Version November 2024
Dosage guidance:
Safety: Avoid in patients taking a beta-blocker or who have heart failure with reduced ejection fraction, sinus node dysfunction, or second- or third-degree atrioventricular block unless a functioning pacemaker has been placed.
Angina:
Chronic stable angina (alternative agent): Note: A beta-blocker is the preferred initial therapy; if there are ongoing symptoms on beta-blocker therapy, a calcium channel blocker (typically a dihydropyridine [eg, amlodipine]) may be added with close monitoring of heart rate; diltiazem may be used as an alternative therapy if there are contraindications or unacceptable adverse effects with beta-blockade (Ref).
Immediate release: Oral: Initial: 30 mg 4 times daily; increase as needed at 1- to 2-day intervals to effective antianginal dose; usual effective dose: 240 to 360 mg/day in 3 to 4 divided doses (Ref).
12-hour (twice-daily) formulations (off label): Oral: Initial: 60 mg twice daily; increase as needed at 7- to 14-day intervals to effective antianginal dose; usual effective dose: 240 to 360 mg/day in 2 divided doses (Ref).
24-hour (once-daily) formulations: Oral: Initial 120 to 180 mg once daily; increase as needed at 7- to 14-day intervals to effective antianginal dose; usual effective dose: 240 to 360 mg/day (Ref).
Vasospastic angina: Note: May use alone or in combination with nitrates (Ref).
Immediate release: Oral: Initial: 30 mg 4 times daily; increase as needed at 1- to 2-day intervals to effective antianginal dose; usual effective dose: 240 to 360 mg/day in 3 to 4 divided doses.
12-hour (twice-daily) formulations (off label): Oral: Initial: 60 mg twice daily; increase as needed at 7- to 14-day intervals to effective antianginal dose; usual effective dose: 240 to 360 mg/day in 2 divided doses (Ref).
24-hour (once-daily) formulations: Oral: Initial: 120 to 180 mg once daily; increase as needed at 7- to 14-day intervals to effective antianginal dose; usual effective dose: 240 to 360 mg/day (Ref).
Chest pain associated with cocaine ingestion, with or without evidence of acute coronary syndrome (off-label use) : Note: Adjunct or alternative to nitroglycerin.
IV: Bolus: Initial: 0.25 mg/kg (actual body weight) over 2 minutes (average dose: 20 mg); may repeat after 15 minutes if needed (Ref).
Atrial fibrillation/flutter, rate control: Note: For rate control in hemodynamically stable patients. Do not use in patients with preexcitation associated with an accessory pathway, as this can lead to ventricular arrhythmias (Ref).
Acute ventricular rate control:
IV: Bolus dose: 0.25 mg/kg (actual body weight) over 2 minutes (average dose: 20 mg; if hypotension is a concern, some experts administer a lower bolus of 5 to 15 mg); if rate control is insufficient after 15 minutes, a repeat bolus dose of 0.35 mg/kg over 2 minutes may be given (average dose: 25 mg). Patients who respond after 1 or 2 bolus doses can be started on a continuous infusion (Ref).
IV: Continuous infusion following bolus(es): Initial: 5 to 10 mg/hour; infusion rate may be increased in 5 mg/hour increments according to ventricular response, up to a maximum of 15 mg/hour. Note: When increasing the infusion rate, an additional bolus dose can be used to provide more immediate onset. In general, the use of a continuous infusion >24 hours or >15 mg/hour is not recommended due to potential for drug accumulation (Ref). See conversion section below to switch from IV infusion to oral.
Chronic ventricular rate control (off-label use):
Immediate release: Oral: Initial: 30 mg 4 times daily; increase as needed to achieve ventricular rate control; usual dose: 120 to 480 mg/day in 3 or 4 divided doses (Ref).
Extended release: Oral: Initial: 120 mg once daily or in 2 divided doses depending on formulation; increase as needed to achieve ventricular rate control; usual dose: 120 to 480 mg/day (Ref).
Hypertension (alternative agent): Note : Reserve nondihydropyridine calcium channel blockers for patients with a relevant comorbidity (eg, rate control in atrial fibrillation or flutter) (Ref). For patients who warrant combination therapy (BP >20/10 mm Hg above goal or suboptimal response to initial monotherapy), may use in combination with another appropriate agent (eg, angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, thiazide diuretic) (Ref).
12-hour (twice-daily) formulations: Oral: Initial: 60 to 120 mg twice daily; increase dose as needed after ~7 to 14 days; usual dose: 240 to 360 mg/day in 2 divided doses.
24-hour (once-daily) formulations: Oral: Initial: 120 to 240 mg once daily; increase dose as needed after ~7 to 14 days; usual dose: 120 to 360 mg once daily (Ref).
Nonsustained ventricular tachycardia or ventricular premature beats, symptomatic (alternative agent) (off-label use): Note: A beta-blocker is the preferred initial therapy; if there are ongoing symptoms on beta-blocker therapy, diltiazem may be added with close monitoring of heart rate; diltiazem may be used as an alternative therapy if beta-blockade cannot be tolerated (Ref).
Oral: Initial: 120 to 180 mg once daily or in divided doses depending on the drug formulation; usual effective dose: 240 to 360 mg/day; maximum dose: 480 mg/day (Ref).
Pulmonary arterial hypertension, group 1 (alternative agent) (off-label use): Note: Only used for group 1 pulmonary arterial hypertension patients with a positive vasoreactivity test and under the care of a pulmonary hypertension specialist (Ref).
12-hour (twice-daily) formulations: Oral: Initial: 60 mg every 12 hours; titrate gradually, with close hemodynamic monitoring; reported daily dose range: 120 to 720 mg/day in 2 divided doses (Ref).
24-hour (once-daily) formulations: Oral: Initial: 120 mg once daily; titrate gradually, with close hemodynamic monitoring; reported daily dose range: 120 to 720 mg/day (Ref).
Supraventricular tachycardia (eg, atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, focal atrial tachycardia, multifocal atrial tachycardia) (alternative agent): Note: For hemodynamically stable patients if vagal maneuvers and/or adenosine are unsuccessful. Do not use in patients with preexcitation associated with an accessory pathway, as this can lead to ventricular arrhythmias (Ref).
Acute treatment:
IV: Bolus dose: 0.25 mg/kg (actual body weight) over 2 minutes (average dose: 20 mg); if response is insufficient after ≥15 minutes, a repeat bolus dose of 0.35 mg/kg over 2 minutes may be given (average dose: 25 mg). If bolus(es) do not terminate the arrhythmia, consider alternative therapy.
Chronic maintenance (off-label use):
Immediate release: Oral: Initial: 30 mg 4 times daily; increase as needed for heart rate control; usual effective dose: 360 mg/day in divided doses (Ref).
Extended release: Oral: Initial: 120 mg once daily or in 2 divided doses depending on formulation; increase as needed for heart rate control; usual effective dose: 360 mg/day (Ref).
Conversion between dosage forms:
Conversion from immediate-release to extended-release formulations: Patients stabilized on a maintenance regimen between 120 and 360 mg of immediate-release tablets may be switched to an extended-release formulation at the same daily dose administered in 1 or 2 divided doses depending on formulation. In some patients, the dosage of the extended-release formulation may require adjustment following conversion.
Conversion from IV infusion to oral: Immediate release can be started ~1 hour before stopping infusion. Oral daily dose may be estimated from the IV infusion rate by using the equation below. Round oral doses to the nearest appropriate strength and formulation.
Oral dose (mg per day) = [infusion rate (mg/hour) × 3 + 3] × 10
5 mg/hour = 180 mg/day.
10 mg/hour = 300 to 360 mg/day.
15 mg/hour = 480 mg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed: No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Not significantly dialyzed: No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution; extensively metabolized by the liver; half-life is increased in patients with cirrhosis.
Refer to adult dosing. In the management of hypertension, consider lower initial doses (eg, 120 mg once daily using extended-release capsule) and titrate to response (Ref).
(For additional information see "Diltiazem: Pediatric drug information")
Atrial tachyarrhythmias, rate control (bridge to therapy): Very limited data available: Infants ≥6 months, Children, and Adolescents: IV: Initial bolus: 0.25 mg/kg over 5 minutes (maximum dose: 20 mg/dose [average adult dose]) followed by a continuous IV infusion; reported rate range in one study was 0.05 to 0.15 mg/kg/hour. Note: Usual adult infusion rate for arrhythmia is 5 to 15 mg/hour. Dose should be individualized based on patient response. Dosing based on a small study of 10 patients with atrial tachycardia (age range: 6 months to 21 years; most patients were adolescents) who received an initial bolus of 0.25 mg/kg/dose followed by a continuous infusion titrated to effect, reported effective range was 0.05 to 0.15 mg/kg/hour (mean infusion rate: 0.11 mg/kg/hour). Rate control was achieved in 9 of the 10 patients within 10 minutes of dosing. One patient required an additional bolus of 0.25 mg/kg. Median ventricular rate of study group prior to initial bolus was 275 ± 50 beats per minute (BPM) (range: 185 to 500 BPM), which decreased to a median of 166 BPM prior to initiation of continuous infusion and decreased to a median of 123 BPM after 10 minutes of continuous infusion; blood pressure was not significantly affected by diltiazem; qualitative systolic function did not worsen in the seven patients studied (Ref). Note: In adult patients, infusions >24 hours are not recommended; with administration of diltiazem infusion >24 hours, the possibility of decreased diltiazem clearance, prolonged elimination half-life, and increased diltiazem and/or diltiazem metabolite plasma concentrations should be considered. In trial of 10 pediatric patients, the median duration was 45 hours (mean: 54 hours; range: 14 to 126 hours) (Ref).
Hypertension: Limited data available:
Infants and Children: Oral: Immediate-release formulations: Initial: 1.5 to 2 mg/kg/day in 3 to 4 divided doses (Ref); increase gradually, at 1- to 2-day intervals until optimum response is obtained; usual maximum daily dose: 3.5 mg/kg/day (Ref); some experts recommend a higher maximum daily dose of 6 mg/kg/day up to 360 mg/day; whichever is less (Ref). Note: Once patient is established on a total daily dose, may convert to an extended release dosage form at the appropriate interval (once or twice daily) in children able to swallow capsules whole and receiving adequate mg amount (Ref).
Adolescents (Ref): Oral:
Immediate-release formulations: 30 to 120 mg/dose administered 3 to 4 times daily; usual daily dosage range: 180 to 360 mg/day
Extended-release formulations:
Capsule, extended release (once daily dosing; eg, Cardizem CD, Tiazac): 120 to 300 mg once daily
Capsule, extended release (twice daily dosing; eg, Cardizem SR): 120 to 300 mg/day in 2 divided doses
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
Dialysis: Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.
There are no dosage adjustment provided in the manufacturer’s labeling; use with caution; extensively metabolized by the liver; half-life is increased in patients with cirrhosis.
Diltiazem may cause first-degree atrioventricular (AV) block, second-degree atrioventricular block, complete atrioventricular block, or sinus bradycardia (Ref). Although reversal is possible after discontinuation, some patients continue to have symptoms (Ref). In patients whose symptoms resolve after discontinuation, permanent pacemaker (PPM) therapy will likely not be necessary; however, cases with recurrent or unresolved symptoms after discontinuation may warrant PPM placement (Ref).
Mechanism: Related to the pharmacologic action; inhibits L-type calcium channels, leading to prolonged refractoriness and slowing of AV nodal conduction (Ref).
Onset: Varied; may occur at any time during therapy (Ref).
Risk factors:
• Concurrent use of other AV nodal-blocking agents (eg, beta-blockers) (Ref)
• Older adults (Ref)
• Chronic kidney disease (Ref)
• Underlying AV node dysfunction (Ref)
Diltiazem may cause cutaneous hypersensitivity reactions. Maculopapular rash is the most common cutaneous adverse reaction reported (Ref). Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis (AGEP) have occurred rarely (Ref). In general, improvement is observed 1 to 2 weeks after discontinuation (Ref). Other cutaneous reactions associated with diltiazem include subacute cutaneous lupus erythematosus, erythema multiforme, erythroderma, exfoliative dermatitis, and hypersensitivity angiitis (Ref). In comparison to other calcium channel blockers, diltiazem has been associated with more reports of cutaneous reactions (Ref).
Skin hyperpigmentation, often in a photodistributed pattern, has also been associated with diltiazem; may present as reticulated, brown, slate-gray, or gray-blue macules or patches most commonly on the face, neck, forearms, and chest (Ref). Gradual improvement is observed after discontinuation (Ref).
Mechanism: Delayed hypersensitivity reactions (including SCARs): Non–dose-related; immunologic. Type IV immune-mediated (T-cell mediated) hypersensitivity reactions (Ref). Skin hyperpigmentation: Not clearly established (Ref).
Onset: Varied; maculopapular rashes usually occur within 10 days after initiation (Ref). SCARs usually occur between 1 to 8 weeks of treatment (Ref); although, some cases of SJS/TEN may have a more rapid onset (Ref). AGEP usually occurs 1 to 2 weeks after initiation (Ref). Reports of skin hyperpigmentation range from 3 weeks to 12.5 years (Ref).
Risk factors:
• Prior hypersensitivity reaction to diltiazem. Note: Cross-reactivity between diltiazem and other calcium channel blockers is not well defined. There are limited case reports of cross-reactivity (Ref), but these are inconsistent and may not be distinct reactions (Ref).
• Skin hyperpigmentation:
- Extended-release formulations (Ref)
- Patients with Fitzpatrick phototype V and VI skin (Ref)
- Females (Ref)
- Older adults (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidences represent ranges for various dosage forms. Patients with impaired ventricular function and/or conduction abnormalities may have higher incidence of adverse reactions.
>10%: Cardiovascular: Peripheral edema (5% to 15%; dose-related)
1% to 10%:
Cardiovascular: Bradycardia (3% to 4%), bundle branch block (<2%), cardiac arrhythmia (1%), complete atrioventricular block (<2%), ECG abnormality (<2%), edema (2% to 3%), extrasystoles (2%), first-degree atrioventricular block (3% to 4%), heart failure (<2%), hypotension (3% to 4%), lower extremity edema (5% to 8%), palpitations (1% to 2%), second-degree atrioventricular block (<2%), syncope (<2%), vasodilation (2% to 3%)
Dermatologic: Pruritus (<2%), skin photosensitivity (<2%) (Ramirez 2007), skin rash (1% to 2%) (Tuchinda 2014) (table 1)
|
Drug (Diltiazem) |
Placebo |
Dose |
Number of Patients (Diltiazem) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
2% |
0% |
540 mg |
49 |
50 |
|
1% |
0% |
Up to 360 mg |
158 |
50 |
Endocrine & metabolic: Albuminuria (<2%), gynecomastia (<2%), hyperglycemia (<2%), hyperuricemia (<2%), increased lactate dehydrogenase (<2%), increased thirst (<2%), weight gain (<2%)
Gastrointestinal: Abdominal swelling (2%), anorexia (<2%), constipation (<2%), diarrhea (1% to 2%), dysgeusia (<2%), dyspepsia (1% to 6%), nausea (2%), vomiting (<2%), xerostomia (<2%)
Genitourinary: Crystalluria (<2%), erectile dysfunction (2%), nocturia (<2%), polyuria (<2%), sexual difficulty (<2%)
Hematologic & oncologic: Petechia (<2%)
Hepatic: Increased serum alanine aminotransferase (<2%), increased serum alkaline phosphatase (<2%), increased serum aspartate transaminase (<2%)
Hypersensitivity: Hypersensitivity reaction (<2%)
Infection: Infection (1% to 6%)
Local: Burning sensation at injection site (≤4%), injection-site pruritus (≤4%)
Nervous system: Abnormal dreams (<2%), abnormal gait (<2%), amnesia (<2%), asthenia (1% to 4%), depression (<2%), dizziness (2% to 10%), drowsiness (<2%), fatigue (5%), hallucination (<2%), headache (2% to 8%), insomnia (<2%), nervousness (2%), pain (6%), paresthesia (<2%), personality changes (<2%), tremor (<2%)
Neuromuscular & skeletal: Gout (1% to 2%), increased creatine phosphokinase in blood specimen (<2%), muscle cramps (<2%), myalgia (2%), neck stiffness (<2%), osteoarthritis (<2%)
Ophthalmic: Amblyopia (<2%), conjunctivitis (2%), eye irritation (<2%)
Otic: Tinnitus (<2%)
Respiratory: Bronchitis (1% to 4%), cough (1% to 2%), dyspnea (1% to 6%), epistaxis (<2%), flu-like symptoms (2%), paranasal sinus congestion (1% to 2%), pharyngitis (6%), rhinitis (<2%)
<1%:
Cardiovascular: Atrial flutter, sinus node dysfunction, ventricular fibrillation, ventricular tachycardia
Dermatologic: Urticaria
Frequency not defined: Hepatic: Hepatic injury (Deng 2013; Shallcross 1987), increased serum bilirubin
Postmarketing:
Cardiovascular: Asystole (Moser 1996; Subahi 2018)
Dermatologic: Acute generalized exanthematous pustulosis (Gesierich 2006; Knowles 1998; Sáenz de Santa María García 2016; Vicente-Calleja 1997), alopecia, cutaneous lupus erythematosus (Crowson 1995; Srivastava 2003), erythema multiforme (Stern 1989; Wittal 1992), exfoliative dermatitis (Odeh 1997; Sousa-Basto 1993), maculopapular rash (Cholez 2003; Gonzalo Garijo 2005), psoriasis (Song 2021), skin hyperpigmentation (Siegel 2020), Stevens-Johnson syndrome (Sanders 1993; Taylor 1990), toxic epidermal necrolysis
Gastrointestinal: Gingival hyperplasia (Bowman 1988; Steele 1994)
Hematologic & oncologic: Hemolytic anemia, leukopenia, prolonged bleeding time, purpuric disease (Inui 2001), thrombocytopenia (Michalets 1997)
Hypersensitivity: Angioedema, hypersensitivity angiitis (Sheehan-Dare 1988)
Nervous system: Extrapyramidal reaction
Neuromuscular & skeletal: Myopathy (Ahmad 1993)
Ophthalmic: Periorbital edema (Friedland 1993), retinopathy
Oral: Hypersensitivity to diltiazem or any component of the formulation; sick sinus syndrome (except in patients with a functioning artificial pacemaker); second- or third-degree AV block (except in patients with a functioning artificial pacemaker); hypotension (systolic <90 mm Hg); acute MI and pulmonary congestion
Intravenous (IV): Hypersensitivity to diltiazem or any component of the formulation; sick sinus syndrome (except in patients with a functioning artificial pacemaker); second- or third-degree AV block (except in patients with a functioning artificial pacemaker); severe hypotension; cardiogenic shock; administration concomitantly or within a few hours of the administration of IV beta-blockers; atrial fibrillation or flutter associated with accessory bypass tract (eg, Wolff-Parkinson-White syndrome, short PR syndrome); ventricular tachycardia (with wide-complex tachycardia [QRS ≥0.12 seconds], must determine whether origin is supraventricular or ventricular)
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Pregnancy; use in women of childbearing potential; breastfeeding; concurrent use with IV dantrolene, ivabradine, or lomitapide; severe bradycardia (<40 beats per minute).
Concerns related to adverse effects:
• Hepatic effects: Mild elevations of transaminases with and without concomitant elevation in alkaline phosphatase and bilirubin have been observed and frequently resolve spontaneously. Significant elevations in hepatic transaminases (eg, alkaline phosphatase, LDH, AST, ALT) and signs of acute hepatic injury have also been observed 1 to 8 weeks after therapy initiation and have been reversible upon discontinuation.
• Hypotension/syncope: Symptomatic hypotension with or without syncope can rarely occur; blood pressure must be lowered at a rate appropriate for the patient's clinical condition.
Disease-related concerns:
• Accessory bypass tract (eg, Wolff-Parkinson-White [WPW] syndrome): During an episode of atrial fibrillation or flutter in patients with an accessory bypass tract or preexcitation syndrome, use has been associated with increased anterograde conduction down the accessory pathway leading to ventricular fibrillation; avoid use in such patients (ACLS [Neumar 2010]; ACC/AHA [Joglar 2024]).
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Left ventricular dysfunction: Use with caution in left ventricular dysfunction; due to negative inotropic effects, may exacerbate condition. Avoid use in patients with heart failure due to lack of benefit and/or worse outcomes with calcium channel blockers in general (AHA/ACC/HFSA [Heidenreich 2022]).
• Renal impairment: Use with caution in patients with renal impairment.
Other warnings/precautions:
• Appropriate use: IV: Unless otherwise contraindicated, appropriate vagal maneuvers should be attempted prior to administration of IV diltiazem. Use with caution in patients hemodynamically compromised; continuously monitor ECG and blood pressure during administration (especially during continuous IV infusion). Initial use should be, if possible, in a setting where monitoring and resuscitation equipment, including DC cardioversion/defibrillation, are present.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule Extended Release 12 Hour, Oral, as hydrochloride:
Generic: 60 mg, 90 mg, 120 mg
Capsule Extended Release 24 Hour, Oral, as hydrochloride:
Cardizem CD: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg [contains fd&c blue #1 (brilliant blue)]
Cartia XT: 120 mg, 180 mg, 240 mg
Cartia XT: 300 mg [contains fd&c blue #1 (brill blue) aluminum lake, fd&c blue #1 (brilliant blue), fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40 (allura red ac dye), fd&c red #40(allura red ac)aluminum lake, quinoline (d&c yellow #10) aluminum lake, quinoline yellow (d&c yellow #10)]
Dilt-XR: 120 mg, 180 mg, 240 mg [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye), quinoline yellow (d&c yellow #10)]
Taztia XT: 120 mg [contains corn starch, fd&c blue #1 (brill blue) aluminum lake, fd&c blue #1 (brilliant blue), fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40 (allura red ac dye), fd&c red #40(allura red ac)aluminum lake, quinoline (d&c yellow #10) aluminum lake]
Taztia XT: 180 mg [contains corn starch, fd&c blue #1 (brill blue) aluminum lake, fd&c blue #1 (brilliant blue), fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40(allura red ac)aluminum lake, fd&c yellow #6 (sunset yellow), quinoline (d&c yellow #10) aluminum lake, quinoline yellow (d&c yellow #10)]
Taztia XT: 240 mg [contains corn starch, fd&c blue #1 (brill blue) aluminum lake, fd&c blue #1 (brilliant blue), fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40 (allura red ac dye), fd&c red #40(allura red ac)aluminum lake, quinoline (d&c yellow #10) aluminum lake]
Taztia XT: 300 mg [contains corn starch, fd&c blue #1 (brill blue) aluminum lake, fd&c blue #1 (brilliant blue), fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40 (allura red ac dye), fd&c red #40(allura red ac)aluminum lake, fd&c yellow #6 (sunset yellow), quinoline (d&c yellow #10) aluminum lake, quinoline yellow (d&c yellow #10)]
Taztia XT: 360 mg [contains corn starch, fd&c blue #1 (brill blue) aluminum lake, fd&c blue #1 (brilliant blue), fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40(allura red ac)aluminum lake, quinoline (d&c yellow #10) aluminum lake]
Tiadylt ER: 120 mg [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]
Tiadylt ER: 180 mg [contains fd&c blue #1 (brilliant blue)]
Tiadylt ER: 240 mg, 300 mg [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]
Tiadylt ER: 360 mg [contains fd&c blue #1 (brilliant blue)]
Tiadylt ER: 420 mg
Tiazac: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]
Generic: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg
Solution, Intravenous, as hydrochloride:
Generic: 25 mg/5 mL (5 mL); 50 mg/10 mL (10 mL); 125 mg/25 mL (25 mL)
Solution, Intravenous, as hydrochloride [preservative free]:
Generic: 25 mg/5 mL (5 mL [DSC]); 50 mg/10 mL (10 mL [DSC]); 125 mg/25 mL (25 mL [DSC])
Solution Reconstituted, Intravenous, as hydrochloride:
Generic: 100 mg (1 ea)
Tablet, Oral, as hydrochloride:
Cardizem: 30 mg [contains fd&c blue #1 (brill blue) aluminum lake, quinoline (d&c yellow #10) aluminum lake]
Cardizem: 60 mg [scored; contains fd&c blue #1 (brill blue) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, methylparaben, quinoline (d&c yellow #10) aluminum lake]
Cardizem: 120 mg [scored; contains fd&c yellow #6(sunset yellow)alumin lake, methylparaben, quinoline (d&c yellow #10) aluminum lake]
Generic: 30 mg, 60 mg, 90 mg, 120 mg
Tablet Extended Release 24 Hour, Oral, as hydrochloride:
Cardizem LA: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg
Matzim LA: 180 mg, 240 mg, 300 mg, 360 mg, 420 mg
Generic: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg
Yes
Capsule ER 24 Hour Therapy Pack (Cardizem CD Oral)
120 mg (per each): $34.14
180 mg (per each): $43.07
240 mg (per each): $58.39
300 mg (per each): $76.48
360 mg (per each): $111.59
Capsule ER 24 Hour Therapy Pack (Cartia XT Oral)
120 mg (per each): $1.20
180 mg (per each): $1.45
240 mg (per each): $2.05
300 mg (per each): $2.66
Capsule ER 24 Hour Therapy Pack (dilTIAZem HCl ER Beads Oral)
120 mg (per each): $0.75 - $1.04
180 mg (per each): $0.90 - $1.25
240 mg (per each): $1.96
300 mg (per each): $2.54
360 mg (per each): $2.59
420 mg (per each): $1.77 - $2.85
Capsule ER 24 Hour Therapy Pack (dilTIAZem HCl ER Coated Beads Oral)
120 mg (per each): $0.91 - $1.20
180 mg (per each): $1.02 - $1.45
240 mg (per each): $1.40 - $2.05
300 mg (per each): $1.90 - $2.66
360 mg (per each): $9.17 - $10.23
Capsule ER 24 Hour Therapy Pack (dilTIAZem HCl ER Oral)
120 mg (per each): $1.14
180 mg (per each): $1.34
240 mg (per each): $1.43
Capsule ER 24 Hour Therapy Pack (Taztia XT Oral)
120 mg (per each): $1.14
180 mg (per each): $1.38
240 mg (per each): $1.96
300 mg (per each): $2.54
360 mg (per each): $2.59
Capsule ER 24 Hour Therapy Pack (Tiadylt ER Oral)
120 mg (per each): $1.04
180 mg (per each): $1.25
240 mg (per each): $1.78
300 mg (per each): $2.30
360 mg (per each): $2.34
420 mg (per each): $2.46
Capsule ER 24 Hour Therapy Pack (Tiazac Oral)
120 mg (per each): $2.36
180 mg (per each): $2.85
240 mg (per each): $4.05
300 mg (per each): $5.24
360 mg (per each): $5.34
420 mg (per each): $5.60
Capsule, 12-hour (dilTIAZem HCl ER Oral)
60 mg (per each): $3.17 - $3.97
90 mg (per each): $3.62 - $4.67
120 mg (per each): $4.73 - $6.52
Solution (dilTIAZem HCl Intravenous)
25 mg/5 mL (per mL): $0.52 - $0.91
50 mg/10 mL (per mL): $0.48 - $0.83
125 mg/25 mL (per mL): $0.28 - $0.53
Solution (reconstituted) (dilTIAZem HCl Intravenous)
100 mg (per each): $13.69
Tablet, 24-hour (Cardizem LA Oral)
120 mg (per each): $4.56
180 mg (per each): $4.82
240 mg (per each): $5.41
300 mg (per each): $7.03
360 mg (per each): $7.56
420 mg (per each): $8.19
Tablet, 24-hour (dilTIAZem HCl ER Oral)
120 mg (per each): $2.82 - $4.10
180 mg (per each): $2.86 - $2.98
240 mg (per each): $3.20 - $3.34
300 mg (per each): $4.16 - $4.34
360 mg (per each): $4.48 - $4.67
420 mg (per each): $4.85 - $5.06
Tablet, 24-hour (Matzim LA Oral)
180 mg (per each): $2.98
240 mg (per each): $3.34
300 mg (per each): $4.34
360 mg (per each): $4.67
420 mg (per each): $5.06
Tablets (Cardizem Oral)
30 mg (per each): $7.68
60 mg (per each): $12.05
120 mg (per each): $22.18
Tablets (dilTIAZem HCl Oral)
30 mg (per each): $1.00
60 mg (per each): $1.57
90 mg (per each): $2.14
120 mg (per each): $2.88
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule Extended Release 24 Hour, Oral, as hydrochloride:
Cardizem CD: 120 mg [DSC], 180 mg [DSC], 240 mg [DSC], 300 mg [DSC]
Tiazac: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]
Generic: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg
Solution, Intravenous:
Generic: 5 mg/mL (5 mL, 10 mL)
Tablet, Oral, as hydrochloride:
Generic: 30 mg, 60 mg
Tablet Extended Release 24 Hour, Oral, as hydrochloride:
Tiazac XC: 120 mg, 360 mg, 180 mg/24 hr, 240 mg/24 hr, 300 mg/24 hr
Generic: 180 mg, 240 mg, 300 mg, 360 mg
Oral:
IR tablet (eg, Cardizem): Administer before meals and at bedtime. Tablets may be swallowed whole, crushed, or chewed; do not split nonscored tablets.
Long-acting dosage forms: Do not open, chew, or crush; swallow whole. Administer at same time of day either morning or evening.
Cardizem CD, Cardizem LA, Cartia XT, Matzim LA: Administer without regard to meals.
Dilt-XR: Administer on an empty stomach in the morning.
Taztia XT, Tiazac: Capsules may be opened and sprinkled on a spoonful of applesauce. Applesauce should not be hot and should be swallowed without chewing, followed by drinking a glass of water.
Tiazac XC [Canadian product]: Administer at bedtime.
Bariatric surgery: Capsule and tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Tiazac or generic equivalent capsule may be opened and contents sprinkled onto soft food of choice. Other ER formulations, such as Cardizem CD, LA, SR or generic equivalents have no data on opening capsule. Dilacor XR or generic equivalent manufacturers say do not open capsule.
IV: Bolus doses given over 2 minutes with continuous ECG and blood pressure monitoring. Continuous infusion should be via infusion pump. May increase infusion rate in 5 mg/hour increments as needed (maximum: 15 mg/hour). Response to bolus may require several minutes to reach maximum. Response may persist for several hours after infusion is discontinued.
Oral:
Tablet, immediate release (eg, Cardizem): Administer before meals and at bedtime. Tablets may be swallowed whole, crushed, or chewed; scored tablets may be split.
Extended-release preparations: Swallow whole; do not chew, break, or crush. Administer at the same time of day, either morning or evening.
Cardizem CD, Cardizem LA, Cartia XT, Matzim LA: May be administered with or without food, but should be administered consistently with relation to meals; administer with a full glass of water.
Taztia XT and Tiazac: Capsules may be opened and sprinkled on applesauce; swallow applesauce immediately, do not chew; follow with some cool water (adults: 1 glass) to ensure complete swallowing; do not use hot applesauce; do not divide capsule contents (ie, do not administer partial doses); do not store mixture of applesauce and capsule contents, use immediately.
Parenteral:
IV bolus: Pediatric patients ≥6 months of age: Administration over 5 minutes at a concentration ≤5 mg/mL with continuous ECG monitoring has been used (Ref).
Continuous IV infusion: Administer as a continuous IV infusion with the use of an infusion pump with continuous ECG monitoring. Response may persist for several hours after infusion is discontinued.
IV infusion: 125 mg in 125 mL (total volume) (concentration: 1 mg/mL) of D5W or NS
Oral: Hypertension, chronic stable angina, vasospastic angina
Injection: Atrial fibrillation or atrial flutter for acute ventricular rate control, conversion of supraventricular tachycardia
Atrial fibrillation or atrial flutter, chronic ventricular rate control; Chest pain associated with cocaine ingestion, with or without evidence of acute coronary syndrome; Hypertrophic cardiomyopathy; Idiopathic ventricular tachycardia; Nonsustained ventricular tachycardia or ventricular premature beats, symptomatic; Pulmonary arterial hypertension, group 1; Supraventricular tachycardia (eg, atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, focal atrial tachycardia, multifocal atrial tachycardia)
Cardizem may be confused with Cardene, Cardene SR, Cardizem CD, Cardizem SR, cortisone
Cartia XT may be confused with Procardia XL
DilTIAZem may be confused with Calan, diazePAM, Dilantin
Tiazac may be confused with Tigan, Tiazac XC [CAN], Ziac
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (antiarrhythmic agent, IV) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care Settings).
Diltiazem is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age). Some disease states of concern include heart failure, bradycardia, heart block (type II or complete), and severe symptomatic aortic stenosis (O’Mahony 2023).
Significant differences exist between oral and IV dosing. Use caution when converting from one route of administration to another.
Cardizem [US, Canada, and multiple international markets] may be confused with Cardem brand name for celiprolol [Spain]
Cartia XT [US] may be confused with Cartia brand name for aspirin [multiple international markets]
DilacorXR [New Zealand, Puerto Rico] may be confused with Pilocar brand name for Pilocarpine, Ophthalmic [multiple international markets]
Dipen [Greece] may be confused with Depen brand name for penicillamine [US]; Depin brand name for nifedipine [India]; Depon brand name for acetaminophen [Greece]
Tiazac: Brand name for dilTIAZem [US, Canada], but also the brand name for pioglitazone [Chile]
Substrate of CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (weak), CYP3A4 (moderate)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Abemaciclib. Management: Monitor for increased abemaciclib toxicities if combined with moderate CYP3A4 inhibitors. Consider reducing the abemaciclib dose in 50 mg decrements if necessary. Risk C: Monitor therapy
Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Risk D: Consider therapy modification
ALfentanil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ALfentanil. Management: If use of alfentanil and moderate CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider therapy modification
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Alfuzosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Alfuzosin. Risk C: Monitor therapy
Alitretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Alitretinoin (Systemic). Risk C: Monitor therapy
ALPRAZolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ALPRAZolam. Management: Consider alternatives to this combination when possible. If combined, consider an alprazolam dose reduction and monitor for increased alprazolam effects and toxicities (eg, sedation, lethargy). Risk D: Consider therapy modification
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amiodarone: Calcium Channel Blockers (Nondihydropyridine) may enhance the bradycardic effect of Amiodarone. Sinus arrest has been reported. Risk C: Monitor therapy
AmLODIPine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of AmLODIPine. Risk C: Monitor therapy
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Apixaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Apixaban. Risk C: Monitor therapy
Aprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Aprepitant. Risk X: Avoid combination
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy
ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor therapy
Aspirin: Calcium Channel Blockers (Nondihydropyridine) may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Astemizole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Astemizole. Management: Avoid concomitant use of astemizole and moderate CYP3A4 inhibitors whenever possible. If combined, monitor closely for increased astemizole toxicities, especially for QTc interval prolongation. Risk D: Consider therapy modification
Atazanavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Atazanavir. Risk C: Monitor therapy
Atogepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Atogepant. Risk C: Monitor therapy
Atorvastatin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Risk C: Monitor therapy
Avacopan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avacopan. Risk C: Monitor therapy
Avanafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil. Management: The maximum avanafil dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects (eg, hypotension, syncope, priapism). Risk D: Consider therapy modification
Avapritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avapritinib. Management: Avoid use of moderate CYP3A4 inhibitors with avapritinib. If this combination cannot be avoided, reduce the avapritinib dose to 100 mg daily for the treatment of GIST or to 50 mg daily for the treatment of advanced systemic mastocytosis. Risk D: Consider therapy modification
Axitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Axitinib. Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Barnidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Barnidipine. Risk C: Monitor therapy
Bedaquiline: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bedaquiline. Risk C: Monitor therapy
Benidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benidipine. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benzhydrocodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor therapy
Blonanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin. Risk C: Monitor therapy
Bortezomib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bortezomib. Risk C: Monitor therapy
Bosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib. Risk X: Avoid combination
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy
Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Risk C: Monitor therapy
Brigatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider therapy modification
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Risk D: Consider therapy modification
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Oral Inhalation). Risk C: Monitor therapy
Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic). Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and CYP3A4 inhibitors, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider therapy modification
Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Risk X: Avoid combination
Buprenorphine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Buprenorphine. Risk C: Monitor therapy
BusPIRone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of BusPIRone. Risk C: Monitor therapy
Cabozantinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
Cannabis: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor therapy
Capivasertib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Capivasertib. Management: If capivasertib is combined with moderate CYP3A4 inhibitors, reduce the capivasertib dose to 320 mg twice daily for 4 days, followed by 3 days off. Monitor patients closely for adverse reactions. Risk D: Consider therapy modification
CarBAMazepine: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Calcium Channel Blockers (Nondihydropyridine). Management: Consider alternatives to this combination when possible. If combined, monitor for increased carbamazepine concentrations and toxicities and monitor for decreased calcium channel blocker efficacy. Risk D: Consider therapy modification
Cardiac Glycosides: Calcium Channel Blockers (Nondihydropyridine) may enhance the AV-blocking effect of Cardiac Glycosides. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy
Cariprazine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Cariprazine. Specifically, concentrations of didesmethylcariprazine (DDCAR), the primary active metabolite of cariprazine, may increase. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cariprazine. Risk C: Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider therapy modification
Cilostazol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Cimetidine: May increase the serum concentration of Calcium Channel Blockers. Risk C: Monitor therapy
Cisapride: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cisapride. Management: Consider alternatives to this combination. Prescribing information for some moderate CYP3A4 inhibitors state coadministration with cisapride is contraindicated, while some others recommend monitoring and dose titration. Risk D: Consider therapy modification
Clindamycin (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Clindamycin (Systemic). Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy
CloZAPine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib. Management: Avoid this combination when possible. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose from 60 mg to 20 mg daily. Avoid concomitant use in patients already receiving reduced cobimetinib doses. Risk D: Consider therapy modification
Codeine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy
Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Avoidance, dose reduction, or increased monitoring for colchicine toxicity may be needed and will depend on brand, indication for colchicine use, renal/hepatic function, and use of a P-gp inhibitor. See full monograph for details. Risk D: Consider therapy modification
Conivaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Conivaptan. Risk C: Monitor therapy
Copanlisib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Copanlisib. Risk C: Monitor therapy
Crizotinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Crizotinib. Risk C: Monitor therapy
CycloSPORINE (Systemic): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of DilTIAZem. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of DilTIAZem. Management: Consider alternatives to this combination when possible. If combined, monitor for decreased diltiazem efficacy. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of DilTIAZem. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of DilTIAZem. Risk C: Monitor therapy
Dabrafenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dabrafenib. Risk C: Monitor therapy
Dantrolene: May enhance the hyperkalemic effect of Calcium Channel Blockers. Dantrolene may enhance the negative inotropic effect of Calcium Channel Blockers. Risk X: Avoid combination
Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4. Risk D: Consider therapy modification
Daridorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Daridorexant. Management: Limit the daridorexant dose to 25 mg, no more than once per night, when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Darifenacin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Darifenacin. Risk C: Monitor therapy
Dasatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dasatinib. Risk C: Monitor therapy
Deflazacort: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Risk D: Consider therapy modification
Delamanid: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Delamanid. Risk C: Monitor therapy
DexAMETHasone (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
DiazePAM: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DiazePAM. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dienogest: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dienogest. Risk C: Monitor therapy
Disopyramide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Disopyramide. Risk C: Monitor therapy
DOCEtaxel: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOCEtaxel. Risk C: Monitor therapy
Dofetilide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
Domperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone. Risk X: Avoid combination
DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DroNABinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DroNABinol. Risk C: Monitor therapy
Dronedarone: Calcium Channel Blockers (Nondihydropyridine) may enhance the AV-blocking effect of Dronedarone. Other electrophysiologic effects of Dronedarone may also be increased. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Dronedarone. Dronedarone may increase the serum concentration of Calcium Channel Blockers (Nondihydropyridine). Management: Use lower starting doses of the nondihydropyridine calcium channel blockers and only increase calcium channel blocker dose after obtaining ECG-based evidence that the combination is being well-tolerated. Monitor closely during coadministration. Risk D: Consider therapy modification
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Ebastine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ebastine. Risk C: Monitor therapy
Elacestrant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elacestrant. Risk X: Avoid combination
Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elbasvir and Grazoprevir. Risk C: Monitor therapy
Eletriptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eletriptan. Risk X: Avoid combination
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, elexacaftor/tezacaftor/ivacaftor should be given in the morning, every other day. Ivacaftor alone should be given in the morning, every other day on alternate days. Risk D: Consider therapy modification
Eliglustat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with moderate CYP3A4 inhibitors. Avoid use of moderate CYP3A4 inhibitors in CYP2D6 IMs or PMs. Use in CYP2D6 EMs or IMs also taking strong or moderate CYP2D6 inhibitors is contraindicated. Risk D: Consider therapy modification
Encorafenib: DilTIAZem may increase the serum concentration of Encorafenib. Encorafenib may decrease the serum concentration of DilTIAZem. Management: Avoid use of encorafenib and diltiazem when possible. If combined, decrease the encorafenib dose from 450 mg to 225 mg; 300 mg to 150 mg; and 225 mg or 150 mg to 75 mg. Monitor for reduced diltiazem efficacy. Risk D: Consider therapy modification
Entrectinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Entrectinib. Management: Avoid moderate CYP3A4 inhibitors if possible. If needed, reduce entrectinib dose to 50 mg/day if starting dose 200 mg; to 100 mg/day if starting dose 300 mg; to 200 mg if starting dose 400 mg or 600 mg. Risk D: Consider therapy modification
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: If coadministered with moderate CYP3A4 inhibitors, the max dose of eplerenone is 25 mg daily if used for heart failure; if used for hypertension initiate eplerenone 25 mg daily, titrate to max 25 mg twice daily. Risk D: Consider therapy modification
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Erlotinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Erlotinib. Risk C: Monitor therapy
Erythromycin (Systemic): May increase the serum concentration of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Erythromycin (Systemic). Risk C: Monitor therapy
Esmolol: Calcium Channel Blockers (Nondihydropyridine) may enhance the bradycardic effect of Esmolol. Management: Administration of IV verapamil or diltiazem together with esmolol is contraindicated if one agent is given while the effects of the other are still present. Canadian esmolol labeling specifies that use within 24 hours is contraindicated. Risk D: Consider therapy modification
Eszopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eszopiclone. Risk C: Monitor therapy
Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Etravirine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Etravirine. Risk C: Monitor therapy
Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Risk C: Monitor therapy
Fedratinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fedratinib. Risk C: Monitor therapy
Felodipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Felodipine. Risk C: Monitor therapy
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Consider fentanyl dose reductions when combined with a moderate CYP3A4 inhibitor. Monitor for respiratory depression and sedation. Upon discontinuation of a CYP3A4 inhibitor, consider a fentanyl dose increase; monitor for signs and symptoms of withdrawal. Risk D: Consider therapy modification
Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification
Flibanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin. Management: Use of flibanserin with moderate CYP3A4 inhibitors is contraindicated. If starting flibanserin, start 2 weeks after the last dose of the CYP3A4 inhibitor. If starting a CYP3A4 inhibitor, start 2 days after the last dose of flibanserin. Risk X: Avoid combination
Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Fluticasone (Nasal): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fluticasone (Nasal). Risk C: Monitor therapy
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fluticasone (Oral Inhalation). Risk C: Monitor therapy
Fosamprenavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosamprenavir. Risk C: Monitor therapy
Fosaprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosaprepitant. Risk X: Avoid combination
Fosphenytoin-Phenytoin: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may decrease the serum concentration of Calcium Channel Blockers (Nondihydropyridine). Management: Consider alternatives to this combination when possible. If combined, monitor for increased phenytoin concentrations and toxicities and monitor for decreased calcium channel blocker efficacy. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider therapy modification
Gepirone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Gepirone. Management: Reduce the gepirone dose by 50% if combined with moderate CYP3A4 inhibitors. Monitor for QTc interval prolongation with combined use. Risk D: Consider therapy modification
Gilteritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Gilteritinib. Risk C: Monitor therapy
Glasdegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Glasdegib. Risk C: Monitor therapy
GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a moderate CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider therapy modification
Guggul: May decrease the serum concentration of DilTIAZem. Risk C: Monitor therapy
Halofantrine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Risk C: Monitor therapy
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HYDROcodone. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions. Risk D: Consider therapy modification
Ifosfamide: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy
Iloperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Iloperidone. Risk C: Monitor therapy
Iloperidone: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Infigratinib: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Infigratinib. Risk X: Avoid combination
Inhalational Anesthetics: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Irinotecan Products: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, the serum concentration of SN-38 may be increased. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Irinotecan Products. Risk C: Monitor therapy
Isavuconazonium Sulfate: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Moderate) may increase isavuconazole serum concentrations. Risk C: Monitor therapy
Isocarboxazid: May enhance the antihypertensive effect of Antihypertensive Agents. Risk X: Avoid combination
Isradipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Isradipine. Risk C: Monitor therapy
Itraconazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Itraconazole. Risk C: Monitor therapy
Ivabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine. Risk X: Avoid combination
Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions may be required; consult full drug interaction monograph content for age- and weight-specific dosage recommendations. Risk D: Consider therapy modification
Ivosidenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivosidenib. Management: Avoid use of moderate CYP3A4 inhibitors with ivosidenib whenever possible. If combined, monitor for increased ivosidenib toxicities, including QTc prolongation. Risk D: Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Lapatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lapatinib. Risk C: Monitor therapy
Larotrectinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy
Lefamulin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lefamulin. Management: Monitor for lefamulin adverse effects during coadministration of lefamulin tablets with moderate CYP3A4 inhibitors. Risk C: Monitor therapy
Lemborexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lemborexant. Risk X: Avoid combination
Leniolisib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Leniolisib. Risk C: Monitor therapy
Lercanidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lercanidipine. Risk C: Monitor therapy
Levamlodipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levamlodipine. Risk C: Monitor therapy
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Levoketoconazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levoketoconazole. Risk C: Monitor therapy
Levomethadone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levomethadone. Risk C: Monitor therapy
Levomilnacipran: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levomilnacipran. Risk C: Monitor therapy
Lidocaine (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Lidocaine (Systemic). Specifically, concentrations of monoethylglycinexylidide (MEGX) may be increased. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy
Lithium: Calcium Channel Blockers (Nondihydropyridine) may enhance the neurotoxic effect of Lithium. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Lithium. Decreased or unaltered lithium concentrations have also been reported with this combination. Risk C: Monitor therapy
Lomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide. Risk X: Avoid combination
Lonafarnib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lonafarnib. Risk C: Monitor therapy
Loop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Lopinavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lopinavir. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Lovastatin: DilTIAZem may increase the serum concentration of Lovastatin. Management: Initiate immediate release lovastatin at a dose of 10 mg/day, and do not exceed 20 mg/day for immediate or extended release lovastatin, in patients receiving diltiazem. Monitor closely for signs of lovastatin toxicity (eg, myositis, rhabdomyolysis). Risk D: Consider therapy modification
Lumateperone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lumateperone. Management: Limit the lumateperone dose to 21 mg once daily when used with a moderate CYP3A4 inhibitor. Risk D: Consider therapy modification
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: US labeling recommends reducing lurasidone dose by 50% with a moderate CYP3A4 inhibitor and initiating 20 mg/day, max 80 mg/day. Some non-US labels recommend initiating lurasidone 20 mg/day, max 40 mg/day. Avoid concurrent use of grapefruit products. Risk D: Consider therapy modification
Lurbinectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, consider a lurbinectedin dose reduction as clinically indicated. Risk D: Consider therapy modification
Macitentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Macitentan. Risk C: Monitor therapy
Manidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Manidipine. Risk C: Monitor therapy
Maraviroc: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Maraviroc. Risk C: Monitor therapy
Mavacamten: Calcium Channel Blockers (Nondihydropyridine) may enhance the adverse/toxic effect of Mavacamten. Specifically, negative inotropic effects may be increased. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a non-DHP CCB. For those stable on mavacamten who are initiating a non-DHP CCB, reduce mavacamten dose by one dose level. Monitor for excessive negative inotropic effects. Risk D: Consider therapy modification
Mavorixafor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mavorixafor. Risk C: Monitor therapy
Meperidine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Meperidine. Risk C: Monitor therapy
Methadone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Methadone. Management: If coadministration with moderate CYP3A4 inhibitors is necessary, consider methadone dose reductions until stable effects are achieved. Monitor patients closely for respiratory depression and sedation. Risk D: Consider therapy modification
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
MethylPREDNISolone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of MethylPREDNISolone. Risk C: Monitor therapy
Methysergide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Methysergide. Risk X: Avoid combination
Midazolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Midazolam. Management: Avoid concomitant use of nasal midazolam and moderate CYP3A4 inhibitors. Consider alternatives to use with oral midazolam whenever possible and consider using lower midazolam doses. Monitor patients for sedation and respiratory depression if combined. Risk D: Consider therapy modification
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Midostaurin: DilTIAZem may increase the serum concentration of Midostaurin. Management: Seek alternatives to the concomitant use of midostaurin and diltiazem if possible. If concomitant use cannot be avoided, monitor patients for increased risk of adverse reactions. Risk D: Consider therapy modification
MiFEPRIStone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of MiFEPRIStone. Risk C: Monitor therapy
Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil. Risk C: Monitor therapy
Mitapivat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mitapivat. Management: When coadministered with moderate CYP3A4 inhibitors, doses of mitapivat should not exceed 20 mg twice daily. Additionally, patients should be monitored for changes in hemoglobin response and increased mitapivat adverse effects. Risk D: Consider therapy modification
Mobocertinib: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mobocertinib. Management: Avoid use of moderate CYP3A4 inhibitors with mobocertinib when possible. If combined, the mobocertinib dose should be reduced by approximately 50% (ie, from 160 mg to 80 mg, 120 mg to 40 mg, or 80 mg to 40 mg). Monitor QTc interval closely. Risk D: Consider therapy modification
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naldemedine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nalfurafine. Risk C: Monitor therapy
Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. Management: The use of naloxegol and moderate CYP3A4 inhibitors should be avoided. If concurrent use is unavoidable, reduce naloxegol dose to 12.5 mg once daily and monitor for signs of opiate withdrawal (eg, hyperhidrosis, chills, diarrhea, anxiety, irritability). Risk D: Consider therapy modification
Neratinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Neratinib. Risk C: Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
NIFEdipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NIFEdipine. Risk C: Monitor therapy
Nilotinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nilotinib. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Nirogacestat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nirogacestat. Risk X: Avoid combination
Nisoldipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nisoldipine. Risk X: Avoid combination
Nitrendipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nitrendipine. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Olaparib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 150 mg twice daily and the dose of olaparib capsules should be reduced to 200 mg twice daily. Risk D: Consider therapy modification
Oliceridine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Oliceridine. Risk C: Monitor therapy
Olmutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy
Omaveloxolone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Omaveloxolone. Management: Avoid this combination if possible. If coadministration is required, decrease the omaveloxolone dose to 100 mg daily and monitor closely for adverse reactions. If adverse reactions occur, decrease omaveloxolone to 50 mg daily. Risk D: Consider therapy modification
Orelabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Orelabrutinib. Risk X: Avoid combination
OxyCODONE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor therapy
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
PACLitaxel (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy
Pacritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pacritinib. Risk X: Avoid combination
Palbociclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Palbociclib. Risk C: Monitor therapy
Palovarotene: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Palovarotene. Management: Avoid concomitant use of palovarotene and moderate CYP3A4 inhibitors when possible. If combined, decrease palovarotene dose by 50% as described in the full interaction monograph. Monitor for palovarotene toxicities when combined. Risk D: Consider therapy modification
Panobinostat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Panobinostat. Risk C: Monitor therapy
PAZOPanib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PAZOPanib. Risk C: Monitor therapy
Pemigatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pemigatinib. Management: If combined use cannot be avoided, reduce the pemigatinib dose from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior pemigatinib dose after stopping the moderate inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pexidartinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pexidartinib. Management: If combined use cannot be avoided, pexidartinib dose should be reduced as follows: reduce pexidartinib doses of 500 mg or 375 mg daily to 125 mg twice daily; reduce pexidartinib 250 mg daily to 125 mg once daily. Risk D: Consider therapy modification
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Pimavanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimavanserin. Risk C: Monitor therapy
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Piperaquine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Piperaquine. Risk C: Monitor therapy
Pirtobrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pirtobrutinib. Risk C: Monitor therapy
PONATinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PONATinib. Risk C: Monitor therapy
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification
Pralsetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider therapy modification
Pramipexole: DilTIAZem may enhance the hypotensive effect of Pramipexole. DilTIAZem may increase the serum concentration of Pramipexole. Risk C: Monitor therapy
Prazepam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Prazepam. Risk C: Monitor therapy
Praziquantel: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Praziquantel. Risk C: Monitor therapy
Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
QUEtiapine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of QUEtiapine. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
QuiNIDine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of QuiNIDine. Risk C: Monitor therapy
Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor therapy
QuiNINE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of QuiNINE. Risk C: Monitor therapy
Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors. Monitor for increased ranolazine effects and toxicities during concomitant use. Risk D: Consider therapy modification
Red Yeast Rice: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin (and possibly other related compounds) may be increased. Management: Initiate immediate release lovastatin at a dose of 10 mg/day, and do not exceed 20 mg/day for immediate or extended release lovastatin. Monitor closely for signs of lovastatin toxicity (eg, myositis, rhabdomyolysis). Risk D: Consider therapy modification
Regorafenib: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Regorafenib. Risk C: Monitor therapy
Repotrectinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Repotrectinib. Risk X: Avoid combination
Ribociclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ribociclib. Risk C: Monitor therapy
Rifabutin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rifabutin. Risk C: Monitor therapy
Rimegepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rimegepant. Management: If taking rimegepant for the acute treatment of migraine, avoid a second dose of rimegepant within 48 hours when used concomitantly with moderate CYP3A4 inhibitors. No dose adjustment needed if using rimegepant for prevention of episodic migraine. Risk D: Consider therapy modification
Rivaroxaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rivaroxaban. This warning is more specifically for drugs that are inhibitors of both CYP3A4 and P-glycoprotein. For erythromycin, refer to more specific erythromycin-rivaroxaban monograph recommendations. Risk C: Monitor therapy
Roflumilast-Containing Products: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
Rupatadine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rupatadine. Risk C: Monitor therapy
Ruxolitinib (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ruxolitinib (Systemic). Risk C: Monitor therapy
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy
Saquinavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SAXagliptin. Risk C: Monitor therapy
Selpercatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Selpercatinib. Management: Avoid combination if possible. If use is necessary, reduce selpercatinib dose as follows: from 120 mg twice/day to 80 mg twice/day, or from 160 mg twice/day to 120 mg twice/day. Risk D: Consider therapy modification
Selumetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Selumetinib. Management: Avoid concomitant use when possible. If combined, selumetinib dose reductions are recommended and vary based on body surface area and selumetinib dose. For details, see the full drug interaction monograph or selumetinib prescribing information. Risk D: Consider therapy modification
Sertindole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sertindole. Risk X: Avoid combination
Sildenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sildenafil. Risk C: Monitor therapy
Silodosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Silodosin. Risk C: Monitor therapy
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Simeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir. Risk X: Avoid combination
Simvastatin: May decrease the serum concentration of DilTIAZem. DilTIAZem may increase the serum concentration of Simvastatin. Management: Avoid concurrent use of diltiazem with simvastatin when possible. If used together, limit adult doses to simvastatin 10 mg daily and diltiazem 240 mg per day; monitor closely for signs of simvastatin toxicity (eg, myositis, rhabdomyolysis). Risk D: Consider therapy modification
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification
Sirolimus (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sirolimus (Conventional). Management: Monitor for increased serum concentrations of sirolimus if combined with a moderate CYP3A4 inhibitor. Lower initial sirolimus doses or sirolimus dose reductions will likely be required. Risk D: Consider therapy modification
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a moderate CYP3A4 inhibitor. Risk D: Consider therapy modification
Solifenacin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Solifenacin. Risk C: Monitor therapy
Sonidegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Risk D: Consider therapy modification
Sparsentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sparsentan. Risk C: Monitor therapy
SUFentanil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SUFentanil. Risk C: Monitor therapy
SUNItinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SUNItinib. Risk C: Monitor therapy
Suvorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Risk D: Consider therapy modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tacrolimus (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tacrolimus (Topical). Risk C: Monitor therapy
Tadalafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tadalafil. Risk C: Monitor therapy
Talazoparib: DilTIAZem may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Risk C: Monitor therapy
Tazemetostat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tazemetostat. Management: Avoid when possible. If combined, reduce tazemetostat dose from 800 mg twice daily to 400 mg twice daily, from 600 mg twice daily to 400 mg in AM and 200 mg in PM, or from 400 mg twice daily to 200 mg twice daily. Risk D: Consider therapy modification
Temsirolimus: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Risk C: Monitor therapy
Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. Risk C: Monitor therapy
Terfenadine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Terfenadine. Risk C: Monitor therapy
Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy
Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tezacaftor and Ivacaftor. Management: If combined with moderate CYP3A4 inhibitors, give tezacaftor/ivacaftor in the morning, every other day; give ivacaftor in the morning, every other day on alternate days. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph Risk D: Consider therapy modification
Thioridazine: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Risk D: Consider therapy modification
Thiotepa: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Thiotepa. Risk C: Monitor therapy
Ticagrelor: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor. Risk C: Monitor therapy
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Tofacitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tofacitinib. Risk C: Monitor therapy
Tolterodine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolterodine. Risk C: Monitor therapy
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Management: Avoid this combination with Samsca brand of tolvaptan. Reduce dose for Jynarque brand: 90 mg AM and 30 mg PM, reduce to 45 mg AM and 15 mg PM; 60 mg AM and 30 mg PM, reduce to 30 mg AM and 15 mg PM; 45 mg AM and 15 mg PM, reduce to 15 mg AM and PM. Risk D: Consider therapy modification
Toremifene: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Toremifene. Risk C: Monitor therapy
Trabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin. Risk C: Monitor therapy
TraMADol: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of TraMADol. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of TraMADol. Risk C: Monitor therapy
TraZODone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of TraZODone. Risk C: Monitor therapy
Triazolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Ubrogepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and avoid a second dose for 24 hours when used with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Udenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Udenafil. Risk C: Monitor therapy
Ulipristal: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Risk C: Monitor therapy
Urapidil: Antihypertensive Agents may enhance the hypotensive effect of Urapidil. Risk C: Monitor therapy
Valbenazine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Valbenazine. Risk C: Monitor therapy
Vamorolone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vamorolone. Risk C: Monitor therapy
Vardenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 5 mg dose within a 24-hour period if combined with moderate CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and moderate CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider therapy modification
Vemurafenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vemurafenib. Risk C: Monitor therapy
Venetoclax: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with moderate CYP3A4 inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Verapamil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Verapamil. Risk C: Monitor therapy
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Risk C: Monitor therapy
VinBLAStine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinBLAStine. Risk C: Monitor therapy
VinCRIStine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinCRIStine. Risk C: Monitor therapy
VinCRIStine (Liposomal): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinCRIStine (Liposomal). Risk C: Monitor therapy
Vindesine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine. Risk C: Monitor therapy
Vinflunine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Vinflunine. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vinflunine. Risk C: Monitor therapy
Voclosporin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Voclosporin. Management: Decrease the voclosporin dose to 15.8 mg in the morning and 7.9 mg in the evening when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Vorapaxar: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vorapaxar. Risk C: Monitor therapy
Zanubrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg twice daily during coadministration with a moderate CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider therapy modification
Zopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone. Risk C: Monitor therapy
Zuranolone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuranolone. Risk C: Monitor therapy
Grapefruit juice may increase the serum concentration of diltiazem. Management: Monitor response to diltiazem with concurrent use.
Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be continued in patients trying to conceive. Diltiazem is not considered a preferred agent for use in pregnant patients; consider transitioning to a preferred agent in patients planning to become pregnant (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019).
Adverse events have been observed in animal reproduction studies.
Chronic maternal hypertension is associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019).
Patients with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]). When treatment of chronic hypertension during pregnancy is indicated, agents other than diltiazem may be preferred (ACOG 2019; ESC [Cífková 2020]; ESC [Regitz-Zagrosek 2018]; SOGC [Magee 2022]).
Diltiazem is present in breast milk.
Data related to the presence of diltiazem in breast milk are available from a case report. Oral diltiazem 60 mg four times a day was started in a mother on postpartum day 14 for arrythmia. Four days later maternal blood and breast milk were sampled. Peak breast milk concentrations of diltiazem were 200 ng/mL, similar to those in the maternal serum. Breast milk concentrations decreased to <50 mg/mL 22 hours after the final diltiazem dose (Okada 1985).
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother; however, other sources consider diltiazem compatible for use in patients who are breastfeeding (ESC [Cífková 2020]).
BP; heart rate; liver function.
Inhibits calcium ion from entering the “slow channels” or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization; produces relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina.
Onset of action: Oral: Immediate release tablet: 30 to 60 minutes; IV: Bolus: 3 minutes
Duration: IV: Bolus: 1 to 3 hours; Continuous infusion (after discontinuation): 0.5 to 10 hours
Absorption: Immediate release tablet: ~98%; Extended release capsule: ~93% to >95%
Distribution: Vd: 3 to 13 L/kg
Protein binding: 70% to 80%
Metabolism: Hepatic (extensive first-pass effect) via CYP-450 and conjugation; forms metabolites N-monodesmethyldiltiazem, desacetyldiltiazem, desacetyl-Nmonodesmethyldiltiazem, desacetyl-O-desmethyldiltiazem, and desacetyl-N, O-desmethyldiltiazem; following single IV injection, plasma concentrations of N-monodesmethyldiltiazem and desacetyldiltiazem are typically undetectable; however, these metabolites accumulate to detectable concentrations following 24-hour constant rate infusion.
Bioavailability: Oral: ~40% (undergoes extensive first-pass metabolism)
Half-life elimination: Immediate release tablet: 3 to 4.5 hours; Extended release tablet: 6 to 9 hours; Extended release capsules: 4 to 9.5 hours; IV: single dose: ~3.4 hours; continuous infusion: 4 to 5 hours
Time to peak, serum: Immediate release tablet: 2 to 4 hours; Extended release tablet: 11 to 18 hours; Extended release capsule: 10 to 14 hours
Excretion: Urine (2% to 4% as unchanged drug); feces
Hepatic function impairment: Bioavailability is increased, and half-life is prolonged.
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