Drug Interactions with Sildenafil Citrate

Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with sildenafil.

• Contraindications include use with nitrates and recent heart attack.
• Patients with contraindications should avoid sildenafil entirely.
• Visual disturbances including blue-tinted vision may occur.
• Use caution in patients with liver or kidney impairment.
• Sildenafil can interact with certain antibiotics and antifungals.
• Always inform your doctor about other medications you're taking.
• It does not protect against sexually transmitted infections.

It can be expected that concomitant administration of CYP3A4 enzyme-inducers, such as rifampin, will decrease plasma levels of sildenafil, however, no interaction studies have been performed.

How Sildenafil Works

Monitor the therapeutic effect of sildenafil during coadministration with fenofibric acid. Fluconazole: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with fluconazole is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Fluvoxamine: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with fluvoxamine is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. In a drug interaction study, coadministration of fluvoxamine increased the sildenafil AUC by 40%. Fosamprenavir: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with fosamprenavir is necessary; consider a starting dose of 25 mg of sildenafil from canada sildenafil when prescribed for erectile dysfunction.

How sildenafil is used

When used for pulmonary arterial hypertension, this combination is listed as a contraindication in the fosamprenavir FDA-approved labeling. In a drug interaction study, coadministration with a moderate CYP3A inhibitor increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Glycerol Phenylbutyrate: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with glycerol phenylbutyrate is necessary as concurrent use may decrease sildenafil exposure. Grapefruit juice: (Moderate) Sildenafil is metabolized via the cytochrome CYP 3A4 isozyme. Grapefruit juice contains a compound that inhibits CYP3A4 in enterocytes in the GI tract. Isoniazid, INH; Rifampin: (Minor) Sildenafil is metabolized principally by cytochrome P450 3A4 and 2C9 enzymes.

Itraconazole: (Major) Avoid use of sildenafil for the treatment of pulmonary hypertension during and for 2 weeks after discontinuation of itraconazole treatment.

Continuing Education Activity

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 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.

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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 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. When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving itraconazole.

7. Interactions

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.

Warnings for people with certain health conditions

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. 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. Encorafenib: (Moderate) Coadministration of encorafenib with sildenafil may result in increased toxicity or decreased efficacy of sildenafil. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. Ivacaftor: (Moderate) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as sildenafil.

Effectiveness of Sildenafil

Indinavir: (Major) Sildenafil is contraindicated for use with indinavir when used for pulmonary arterial hypertension (PAH). In a small pharmacokinetic study, the coadministration of a single dose of sildenafil (25 mg) to patients receiving indinavir (800 mg every 8 hours) resulted in markedly increased sildenafil AUC values (340% increase), as compared to historical controls. In two of the six subjects, prolonged clinical effects of sildenafil were noted for 72 hours after a single dose of sildenafil. Isavuconazonium: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with isavuconazonium is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with sildenafil. Ivosidenib: (Moderate) Monitor for loss of efficacy of sildenafil during coadministration of ivosidenib; a sildenafil dose adjustment may be necessary.

• Sildenafil citrate is manufactured by several pharmaceutical companies.
• Its chemical formula is C22H30N6O4S.
• It has a half-life of approximately 4 hours in the body.
• The drug enhances nitric oxide activity in the corpus cavernosum.
• It’s important to follow prescribed dosing to avoid adverse effects.
• It is classified as a phosphodiesterase type 5 inhibitor.
• Sildenafil was initially researched for angina before ED use.

Sildenafil is a sensitive substrate of CYP3A4; ivosidenib induces CYP3A4 and may lead to decreased sildenafil concentrations.

• Some users report headaches and dizziness after taking sildenafil.
• A common side effect is facial flushing and nasal congestion.
• Rare side effects include sudden hearing loss or vision loss.
• Priapism requires urgent medical attention to prevent tissue damage.
• Sudden vision loss should be immediately evaluated by a doctor.
• Allergic reactions such as rash, hives, or swelling are possible.
• Discontinue use and seek medical help if serious side effects occur.

Ketoconazole: (Major) Coadministration of ketoconazole is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH).

What Is Silenafil and How Does It Work?

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. 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. In a drug interaction study, coadministration with erythromycin increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Etravirine: (Moderate) Etravirine is an inducer of CYP3A4; coadministration may result in decreased sildenafil concentrations.

Does sildenafil interact with foods or drinks?

Dosage adjustments may be needed based on clinical efficacy. 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. Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as sildenafil , has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving ketoconazole.

What should I know about storage and disposal of this medication?

Sildenafil levels may increase; it is possible that sildenafil-induced side effects could also be increased in some individuals. One study has confirmed a potential interaction; sildenafil's AUC increased 23 percent with coadministration of grapefruit juice. Guaifenesin; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. Hydantoins: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with phenytoin is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and phenytoin is a strong CYP3A inducer. Lansoprazole; Amoxicillin; Clarithromycin: (Major) Coadministration of clarithromycin is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH).

Patient Counseling Information

Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina. Idelalisib: (Major) Coadministration of idelalisib 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 idelalisib. Imatinib: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with imatinib is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Lefamulin: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with oral lefamulin is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction.