Cimetidine 800 mg caused a 56% increase in plasma sildenafil
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Aliskiren can enhance the effects of sildenafil on blood pressure if given concomitantly. Alpha-blockers: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest dose of sildenafil. Conversely, patients already receiving an optimized dose of sildenafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of sildenafil and an alpha-blocker. Ambrisentan: (Moderate) Although no specific interactions have been documented, ambrisentan has vasodilatory effects and may contribute additive hypotensive effects when given with other antihypertensive agents.
Patients receiving ambrisentan in combination with other antihypertensive agents should be monitored for decreases in blood pressure. Amiodarone: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with amiodarone is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. In a drug interaction study, coadministration with a moderate CYP3A4 inhibitor increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A4 inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration. Amlodipine: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. concentrations when coadministered with sildenafil
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50 mg to healthy volunteers.
Cenobamate: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with cenobamate is necessary as concurrent use may decrease sildenafil exposure. Ceritinib: (Major) Coadministration with ceritinib is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving ceritinib. Chloramphenicol: (Major) Coadministration of chloramphenicol is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving chloramphenicol.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. Chlorpheniramine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. Cimetidine: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with cimetidine is necessary. Concomitant use may increase sildenafil plasma concentrations. Ciprofloxacin: (Moderate) Monitor for an increase in
sildenafil-related adverse reactions if
Brigatinib: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with brigatinib is necessary as concurrent use may decrease sildenafil exposure. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A4 inducers. Brompheniramine; Dextromethorphan; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. Brompheniramine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. Carbamazepine: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with carbamazepine is necessary as concurrent use may decrease sildenafil exposure.
Sildenafil is a sensitive CYP3A substrate and carbamazepine is a strong CYP3A inducer. Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction sildenafil premature ejaculation if hypotension occurs. coadministration with ciprofloxacin is
necessary; consider a starting dose of 25
Apalutamide: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with apalutamide is necessary. Concomitant administration of strong CYP3A inducers is expected to substantially decrease plasma concentrations of sildenafil. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A inducers. Aprepitant, Fosaprepitant: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministered with multi-day regimens of oral aprepitant. A dose reduction of sildenafil may be required when using for erectile dysfunction.
Sildenafil is a CYP3A4 substrate and aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor. When administered as a single oral or single intravenous dose, the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate. Atazanavir: (Major) Sildenafil is contraindicated sildenafil 50mg tablet for use with atazanavir when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. mg of sildenafil when prescribed for erectile dysfunction.
| Country | Approval Status | Regulatory Agency | Notes |
|---|---|---|---|
| USA | Approved | FDA | For ED and pulmonary hypertension |
| European Union | Approved | EMA | Similar indications |
| India | Approved | CDSCO | Generic versions available |
| Australia | Approved | TGA | Prescription required |
Clarithromycin: (Major) Coadministration of clarithromycin is not recommended
When sildenafil 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure (SBP) was 8 mmHg systolic and 7 mmHg diastolic. Amlodipine; Atorvastatin: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. Amlodipine; Benazepril: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. Amlodipine; Celecoxib: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. Amlodipine; Olmesartan: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure.
Amlodipine; Valsartan: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. Amlodipine; pfizer sildenafil 100 Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. Amoxicillin; Clarithromycin; Omeprazole: (Major) Coadministration of clarithromycin is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving clarithromycin. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold. in patients receiving sildenafil for pulmonary arterial hypertension (PAH).
Atazanavir; Cobicistat: (Major) Sildenafil is contraindicated for use with atazanavir when used for pulmonary arterial hypertension (PAH). (Major) Sildenafil is contraindicated for use with cobicistat when used for pulmonary arterial hypertension (PAH). Atropine; Difenoxin: (Moderate) Diphenoxylate/difenoxin is a synthetic opiate agonist with a chemical structure similar to that of meperidine. Prolonged erections have been reported in two patients taking sildenafil with dihydrocodeine. In both cases, patients reported erections subsided immediately after orgasm when taking sildenafil alone.
Although more data are needed, use caution when prescribing opiate agonists and sildenafil concomitantly. Barbiturates: (Minor) Sildenafil is metabolized principally by the hepatic CYP3A4 and CYP2C9 isoenzymes. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of sildenafil, however, no interaction studies have been performed. Belzutifan: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with belzutifan is necessary as concurrent use may decrease sildenafil exposure. Berotralstat: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with berotralstat is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction.