased, or decreased effects if diltiazem are discontinued/dose decreased.

              diltiazem and nicardipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • nifedipine

              diltiazem will increase the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Exercise caution when coadministering diltiazem and nifedipine and consider reducing nifedipine dose.

              nifedipine will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              diltiazem and nifedipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • nilotinib

              diltiazem will increase the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              nilotinib will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nimodipine

              diltiazem will increase the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nisoldipine

              diltiazem will increase the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              diltiazem and nisoldipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • nitroglycerin rectal

              nitroglycerin rectal, diltiazem. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Marked orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used concomitantly. Observe for possible additive hypotensive effects during concomitant use. .

            • nitroprusside sodium

              diltiazem increases effects of nitroprusside sodium by pharmacodynamic synergism. Use Caution/Monitor.

            • oliceridine

              diltiazem will increase the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              ombitasvir/paritaprevir/ritonavir & dasabuvir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • oxybutynin

              diltiazem will increase the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • oxycodone

              diltiazem will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • paclitaxel

              diltiazem will increase the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for dose-related toxicities (eg, diarrhea, mucositis, myelosuppression, peripheral neuropathy) of paclitaxel during coadministration.

            • paclitaxel protein bound

              diltiazem will increase the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for dose-related toxicities (eg, diarrhea, mucositis, myelosuppression, peripheral neuropathy) of paclitaxel during coadministration.

            • palbociclib

              diltiazem will increase the level or effect of palbociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pazopanib

              diltiazem will increase the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • penbutolol

              penbutolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • pentobarbital

              pentobarbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • phendimetrazine

              phendimetrazine will decrease the level or effect of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor. Amphetamines may diminish antihypertensive effects of diltiazem. Monitor BP.

            • phenobarbital

              phenobarbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • phenoxybenzamine

              phenoxybenzamine and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • phentermine

              phentermine will decrease the level or effect of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor. Amphetamines may diminish antihypertensive effects of diltiazem. Monitor BP.

            • phentolamine

              phentolamine and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • phenytoin

              phenytoin will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pindolol

              pindolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • pioglitazone

              diltiazem will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • posaconazole

              posaconazole will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • prazosin

              prazosin and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • prednisolone

              diltiazem will increase the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Closely monitor for evidence of excessive response to corticosteroid therapy if used with diltiazem. Consider dosage adjustment if necessary.

            • prednisone

              diltiazem will increase the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Closely monitor for evidence of excessive response to corticosteroid therapy if used with diltiazem. Consider dosage adjustment if necessary.

            • propranolol

              propranolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • quetiapine

              diltiazem will increase the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • quinidine

              diltiazem will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              quinidine will increase the level or effect of diltiazem by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • quinine

              diltiazem will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ranolazine

              diltiazem will increase the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limit the dose of ranolazine to a maximum of 500 mg twice a day when used concomitantly with diltiazem.

            • repaglinide

              diltiazem will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor glucose and hypoglycemic symptoms (eg, headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, palpitations).

            • ribociclib

              ribociclib will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifabutin

              rifabutin will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with diltiazem and rifamycin derivatives may decrease diltiazem levels. Consider dosage adjustment and close monitoring of pharmacologic effects (eg, blood pressure) whenever a rifamycin derivative is added to or discontinued from therapy.

            • rifapentine

              rifapentine will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with diltiazem and rifamycin derivatives may decrease diltiazem levels. Consider dosage adjustment and close monitoring of pharmacologic effects (eg, blood pressure) whenever a rifamycin derivative is added to or discontinued from therapy.

            • rimegepant

              diltiazem will increase the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid repeating rimegepant dose within 48 hr if coadministered with a moderate CYP3A4 inhibitor.

            • riociguat

              riociguat, diltiazem. Either increases effects of the other by anti-hypertensive channel blocking. Use Caution/Monitor. Monitor patients closely for additive hypotensive effects if two or more of these agents are combined.

            • ritonavir

              diltiazem will increase the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              ritonavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rivaroxaban

              diltiazem increases levels of rivaroxaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Patients with renal impairment receiving rivaroxaban with drugs that are combined P-gp and weak or moderate CYP3A4 inhibitors may have significant increases in exposure compared with patients with normal renal function and no inhibitor use, since both pathways of rivaroxaban elimination are affected. Since these increases may increase bleeding risk, use rivaroxaban in this situation only if the potential benefit justifies the potential risk.

            • rucaparib

              rucaparib will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • rufinamide

              rufinamide will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ruxolitinib

              diltiazem will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • saquinavir

              diltiazem will increase the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              saquinavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sarecycline

              sarecycline will increase the level or effect of diltiazem by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

            • saxagliptin

              diltiazem will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Closely monitor glucose when saxagliptin is concomitantly used with moderate CYP3A4 inhibitors.

            • secobarbital

              secobarbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • shepherd's purse

              shepherd's purse, diltiazem. Other (see comment). Use Caution/Monitor. Comment: Theoretically, shepherd's purse may interfere with BP control.

            • sildenafil

              diltiazem will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • silodosin

              diltiazem will increase the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              silodosin and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • sirolimus

              diltiazem will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              diltiazem, sodium sulfate/?magnesium sulfate/potassium chloride. Either decreases toxicity of the other by unknown mechanism. Use Caution/Monitor. Monitor for hypotension or muscle weakness in patients receiving calcium channel blockers with elevated serum magnesium concentrations.

            • sodium sulfate/potassium sulfate/magnesium sulfate

              diltiazem, sodium sulfate/potassium sulfate/magnesium sulfate. Either decreases toxicity of the other by unknown mechanism. Use Caution/Monitor. Monitor for hypotension or muscle weakness in patients receiving calcium channel blockers with elevated serum magnesium concentrations.

            • solifenacin

              diltiazem will increase the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sotalol

              sotalol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • stiripentol

              stiripentol, diltiazem. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

            • sufentanil

              diltiazem will increase the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. The incidence and degree of bradycardia and hypotension during induction with sufentanil citrate may be greater in patients on chronic calcium channel and beta blocker therapy.

            • sufentanil SL

              diltiazem will increase the level or effect of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of sufentanil SL with any CYP3A4 inhibitor may increase sufentanil plasma concentration, and, thereby increase or prolonged adverse effects, including potentially fatal respiratory depression.

            • sunitinib

              diltiazem will increase the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • suvorexant

              diltiazem will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitors

            • tacrolimus

              diltiazem will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tadalafil

              diltiazem will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Risk of hypotension.

            • tamoxifen

              diltiazem, tamoxifen. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibition decreases metabolism of tamoxifen to N-desmethyl tamoxifen (active metabolite with similar biologic activity).

            • tamsulosin

              diltiazem increases levels of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • tazemetostat

              tazemetostat will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • temsirolimus

              diltiazem will increase the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              diltiazem increases toxicity of temsirolimus by Other (see comment). Use Caution/Monitor. Comment: Combination of mTOR inhibitors with calcium channel blockers increases risk of angioedema.

            • terazosin

              terazosin and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • tezacaftor

              diltiazem will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. When tezacaftor/ivacaftor is combined with moderate CYP3A4 inhibitors, administer tezacaftor/ivacaftor (100 mg/150 mg) in the morning, every other day. Administer ivacaftor 150 mg alonein the evening, every other day, on alternate days from tezacaftor/ivacaftor.

            • theophylline

              diltiazem will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • timolol

              timolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • tipranavir

              diltiazem will increase the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              tipranavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tofacitinib

              diltiazem increases levels of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No specific dose adjustment recommended when tofacitinib coadministered with moderate CYP3A4 inhibitors; decrease tofacitinib dose if coadministered with both moderate CYP3A4 and potent CYP2C19 inhibitors.

            • tolterodine

              diltiazem will increase the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • topiramate

              topiramate will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • trabectedin

              diltiazem will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • trazodone

              diltiazem will increase the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • triamcinolone acetonide injectable suspension

              diltiazem will increase the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • triazolam

              diltiazem will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • trimagnesium citrate anhydrous

              trimagnesium citrate anhydrous, diltiazem. Either increases effects of the other by Other (see comment). Use Caution/Monitor. Comment: Possible additive effect of magnesium and calcium channel blockers on reduction of ionic calcium may increase risk of hypotension or muscle weakness.

            • trimipramine

              diltiazem will increase the level or effect of trimipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tucatinib

              tucatinib will increase the level or effect of diltiazem by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

            • vardenafil

              diltiazem will increase the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • vemurafenib

              vemurafenib increases levels of diltiazem by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • verapamil

              diltiazem will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. These agents have additive hypotensive effects that may be beneficial however, it is important to monitor patients carefully.

              diltiazem and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor. Antihypertensives may enhance the hypotensive effects of other antihypertensive agents when used together.

            • vinblastine

              diltiazem will increase the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • vincristine

              diltiazem will increase the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • vincristine liposomal

              diltiazem will increase the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • vinorelbine

              diltiazem will increase the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • voclosporin

              diltiazem will increase the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce voclosporin daily dosage to 15.8 mg PO in AM and 7.9 mg PO in PM.

            • voriconazole

              voriconazole will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Combo may increase risk of hypotension, bradycardia, AV block.

              voriconazole increases levels of diltiazem by decreasing metabolism. Use Caution/Monitor.

            • xipamide

              xipamide increases effects of diltiazem by pharmacodynamic synergism. Use Caution/Monitor.

            • zanubrutinib

              diltiazem will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib dose when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib. See zanubrutinib Dosage Modifications for precise recommendation.

            Minor (30)

            • agrimony

              agrimony increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

            • aspirin

              diltiazem increases effects of aspirin by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

            • aspirin rectal

              diltiazem increases effects of aspirin rectal by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

            • aspirin/citric acid/sodium bicarbonate

              diltiazem increases effects of aspirin/citric acid/sodium bicarbonate by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

            • atracurium

              diltiazem increases effects of atracurium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • brimonidine

              brimonidine increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

            • choline magnesium trisalicylate

              diltiazem increases effects of choline magnesium trisalicylate by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

            • cisatracurium

              diltiazem increases effects of cisatracurium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • dutasteride

              diltiazem will increase the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • estradiol vaginal

              diltiazem will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fo-ti

              fo-ti increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

            • forskolin

              forskolin increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

            • galantamine

              diltiazem will increase the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • lily of the valley

              diltiazem, lily of the valley. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown.

            • maitake

              maitake increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

            • metformin

              diltiazem will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • metipranolol ophthalmic

              metipranolol ophthalmic increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

            • octacosanol

              octacosanol increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

            • ondansetron

              diltiazem will increase the level or effect of ondansetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. No dosage adjustment for ondansetron is recommended.

            • pancuronium

              diltiazem increases effects of pancuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • rapacuronium

              diltiazem increases effects of rapacuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • reishi

              reishi increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

            • rocuronium

              diltiazem increases effects of rocuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • succinylcholine

              diltiazem increases effects of succinylcholine by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • sulfamethoxazole

              sulfamethoxazole will increase the level or effect of diltiazem by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • tizanidine

              tizanidine increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

            • treprostinil

              treprostinil increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

            • vecuronium

              diltiazem increases effects of vecuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • verteporfin

              diltiazem increases levels of verteporfin by pharmacodynamic synergism. Minor/Significance Unknown.

            • willow bark

              diltiazem increases effects of willow bark by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

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            Adverse Effects

            >10%

            Edema (2-15%)

            Headache (5-12%)

            1-10%

            Dizziness (3-10%)

            AV block (2-8%)

            Peripheral edema (2-8%)

            Bradyarrhythmia (2-6%)

            Headache (1-5%)

            Hypotension (2-4%)

            Nausea (3%)

            Vomiting (2%)

            Vasodilation (2-3%)

            Extrasystoles (2%)

            Flushing (1-2%)

            Drug-induced gingival hyperplasia (<2%)

            Myalgia (2%)

            Diarrhea (1-2%)

            Constipation (2-4%)

            Bronchitis (1-4%)

            Sinus congestion (1-2%)

            Dyspnea (1-6%)

            Congestion (1-2%)

            < 1%

            Increased Alkaline phosphatase as well as ALT and AST

            CHF

            Thrombocytopenia

            Toxic epidermal necrolysis

            Hemolytic anemia

            Photosensitivity

            Extrapyramidal symptoms

            Syncope

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            Warnings

            Contraindications

            Hypersensitivity

            Wolff-Parkinson-White syndrome, Lown-Ganong-Levine syndrome, symptomatic severe hypotension (systolic BP <90 mm Hg), sick sinus syndrome (if no pacemaker), 2°/3° (if no pacemaker); heart block

            PO: Acute MI and pulmonary congestion

            IV: Use in newborns (because of benzyl alcohol), concomitant beta-blocker therapy, cardiogenic shock, ventricular tachycardia (must determine whether origin is supraventricular or ventricular)

            Cautions

            May cause abnormally slow heart rates or second- or third-degree AV block’ patients with sick sinus syndrome are at increased risk of bradycardia (risk increases with agents known to slow cardiac conduction

            Stevens-Johnson syndrome, toxic epidermal necrolusis, erythema multiforme and/or exfoliative dermatitis reported

            Significant elevations in liver enzymes such as alkaline phosphatase, LDH, AST (SGOT), ALT (SGPT) and signs of acute hepatic injury reported; reversible upon discontinuation of drug therapy

            Mild elevations of transaminases with and without concomitant elevation in alkaline phosphatase and bilirubin observed; elevations were usually resolved even with continued diltiazem treatment

            Symptomatic hypotension with or without syncope reported

            Peripheral edema occurs within 2-3 weeks of starting therapy

            Use with caution in hypertrophic obstructive cariomyopathy, hepatic/renal impairment, left ventricular dysfunction

            Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction; sinus bradycardia resulting in hospitalization reported with concurrent use of clonidine and other agents that slow cardiac conduction

            May increase the risk of adverse cardiac events in patients with heart failure due to negative inotropic effects (risk directly related to the severity of baseline HF)

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            Pregnancy & Lactation

            Pregnancy category: C

            Lactation: Drug enters breast milk; because of risk for serious adverse reactions in nursing infants from diltiazem, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Nondihydropyridine calcium-channel blocker: Inhibits extracellular calcium ion influx across membranes of myocardial cells and vascular smooth muscle cells, resulting in inhibition of cardiac and vascular smooth muscle contraction and thereby dilating main coronary and systemic arteries; no effect on serum calcium concentrations; substantial inhibitory effects on cardiac conduction system, acting principally at AV node, with some effects at sinus node

            Absorption

            Bioavailability: 40% (PO)

            Onset (hypertension): 30-60 min (IR); 3 min (IV)

            Duration (SVT): 1-3 hr (IV bolus); 0.5-10 hr (following discontinuation of continuous IV infusion)

            Peak serum time: 2-4 hr (IR); 10-14 hr (ER capsule); 11-18 hr (ER tablet)

            Distribution

            Protein bound: 70-80%

            Vd: 3-13 L/kg

            Metabolism

            Metabolized via hepatic CYP3A4

            Metabolites: Desacetyldiltiazem (active), 25-50% as potent as diltiazem in coronary vasodilation; N-monodesmethyldiltiazem (inactive)

            Elimination

            Half-life: 3-4.5 hr (IR); 6-9 hr (ER tablet), 5-10 hr (ER capsule); 3-4 hr (single dose IV); 4-5 hr (continuous infusion)

            Clearance: 11.8 mL/min/kg

            Excretion: Urine (2-4% as unchanged; 6-7% as metabolites), feces

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            Administration

            IV Incompatibilities

            Y-site: Allopurinol, amphotericin B, cefepime, cefoperazone, diazepam, furosemide, ketorolac, lansoprazole, pantoprazole, phenytoin, rifampin, thiopental

            IV Compatibilities

            Solution: D5W, NS

            Y-site (partial list): Acetazolamide (may be incompatible at higher concentrations), acyclovir (may be incompatible at higher concentrations), ceftriaxone, ciprofloxacin, clindamycin, digoxin, dobutamine, dopamine, epinephrine, erythromycin, fentanyl, fluconazole, heparin(?), labetalol, lidocaine, lorazepam, meperidine, metoclopramide, metronidazole, midazolam, milrinone, morphine sulfate, nafcillin (may be incompatible at higher concentrations), nitroglycerin, norepinephrine, potassium chloride, sodium bicarbonate, vancomycin

            IV Preparation

            IV push may be given by using undiluted 5 mg/mL injection

            Infusion

            • Accepted diluents are D5W, NS, and D5/½NS
            • Add 25 mL of 5 mg/mL solution in 100 mL diluent (1 mg/mL solution)
            • Add 50 mL of 5 mg/mL solution in 250 mL diluent (0.83 mg/mL solution)
            • Add 50 mL of 5 mg/mL solution in 500 mL diluent (0.45 mg/mL solution)
            • Dilute 1 monovial (100 mg) in 100 mL diluent (1 mg/mL solution)
            • Dilute 2 monovials (200 mg) in 250 mL diluent (0.8 mg/mL solution)
            • Dilute 2 monovials (200 mg) in 500 mL diluent (0.4 mg/mL solution)

            IV Administration

            Give bolus over 2 minutes with continuous ECG and BP monitoring

            Response to bolus may require several minutes to reach maximum; response may persist for several hours after infusion is discontinued

            Continuous infusion is done via infusion pump

            Infusion for >24 hours is not recommended

            Storage

            Refrigerate liquid injection vials; protect from freezing

            May store at room temperature for 1 month

            Powder: Store at room temperature; do not freeze

            Reconstituted solution stable at room temperature for 24 hours

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            Images

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            120 mg tablet
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            300 mg capsule
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            240 mg capsule
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            120 mg capsule
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            90 mg capsule
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            300 mg capsule
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            60 mg capsule
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            60 mg tablet
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            30 mg tablet
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            90 mg tablet
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            360 mg capsule
            diltiazem oral
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            360 mg capsule
            diltiazem oral
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            120 mg capsule
            diltiazem oral
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            120 mg capsule
            diltiazem oral
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            180 mg capsule
            diltiazem oral
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            120 mg capsule
            diltiazem oral
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            360 mg capsule
            diltiazem oral
            -
            360 mg capsule
            diltiazem oral
            -
            180 mg capsule
            diltiazem oral
            -
            300 mg capsule
            diltiazem oral
            -
            180 mg capsule
            diltiazem oral
            -
            120 mg capsule
            diltiazem oral
            -
            120 mg tablet
            diltiazem oral
            -
            360 mg capsule
            diltiazem oral
            -
            90 mg tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Select a drug:
            Patient Education
            diltiazem intravenous

            NO MONOGRAPH AVAILABLE AT THIS TIME

            USES: Consult your pharmacist.

            HOW TO USE: Consult your pharmacist.

            SIDE EFFECTS: Consult your pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Consult your pharmacist.

            DRUG INTERACTIONS: Consult your pharmacist.Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

            NOTES: No monograph available at this time.

            MISSED DOSE: Consult your pharmacist.

            STORAGE: Consult your pharmacist.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

            Information last revised July 2016. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.