Version July 2025
Supraventricular tachycardia (SVT): Note: Although verapamil is effective in the treatment of SVT, it is not included in the PALS tachyarrhythmia algorithm due to its adverse effects (Ref).
IV:
Infants: Note: May decrease cardiac output resulting in hypotension and possible cardiac arrest in infants; some experts consider verapamil use contraindicated (Ref). If used, it should only be with expert consultation and continuous ECG monitoring with IV calcium at the bedside: 0.1 to 0.2 mg/kg/dose (usual: 0.75 to 2 mg/dose) may repeat dose after at least 30 minutes if response inadequate; optimal interval not defined; patient should be monitored closely (Ref).
Children and Adolescents 1 to 15 years: 0.1 to 0.3 mg/kg/dose (usual dose: 2 to 5 mg/dose); maximum dose: 5 mg/dose; may repeat dose in 15 to 30 minutes if response inadequate; maximum dose for second dose: 10 mg/dose (Ref). Note: May also be administered intraosseous. Optimal interval for subsequent doses is unknown and must be individualized for each specific patient.
Adolescents ≥16 years:
Initial dose:
PALS guidelines: 0.1 to 0.3 mg/kg/dose; maximum dose: 5 mg/dose (Ref).
Manufacturer's labeling: 5 to 10 mg (0.075 to 0.15 mg/kg/dose); maximum dose: 10 mg/dose (Ref); similar dosing recommended in the adult ACC/AHA/HRS SVT guidelines: 5 to 10 mg (0.075 to 0.15 mg/kg) over 2 minutes (Ref).
Repeat dose: May repeat dose in 15 to 30 minutes if adequate response not achieved; maximum dose for second dose: 10 mg/dose (Ref). Note: Optimal interval for subsequent doses is unknown and must be individualized for each specific patient.
Oral: Limited data available: Children and Adolescents: Immediate release: 2 to 8 mg/kg/day in 3 divided doses; maximum daily dose: 480 mg/day (Ref). A mean daily dose of ~5 mg/kg/day (range: 2.3 to 8.1 mg/kg/day) was used in 22 children 15 days to 17 years of age receiving chronic oral therapy for SVT (n=20) or hypertrophic cardiomyopathy (n=2) (Ref).
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 pediatric specific recommendations. Based on experience in adult patients, use with caution and consider additional ECG monitoring; data suggest clearance of verapamil and its metabolite (norverapamil) is decreased; dosing adjustment suggested.
Dialysis: Not removed by hemodialysis; supplemental dose is not necessary.
There are no pediatric specific recommendations; based on in experience in adult patients, dosing adjustment suggested.
(For additional information see "Verapamil: Drug information")
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; verapamil may be used as an alternative therapy if there are contraindications or unacceptable adverse effects with beta blockade (Ref).
Oral:
Immediate release: Initial: 80 to 120 mg 3 times daily; increase as needed at ≥1- to 2-day intervals to effective antianginal dose; maximum dose: 480 mg/day in 3 divided doses (Ref).
Extended release: Initial: 180 mg once daily; increase as needed at 7- to 14-day intervals to effective antianginal dose; maximum dose: 480 mg/day in 1 to 2 divided doses (Ref).
Vasospastic angina:
Note: May use alone or in combination with nitrates (Ref).
Oral:
Immediate release: Initial: 80 to 120 mg 3 times daily; increase as needed at ≥1- to 2-day intervals to effective antianginal dose; maximum dose: 480 mg/day in 3 divided doses.
Extended release: Initial: 180 mg once daily; increase as needed at 7- to 14-day intervals to effective antianginal dose; maximum dose: 480 mg/day in 1 to 2 divided doses.
Atrial fibrillation/flutter, rate control (alternative agent):
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). May be associated with more hypotension compared to diltiazem (Ref).
Acute ventricular rate control:
IV:
Bolus: Initial: 5 to 10 mg over ≥2 minutes; if there is inadequate response, dose may be repeated after 15 to 30 minutes; if there is adequate response after 1 to 2 bolus doses, then may begin a continuous infusion (Ref).
Continuous infusion: Initial: 5 mg/hour; titrate to goal heart rate up to a maximum of 20 mg/hour (Ref).
Chronic ventricular rate control:
Oral:
Immediate release: Initial: 40 mg 3 to 4 times daily; increase as needed to achieve rate control; maximum dose: 480 mg/day in 3 to 4 divided doses (Ref).
Extended release (off-label use): Initial: 120 or 180 mg once daily; increase as needed to achieve rate control; maximum dose: 480 mg/day in 1 to 2 divided doses (Ref).
Chest pain associated with cocaine ingestion, with or without evidence of acute coronary syndrome (off-label use):
Note: Adjunct or alternative agent in patients not controlled with nitroglycerin.
IV: Bolus: Initial: 2.5 to 5 mg over ≥2 minutes; may repeat after 15 minutes if needed (Ref).
Cluster headache, prevention (off-label use):
Note: May be used as monotherapy or in combination with other preventive and/or bridging agents (eg, glucocorticoids (Ref)). Example regimens are presented below. Obtain an ECG prior to treatment and after each titration when dose is >480 mg/day (Ref).
Oral:
Immediate release: Initial: 40 to 80 mg 3 times daily; increase dose every 1 to 2 weeks until headaches subside or adverse reactions develop; usual effective dose: 240 to 480 mg/day in 3 to 4 divided doses (Ref).
Extended release: Initial: 240 mg in 2 divided doses; increase dose every 1 to 2 weeks until headaches subside or adverse reactions develop; usual effective dose: 240 to 480 mg/day in 2 divided doses (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).
Oral:
Immediate release: Initial: 40 to 80 mg 3 times daily; increase dose as needed at weekly intervals; usual dose: 120 to 360 mg/day in 3 divided doses (Ref); maximum dose: 480 mg/day in 3 divided doses.
Extended release: Initial: 120 or 180 mg once daily; increase dose as needed at weekly intervals; usual dose: 120 to 360 mg/day in 1 to 2 divided doses (Ref); maximum dose: 480 mg/day in 1 to 2 divided doses.
Extended release (delayed-onset/PM formulation): Initial: 100 or 200 mg once daily at bedtime; increase dose as needed at weekly intervals; usual dose: 100 to 300 mg once daily at bedtime (Ref); maximum dose: 400 mg once daily at bedtime.
Migraine, prevention (off-label use):
Note: Tolerance may develop; consider increasing dose or switching to another calcium channel blocker if tolerance occurs (Ref). An adequate trial for assessment of effect is considered to be at least 2 to 3 months at a therapeutic dose (Ref).
Oral:
Immediate release: Initial: 40 mg 3 times daily; titrate every 1 to 2 weeks based on patient response and tolerability up to 480 mg/day in 3 to 4 divided doses (Ref).
Extended release: Initial: 120 mg once daily; titrate every 1 to 2 weeks based on patient response and tolerability up to 480 mg/day in 2 to 3 divided doses (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 (off-label use):
IV: Bolus: Initial: 5 to 10 mg over ≥2 minutes; if response is insufficient after 15 to 30 minutes, a second bolus dose of 10 mg over 2 minutes may be administered. If 2 bolus doses do not terminate the arrhythmia, consider alternative therapy (Ref).
Chronic maintenance:
Oral:
Immediate release: Initial: 40 mg 3 to 4 times daily; increase as needed for heart rate control; maximum dose: 480 mg/day in 3 to 4 divided doses (Ref).
Extended release (off-label use): Initial: 120 mg once daily; increase as needed for heart rate control; maximum dose: 480 mg/day in 1 to 2 divided doses (Ref).
Ventricular arrhythmias:
Idiopathic left ventricular tachycardia (off-label use):
Note: In patients with wide QRS complex ventricular tachycardia of unknown origin, calcium channel blockers are potentially harmful. However, verapamil is safe and effective in patients with idiopathic left ventricular tachycardia (Ref).
Acute idiopathic left ventricular tachycardia:
IV: Bolus: 5 to 10 mg over ≥2 minutes; if no response after 15 to 30 minutes, may give 1 additional 10 mg bolus dose (Ref).
Prevention of idiopathic left ventricular arrhythmias:
Oral:
Immediate release: 120 mg 3 times daily (Ref).
Extended release: 240 to 480 mg/day in 1 to 2 divided doses (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, verapamil may be added with close monitoring of heart rate; verapamil may be used as an alternative therapy if beta-blockade cannot be tolerated (Ref).
Oral:
Immediate release: Initial: 40 or 80 mg 3 times daily; titrate as needed based on symptom control and tolerability; maximum dose: 360 mg/day in 3 to 4 divided doses (Ref).
Extended release: Initial: 120 or 180 mg once daily; titrate as needed based on symptom control and tolerability; maximum dose: 360 mg/day in 1 to 2 divided doses (Ref).
Conversion between oral formulations: When switching from IR to ER formulations, the total daily dose remains the same unless formulation strength does not allow for equal conversion. At higher doses, some ER products are recommended to be given twice daily.
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 A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (Ref).
Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed: No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzed (highly protein bound, large Vd (Ref)): No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
Oral: In cirrhosis, reduce dose to 20% of normal and monitor ECG (Ref).
Extended release: Administer 30% of the normal dose in severe hepatic impairment.
Extended release (delayed-onset/PM formulation): Initial: 100 mg once daily at bedtime.
Injection: There are no dosage adjustments provided in the manufacturer's labeling; use with caution and consider additional ECG monitoring in severe impairment. In cirrhosis, reduce dose to 50% of normal and monitor ECG (Ref). Repeated injections in patients with hepatic failure may lead to accumulation. If repeated injections are essential, monitor BP and PR interval closely and use smaller doses.
In patients with left ventricular systolic dysfunction, use of verapamil may result in acute decompensation and deterioration with development of pulmonary edema and/or hypotension (Ref). Acute cardiac failure associated with verapamil in patients with no prior history of chronic heart failure have also been reported (Ref). Decompensated state should return to baseline after discontinuation (Ref).
Mechanism: Dose-related; related to the pharmacologic action. Exhibits significant negative inotropic and vasodilator properties. Patients with left ventricular dysfunction may not be able to compensate or tolerate these hemodynamic effects (Ref).
Onset: Rapid; typically within 4 to 5 days of therapy initiation (Ref).
Risk factors:
• Severe left ventricular dysfunction (Ref)
• Older patients (Ref)
• Cardiac amyloidosis (Ref)
Verapamil may cause first-, second-, or third-degree atrioventricular (AV) 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: Dose-related; related to the pharmacologic action. Verapamil blocks L-type calcium channels, leading to prolonged refractoriness and slowing of conduction through the AV node (Ref).
Onset: Varied; in one study, bradycardia occurred 5 minutes after administration with a peak effect at 30 to 60 minutes (Ref). Other studies have suggested that conduction abnormalities may take a few weeks to develop (Ref).
Risk factors:
• Concurrent use with other AV nodal-blocking agents (eg, beta-blockers) (Ref)
• Sick sinus syndrome (Ref)
• Underlying AV node dysfunction (Ref)
Mild-to-moderate increased serum transaminases, increased serum alkaline phosphatase, and increased serum bilirubin have been reported, including self-limited jaundice. Complete recovery is generally expected within 2 to 4 weeks of discontinuation and may resolve with continuation of therapy (Ref). Rechallenge may result in rapid recurrence of hepatocellular injury (Ref).
Mechanism: Non–dose-related; hypersensitivity or idiosyncratic (Ref). Mechanism of hepatotoxicity is likely related to hypersensitivity (Ref). Verapamil is a derivative of papaverine, which is known to cause allergic hepatitis (Ref). The idiosyncratic cause may be due to mutations in efflux transport of verapamil (Ref).
Onset: Varied; 2 to 6 weeks after initiation (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions presented are for the oral formulation unless otherwise indicated.
>10%: Nervous system: Headache (IV, oral: 1% to 12%)
1% to 10%:
Cardiovascular: Acute myocardial infarction (≤1%), angina pectoris (≤1%), ankle edema (1%), atrioventricular block (IV, oral: ≤1%), atrioventricular dissociation (≤1%), bradycardia (IV, oral: ≤1%), cardiac failure (≤2%), cerebrovascular accident (≤1%), chest pain (≤1%), claudication (≤1%), ECG abnormality (≤2%), edema (2%), hypotension (IV, oral: 2% to 3%, can be symptomatic), palpitations (≤1%), peripheral edema (4%) (table 1), syncope (≤1%), tachycardia (IV: 1%; severe)
|
Drug (Verapamil) |
Placebo |
Dosage Form |
Dose |
Number of Patients (Verapamil) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
4% |
0.9% |
Extended release |
All doses studied |
297 |
116 |
Dermatologic: Alopecia (≤1%), diaphoresis (IV, oral: ≤1%), ecchymoses (≤1%), erythema multiforme (≤1%), hyperkeratosis (≤1%), macular eruption (≤1%), skin rash (≤1%), Stevens-Johnson syndrome (≤1%), urticaria (≤1%)
Endocrine & metabolic: Galactorrhea not associated with childbirth (≤1%), gynecomastia (≤1%), hyperprolactinemia (≤1%), spotty menstruation (≤1%)
Gastrointestinal: Constipation (4% to 9%) (table 2), diarrhea (≤1%), dyspepsia (3%), gastrointestinal distress (≤1%), gingival hyperplasia (≤1%), nausea (IV, oral: ≤3%), xerostomia (≤1%)
|
Drug (Verapamil) |
Placebo |
Dosage Form |
Dose |
Number of Patients (Verapamil) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
9% |
0.9% |
Extended release |
All doses studied |
297 |
116 |
|
7% |
N/A |
Immediate release |
N/A |
285 |
N/A |
|
7% |
N/A |
Extended release |
N/A |
4,954 |
N/A |
|
4% |
N/A |
Extended release |
200 mg/day |
N/A |
N/A |
Genitourinary: Impotence (≤1%)
Hematologic & oncologic: Bruise (≤1%), purpuric vasculitis (≤1%)
Hepatic: Increased serum transaminases (≤2%)
Nervous system: Balance impairment (≤1%), confusion (≤1%), dizziness (IV, oral: 1% to 4%), drowsiness (IV, oral: ≤1%), extrapyramidal reaction (≤1%), fatigue (2%), insomnia (≤1%), lethargy (3%), paresthesia (≤1%), psychosis (≤1%), shakiness (≤1%), sleep disorder (1%)
Neuromuscular & skeletal: Arthralgia (≤1%), asthenia (≤2%), muscle cramps (≤1%), myalgia (1%)
Ophthalmic: Blurred vision (≤1%)
Otic: Tinnitus (≤1%)
Renal: Polyuria (≤1%)
Respiratory: Dyspnea (≤1%), flu-like symptoms (4%), pulmonary edema (≤2%)
<1%:
Cardiovascular: Asystole, flushing, ventricular tachycardia
Gastrointestinal: Abdominal distress, paralytic ileus (nonobstructive)
Postmarketing:
Cardiovascular: Ventricular fibrillation
Dermatologic: Psoriasis (Song 2021)
Hepatic: Increased serum alkaline phosphatase (Hare 1986), increased serum bilirubin (Hare 1986), jaundice (Guarascio 1984)
Nervous system: Depression (Dassylva 1993), seizure (during IV injection) (Maiteh 2001), vertigo
Neuromuscular & skeletal: Muscle fatigue
Ophthalmic: Rotary nystagmus
Respiratory: Respiratory failure (Zalman 1983)
Oral: Hypersensitivity to verapamil or any component of the formulation; severe left ventricular dysfunction; hypotension (systolic pressure <90 mm Hg) or cardiogenic shock; sick sinus syndrome (except in patients with a functioning artificial ventricular pacemaker); second- or third-degree atrioventricular (AV) block (except in patients with a functioning artificial ventricular pacemaker); atrial flutter or fibrillation and an accessory pathway (Wolff-Parkinson-White [WPW] syndrome, Lown-Ganong-Levine syndrome).
Canadian labeling: Additional contraindications (not in US labeling): Complicated myocardial infarction (MI) (ventricular failure manifested by pulmonary congestion); severe congestive heart failure and/or severe left ventricular dysfunction (eg, ejection fraction <40%) unless secondary to a supraventricular tachycardia amendable to oral verapamil; marked bradycardia; concurrent use of ivabradine or flibanserin; concurrent use with beta-blockers in patients with poor ventricular function and in the treatment of hypertension; concurrent use of grapefruit juice; breastfeeding.
IV: Hypersensitivity to verapamil or any component of the formulation; severe heart failure (unless secondary to a supraventricular tachycardia amenable to verapamil); severe hypotension or cardiogenic shock; sick sinus syndrome (except in patients with a functioning artificial ventricular pacemaker); second- or third-degree AV block (except in patients with a functioning artificial ventricular pacemaker); concurrent use of IV beta-blocking agents; atrial flutter or fibrillation and an accessory pathway (WPW syndrome, Lown-Ganong-Levine syndrome); ventricular tachycardia.
Canadian labeling: Additional contraindications (not in US labeling): Complicated MI (ventricular failure manifested by pulmonary congestion); severe left ventricular dysfunction; marked bradycardia; concurrent use of ivabradine or flibanserin; breastfeeding.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Disease-related concerns:
• Accessory pathway (eg, Wolff-Parkinson-White syndrome): During an episode of atrial fibrillation or flutter in patients with an accessory pathway 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]).
• Arrhythmia: Considered contraindicated in patients with wide complex tachycardias unless known to be supraventricular in origin; severe hypotension likely to occur upon administration (AHA [Panchal 2020]).
• Attenuated neuromuscular transmission: Decreased neuromuscular transmission has been reported; use with caution in patients with attenuated neuromuscular transmission (Duchenne muscular dystrophy, myasthenia gravis); dosage reduction may be required.
• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage reduction may be required; monitor hemodynamics and possibly ECG in severe impairment. Avoid repeated injections of IV verapamil in patients with significant hepatic failure.
• Increased intracranial pressure: IV verapamil has increased intracranial pressure in patients with supratentorial tumors at the time of anesthesia induction; use with caution in these patients.
• Left ventricular dysfunction: 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]; AHA [Panchal 2020]).
• Renal impairment: Use with caution in patients with renal impairment; monitor hemodynamics and possibly ECG in severe impairment.
Special populations:
• Bariatric surgery: Presurgical assessment of the indication for use, symptoms, and goals of therapy should be documented to enable postsurgical assessment. Monitor for continued efficacy and tolerability after bariatric surgery and consider switching to an alternate medication if symptoms worsen.
• Pediatric: In neonates and young infants, avoid IV use for supraventricular tachycardia due to severe apnea, bradycardia, hypotensive reactions, and cardiac arrest; in older children, use IV with caution as myocardial depression and hypotension may occur (PALS [Kleinman 2010]).
Although effective in terminating SVT in older children, verapamil is not the drug of choice (due to adverse effects) and is not included in the current PALS tachyarrhythmia algorithm.
Some ER oral products may be referred to as sustained release in the manufacturer's labeling; however, there are generally no differences between products of the same dosage form described as ER or sustained release. All products are referred to as ER throughout the monograph.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule Extended Release 24 Hour, Oral, as hydrochloride:
Verelan: 120 mg, 180 mg [contains fd&c red #40 (allura red ac dye), methylparaben, propylparaben]
Verelan: 240 mg, 360 mg [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye), methylparaben, propylparaben]
Verelan PM: 100 mg [DSC], 200 mg [DSC], 300 mg [DSC] [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]
Generic: 100 mg, 120 mg, 180 mg, 200 mg, 240 mg, 300 mg, 360 mg
Solution, Intravenous, as hydrochloride:
Generic: 2.5 mg/mL (2 mL, 4 mL)
Solution, Intravenous, as hydrochloride [preservative free]:
Generic: 2.5 mg/mL (2 mL, 4 mL)
Tablet, Oral, as hydrochloride:
Generic: 40 mg, 80 mg, 120 mg
Tablet Extended Release, Oral, as hydrochloride:
Calan SR: 120 mg [DSC]
Calan SR: 180 mg [DSC] [scored]
Calan SR: 240 mg [DSC] [contains fd&c blue #2 (indigo carm) aluminum lake, quinoline (d&c yellow #10) aluminum lake]
Generic: 120 mg, 180 mg, 240 mg
Yes
Capsule ER 24 Hour Therapy Pack (Verapamil HCl ER Oral)
100 mg (per each): $6.00
120 mg (per each): $1.75 - $6.91
180 mg (per each): $1.83 - $7.24
200 mg (per each): $7.54
240 mg (per each): $2.06 - $8.17
300 mg (per each): $10.96
360 mg (per each): $6.38 - $12.01
Capsule ER 24 Hour Therapy Pack (Verelan Oral)
120 mg (per each): $7.68
180 mg (per each): $8.05
240 mg (per each): $9.08
360 mg (per each): $13.35
Solution (Verapamil HCl Intravenous)
2.5 mg/mL (per mL): $2.70 - $17.63
Tablet, controlled release (Verapamil HCl ER Oral)
120 mg (per each): $1.07
180 mg (per each): $1.44
240 mg (per each): $1.64
Tablets (Verapamil HCl Oral)
40 mg (per each): $0.28
80 mg (per each): $0.37 - $0.53
120 mg (per each): $0.56 - $0.68
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
Solution, Intravenous, as hydrochloride:
Generic: 2.5 mg/mL (2 mL)
Tablet, Oral, as hydrochloride:
Generic: 80 mg, 120 mg
Tablet Extended Release, Oral, as hydrochloride:
Isoptin SR: 120 mg, 180 mg [DSC]
Isoptin SR: 240 mg [DSC] [contains fd&c blue #2 (indigo carm) aluminum lake, quinoline (d&c yellow #10) aluminum lake]
Generic: 120 mg, 180 mg, 240 mg
A 50 mg/mL oral suspension may be made with immediate release tablets and either a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of Ora-Sweet SF and Ora-Plus or cherry syrup. When using cherry syrup, dilute cherry syrup concentrate 1:4 with simple syrup, NF. Crush seventy-five verapamil hydrochloride 80 mg tablets in a mortar and reduce to a fine powder. Add small portions of chosen vehicle (40 mL total) and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label "shake well", "refrigerate", and "protect from light". Stable for 60 days refrigerated (preferred) or at room temperature (Allen, 1996).
A 50 mg/mL oral suspension may be made with immediate release tablets, a 1:1 preparation of methylcellulose 1% and simple syrup, and purified water. Crush twenty 80 mg verapamil tablets in a mortar and reduce to a fine powder. Add 3 mL purified water USP and mix to a uniform paste; mix while adding the vehicle incremental proportions to almost 32 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 32 mL. Label "shake well" and "refrigerate". Stable for 91 days refrigerated (preferred) or at room temperature (Nahata, 1997).
Oral: Immediate release: Can be administered with or without food.
Parenteral: IV: Administer undiluted dose over 2 to 3 minutes; infuse over 3 to 4 minutes if blood pressure is in the lower range of normal
Oral: Do not crush or chew ER products.
Calan SR, Isoptin SR (Canadian product): Administer with food. Isoptin SR 240 mg tablet may be split in half.
Verelan, Verelan PM: Administer with or without food. Capsules may be opened and the contents sprinkled on 1 tablespoonful of applesauce, swallow immediately (without chewing) and follow with a glass of cool water. Do not subdivide contents of capsules.
Bariatric surgery: Verapamil is available as ER formulations. Bariatric surgery may significantly alter the release characteristics in an unknown manner. Providers should determine if the condition being treated can be safely monitored or if a switch to an alternative formulation is necessary (Ref). Verapamil is also available in an IR formulation.
IV:
IV push: Administer IV push over ≥2 minutes; in older patients for the acute treatment of supraventricular tachycardia, Advanced Cardiac Life Support guidelines recommend administering over 3 minutes (Ref).
IV continuous infusion: Refer to indication-specific infusion rates in dosing for detailed recommendations.
Injection: Store intact vials at 20°C to 25°C (68°F to 77°F). Solution diluted for infusion in a compatible solution is chemically stable for at least 24 hours at 25°C (77°F); consult IV compatibility database for further information.
Oral:
Calan, Calan SR: Store at 15°C to 25°C (59°F to 77°F). Protect from light and moisture.
Verelan: Store at 20°C to 25°C (68°F to 77°F). Avoid excessive heat; protect from moisture. Brief temperature >25°C (77°F) should be avoided.
Verelan PM: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59 to 86°F). Protect from moisture.
Oral: Treatment of hypertension (all oral products) (FDA approved in adults); angina pectoris (vasospastic, chronic stable, unstable) (Calan, Covera-HS) (FDA approved in adults); supraventricular tachyarrhythmia [PSVT (prophylaxis), atrial fibrillation/flutter (rate control)] (Calan) (FDA approved in adults)
IV: Supraventricular tachyarrhythmia [PSVT; atrial fibrillation/flutter (rate control)] (FDA approved in all ages)
Calan may be confused with Colace, dilTIAZem
Covera HS (DSC) may be confused with Covaryx HS
Isoptin may be confused with Isopto Tears
Verelan may be confused with Voltaren
KIDs List: Verapamil, when used in infants <1 year of age, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list; use should be avoided due to risk of asystole (weak recommendation; low quality of evidence) (PPA [Meyers 2020]).
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).
Significant differences exist between oral and IV dosing. Use caution when converting from one route of administration to another.
Dilacor [Brazil] may be confused with Dilacor XR brand name for dilTIAZem [US]
Substrate of CYP1A2 (Minor), CYP2B6 (Minor), CYP2C9 (Minor), CYP2E1 (Minor), CYP3A4 (Major), P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (Weak), CYP3A4 (Moderate), P-glycoprotein;
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.
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
Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase 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
Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase 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
Acrivastine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Acrivastine. Risk C: Monitor
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider Therapy Modification
ALfentanil: CYP3A4 Inhibitors (Moderate) may increase 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: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Alfuzosin. Risk C: Monitor
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Aliskiren. Risk C: Monitor
Alitretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Alitretinoin (Systemic). Risk C: Monitor
ALPRAZolam: CYP3A4 Inhibitors (Moderate) may increase 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 increase hypotensive effects 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 increase bradycardic effects of Amiodarone. Sinus arrest has been reported. Risk C: Monitor
AmLODIPine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of AmLODIPine. Risk C: Monitor
Amphetamines: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Apixaban: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase serum concentration of Apixaban. Risk C: Monitor
Aprepitant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Aprepitant. Risk X: Avoid
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor
ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase 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
Aspirin: Calcium Channel Blockers (Nondihydropyridine) may increase antiplatelet effects of Aspirin. Risk C: Monitor
Atazanavir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Atazanavir. Risk C: Monitor
Atogepant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Atogepant. Risk C: Monitor
Atorvastatin: May increase serum concentration of Verapamil. Verapamil may increase serum concentration of Atorvastatin. Management: Consider using lower doses of atorvastatin when used together with verapamil, and monitor closely for signs of HMG-CoA reductase inhibitor toxicity (eg, myositis, rhabdomyolysis, hepatotoxicity). Risk D: Consider Therapy Modification
Atosiban: Calcium Channel Blockers may increase adverse/toxic effects of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Risk C: Monitor
Avanafil: CYP3A4 Inhibitors (Moderate) may increase 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 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 serum concentration of Axitinib. Risk C: Monitor
Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Barnidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Barnidipine. Risk C: Monitor
Bedaquiline: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bedaquiline. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Bedaquiline. Risk C: Monitor
Benidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Benidipine. Risk C: Monitor
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benzhydrocodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor
Beta-Acetyldigoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Beta-Acetyldigoxin. Risk C: Monitor
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Bilastine. Risk X: Avoid
Blonanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Blonanserin. Risk C: Monitor
Bortezomib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bortezomib. Risk C: Monitor
Bosutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bosutinib. Risk X: Avoid
Bradycardia-Causing Agents: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase 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
Brigatinib: CYP3A4 Inhibitors (Moderate) may increase 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 increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase 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 decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Budesonide (Oral Inhalation). Risk C: Monitor
Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Budesonide (Topical). Risk X: Avoid
Buprenorphine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Buprenorphine. Risk C: Monitor
BusPIRone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of BusPIRone. Risk C: Monitor
Cabozantinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cabozantinib. Risk C: Monitor
Calcium Salts: May decrease therapeutic effects of Calcium Channel Blockers. Risk C: Monitor
Cannabis: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor
Capivasertib: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of CarBAMazepine. CarBAMazepine may decrease 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 increase AV-blocking effects of Cardiac Glycosides. Calcium Channel Blockers (Nondihydropyridine) may increase serum concentration of Cardiac Glycosides. Risk C: Monitor
Cariprazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cariprazine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Cariprazine. Management: Cariprazine dose adjustments are recommended and depend upon whether a patient is initiating a moderate CYP3A4 inhibitor or cariprazine, as well as cariprazine indication. See full mono for details. Some non-US labels contraindicate this combination. Risk D: Consider Therapy Modification
Celiprolol: Verapamil may increase bradycardic effects of Celiprolol. Verapamil may increase serum concentration of Celiprolol. Management: Concomitant use of verapamil and celiprolol is not recommended, particularly in patients with pre-existing conduction abnormalities. When switching from one agent to the other, a drug-free period is recommended, and heart rate should be monitored closely. Risk D: Consider Therapy Modification
Ceritinib: Bradycardia-Causing Agents may increase bradycardic effects 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 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 serum concentration of Calcium Channel Blockers. Risk C: Monitor
Cisapride: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Clindamycin (Systemic). Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CloZAPine: CYP1A2 Inhibitors (Weak) may increase serum concentration of CloZAPine. Risk C: Monitor
Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase 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 active metabolite exposure of Codeine. Risk C: Monitor
Colchicine: CYP3A4 Inhibitors (Moderate) may increase 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
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider Therapy Modification
Conivaptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Conivaptan. Risk C: Monitor
Copanlisib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Copanlisib. Risk C: Monitor
Crizotinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Crizotinib. Risk C: Monitor
CycloSPORINE (Systemic): Calcium Channel Blockers (Nondihydropyridine) may decrease metabolism of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may decrease metabolism of Calcium Channel Blockers (Nondihydropyridine). Risk C: Monitor
CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Verapamil. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Verapamil. Management: Consider alternatives to this combination. If combined, monitor for reduced verapamil efficacy. Verapamil dose increases may be necessary. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Verapamil. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Verapamil. Risk C: Monitor
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase active metabolite exposure of Dabigatran Etexilate. Risk C: Monitor
Dabrafenib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dabrafenib. Risk C: Monitor
Dantrolene: May increase hyperkalemic effects of Calcium Channel Blockers. Dantrolene may increase negative inotropic effects of Calcium Channel Blockers. Risk X: Avoid
Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase 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 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 serum concentration of Darifenacin. Risk C: Monitor
Dasatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dasatinib. Risk C: Monitor
Deflazacort: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure 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 serum concentration of Delamanid. Risk C: Monitor
DexAMETHasone (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of DexAMETHasone (Systemic). Risk C: Monitor
Dexmethylphenidate: May decrease therapeutic effects of Antihypertensive Agents. Risk C: Monitor
DiazePAM: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DiazePAM. Risk C: Monitor
Diazoxide Choline: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Diazoxide Choline. Risk C: Monitor
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Dienogest: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dienogest. Risk C: Monitor
Digitoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digitoxin. Risk C: Monitor
DilTIAZem: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DilTIAZem. Risk C: Monitor
Disopyramide: Verapamil may increase adverse/toxic effects of Disopyramide. Of particular concern is the potential for profound depression of myocardial contractility. Management: Concurrent use of disopyramide within 48 hours prior to or 24 hours after verapamil should be avoided. Risk X: Avoid
DOCEtaxel: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DOCEtaxel. Risk C: Monitor
Dofetilide: Verapamil may increase serum concentration of Dofetilide. Risk X: Avoid
Domperidone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Domperidone. Risk X: Avoid
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor
DroNABinol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DroNABinol. Risk C: Monitor
Dronedarone: Calcium Channel Blockers (Nondihydropyridine) may increase AV-blocking effects of Dronedarone. Other electrophysiologic effects of Dronedarone may also be increased. Calcium Channel Blockers (Nondihydropyridine) may increase serum concentration of Dronedarone. Dronedarone may increase 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 increase hypotensive effects of DULoxetine. Risk C: Monitor
Ebastine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ebastine. Risk C: Monitor
Edoxaban: Verapamil may increase serum concentration of Edoxaban. Management: In patients treated for DVT/PE, reduce the edoxaban dose to 30 mg daily when combined with verapamil. No dose adjustment is recommended for patients treated for atrial fibrillation. Monitor for increased edoxaban toxicities (ie, bleeding) when combined. Risk D: Consider Therapy Modification
Elacestrant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elacestrant. Risk X: Avoid
Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elbasvir and Grazoprevir. Risk C: Monitor
Eletriptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eletriptan. Risk X: Avoid
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase 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 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: Verapamil may increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Verapamil. Management: Avoid use of encorafenib and verapamil 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 verapamil efficacy. Risk D: Consider Therapy Modification
Ensartinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ensartinib. Risk X: Avoid
Ensartinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ensartinib. Risk X: Avoid
Entrectinib: CYP3A4 Inhibitors (Moderate) may increase 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 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 serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor
Erlotinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Erlotinib. Risk C: Monitor
Erythromycin (Systemic): May increase serum concentration of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase serum concentration of Erythromycin (Systemic). Risk C: Monitor
Esmolol: Calcium Channel Blockers (Nondihydropyridine) may increase bradycardic effects 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 serum concentration of Eszopiclone. Risk C: Monitor
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide Phosphate. Risk C: Monitor
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide. Risk C: Monitor
Etrasimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Etravirine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Etravirine. Risk C: Monitor
Everolimus: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase serum concentration of Everolimus. Management: Afinitor: For TSC-associated SEGA or TSC-associated seizures reduce everolimus dose 50%. For other Afinitor indications, reduce everolimus dose to 2.5 mg/day, increase to 5 mg/day if tolerated. Zortress: Monitor for increased everolimus concentrations. Risk D: Consider Therapy Modification
Fedratinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fedratinib. Risk C: Monitor
Felodipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Felodipine. Risk C: Monitor
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase 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 increase arrhythmogenic effects of Fexinidazole. Risk X: Avoid
Fezolinetant: CYP1A2 Inhibitors (Weak) may increase serum concentration of Fezolinetant. Risk X: Avoid
Finerenone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Finerenone. Risk C: Monitor
Fingolimod: Bradycardia-Causing Agents may increase bradycardic effects 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
Flecainide: Verapamil may increase adverse/toxic effects of Flecainide. In particular, this combination may significantly impair myocardial contractility and AV nodal conduction. Risk C: Monitor
Flibanserin: CYP3A4 Inhibitors (Moderate) may increase 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
Flunarizine: May increase therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Fluticasone (Nasal): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fluticasone (Nasal). Risk C: Monitor
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fluticasone (Oral Inhalation). Risk C: Monitor
Fosamprenavir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fosamprenavir. Risk C: Monitor
Fosaprepitant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fosaprepitant. Risk X: Avoid
Fosphenytoin-Phenytoin: Calcium Channel Blockers (Nondihydropyridine) may increase serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may decrease 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 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
Futibatinib: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase serum concentration of Futibatinib. Risk C: Monitor
Gepirone: CYP3A4 Inhibitors (Moderate) may increase 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
Gepotidacin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Gepotidacin. Risk C: Monitor
Gilteritinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Gilteritinib. Risk C: Monitor
Glasdegib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Glasdegib. Risk C: Monitor
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
Grapefruit Juice: May increase serum concentration of Verapamil. Risk C: Monitor
GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase 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
Halofantrine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Halofantrine. Risk C: Monitor
Herbal Products with Blood Pressure Increasing Effects: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of HYDROcodone. Risk C: Monitor
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase 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 increase adverse/toxic effects of Ifosfamide. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor
Iloperidone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Iloperidone. Risk C: Monitor
Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Indoramin: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Inhalational Anesthetics: May increase hypotensive effects of Calcium Channel Blockers. Risk C: Monitor
Irinotecan Products: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Irinotecan Products. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Irinotecan Products. Specifically, the serum concentration of SN-38 may be increased. Risk C: Monitor
Isavuconazonium Sulfate: May increase serum concentration of Verapamil. Verapamil may increase serum concentration of Isavuconazonium Sulfate. Risk C: Monitor
Isocarboxazid: May increase antihypertensive effects of Antihypertensive Agents. Risk X: Avoid
Isradipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Isradipine. Risk C: Monitor
Itraconazole: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Itraconazole. Risk C: Monitor
Ivabradine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ivabradine. Risk X: Avoid
Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase 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 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 serum concentration of Ixabepilone. Risk C: Monitor
Lacosamide: Bradycardia-Causing Agents may increase AV-blocking effects of Lacosamide. Risk C: Monitor
Landiolol: Bradycardia-Causing Agents may increase bradycardic effects of Landiolol. Risk X: Avoid
Lapatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lapatinib. Risk C: Monitor
Larotrectinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Larotrectinib. Risk C: Monitor
Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Risk D: Consider Therapy Modification
Lemborexant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lemborexant. Risk X: Avoid
Leniolisib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Leniolisib. Risk C: Monitor
Lercanidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lercanidipine. Risk C: Monitor
Levamlodipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levamlodipine. Risk C: Monitor
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Levoketoconazole: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levoketoconazole. Risk C: Monitor
Levomethadone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levomethadone. Risk C: Monitor
Levomilnacipran: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levomilnacipran. Risk C: Monitor
Lidocaine (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lidocaine (Systemic). CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Lidocaine (Systemic). Specifically, concentrations of monoethylglycinexylidide (MEGX) may be increased. Risk C: Monitor
Lithium: Calcium Channel Blockers (Nondihydropyridine) may increase neurotoxic effects of Lithium. Calcium Channel Blockers (Nondihydropyridine) may increase serum concentration of Lithium. Decreased or unaltered lithium concentrations have also been reported with this combination. Risk C: Monitor
Lomitapide: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lomitapide. Risk X: Avoid
Lonafarnib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lonafarnib. Risk C: Monitor
Loop Diuretics: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Lopinavir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lopinavir. Risk C: Monitor
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Lovastatin: Verapamil may increase 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 verapamil. Monitor closely for signs of lovastatin toxicity (eg, myositis, rhabdomyolysis). Risk D: Consider Therapy Modification
Lumateperone: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Lurasidone. Management: Reduce the lurasidone dose by half when initiating therapy with a moderate CYP3A4 inhibitor. If initiating lurasidone in a patient already receiving a moderate CYP3A4 inhibitor, start lurasidone at 20 mg/day with a max dose of 80 mg/day. Risk D: Consider Therapy Modification
Lurbinectedin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, reduce the lurbinectedin dose by 50%. Risk D: Consider Therapy Modification
Macitentan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Macitentan. Risk C: Monitor
Manidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Manidipine. Risk C: Monitor
Maraviroc: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Maraviroc. Risk C: Monitor
Mavacamten: Calcium Channel Blockers (Nondihydropyridine) may increase adverse/toxic effects of Mavacamten. Specifically, negative inotropic effects may be increased. Calcium Channel Blockers (Nondihydropyridine) may increase 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 serum concentration of Mavorixafor. Risk C: Monitor
Meperidine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Meperidine. Risk C: Monitor
Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor
MetFORMIN: Verapamil may decrease therapeutic effects of MetFORMIN. Risk C: Monitor
Methadone: CYP3A4 Inhibitors (Moderate) may increase 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 decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
MethylPREDNISolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of MethylPREDNISolone. Risk C: Monitor
Methysergide: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Methysergide. Risk X: Avoid
Midazolam: CYP3A4 Inhibitors (Moderate) may increase 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 increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Midostaurin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Midostaurin. Risk C: Monitor
MiFEPRIStone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of MiFEPRIStone. Risk C: Monitor
Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mirodenafil. Risk C: Monitor
Mitapivat: CYP3A4 Inhibitors (Moderate) may increase 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 active metabolite exposure of Mobocertinib. CYP3A4 Inhibitors (Moderate) may increase 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 increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Morphine (Systemic). Risk C: Monitor
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Nadolol. Risk C: Monitor
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Naldemedine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Naldemedine. Risk C: Monitor
Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nalfurafine. Risk C: Monitor
Naloxegol: CYP3A4 Inhibitors (Moderate) may increase 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: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase serum concentration of Neratinib. Risk X: Avoid
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may increase neuromuscular-blocking effects of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
NIFEdipine (Topical): CYP3A4 Inhibitors (Moderate) may increase serum concentration of NIFEdipine (Topical). Risk C: Monitor
NIFEdipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of NIFEdipine. Risk C: Monitor
NiMODipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of NiMODipine. Risk C: Monitor
Nintedanib: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase serum concentration of Nintedanib. Risk C: Monitor
Nirogacestat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nirogacestat. Risk X: Avoid
Nisoldipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nisoldipine. Risk X: Avoid
Nitrendipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nitrendipine. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Obinutuzumab: May increase hypotensive effects 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 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 serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Olmutinib. Risk C: Monitor
Omaveloxolone: CYP3A4 Inhibitors (Moderate) may increase 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
OxyCODONE: CYP3A4 Inhibitors (Moderate) may increase serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor
Ozanimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
PACLitaxel (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Conventional). Risk C: Monitor
PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor
Pacritinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pacritinib. Risk C: Monitor
Palbociclib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Palbociclib. Risk C: Monitor
Palovarotene: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Panobinostat. Risk C: Monitor
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of PAZOPanib. Risk X: Avoid
Pemigatinib: CYP3A4 Inhibitors (Moderate) may increase 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 increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Perazine: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Pexidartinib: CYP3A4 Inhibitors (Moderate) may increase 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 increase hypotensive effects of Pholcodine. Risk C: Monitor
Pimavanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pimavanserin. Risk C: Monitor
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease metabolism of Pimecrolimus. Risk C: Monitor
Pimozide: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pimozide. Risk X: Avoid
Piperaquine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Piperaquine. Risk C: Monitor
Pirtobrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pirtobrutinib. Risk C: Monitor
PONATinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of PONATinib. Risk C: Monitor
Ponesimod: Bradycardia-Causing Agents may increase bradycardic effects 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: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase 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: Verapamil may increase hypotensive effects of Pramipexole. Verapamil may increase serum concentration of Pramipexole. Risk C: Monitor
Prazepam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Prazepam. Risk C: Monitor
Praziquantel: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Praziquantel. Risk C: Monitor
Prazosin: Antihypertensive Agents may increase hypotensive effects of Prazosin. Risk C: Monitor
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
QUEtiapine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of QUEtiapine. Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor
QuiNIDine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of QuiNIDine. Risk C: Monitor
QuiNINE: CYP3A4 Inhibitors (Moderate) may increase serum concentration of QuiNINE. Risk C: Monitor
Ranolazine: CYP3A4 Inhibitors (Moderate) may increase 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 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 increase serum concentration of Regorafenib. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Regorafenib. Risk C: Monitor
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider Therapy Modification
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider Therapy Modification
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Repotrectinib. Risk X: Avoid
Ribociclib: May increase serum concentration of Verapamil. Verapamil may increase serum concentration of Ribociclib. Risk C: Monitor
Rifabutin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rifabutin. Risk C: Monitor
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RifAXIMin. Risk C: Monitor
Rimegepant: CYP3A4 Inhibitors (Moderate) may increase 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
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider Therapy Modification
Riociguat: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase serum concentration of Riociguat. Risk C: Monitor
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RisperiDONE. Risk C: Monitor
Rivaroxaban: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase serum concentration of Rivaroxaban. Management: No action is needed in patients with normal renal function. Do not use this combination in patients with estimated creatinine clearance 15 to 80 mL/min unless prospective benefits outweigh the risks. Risk D: Consider Therapy Modification
Roflumilast-Containing Products: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Roflumilast-Containing Products. Risk C: Monitor
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RomiDEPsin. Risk C: Monitor
Rupatadine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rupatadine. Risk C: Monitor
Ruxolitinib (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ruxolitinib (Systemic). Risk C: Monitor
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Salmeterol. Risk C: Monitor
Saquinavir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Saquinavir. Risk C: Monitor
Saquinavir: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Saquinavir. Risk C: Monitor
SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of SAXagliptin. Risk C: Monitor
Selpercatinib: CYP3A4 Inhibitors (Moderate) may increase 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 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 serum concentration of Sertindole. Risk X: Avoid
Sildenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sildenafil. Risk C: Monitor
Silodosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Silodosin. Risk C: Monitor
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Simeprevir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Simeprevir. Risk X: Avoid
Simvastatin: Verapamil may increase serum concentration of Simvastatin. Verapamil may increase active metabolite exposure of Simvastatin. Management: Carefully consider the potential risks and benefits of this combination. If coadministered, limit adult simvastatin dose to 10 mg daily, and monitor closely for signs of simvastatin toxicity (eg, myositis, rhabdomyolysis). Risk D: Consider Therapy Modification
Sincalide: Drugs that Affect Gallbladder Function may decrease therapeutic effects 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 increase bradycardic effects 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 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 (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider Therapy Modification
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
Solifenacin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Solifenacin. Risk C: Monitor
Sonidegib: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Sparsentan. Risk C: Monitor
SUFentanil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of SUFentanil. Risk C: Monitor
SUNItinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of SUNItinib. Risk C: Monitor
Suvorexant: CYP3A4 Inhibitors (Moderate) may increase 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
Suzetrigine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Suzetrigine. Management: Reduce suzetrigine dose as follows: initiate with 100 mg for 1 dose; then 12 hours after first dose, give 50 mg every 12 hours for doses 2, 3, and 4; then 50 mg every 24 hours for dose 5 and thereafter. Risk D: Consider Therapy Modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tacrolimus (Topical): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tacrolimus (Topical). Risk C: Monitor
Tadalafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tadalafil. Risk C: Monitor
Talazoparib: Verapamil may increase serum concentration of Talazoparib. Management: In breast cancer, if concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. In prostate cancer, monitor patients for increased adverse events. Risk D: Consider Therapy Modification
Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tamsulosin. Risk C: Monitor
Tazemetostat: CYP3A4 Inhibitors (Moderate) may increase 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 active metabolite exposure of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Risk C: Monitor
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Teniposide. Risk C: Monitor
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Terazosin: Antihypertensive Agents may increase hypotensive effects of Terazosin. Risk C: Monitor
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor
Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tetrahydrocannabinol. Risk C: Monitor
Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase 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
Theophylline Derivatives: Verapamil may increase serum concentration of Theophylline Derivatives. Risk C: Monitor
Thiotepa: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Thiotepa. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Thiotepa. Risk C: Monitor
Ticagrelor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ticagrelor. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Ticagrelor. Risk C: Monitor
Tilidine: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Tilidine. CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tilidine. Risk C: Monitor
TiZANidine: CYP1A2 Inhibitors (Weak) may increase serum concentration of TiZANidine. Management: Avoid the use of tizanidine with weak CYP1A2 inhibitors when possible. If combined, monitor closely for increased tizanidine toxicities (eg, hypotension, bradycardia, drowsiness). Tizanidine dose reduction or discontinuation may be necessary. Risk D: Consider Therapy Modification
Tofacitinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tofacitinib. Risk C: Monitor
Tolterodine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tolterodine. Risk C: Monitor
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase 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
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Toremifene: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Toremifene. Risk C: Monitor
Trabectedin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Trabectedin. Risk C: Monitor
TraMADol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of TraMADol. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of TraMADol. Risk C: Monitor
TraZODone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of TraZODone. Risk C: Monitor
Tretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tretinoin (Systemic). Risk C: Monitor
Triamcinolone (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Triamcinolone (Systemic). Risk C: Monitor
Triazolam: CYP3A4 Inhibitors (Moderate) may increase 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 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 serum concentration of Udenafil. Risk C: Monitor
Urapidil: Antihypertensive Agents may increase hypotensive effects of Urapidil. Risk C: Monitor
Valbenazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Valbenazine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Valbenazine. Risk C: Monitor
Vamorolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vamorolone. Risk C: Monitor
Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Management: Age- and weight-specific dose reductions of vanzacaftor, tezacaftor, and deutivacaftor are recommended. Please see full Interact monograph or labeling for details. Risk D: Consider Therapy Modification
Vardenafil: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Vemurafenib. Risk C: Monitor
Venetoclax: CYP3A4 Inhibitors (Moderate) may increase 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
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vilazodone. Risk C: Monitor
VinBLAStine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of VinBLAStine. Risk C: Monitor
VinCRIStine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of VinCRIStine. Risk X: Avoid
Vindesine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vindesine. Risk C: Monitor
Vinflunine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vinflunine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Vinflunine. Risk C: Monitor
Voclosporin: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Vorapaxar. Risk C: Monitor
Zanubrutinib: CYP3A4 Inhibitors (Moderate) may increase 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 serum concentration of Zopiclone. Risk C: Monitor
Zuranolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Zuranolone. Risk C: Monitor
Ethanol: Verapamil may increase blood ethanol levels and prolong its effects. Management: Monitor patients and caution about increased effects.
Food: Grapefruit juice may increase the serum concentration of verapamil. Management: Use with caution and monitor for effects.
Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be used in patients trying to conceive. Verapamil 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).
Verapamil may be effective for prevention of migraines. In general, preventive treatment for migraine in patients trying to become pregnant should be avoided. Options for patients planning a pregnancy should be considered as part of a shared decision-making process. Nonpharmacologic interventions should be considered initially. When needed, preventive treatment should be individualized considering the available safety data and needs of the patient should pregnancy occur. A gradual discontinuation of preventive medications is generally preferred when the decision is made to stop treatment prior to conception (ACOG 2022; AHS [Ailani 2021]).
Verapamil crosses the placenta.
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 hypertension is initiated during pregnancy, agents other than verapamil may be preferred (ACOG 2019; ESC [Cífková 2020]; ESC [Regitz-Zagrosek 2018]; SOGC [Magee 2022]).
Verapamil may be used IV for the acute treatment of supraventricular tachycardia (SVT) in patients who are pregnant when adenosine or beta-blockers are ineffective or contraindicated. Verapamil may also be used for the ongoing management of SVT in highly symptomatic patients. The lowest effective dose is recommended; avoid use during the first trimester if possible (ACC/AHA/HRS [Page 2016]). Additional guidelines are available for management of cardiovascular diseases during pregnancy (ESC [Regitz-Zagrosek 2018]).
In general, preventive treatment for migraine should be avoided during pregnancy. Options for pregnant patients should be considered as part of a shared decision-making process. Nonpharmacologic interventions should be considered initially. When needed, preventive treatment should be individualized considering the available safety data, the potential for adverse maternal and fetal events, and needs of the patient (ACOG 2022; AHS [Ailani 2021]). If preventive therapy is needed, verapamil may be used (ACOG 2022).
Verapamil is used for the prevention of cluster headache (AHS [Robbins 2016]). Verapamil may be used when prophylaxis is needed in pregnant patients; however, use should be avoided during the third trimester if possible (Bjørk 2021).
Monitor blood pressure and heart rate; periodic liver function tests; ECG, especially with renal and/or hepatic impairment
Consult individual institutional policies and procedures.
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; slows automaticity and conduction of AV node.
Note: Lean body weight affects verapamil pharmacokinetics inversely.
Onset of action: Peak effect: Oral: Immediate release: 1 to 2 hours (Singh 1978); IV bolus: 3 to 5 minutes.
Duration: Oral: Immediate release: 6 to 8 hours; IV: 0.5 to 6 hours (Marik 2011).
Absorption: Oral: Well absorbed (>90%).
Distribution: Vd: 3.89 L/kg (Storstein 1984).
Protein binding: ~90%.
Metabolism: Hepatic (extensive first-pass effect) via multiple CYP isoenzymes; primary metabolite is norverapamil (~20% pharmacologic activity of verapamil).
Bioavailability: Oral: 20% to 35%.
Half-life elimination:
Injection: Terminal: 2 to 5 hours.
Oral:
Immediate release: Single dose: 2.8 to 7.4 hours; Multiple doses: 4.5 to 12 hours.
Extended release: ~12 hours.
Severe hepatic impairment: 14 to 16 hours.
Time to peak, serum: Oral:
Immediate release: 1 to 2 hours.
Extended release:
Calan SR: 5.21 hours.
Verelan: 7 to 9 hours.
Verelan PM: ~11 hours; Drug release delayed ~4 to 5 hours.
Excretion: Urine (~70% as metabolites, 3% to 4% as unchanged drug); feces (≥16%).
Hepatic function impairment: Metabolism is delayed, half-life is prolonged, volume of distribution is increased, and plasma clearance is reduced to ~30% of normal.
Older adult: Elimination half-life may be prolonged and bioavailability may be higher in older adults.
Sex: Conflicting data suggest that verapamil clearance decreased with age in females to a greater degree than in males.
