Version May 2024
When pregnancy is detected, discontinue trandolapril/verapamil as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
Note: Not for initial therapy; dose is individualized; may be substituted for individual components in patients currently maintained on both agents separately.
Hypertension: Oral: Trandolapril 1 to 4 mg/verapamil 180 to 240 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
CrCl <30 mL/minute: Dosage adjustment recommended; use with caution.
Hemodialysis: Dosage adjustment recommended; use with caution.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, since verapamil is hepatically metabolized, lower doses are recommended.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Also see individual agents.
1% to 10%:
Cardiovascular: Bradycardia (2%), chest pain (2%), first-degree atrioventricular block (4%)
Gastrointestinal: Constipation (3%), diarrhea (2%), nausea (2%)
Hepatic: Increased liver enzymes (3%; including increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, increased serum bilirubin)
Nervous system: Dizziness (3%), fatigue (3%)
Neuromuscular & skeletal: Arthralgia (2%), limb pain (1%)
Respiratory: Bronchitis (2%), cough (5%), dyspnea (1%)
<1%:
Cardiovascular: Hypotension, presyncope
Hypersensitivity: Angioedema
Frequency not defined:
Cardiovascular: Syncope
Endocrine & metabolic: Hyponatremia, increased lactate dehydrogenase
Hematologic & oncologic: Decreased neutrophils, decreased platelet count, decreased white blood cell count, lymphocytopenia
Hypersensitivity to trandolapril, verapamil, or any component of the formulation; severe left ventricular dysfunction; hypotension (systolic pressure <90 mm Hg); cardiogenic shock; sick sinus syndrome (except in patients with a functioning pacemaker); atrial flutter or atrial fibrillation with an accessory bypass tract (eg, Wolff-Parkinson-White, Lown-Ganong-Levine syndromes); history of angioedema related to previous treatment with an ACE inhibitor; coadministration with or within 36 hours of switching to or from a neprilysin inhibitor (eg, sacubitril); second- or third-degree AV block (except in patients with a functioning pacemaker); coadministration with aliskiren in patients with diabetes; coadministration with flibanserin
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Complicated MI (ventricular failure manifested by pulmonary congestion); marked bradycardia; hypotensive or hemodynamically unstable states; hemodynamically significant bilateral artery stenosis or severe artery stenosis of a solitary functioning kidney; severe renal impairment (CrCl <30 mL/minute); dialysis; hepatic cirrhosis with ascites; concomitant use with ACE inhibitors or angiotensin receptor blockers (ARBs) medications in patients with type 1 or 2 diabetes mellitus, moderate to severe renal impairment (GFR <60 mL/minute/1.73 m2), hyperkalemia (>5 mMol/L), or with heart failure who are hypotensive; concomitant use with aliskiren in patients with moderate to severe renal impairment (GFR <60 mL/minute/1.73 m2), hyperkalemia (>5 mMol/L), or with heart failure who are hypotensive; concomitant use with intravenous beta-adrenergic antagonists (except in an intensive care unit); concomitant use with ivabradine; hereditary/idiopathic angioedema; women who are pregnant, planning to become pregnant, or women of childbearing potential and not using adequate contraception; breastfeeding; children and adolescents <18 years of age
Concerns related to adverse effects:
• Angioedema: At any time during treatment (especially following first dose) angioedema may occur rarely with ACE inhibitors; it may involve the head and neck (potentially compromising the airway) or the intestine (presenting with abdominal pain). African-Americans and patients with idiopathic or hereditary angioedema may be at an increased risk. Risk may also be increased with concomitant use of mTOR inhibitor (eg, everolimus) therapy or a neprilysin inhibitor (eg, sacubitril). Prolonged frequent monitoring may be required especially if tongue, glottis, or larynx are involved as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Aggressive early and appropriate management is critical. Use in patients with previous angioedema associated with ACE inhibitor therapy is contraindicated.
• Conduction abnormalities: Verapamil can cause first-degree AV block and transient bradycardia, sometimes accompanied by nodal escape rhythms; other conduction abnormalities are rare. Marked first-degree AV block or progressive development to second- or third-degree AV block requires a dose discontinuation. Use is contraindicated in patients with sick sinus syndrome, second- or third-degree AV block (except in patients with a functioning pacemaker), or an accessory bypass tract (eg, Wolff-Parkinson-White syndrome).
• Cough: An ACE inhibitor cough is a dry, hacking, nonproductive one that usually occurs within the first few months of treatment and should generally resolve within 1 to 4 weeks after discontinuation of the ACE inhibitor. Other causes of cough should be considered (eg, pulmonary congestion in patients with heart failure) and excluded prior to discontinuation.
• Hematologic effects: Another ACE Inhibitor, captopril, has been associated with neutropenia with myeloid hypoplasia and agranulocytosis; anemia and thrombocytopenia have also occurred. Patients with renal impairment are at high risk of developing neutropenia. Patients with both renal impairment and collagen vascular disease (eg, systemic lupus erythematosus) are at an even higher risk of developing neutropenia. Periodically monitor CBC with differential in these patients.
• Hepatic effects: Elevations of transaminases have been reported with verapamil. Several cases of hepatocellular injury related to verapamil have been proven by rechallenge. A rare toxicity associated with ACE inhibitors includes cholestatic jaundice, which may progress to fulminant hepatic necrosis (same fatal). Discontinue therapy if marked elevation of hepatic transaminases or jaundice occurs.
• Hyperkalemia: May occur with ACE inhibitors; risk factors include renal dysfunction, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely.
• Hypersensitivity reactions: Anaphylactic/anaphylactoid reactions can occur with ACE inhibitors. Severe anaphylactoid reactions may be seen during hemodialysis (eg, CVVHD) with high-flux dialysis membranes (eg, AN69), and rarely, during low density lipoprotein apheresis with dextran sulfate cellulose. Rare cases of anaphylactoid reactions have been reported in patients undergoing sensitization treatment with hymenoptera (bee, wasp) venom while receiving ACE inhibitors.
• Hypotension/syncope: Symptomatic hypotension with or without syncope can occur (usually with the first several doses); effects are most often observed in volume-depleted patients; correct volume depletion prior to initiation; close monitoring of patient is required especially with initial dosing and dosing increases; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Although dose reduction may be necessary, hypotension is not a reason for discontinuation of future ACE inhibitor use especially in patients with heart failure where a reduction in systolic blood pressure is a desirable observation.
• Renal function deterioration: ACE inhibitors may be associated with deterioration of renal function and/or increases in BUN and serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose glomerular filtration rate (GFR) is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small, benign increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function (Bakris 2000).
Disease-related concerns:
• Aortic stenosis: Use trandolapril with caution in patients with aortic stenosis; may reduce coronary perfusion resulting in ischemia.
• Arrhythmia: Verapamil is considered contraindicated in patients with wide complex tachycardias unless known to be supraventricular in origin; severe hypotension likely to occur upon administration (ACLS [Neumar] 2010).
• Attenuated neuromuscular transmission: Decreased neuromuscular transmission has been reported with verapamil; use with caution in patients with attenuated neuromuscular transmission (Duchenne muscular dystrophy, myasthenia gravis); dosage reduction may be required.
• Cardiovascular disease: Initiation of therapy in patients with ischemic heart disease or cerebrovascular disease warrants close observation due to the potential consequences posed by falling blood pressure (eg, MI, stroke). Fluid replacement, if needed, may restore blood pressure; therapy may then be resumed. Discontinue therapy in patients whose hypotension recurs.
• Collagen vascular disease: Use trandolapril with caution in patients with collagen vascular disease especially with concomitant renal impairment; may be at increased risk for hematologic toxicity.
• Heart failure: Avoid verapamil in heart failure; can exacerbate condition. Contraindicated with severe left ventricular dysfunction (eg, ejection fraction <30%, pulmonary wedge pressure >20 mm Hg, severe symptoms of cardiac failure) or cardiogenic shock. In patients with any degree of ventricular dysfunction receiving a beta blocker, avoid use.
• Hepatic impairment: Use with caution in patients with hepatic impairment; lower doses are recommended.
• Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Use with caution in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction (especially those with high gradients, advanced heart failure, or sinus bradycardia); reduction in afterload may worsen symptoms associated with this condition (AHA/ACC [Ommen 2020]). Verapamil should not be used in patients with systemic hypotension or severe dyspnea at rest (Nishimura 2004).
• Renal artery stenosis: Use trandolapril with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment is recommended.
Special populations:
• Black patients: ACE inhibitor effectiveness is less in black patients than in nonblacks. In addition, ACE inhibitors cause a higher rate of angioedema in black than in non-black patients.
• Pregnancy: [US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.
Other warnings/precautions:
• Surgery: In patients on chronic ACE inhibitor therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; use with caution before, during, or immediately after major surgery. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. Use of ACE inhibitors perioperatively will blunt angiotensin II formation and may result in hypotension. However, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis 2011).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Variable Release, Oral:
Tarka: Trandolapril 2 mg [immediate release] and verapamil hydrochloride 180 mg [sustained release] [DSC]; Trandolapril 2 mg [immediate release] and verapamil hydrochloride 240 mg [sustained release] [DSC]; Trandolapril 4 mg [immediate release] and verapamil hydrochloride 240 mg [sustained release] [DSC]
Generic: Trandolapril 1 mg [immediate release] and verapamil hydrochloride 240 mg [sustained release]; Trandolapril 2 mg [immediate release] and verapamil hydrochloride 180 mg [sustained release]; Trandolapril 2 mg [immediate release] and verapamil hydrochloride 240 mg [sustained release]; Trandolapril 4 mg [immediate release] and verapamil hydrochloride 240 mg [sustained release]
Yes
Tablet, controlled release (Trandolapril-Verapamil HCl ER Oral)
1-240 mg (per each): $5.82
2-180 mg (per each): $5.82
2-240 mg (per each): $5.82
4-240 mg (per each): $5.82
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.
Oral: Administer orally with food.
Bariatric surgery: Tablet, variable release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. ER tablets should be swallowed whole. Do not crush or chew. No alternative formulations are available unless broken into individual components. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, consider separating these medications into individual IR components to facilitate expected dose decrease or discontinuation requirement after bariatric surgery.
Hypertension: Management of hypertension
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]).
Refer to individual components.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Abemaciclib. Management: Monitor for increased abemaciclib toxicities if combined with moderate CYP3A4 inhibitors. Consider reducing the abemaciclib dose in 50 mg decrements if necessary. Risk C: Monitor therapy
Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Risk D: Consider therapy modification
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of ALfentanil. Management: If use of alfentanil and moderate CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider therapy modification
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Alfuzosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Alfuzosin. Risk C: Monitor therapy
Aliskiren: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Risk D: Consider therapy modification
Alitretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Alitretinoin (Systemic). Risk C: Monitor therapy
Allopurinol: Angiotensin-Converting Enzyme Inhibitors may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapy
ALPRAZolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ALPRAZolam. Management: Consider alternatives to this combination when possible. If combined, consider an alprazolam dose reduction and monitor for increased alprazolam effects and toxicities (eg, sedation, lethargy). Risk D: Consider therapy modification
Alteplase: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Alteplase. Specifically, the risk for angioedema may be increased. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amiodarone: Calcium Channel Blockers (Nondihydropyridine) may enhance the bradycardic effect of Amiodarone. Sinus arrest has been reported. Risk C: Monitor therapy
AmLODIPine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of AmLODIPine. Risk C: Monitor therapy
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Angiotensin II: Angiotensin-Converting Enzyme Inhibitors may enhance the therapeutic effect of Angiotensin II. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Use of telmisartan and ramipril is not recommended. It is not clear if any other combination of an ACE inhibitor and an ARB would be any safer. Consider alternatives when possible. Monitor blood pressure, renal function, and potassium if combined. Risk D: Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Apixaban: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase the serum concentration of Apixaban. Risk C: Monitor therapy
Aprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Aprepitant. Risk X: Avoid combination
Aprotinin: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy
ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor therapy
Aspirin: Calcium Channel Blockers (Nondihydropyridine) may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Astemizole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Astemizole. Management: Avoid concomitant use of astemizole and moderate CYP3A4 inhibitors whenever possible. If combined, monitor closely for increased astemizole toxicities, especially for QTc interval prolongation. Risk D: Consider therapy modification
Asunaprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir. Risk X: Avoid combination
Atazanavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Atazanavir. Risk C: Monitor therapy
Atogepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Atogepant. Risk C: Monitor therapy
Atorvastatin: May increase the serum concentration of Verapamil. Verapamil may increase the 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 enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Risk C: Monitor therapy
Avacopan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avacopan. Risk C: Monitor therapy
Avanafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil. Management: The maximum avanafil dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects (eg, hypotension, syncope, priapism). Risk D: Consider therapy modification
Avapritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avapritinib. Management: Avoid use of moderate CYP3A4 inhibitors with avapritinib. If this combination cannot be avoided, reduce the avapritinib dose to 100 mg daily for the treatment of GIST or to 50 mg daily for the treatment of advanced systemic mastocytosis. Risk D: Consider therapy modification
Axitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Axitinib. Risk C: Monitor therapy
AzaTHIOprine: Angiotensin-Converting Enzyme Inhibitors may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Barnidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Barnidipine. Risk C: Monitor therapy
Bedaquiline: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bedaquiline. Risk C: Monitor therapy
Benidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benidipine. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benzhydrocodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor therapy
Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination
Blonanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin. Risk C: Monitor therapy
Bortezomib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bortezomib. Risk C: Monitor therapy
Bosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib. Risk X: Avoid combination
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy
Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Risk C: Monitor therapy
Brigatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider therapy modification
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Risk D: Consider therapy modification
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Oral Inhalation). Risk C: Monitor therapy
Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic). Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and CYP3A4 inhibitors, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider therapy modification
Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Risk X: Avoid combination
Buprenorphine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Buprenorphine. Risk C: Monitor therapy
BusPIRone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of BusPIRone. Risk C: Monitor therapy
Cabozantinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
Cannabis: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor therapy
Capivasertib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Capivasertib. Management: If capivasertib is combined with moderate CYP3A4 inhibitors, reduce the capivasertib dose to 320 mg twice daily for 4 days, followed by 3 days off. Monitor patients closely for adverse reactions. Risk D: Consider therapy modification
CarBAMazepine: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Calcium Channel Blockers (Nondihydropyridine). Management: Consider alternatives to this combination when possible. If combined, monitor for increased carbamazepine concentrations and toxicities and monitor for decreased calcium channel blocker efficacy. Risk D: Consider therapy modification
Cardiac Glycosides: Calcium Channel Blockers (Nondihydropyridine) may enhance the AV-blocking effect of Cardiac Glycosides. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy
Cariprazine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Cariprazine. Specifically, concentrations of didesmethylcariprazine (DDCAR), the primary active metabolite of cariprazine, may increase. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cariprazine. Risk C: Monitor therapy
Celiprolol: Verapamil may enhance the bradycardic effect of Celiprolol. Verapamil may increase the 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 enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider therapy modification
Cilostazol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Cimetidine: May increase the serum concentration of Calcium Channel Blockers. Risk C: Monitor therapy
Cisapride: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cisapride. Management: Consider alternatives to this combination. Prescribing information for some moderate CYP3A4 inhibitors state coadministration with cisapride is contraindicated, while some others recommend monitoring and dose titration. Risk D: Consider therapy modification
Clindamycin (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Clindamycin (Systemic). Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy
CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib. Management: Avoid this combination when possible. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose from 60 mg to 20 mg daily. Avoid concomitant use in patients already receiving reduced cobimetinib doses. Risk D: Consider therapy modification
Codeine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy
Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Avoidance, dose reduction, or increased monitoring for colchicine toxicity may be needed and will depend on brand, indication for colchicine use, renal/hepatic function, and use of a P-gp inhibitor. See full monograph for details. Risk D: Consider therapy modification
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of Conivaptan. Risk C: Monitor therapy
Copanlisib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Copanlisib. Risk C: Monitor therapy
Crizotinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Crizotinib. Risk C: Monitor therapy
CycloSPORINE (Systemic): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Risk C: Monitor therapy
CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Verapamil. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the 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 the serum concentration of Verapamil. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Verapamil. Risk C: Monitor therapy
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy
Dabrafenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dabrafenib. Risk C: Monitor therapy
Dantrolene: May enhance the hyperkalemic effect of Calcium Channel Blockers. Dantrolene may enhance the negative inotropic effect of Calcium Channel Blockers. Risk X: Avoid combination
Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4. Risk D: Consider therapy modification
Daridorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Daridorexant. Management: Limit the daridorexant dose to 25 mg, no more than once per night, when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Darifenacin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Darifenacin. Risk C: Monitor therapy
Dasatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dasatinib. Risk C: Monitor therapy
Deflazacort: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Risk D: Consider therapy modification
Delamanid: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Delamanid. Risk C: Monitor therapy
DexAMETHasone (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
DiazePAM: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DiazePAM. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dienogest: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dienogest. Risk C: Monitor therapy
DilTIAZem: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DilTIAZem. Risk C: Monitor therapy
Dipeptidyl Peptidase-IV Inhibitors: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Disopyramide: Verapamil may enhance the adverse/toxic effect 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 combination
DOCEtaxel: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOCEtaxel. Risk C: Monitor therapy
Dofetilide: Verapamil may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Domperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone. Risk X: Avoid combination
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy
DroNABinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DroNABinol. Risk C: Monitor therapy
Dronedarone: Calcium Channel Blockers (Nondihydropyridine) may enhance the AV-blocking effect of Dronedarone. Other electrophysiologic effects of Dronedarone may also be increased. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Dronedarone. Dronedarone may increase the serum concentration of Calcium Channel Blockers (Nondihydropyridine). Management: Use lower starting doses of the nondihydropyridine calcium channel blockers and only increase calcium channel blocker dose after obtaining ECG-based evidence that the combination is being well-tolerated. Monitor closely during coadministration. Risk D: Consider therapy modification
Drospirenone-Containing Products: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Ebastine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ebastine. Risk C: Monitor therapy
Edoxaban: Verapamil may increase the 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 the serum concentration of Elacestrant. Risk X: Avoid combination
Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elbasvir and Grazoprevir. Risk C: Monitor therapy
Eletriptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eletriptan. Risk X: Avoid combination
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, elexacaftor/tezacaftor/ivacaftor should be given in the morning, every other day. Ivacaftor alone should be given in the morning, every other day on alternate days. Risk D: Consider therapy modification
Eliglustat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with moderate CYP3A4 inhibitors. Avoid use of moderate CYP3A4 inhibitors in CYP2D6 IMs or PMs. Use in CYP2D6 EMs or IMs also taking strong or moderate CYP2D6 inhibitors is contraindicated. Risk D: Consider therapy modification
Encorafenib: Verapamil may increase the serum concentration of Encorafenib. Encorafenib may decrease the 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
Entrectinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Entrectinib. Management: Avoid moderate CYP3A4 inhibitors if possible. If needed, reduce entrectinib dose to 50 mg/day if starting dose 200 mg; to 100 mg/day if starting dose 300 mg; to 200 mg if starting dose 400 mg or 600 mg. Risk D: Consider therapy modification
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: If coadministered with moderate CYP3A4 inhibitors, the max dose of eplerenone is 25 mg daily if used for heart failure; if used for hypertension initiate eplerenone 25 mg daily, titrate to max 25 mg twice daily. Risk D: Consider therapy modification
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Erlotinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Erlotinib. Risk C: Monitor therapy
Erythromycin (Systemic): May increase the serum concentration of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Erythromycin (Systemic). Risk C: Monitor therapy
Esmolol: Calcium Channel Blockers (Nondihydropyridine) may enhance the bradycardic effect of Esmolol. Management: Administration of IV verapamil or diltiazem together with esmolol is contraindicated if one agent is given while the effects of the other are still present. Canadian esmolol labeling specifies that use within 24 hours is contraindicated. Risk D: Consider therapy modification
Eszopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eszopiclone. Risk C: Monitor therapy
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy
Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Etravirine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Etravirine. Risk C: Monitor therapy
Everolimus: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase the 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 the serum concentration of Fedratinib. Risk C: Monitor therapy
Felodipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Felodipine. Risk C: Monitor therapy
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Consider fentanyl dose reductions when combined with a moderate CYP3A4 inhibitor. Monitor for respiratory depression and sedation. Upon discontinuation of a CYP3A4 inhibitor, consider a fentanyl dose increase; monitor for signs and symptoms of withdrawal. Risk D: Consider therapy modification
Ferric Gluconate: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Gluconate. Risk C: Monitor therapy
Ferric Hydroxide Polymaltose Complex: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Hydroxide Polymaltose Complex. Specifically, the risk for angioedema or allergic reactions may be increased. Risk C: Monitor therapy
Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Fezolinetant: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Finerenone: Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Finerenone. Risk C: Monitor therapy
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification
Flecainide: Verapamil may enhance the adverse/toxic effect of Flecainide. In particular, this combination may significantly impair myocardial contractility and AV nodal conduction. Risk C: Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin. Management: Use of flibanserin with moderate CYP3A4 inhibitors is contraindicated. If starting flibanserin, start 2 weeks after the last dose of the CYP3A4 inhibitor. If starting a CYP3A4 inhibitor, start 2 days after the last dose of flibanserin. Risk X: Avoid combination
Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Fluticasone (Nasal): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fluticasone (Nasal). Risk C: Monitor therapy
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fluticasone (Oral Inhalation). Risk C: Monitor therapy
Fosamprenavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosamprenavir. Risk C: Monitor therapy
Fosaprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosaprepitant. Risk X: Avoid combination
Fosphenytoin-Phenytoin: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may decrease the serum concentration of Calcium Channel Blockers (Nondihydropyridine). Management: Consider alternatives to this combination when possible. If combined, monitor for increased phenytoin concentrations and toxicities and monitor for decreased calcium channel blocker efficacy. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Futibatinib: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase the serum concentration of Futibatinib. Risk C: Monitor therapy
Gelatin (Succinylated): Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gelatin (Succinylated). Specifically, the risk of a paradoxical hypotensive reaction may be increased. Risk C: Monitor therapy
Gepirone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Gepirone. Management: Reduce the gepirone dose by 50% if combined with moderate CYP3A4 inhibitors. Monitor for QTc interval prolongation with combined use. Risk D: Consider therapy modification
Gilteritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Gilteritinib. Risk C: Monitor therapy
Glasdegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Glasdegib. Risk C: Monitor therapy
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
Grapefruit Juice: May increase the serum concentration of Verapamil. Risk C: Monitor therapy
Grass Pollen Allergen Extract (5 Grass Extract): Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). Specifically, ACE inhibitors may increase the risk of severe allergic reaction to Grass Pollen Allergen Extract (5 Grass Extract). Risk X: Avoid combination
GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a moderate CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider therapy modification
Halofantrine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Risk C: Monitor therapy
Heparin: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HYDROcodone. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions. Risk D: Consider therapy modification
Icatibant: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Ifosfamide: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy
Iloperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Iloperidone. Risk C: Monitor therapy
Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Infigratinib: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Infigratinib. Risk X: Avoid combination
Inhalational Anesthetics: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Irinotecan Products: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, the serum concentration of SN-38 may be increased. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Irinotecan Products. Risk C: Monitor therapy
Iron Dextran Complex: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Iron Dextran Complex. Specifically, patients receiving an ACE inhibitor may be at an increased risk for anaphylactic-type reactions. Risk C: Monitor therapy
Isavuconazonium Sulfate: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Moderate) may increase isavuconazole serum concentrations. Risk C: Monitor therapy
Isradipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Isradipine. Risk C: Monitor therapy
Itraconazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Itraconazole. Risk C: Monitor therapy
Ivabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine. Risk X: Avoid combination
Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions may be required; consult full drug interaction monograph content for age- and weight-specific dosage recommendations. Risk D: Consider therapy modification
Ivosidenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivosidenib. Management: Avoid use of moderate CYP3A4 inhibitors with ivosidenib whenever possible. If combined, monitor for increased ivosidenib toxicities, including QTc prolongation. Risk D: Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Lanthanum: May decrease the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Administer angiotensin-converting enzyme (ACE) inhibitors at least two hours before or after lanthanum. Risk D: Consider therapy modification
Lapatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lapatinib. Risk C: Monitor therapy
Larotrectinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy
Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of Lemborexant. Risk X: Avoid combination
Leniolisib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Leniolisib. Risk C: Monitor therapy
Lercanidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lercanidipine. Risk C: Monitor therapy
Levamlodipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levamlodipine. Risk C: Monitor therapy
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Levoketoconazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levoketoconazole. Risk C: Monitor therapy
Levomethadone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levomethadone. Risk C: Monitor therapy
Levomilnacipran: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levomilnacipran. Risk C: Monitor therapy
Lidocaine (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Lidocaine (Systemic). Specifically, concentrations of monoethylglycinexylidide (MEGX) may be increased. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy
Lithium: Angiotensin-Converting Enzyme Inhibitors may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an ACE inhibitor. Monitor for increased concentrations/toxic effects of lithium if an ACE inhibitor is initiated/dose increased, or if switching between ACE inhibitors. Risk D: Consider therapy modification
Lomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide. Risk X: Avoid combination
Lonafarnib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lonafarnib. Risk X: Avoid combination
Loop Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Loop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Lopinavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lopinavir. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Lovastatin: Verapamil may increase the serum concentration of Lovastatin. Management: Initiate immediate release lovastatin at a dose of 10 mg/day, and do not exceed 20 mg/day for immediate or extended release lovastatin, in patients receiving verapamil. Monitor closely for signs of lovastatin toxicity (eg, myositis, rhabdomyolysis). Risk D: Consider therapy modification
Lumateperone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lumateperone. Management: Limit the lumateperone dose to 21 mg once daily when used with a moderate CYP3A4 inhibitor. Risk D: Consider therapy modification
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: US labeling recommends reducing lurasidone dose by 50% with a moderate CYP3A4 inhibitor and initiating 20 mg/day, max 80 mg/day. Some non-US labels recommend initiating lurasidone 20 mg/day, max 40 mg/day. Avoid concurrent use of grapefruit products. Risk D: Consider therapy modification
Lurbinectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, consider a lurbinectedin dose reduction as clinically indicated. Risk D: Consider therapy modification
Macitentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Macitentan. Risk C: Monitor therapy
Manidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Manidipine. Risk C: Monitor therapy
Maraviroc: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Maraviroc. Risk C: Monitor therapy
Mavacamten: Calcium Channel Blockers (Nondihydropyridine) may enhance the adverse/toxic effect of Mavacamten. Specifically, negative inotropic effects may be increased. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a non-DHP CCB. For those stable on mavacamten who are initiating a non-DHP CCB, reduce mavacamten dose by one dose level. Monitor for excessive negative inotropic effects. Risk D: Consider therapy modification
Meperidine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Meperidine. Risk C: Monitor therapy
MetFORMIN: Verapamil may diminish the therapeutic effect of MetFORMIN. Risk C: Monitor therapy
Methadone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Methadone. Management: If coadministration with moderate CYP3A4 inhibitors is necessary, consider methadone dose reductions until stable effects are achieved. Monitor patients closely for respiratory depression and sedation. Risk D: Consider therapy modification
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
MethylPREDNISolone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of MethylPREDNISolone. Risk C: Monitor therapy
Methysergide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Methysergide. Risk X: Avoid combination
Midazolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Midazolam. Management: Avoid concomitant use of nasal midazolam and moderate CYP3A4 inhibitors. Consider alternatives to use with oral midazolam whenever possible and consider using lower midazolam doses. Monitor patients for sedation and respiratory depression if combined. Risk D: Consider therapy modification
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Midostaurin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Midostaurin. Risk C: Monitor therapy
MiFEPRIStone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of MiFEPRIStone. Risk C: Monitor therapy
Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil. Risk C: Monitor therapy
Mitapivat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mitapivat. Management: When coadministered with moderate CYP3A4 inhibitors, doses of mitapivat should not exceed 20 mg twice daily. Additionally, patients should be monitored for changes in hemoglobin response and increased mitapivat adverse effects. Risk D: Consider therapy modification
Mobocertinib: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mobocertinib. Management: Avoid use of moderate CYP3A4 inhibitors with mobocertinib when possible. If combined, the mobocertinib dose should be reduced by approximately 50% (ie, from 160 mg to 80 mg, 120 mg to 40 mg, or 80 mg to 40 mg). Monitor QTc interval closely. Risk D: Consider therapy modification
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naldemedine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nalfurafine. Risk C: Monitor therapy
Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. Management: The use of naloxegol and moderate CYP3A4 inhibitors should be avoided. If concurrent use is unavoidable, reduce naloxegol dose to 12.5 mg once daily and monitor for signs of opiate withdrawal (eg, hyperhidrosis, chills, diarrhea, anxiety, irritability). Risk D: Consider therapy modification
Neratinib: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase the serum concentration of Neratinib. Risk X: Avoid combination
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
NIFEdipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NIFEdipine. Risk C: Monitor therapy
Nilotinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nilotinib. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Nintedanib: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase the serum concentration of Nintedanib. Risk C: Monitor therapy
Nirogacestat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nirogacestat. Risk X: Avoid combination
Nisoldipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nisoldipine. Risk X: Avoid combination
Nitrendipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nitrendipine. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Olaparib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 150 mg twice daily and the dose of olaparib capsules should be reduced to 200 mg twice daily. Risk D: Consider therapy modification
Oliceridine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Oliceridine. Risk C: Monitor therapy
Olmutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy
Omaveloxolone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Omaveloxolone. Management: Avoid this combination if possible. If coadministration is required, decrease the omaveloxolone dose to 100 mg daily and monitor closely for adverse reactions. If adverse reactions occur, decrease omaveloxolone to 50 mg daily. Risk D: Consider therapy modification
Orelabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Orelabrutinib. Risk X: Avoid combination
OxyCODONE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor therapy
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
PACLitaxel (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy
Pacritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pacritinib. Risk X: Avoid combination
Palbociclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Palbociclib. Risk C: Monitor therapy
Palovarotene: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Palovarotene. Management: Avoid concomitant use of palovarotene and moderate CYP3A4 inhibitors when possible. If combined, decrease palovarotene dose by 50% as described in the full interaction monograph. Monitor for palovarotene toxicities when combined. Risk D: Consider therapy modification
Panobinostat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Panobinostat. Risk C: Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Pemigatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pemigatinib. Management: If combined use cannot be avoided, reduce the pemigatinib dose from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior pemigatinib dose after stopping the moderate inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pexidartinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pexidartinib. Management: If combined use cannot be avoided, pexidartinib dose should be reduced. For the 125 mg capsules: reduce pexidartinib doses of 500 mg or 375 mg daily to 125 mg twice daily. Reduce pexidartinib 250 mg daily to 125 mg once daily. Risk D: Consider therapy modification
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Pimavanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimavanserin. Risk C: Monitor therapy
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Piperaquine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Piperaquine. Risk C: Monitor therapy
Pirtobrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pirtobrutinib. Risk C: Monitor therapy
Polyethylene Glycol-Electrolyte Solution: Angiotensin-Converting Enzyme Inhibitors may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy
PONATinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PONATinib. Risk C: Monitor therapy
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification
Potassium Salts: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Potassium-Sparing Diuretics: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Pralsetinib: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider therapy modification
Pramipexole: Verapamil may enhance the hypotensive effect of Pramipexole. Verapamil may increase the serum concentration of Pramipexole. Risk C: Monitor therapy
Prazepam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Prazepam. Risk C: Monitor therapy
Praziquantel: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Praziquantel. Risk C: Monitor therapy
Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. Risk C: Monitor therapy
Pregabalin: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Pregabalin. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
QUEtiapine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of QUEtiapine. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
QuiNIDine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of QuiNIDine. Risk C: Monitor therapy
Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor therapy
QuiNINE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of QuiNINE. Risk C: Monitor therapy
Racecadotril: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased with this combination. Risk C: Monitor therapy
Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors. Monitor for increased ranolazine effects and toxicities during concomitant use. Risk D: Consider therapy modification
Red Yeast Rice: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin (and possibly other related compounds) may be increased. Management: Initiate immediate release lovastatin at a dose of 10 mg/day, and do not exceed 20 mg/day for immediate or extended release lovastatin. Monitor closely for signs of lovastatin toxicity (eg, myositis, rhabdomyolysis). Risk D: Consider therapy modification
Regorafenib: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Regorafenib. Risk C: Monitor therapy
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the 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
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the 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
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Repotrectinib. Risk X: Avoid combination
Ribociclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ribociclib. Risk C: Monitor therapy
Rifabutin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rifabutin. Risk C: Monitor therapy
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy
Rimegepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rimegepant. Management: If taking rimegepant for the acute treatment of migraine, avoid a second dose of rimegepant within 48 hours when used concomitantly with moderate CYP3A4 inhibitors. No dose adjustment needed if using rimegepant for prevention of episodic migraine. Risk D: Consider therapy modification
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of Riociguat. Risk C: Monitor therapy
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
Rivaroxaban: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase the 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 the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy
Rupatadine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rupatadine. Risk C: Monitor therapy
Ruxolitinib (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ruxolitinib (Systemic). Risk C: Monitor therapy
Sacubitril: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Sacubitril. Specifically, the risk of angioedema may be increased with this combination. Risk X: Avoid combination
Salicylates: May enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy
Saquinavir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
Saquinavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SAXagliptin. Risk C: Monitor therapy
Selpercatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Selpercatinib. Management: Avoid combination if possible. If use is necessary, reduce selpercatinib dose as follows: from 120 mg twice/day to 80 mg twice/day, or from 160 mg twice/day to 120 mg twice/day. Risk D: Consider therapy modification
Selumetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Selumetinib. Management: Avoid concomitant use when possible. If combined, selumetinib dose reductions are recommended and vary based on body surface area and selumetinib dose. For details, see the full drug interaction monograph or selumetinib prescribing information. Risk D: Consider therapy modification
Sertindole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sertindole. Risk X: Avoid combination
Sildenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sildenafil. Risk C: Monitor therapy
Silodosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Silodosin. Risk C: Monitor therapy
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Simeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir. Risk X: Avoid combination
Simvastatin: Verapamil may increase serum concentrations of the active metabolite(s) of Simvastatin. Verapamil may increase the serum concentration 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 diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification
Sirolimus (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sirolimus (Conventional). Management: Monitor for increased serum concentrations of sirolimus if combined with a moderate CYP3A4 inhibitor. Lower initial sirolimus doses or sirolimus dose reductions will likely be required. Risk D: Consider therapy modification
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Sodium Phosphates: Angiotensin-Converting Enzyme Inhibitors may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy
Solifenacin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Solifenacin. Risk C: Monitor therapy
Sonidegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Risk D: Consider therapy modification
Sparsentan: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk X: Avoid combination
SUFentanil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SUFentanil. Risk C: Monitor therapy
SUNItinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SUNItinib. Risk C: Monitor therapy
Suvorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Risk D: Consider therapy modification
Tacrolimus (Systemic): Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tacrolimus (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tacrolimus (Topical). Risk C: Monitor therapy
Tadalafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tadalafil. Risk C: Monitor therapy
Talazoparib: Verapamil may increase the 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 the serum concentration of Tamsulosin. Risk C: Monitor therapy
Tazemetostat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tazemetostat. Management: Avoid when possible. If combined, reduce tazemetostat dose from 800 mg twice daily to 400 mg twice daily, from 600 mg twice daily to 400 mg in AM and 200 mg in PM, or from 400 mg twice daily to 200 mg twice daily. Risk D: Consider therapy modification
Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy
Temsirolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Temsirolimus: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Risk C: Monitor therapy
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. Risk C: Monitor therapy
Terfenadine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Terfenadine. Risk C: Monitor therapy
Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy
Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tezacaftor and Ivacaftor. Management: If combined with moderate CYP3A4 inhibitors, give tezacaftor/ivacaftor in the morning, every other day; give ivacaftor in the morning, every other day on alternate days. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph Risk D: Consider therapy modification
Theophylline Derivatives: Verapamil may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Thiazide and Thiazide-Like Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Thiotepa: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Thiotepa. Risk C: Monitor therapy
Ticagrelor: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor. Risk C: Monitor therapy
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Tofacitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tofacitinib. Risk C: Monitor therapy
Tolterodine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolterodine. Risk C: Monitor therapy
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Management: Avoid this combination with Samsca brand of tolvaptan. Reduce dose for Jynarque brand: 90 mg AM and 30 mg PM, reduce to 45 mg AM and 15 mg PM; 60 mg AM and 30 mg PM, reduce to 30 mg AM and 15 mg PM; 45 mg AM and 15 mg PM, reduce to 15 mg AM and PM. Risk D: Consider therapy modification
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Toremifene: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Toremifene. Risk C: Monitor therapy
Trabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin. Risk C: Monitor therapy
TraMADol: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of TraMADol. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of TraMADol. Risk C: Monitor therapy
TraZODone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of TraZODone. Risk C: Monitor therapy
Triazolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Trimethoprim: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and avoid a second dose for 24 hours when used with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Udenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Udenafil. Risk C: Monitor therapy
Ulipristal: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Risk C: Monitor therapy
Urapidil: May interact via an unknown mechanism with Angiotensin-Converting Enzyme Inhibitors. Management: Avoid concomitant use of urapidil and angiotensin-converting enzyme (ACE) inhibitors. Risk D: Consider therapy modification
Urokinase: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Valbenazine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Valbenazine. Risk C: Monitor therapy
Vamorolone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vamorolone. Risk C: Monitor therapy
Vardenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 5 mg dose within a 24-hour period if combined with moderate CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and moderate CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider therapy modification
Vemurafenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vemurafenib. Risk C: Monitor therapy
Venetoclax: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with moderate CYP3A4 inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Risk C: Monitor therapy
VinBLAStine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinBLAStine. Risk C: Monitor therapy
VinCRIStine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinCRIStine. Risk C: Monitor therapy
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
Vindesine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine. Risk C: Monitor therapy
Vinflunine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Vinflunine. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vinflunine. Risk C: Monitor therapy
Voclosporin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Voclosporin. Management: Decrease the voclosporin dose to 15.8 mg in the morning and 7.9 mg in the evening when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Vorapaxar: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vorapaxar. Risk C: Monitor therapy
Zanubrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg twice daily during coadministration with a moderate CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider therapy modification
Zopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone. Risk C: Monitor therapy
Zuranolone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuranolone. Risk C: Monitor therapy
[US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected. See individual agents.
It is not known if trandolapril is present in breast milk. Verapamil is present in breast milk. Breastfeeding is not recommended by the manufacturer. See individual agents.
Use potassium-containing salt substitutes cautiously in patients with diabetes, renal impairment, or those maintained on potassium supplements or potassium-sparing diuretics.
Blood pressure and heart rate; BUN, serum creatinine and electrolytes; if patient has collagen vascular disease and/or renal impairment, periodically monitor CBC with differential.
Trandolapril: Trandolapril is an ACE inhibitor that prevents the formation of angiotensin II from angiotensin I. Trandolapril must undergo enzymatic hydrolysis, mainly in liver, to its biologically active metabolite, trandolaprilat. A CNS mechanism may also be involved in the hypotensive effect as angiotensin II increases adrenergic outflow from the CNS. Vasoactive kallikreins may be decreased in conversion to active hormones by ACE inhibitors, thus reducing blood pressure.
Verapamil: 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.
See individual agents.
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