diltiazem (Rx)

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

Hypertension (Off-label)

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

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 (81)

• 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.

• ceritinib

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

• 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.

• elacestrant

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

• 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.

• fosaprepitant

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

• 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.

• mavacamten

  diltiazem, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

• 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.

• omaveloxolone

  diltiazem will increase the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, reduce omaveloxolone dose to 100 mg/day. Closely monitor for adverse effects. If adverse effects emerge, further reduce to 50 mg/day.

• pacritinib

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

• 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 (270)

• 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.

• atogepant

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

• 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.

• daridorexant

  diltiazem will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Daridorexant dose should not exceed 25 mg per night when coadministered with moderate CYP3A4 inhibitors.

• 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.

• 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.

• fosaprepitant

  fosaprepitant 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.

• isavuconazonium sulfate

  diltiazem will increase the level or effect of isavuconazonium sulfate 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.

• larotrectinib

  diltiazem will increase the level or effect of larotrectinib 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.

• lenacapavir

  lenacapavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

• 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.

• levoketoconazole

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

• 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.

• lumateperone

  diltiazem will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 21 mg/day if coadministered with moderate CYP3A4 inhibitors.

• 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.

• mavacamten

  diltiazem will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

• 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.

• 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.

• nirmatrelvir

  nirmatrelvir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May consider temporary diltiazem dose reduction.

• nirmatrelvir/ritonavir

  nirmatrelvir/ritonavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing diltiazem dose by 50% during coadministration and for 3 more days after the last nirmatrelvir/ritonavir dose.

• 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 (DSC)

  ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) 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.

• ruxolitinib topical

  diltiazem will increase the level or effect of ruxolitinib topical 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.

• sparsentan

  diltiazem will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors.

• 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. Modify Therapy/Monitor Closely. Vardenafil dose may need to be reduced if coadministered with moderate or strong CYP3A4 inhibitors

• 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 (a CYP3A4 substrate) to 80 mg PO BID to when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib.

Minor (33)

• acetazolamide

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

• agrimony

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

• anastrozole

  anastrozole will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

• cyclophosphamide

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

• 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.

• abametapir

  Serious - Use Alternative (1)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.

• acalabrutinib

  Monitor Closely (1)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

  Monitor Closely (1)acebutolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• acetazolamide

  Minor (1)acetazolamide will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• agrimony

  Minor (1)agrimony increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

• aldesleukin

  Monitor Closely (1)aldesleukin increases effects of diltiazem by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• alfentanil

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)amlodipine and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.Serious - Use Alternative (1)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).

• amobarbital

  Monitor Closely (1)amobarbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• anastrozole

  Minor (1)anastrozole will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• apalutamide

  Serious - Use Alternative (1)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.

• apixaban

  Monitor Closely (1)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

  Monitor Closely (1)aprepitant will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)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.

• aripiprazole

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (1)asenapine and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• aspirin

  Minor (1)diltiazem increases effects of aspirin by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

• aspirin rectal

  Minor (1)diltiazem increases effects of aspirin rectal by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

• aspirin/citric acid/sodium bicarbonate

  Minor (1)diltiazem increases effects of aspirin/citric acid/sodium bicarbonate by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

• atazanavir

  Monitor Closely (1)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

  Monitor Closely (1)atenolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)diltiazem, atenolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• atogepant

  Monitor Closely (1)diltiazem will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• atorvastatin

  Monitor Closely (1)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.

• atracurium

  Minor (1)diltiazem increases effects of atracurium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

• avanafil

  Monitor Closely (1)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.

• avapritinib

  Serious - Use Alternative (1)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.

• axitinib

  Monitor Closely (1)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

  Monitor Closely (1)diltiazem will increase the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• belzutifan

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)betaxolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)diltiazem, betaxolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• bisoprolol

  Monitor Closely (1)bisoprolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)diltiazem, bisoprolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• bortezomib

  Monitor Closely (1)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

  Monitor Closely (2)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.

• bosutinib

  Serious - Use Alternative (1)diltiazem increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• bretylium

  Monitor Closely (1)diltiazem, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

• brexpiprazole

  Monitor Closely (1)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.

• brimonidine

  Minor (1)brimonidine increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

• budesonide

  Serious - Use Alternative (1)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.

• buprenorphine subdermal implant

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)butabarbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• butalbital

  Monitor Closely (1)butalbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cabazitaxel

  Monitor Closely (1)diltiazem will increase the level or effect of cabazitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cabozantinib

  Monitor Closely (1)diltiazem will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• calcium acetate

  Monitor Closely (1)calcium acetate decreases effects of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor.

• calcium carbonate

  Monitor Closely (1)calcium carbonate decreases effects of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor.

• calcium chloride

  Monitor Closely (1)calcium chloride decreases effects of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor.

• calcium citrate

  Monitor Closely (1)calcium citrate decreases effects of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor.

• calcium gluconate

  Monitor Closely (1)calcium gluconate decreases effects of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor.

• cannabidiol

  Monitor Closely (1)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

  Monitor Closely (1)carbamazepine will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• carvedilol

  Monitor Closely (1)carvedilol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• celiprolol

  Monitor Closely (1)celiprolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• cenobamate

  Monitor Closely (1)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.

• ceritinib

  Serious - Use Alternative (1)ceritinib will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• choline magnesium trisalicylate

  Minor (1)diltiazem increases effects of choline magnesium trisalicylate by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

• cilostazol

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (1)diltiazem will increase the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cisatracurium

  Minor (1)diltiazem increases effects of cisatracurium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

• clarithromycin

  Monitor Closely (1)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

  Monitor Closely (1)clevidipine and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• clonidine

  Serious - Use Alternative (1)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.

• clopidogrel

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)cobicistat will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cobimetinib

  Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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.

• conivaptan

  Monitor Closely (1)conivaptan will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conjugated estrogens

  Monitor Closely (1)diltiazem will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conjugated estrogens, vaginal

  Monitor Closely (1)diltiazem will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• copanlisib

  Serious - Use Alternative (1)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.

• cortisone

  Monitor Closely (1)diltiazem will increase the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• crizotinib

  Monitor Closely (2)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. .

• cyclophosphamide

  Minor (1)cyclophosphamide will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Monitor Closely (1)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

  Monitor Closely (1)dabrafenib will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• dantrolene

  Contraindicated (1)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.

• daridorexant

  Monitor Closely (1)diltiazem will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Daridorexant dose should not exceed 25 mg per night when coadministered with moderate CYP3A4 inhibitors.

• darifenacin

  Monitor Closely (1)diltiazem will increase the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• darunavir

  Monitor Closely (2)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

  Monitor Closely (1)diltiazem will increase the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• deferasirox

  Monitor Closely (1)deferasirox will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• deflazacort

  Monitor Closely (1)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.

• dexamethasone

  Monitor Closely (1)diltiazem will increase the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• diazepam

  Monitor Closely (1)diltiazem will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• diazepam intranasal

  Monitor Closely (1)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.

• dihydroergotamine

  Serious - Use Alternative (1)diltiazem will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dihydroergotamine intranasal

  Serious - Use Alternative (1)diltiazem will increase the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• disopyramide

  Monitor Closely (1)diltiazem will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• docetaxel

  Monitor Closely (1)diltiazem will increase the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• donepezil

  Monitor Closely (1)diltiazem will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• doxazosin

  Monitor Closely (1)doxazosin and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• doxorubicin

  Monitor Closely (1)diltiazem will increase the level or effect of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• doxorubicin liposomal

  Monitor Closely (1)diltiazem will increase the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dronedarone

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• dutasteride

  Minor (1)diltiazem will increase the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• duvelisib

  Monitor Closely (1)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

  Monitor Closely (1)efavirenz will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• elacestrant

  Serious - Use Alternative (1)diltiazem will increase the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• elagolix

  Monitor Closely (1)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.

• eletriptan

  Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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 .

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (1)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

  Monitor Closely (1)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.Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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

  Serious - Use Alternative (1)enzalutamide will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• eplerenone

  Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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.

• ergotamine

  Monitor Closely (1)diltiazem will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erlotinib

  Monitor Closely (1)diltiazem will increase the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin base

  Serious - Use Alternative (2)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

  Serious - Use Alternative (2)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

  Serious - Use Alternative (2)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

  Serious - Use Alternative (2)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.

• eslicarbazepine acetate

  Monitor Closely (1)eslicarbazepine acetate will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• esmolol

  Monitor Closely (1)esmolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)diltiazem, esmolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• estradiol

  Monitor Closely (1)diltiazem will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estradiol vaginal

  Minor (1)diltiazem will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• estrogens conjugated synthetic

  Monitor Closely (1)diltiazem will increase the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estrogens esterified

  Monitor Closely (1)diltiazem will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estropipate

  Monitor Closely (1)diltiazem will increase the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• etravirine

  Monitor Closely (2)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)diltiazem will increase the level or effect of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fexinidazole

  Serious - Use Alternative (1)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.

• finerenone

  Monitor Closely (1)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

  Monitor Closely (1)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.

• flibanserin

  Contraindicated (1)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.

• fluconazole

  Monitor Closely (1)fluconazole will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fludrocortisone

  Monitor Closely (1)diltiazem will increase the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluvoxamine

  Monitor Closely (1)fluvoxamine will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fo-ti

  Minor (1)fo-ti increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

• forskolin

  Minor (1)forskolin increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

• fosamprenavir

  Monitor Closely (2)fosamprenavir 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 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.

• fosaprepitant

  Monitor Closely (1)fosaprepitant will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)diltiazem will increase the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Moderate CYP3A4 inhibitors may increase serum concentrations and/or toxicities of aprepitant.

• fosphenytoin

  Monitor Closely (2)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

  Monitor Closely (1)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.

• galantamine

  Minor (1)diltiazem will increase the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• glecaprevir/pibrentasvir

  Monitor Closely (1)glecaprevir/pibrentasvir will increase the level or effect of diltiazem by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• grapefruit

  Monitor Closely (1)grapefruit will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• griseofulvin

  Monitor Closely (1)griseofulvin will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• guanfacine

  Monitor Closely (1)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

  Monitor Closely (1)hawthorn increases effects of diltiazem by pharmacodynamic synergism. Use Caution/Monitor.

• hydrocortisone

  Monitor Closely (1)diltiazem will increase the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ibrutinib

  Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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

• ifosfamide

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)diltiazem will increase the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• imipramine

  Monitor Closely (1)diltiazem will increase the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• indinavir

  Monitor Closely (1)diltiazem will increase the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)indinavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• infigratinib

  Serious - Use Alternative (1)diltiazem will increase the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• irinotecan

  Monitor Closely (1)diltiazem will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• irinotecan liposomal

  Monitor Closely (1)diltiazem will increase the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isavuconazonium sulfate

  Monitor Closely (1)diltiazem will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isradipine

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (2)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.

• ivabradine

  Serious - Use Alternative (2)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.

• ivacaftor

  Monitor Closely (1)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.

• ivosidenib

  Serious - Use Alternative (2)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.

• ixabepilone

  Monitor Closely (1)diltiazem will increase the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ketoconazole

  Monitor Closely (2)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

  Monitor Closely (1)labetalol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• lapatinib

  Monitor Closely (1)diltiazem will increase the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• larotrectinib

  Monitor Closely (1)diltiazem will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lasmiditan

  Monitor Closely (1)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.Serious - Use Alternative (1)lasmiditan increases levels of diltiazem by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• lefamulin

  Monitor Closely (1)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.

• lemborexant

  Serious - Use Alternative (1)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.

• lenacapavir

  Monitor Closely (1)lenacapavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

• letermovir

  Monitor Closely (1)diltiazem will increase the level or effect of letermovir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levamlodipine

  Monitor Closely (1)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.

• levobunolol

  Serious - Use Alternative (1)diltiazem, levobunolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• levodopa

  Monitor Closely (1)levodopa increases effects of diltiazem by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

• levoketoconazole

  Monitor Closely (2)levoketoconazole will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  diltiazem will increase the level or effect of levoketoconazole 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.

• lily of the valley

  Minor (1)diltiazem, lily of the valley. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown.

• lithium

  Monitor Closely (1)diltiazem increases toxicity of lithium by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of neurotoxicity.

• lofexidine

  Serious - Use Alternative (1)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.

• lomitapide

  Contraindicated (1)diltiazem increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increases lomitapide levels several folds.

• lonafarnib

  Contraindicated (1)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.

• lopinavir

  Monitor Closely (1)diltiazem will increase the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)lopinavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lorlatinib

  Serious - Use Alternative (1)lorlatinib will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lovastatin

  Serious - Use Alternative (1)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

• lumateperone

  Monitor Closely (1)diltiazem will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 21 mg/day if coadministered with moderate CYP3A4 inhibitors.

• lumefantrine

  Monitor Closely (2)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

  Monitor Closely (1)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.

• lurbinectedin

  Serious - Use Alternative (1)diltiazem will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• magnesium supplement

  Monitor Closely (1)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.

• maitake

  Minor (1)maitake increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

• maraviroc

  Monitor Closely (1)diltiazem will increase the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• marijuana

  Monitor Closely (1)diltiazem will increase the level or effect of marijuana by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mavacamten

  Monitor Closely (1)diltiazem will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose. Serious - Use Alternative (1)diltiazem, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

• mefloquine

  Monitor Closely (2)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

  Monitor Closely (1)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.Minor (1)diltiazem will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• methadone

  Monitor Closely (1)diltiazem will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• methamphetamine

  Monitor Closely (1)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

  Monitor Closely (1)methylphenidate will decrease the level or effect of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor. Methylphenidate may diminish antihypertensive effects. Monitor BP.

• methylprednisolone

  Monitor Closely (1)diltiazem will increase the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• metipranolol ophthalmic

  Minor (1)metipranolol ophthalmic increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

• metoprolol

  Monitor Closely (1)metoprolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)diltiazem, metoprolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• midazolam

  Monitor Closely (1)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).

• midazolam intranasal

  Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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.

• mifepristone

  Monitor Closely (2)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

  Monitor Closely (1)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.

• mobocertinib

  Serious - Use Alternative (1)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.

• moxisylyte

  Monitor Closely (1)moxisylyte and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• nadolol

  Monitor Closely (1)nadolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)diltiazem, nadolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• nafcillin

  Monitor Closely (1)nafcillin will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• naldemedine

  Monitor Closely (1)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.

• naloxegol

  Serious - Use Alternative (1)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

  Monitor Closely (1)nebivolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)diltiazem, nebivolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• nefazodone

  Monitor Closely (1)nefazodone will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• nelfinavir

  Monitor Closely (2)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.

• neratinib

  Serious - Use Alternative (1)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.

• nevirapine

  Monitor Closely (1)nevirapine will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nicardipine

  Monitor Closely (2)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

  Monitor Closely (3)nifedipine 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 nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Exercise caution when coadministering diltiazem and nifedipine and consider reducing nifedipine dose.
  
  diltiazem and nifedipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• nilotinib

  Monitor Closely (2)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

  Monitor Closely (1)diltiazem will increase the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nirmatrelvir

  Monitor Closely (1)nirmatrelvir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May consider temporary diltiazem dose reduction.

• nirmatrelvir/ritonavir

  Monitor Closely (1)nirmatrelvir/ritonavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing diltiazem dose by 50% during coadministration and for 3 more days after the last nirmatrelvir/ritonavir dose.

• nisoldipine

  Monitor Closely (2)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

  Monitor Closely (1)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

  Monitor Closely (1)diltiazem increases effects of nitroprusside sodium by pharmacodynamic synergism. Use Caution/Monitor.

• octacosanol

  Minor (1)octacosanol increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

• olaparib

  Serious - Use Alternative (1)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.

• oliceridine

  Monitor Closely (1)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.

• omaveloxolone

  Serious - Use Alternative (1)diltiazem will increase the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, reduce omaveloxolone dose to 100 mg/day. Closely monitor for adverse effects. If adverse effects emerge, further reduce to 50 mg/day.

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  Monitor Closely (1)ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• ondansetron

  Minor (1)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.

• oxcarbazepine

  Monitor Closely (1)oxcarbazepine will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• oxybutynin

  Monitor Closely (1)diltiazem will increase the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• oxycodone

  Monitor Closely (1)diltiazem will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• paclitaxel

  Monitor Closely (1)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

  Monitor Closely (1)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.

• pacritinib

  Serious - Use Alternative (1)diltiazem will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• palbociclib

  Monitor Closely (1)diltiazem will increase the level or effect of palbociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• pancuronium

  Minor (1)diltiazem increases effects of pancuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

• pazopanib

  Monitor Closely (1)diltiazem will increase the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• pemigatinib

  Serious - Use Alternative (1)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.

• penbutolol

  Monitor Closely (1)penbutolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• pentobarbital

  Monitor Closely (1)pentobarbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• pexidartinib

  Serious - Use Alternative (1)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.

• phendimetrazine

  Monitor Closely (1)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

  Monitor Closely (1)phenobarbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• phenoxybenzamine

  Monitor Closely (1)phenoxybenzamine and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• phentermine

  Monitor Closely (1)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

  Monitor Closely (1)phentolamine and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• phenytoin

  Monitor Closely (1)phenytoin will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• pimozide

  Contraindicated (1)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).

• pindolol

  Monitor Closely (1)pindolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• pioglitazone

  Monitor Closely (1)diltiazem will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ponesimod

  Serious - Use Alternative (1)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).

• posaconazole

  Monitor Closely (1)posaconazole will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• prazosin

  Monitor Closely (1)prazosin and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• prednisolone

  Monitor Closely (1)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

  Monitor Closely (1)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.

• primidone

  Serious - Use Alternative (1)primidone will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• propafenone

  Serious - Use Alternative (1)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

  Monitor Closely (1)propranolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)diltiazem, propranolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• quetiapine

  Monitor Closely (1)diltiazem will increase the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quinidine

  Monitor Closely (2)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

  Monitor Closely (1)diltiazem will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quinupristin/dalfopristin

  Monitor Closely (1)quinupristin/dalfopristin will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ranolazine

  Monitor Closely (1)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.

• rapacuronium

  Minor (1)diltiazem increases effects of rapacuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

• reishi

  Minor (1)reishi increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

• repaglinide

  Monitor Closely (1)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

  Monitor Closely (1)ribociclib will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifabutin

  Monitor Closely (1)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.

• rifampin

  Serious - Use Alternative (1)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.

• rifapentine

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (1)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.

• rocuronium

  Minor (1)diltiazem increases effects of rocuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

• rucaparib

  Monitor Closely (1)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

  Monitor Closely (1)rufinamide will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ruxolitinib

  Monitor Closely (1)diltiazem will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ruxolitinib topical

  Monitor Closely (1)diltiazem will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• saquinavir

  Monitor Closely (2)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)secobarbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• selumetinib

  Serious - Use Alternative (1)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.

• shepherd's purse

  Monitor Closely (1)shepherd's purse, diltiazem. Other (see comment). Use Caution/Monitor. Comment: Theoretically, shepherd's purse may interfere with BP control.

• sildenafil

  Monitor Closely (1)diltiazem will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• silodosin

  Monitor Closely (2)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.

• simvastatin

  Serious - Use Alternative (1)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

  Serious - Use Alternative (2)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.

• sirolimus

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)diltiazem will increase the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• sonidegib

  Serious - Use Alternative (1)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

  Monitor Closely (1)sotalol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)diltiazem, sotalol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• sotorasib

  Serious - Use Alternative (1)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.

• sparsentan

  Monitor Closely (1)diltiazem will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors.

• St John's Wort

  Serious - Use Alternative (1)St John's Wort will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• stiripentol

  Monitor Closely (1)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.

• succinylcholine

  Minor (1)diltiazem increases effects of succinylcholine by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

• sufentanil

  Monitor Closely (1)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

  Monitor Closely (1)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.

• sulfamethoxazole

  Minor (1)sulfamethoxazole will increase the level or effect of diltiazem by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sunitinib

  Monitor Closely (1)diltiazem will increase the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• suvorexant

  Monitor Closely (1)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

  Monitor Closely (1)diltiazem will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tadalafil

  Monitor Closely (1)diltiazem will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Risk of hypotension.

• tamoxifen

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)tazemetostat will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)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).

• tecovirimat

  Monitor Closely (1)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

  Monitor Closely (2)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.

• tepotinib

  Serious - Use Alternative (1)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.

• terazosin

  Monitor Closely (1)terazosin and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• tezacaftor

  Monitor Closely (1)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

  Monitor Closely (1)diltiazem will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• timolol

  Monitor Closely (1)timolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)diltiazem, timolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• tipranavir

  Monitor Closely (2)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.

• tizanidine

  Minor (1)tizanidine increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

• tofacitinib

  Monitor Closely (1)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

  Monitor Closely (1)diltiazem will increase the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tolvaptan

  Serious - Use Alternative (1)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.

• topiramate

  Monitor Closely (1)topiramate will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• trabectedin

  Monitor Closely (1)diltiazem will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• trazodone

  Monitor Closely (1)diltiazem will increase the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• treprostinil

  Minor (1)treprostinil increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

• triamcinolone acetonide injectable suspension

  Monitor Closely (1)diltiazem will increase the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• triazolam

  Monitor Closely (1)diltiazem will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• trimagnesium citrate anhydrous

  Monitor Closely (1)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

  Monitor Closely (1)diltiazem will increase the level or effect of trimipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tucatinib

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• vardenafil

  Monitor Closely (1)diltiazem will increase the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Vardenafil dose may need to be reduced if coadministered with moderate or strong CYP3A4 inhibitors

• vecuronium

  Minor (1)diltiazem increases effects of vecuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

• vemurafenib

  Monitor Closely (1)vemurafenib increases levels of diltiazem by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• venetoclax

  Serious - Use Alternative (1)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.

• verapamil

  Monitor Closely (3)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.

• verteporfin

  Minor (1)diltiazem increases levels of verteporfin by pharmacodynamic synergism. Minor/Significance Unknown.

• vilazodone

  Serious - Use Alternative (1)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.

• vinblastine

  Monitor Closely (1)diltiazem will increase the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vincristine

  Monitor Closely (1)diltiazem will increase the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vincristine liposomal

  Monitor Closely (1)diltiazem will increase the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vinorelbine

  Monitor Closely (1)diltiazem will increase the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• voclosporin

  Monitor Closely (1)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

  Monitor Closely (2)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.

• voxelotor

  Serious - Use Alternative (1)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.

• willow bark

  Minor (1)diltiazem increases effects of willow bark by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

• xipamide

  Monitor Closely (1)xipamide increases effects of diltiazem by pharmacodynamic synergism. Use Caution/Monitor.

• zanubrutinib

  Monitor Closely (1)diltiazem will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib (a CYP3A4 substrate) to 80 mg PO BID to when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib.