
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as sildenafil. Ivacaftor is an inhibitor of CYP3A and a weak inhibitor of CYP2C9; sildenafil is metabolized by CYP3A and CYP2C9.
Conversely, patients already receiving an optimized dose of sildenafil should be started on the lowest dose of tamsulosin; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent sildenafil citrate tablets 200mg antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of sildenafil and tamsulosin. Duvelisib: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with duvelisib is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Efavirenz: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as sildenafil. Elagolix: (Moderate) Monitor for reduced therapeutic effect of sildenafil if coadministered with elagolix. Co-administration of ivacaftor with CYP3A and CYP2C9 substrates, such as sildenafil, can theoretically increase sildenafil exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
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Encorafenib: (Moderate) Coadministration of encorafenib with sildenafil may result in increased toxicity or decreased efficacy of sildenafil.
| Indication | Patient Group | Dosage Recommendation | Additional Notes |
|---|---|---|---|
| Erectile Dysfunction | Men aged 18-65 | 50 mg30-1 hour before activity | Adjust based on efficacy and tolerability |
| Pulmonary Hypertension | Adults with PAH | 20 mg three times daily | Extended release available |
| Raynaud's Phenomenon | People with secondary Raynaud's | Off-label use, consult physician | Limited clinical evidence |
In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4.
Cobicistat: (Major) Sildenafil is contraindicated for use with cobicistat when used for pulmonary arterial hypertension (PAH). Codeine; Phenylephrine; Promethazine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. Conivaptan: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with conivaptan 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 CYP3A inhibitor increased the peak and overall exposure of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Crizotinib: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with crizotinib is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Dabrafenib: (Major) The concomitant use of dabrafenib and sildenafil may lead to sildenafil price ireland decreased sildenafil concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of sildenafil efficacy. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Danazol: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with danazol is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Darunavir: (Major) Sildenafil is contraindicated for use with darunavir when used for pulmonary arterial hypertension (PAH). Darunavir; Cobicistat: (Major) Sildenafil is contraindicated for use with cobicistat when used for pulmonary arterial hypertension (PAH). (Major) Sildenafil is contraindicated for use with darunavir when used for pulmonary arterial hypertension (PAH). Delavirdine: (Major) Coadministration of delavirdine is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established.
Enzalutamide: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with enzalutamide is necessary.
When sildenafil is used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours. Dexamethasone: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with dexamethasone is necessary as concurrent use may decrease sildenafil exposure. Dextromethorphan; Diphenhydramine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. Dextromethorphan; Quinidine: (Moderate) Sildenafil is metabolized principally by the hepatic isoenzymes CYP3A4 and CYP2C9.
Inhibitors of these isoenzymes, such as quinidine, may reduce sildenafil clearance. Increased systemic exposure to sildenafil may result in an increase in sildenafil-induced adverse effects. Diltiazem: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with diltiazem is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Diphenhydramine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. Doxazosin: (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.
Dronedarone: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with dronedarone is necessary; a dose reduction of sildenafil may be necessary when sildenafil citrate chewable tablets prescribed for erectile dysfunction. Duloxetine: (Moderate) Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of antihypertensive agents and duloxetine may increase the risk of hypotension. It is advisable to monitor blood pressure if the combination is necessary. Dutasteride; Tamsulosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on tamsulosin therapy before initiating therapy with the lowest dose of sildenafil. Erythromycin: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with erythromycin is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction.
| Condition | Temperature Range | Light Exposure | Additional Notes |
|---|---|---|---|
| General storage | 20-25°C (68-77°F) | Keep in original container | Avoid moisture and heat |
| Refrigeration | Not required | No | If needed, store in fridge |
| Avoid exposure | Humidity, direct sunlight | Yes | To preserve potency |
In a drug interaction study, coadministration with erythromycin increased the Cmax and AUC of sildenafil by 160% and 182%, respectively.
| Country | Legal Status | Prescription Requirement | Notes |
|---|---|---|---|
| USA | Prescription-only medication | Yes | FDA approved |
| UK | Prescription-only | Yes | MHRA regulated |
| India | Over-the-counter and prescription | Both are possible | Varies by state |
| Australia | Prescription only | Yes | TGA regulated |
Etravirine: (Moderate) Etravirine is an inducer of CYP3A4; coadministration may result in decreased sildenafil concentrations.
Concurrent use may decrease sildenafil plasma concentrations. Population pharmacokinetic analysis of data from patients in clinical trials indicated approximately 3-fold the sildenafil clearance when it was coadministered with weak CYP3A inducers. Elagolix; Estradiol; Norethindrone acetate: (Moderate) Monitor for reduced therapeutic effect of sildenafil if coadministered with elagolix. Elbasvir; Grazoprevir: (Moderate) Administering sildenafil with elbasvir; grazoprevir may result in elevated sildenafil plasma concentrations. If these drugs are used together, closely monitor for signs of adverse events. Dosage adjustments may be needed based on clinical efficacy.
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 if hypotension occurs. 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. Cimetidine 800 mg caused a 56% increase in plasma sildenafil concentrations when coadministered with sildenafil 50 mg to healthy volunteers. Ciprofloxacin: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with ciprofloxacin is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Clarithromycin: (Major) Coadministration of clarithromycin is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). Fedratinib: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with fedratinib is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction.