Sildenafil is a medicine used to treat erectile dysfunction. Its effect starts about 30 to 60 minutes after taking it and lasts up to 4 to 6 hours. It must not be taken with nitrates (such as nitroglycerin).
Also known as: Viagra
Rifampin lowers Sildenafil levels — loss of efficacy (or need for higher doses).
Sildenafil is metabolised by CYP3A4; rifampicin induces this enzyme and can markedly reduce its concentrations, decreasing the effect in erectile dysfunction or pulmonary hypertension. Monitor the response and consider increasing the sildenafil dose (within approved limits) during the combination, or prefer an alternative less dependent on CYP3A4.
Sildenafil + rifampicin: rifampicin lowers sildenafil levels (CYP3A4 induction), reducing efficacy. Consider dose adjustment.
CYP3A4 induction, the Sildenafil metabolic pathway.
Clinical response.
Lack of effect.
Monitor response; adjust dose (without exceeding the daily maximum).
DailyMed/FDA (NIH/NLM) — approved Rifampin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b ; approved Sildenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00ee09dd-2de0-4dc4-85f6-b51ed6eabd5b
Voriconazole raises Sildenafil concentrations (CYP3A4 inhibition), with a risk of hypotension and adverse effects.
Sildenafil is metabolised by CYP3A4, and voriconazole is a strong inhibitor of this enzyme: the sildenafil label recommends "considering a starting dose of 25 mg in patients treated with strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, saquinavir) or erythromycin". Voriconazole also prolongs the QT (the label states that "some azoles, including voriconazole, have been associated with prolongation of the QT interval" and recommends correcting potassium, magnesium and calcium before use), and sildenafil at high levels can cause hypotension, headache, flushing and visual disturbances. Use the lowest effective sildenafil dose (not exceeding 25 mg), space the doses, monitor blood pressure and signs of hypotension.
Sildenafil + voriconazole: voriconazole inhibits CYP3A4 and raises sildenafil levels. Consider a 25 mg starting dose; watch hypotension and QT.
CYP3A4 inhibition by voriconazole increases sildenafil exposure.
Blood pressure, headache, flushing, palpitations.
Hypotension, syncope.
Limit the sildenafil dose during voriconazole therapy; monitor blood pressure.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Sildenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00ee09dd-2de0-4dc4-85f6-b51ed6eabd5b
Combining Ritonavir with Sildenafil markedly increases Sildenafil concentrations and effects, with an increased risk of hypotension and priapism.
Sildenafil is metabolised by CYP3A4, and ritonavir (a potent inhibitor) markedly raises its concentrations: the ritonavir label recommends for erectile dysfunction "sildenafil 25 mg every 48 hours" and contraindicates sildenafil (Revatio) in pulmonary hypertension; the label lists the sildenafil-associated adverse events — visual abnormalities, hypotension, prolonged erection and syncope. Raised sildenafil levels potentiate the risk of hypotension, headache, flushing, dyspepsia, priapism and visual disturbances. For erectile dysfunction, never exceed 25 mg every 48 hours; for pulmonary hypertension, the combination is contraindicated — seek an alternative.
Ritonavir + sildenafil: ritonavir inhibits CYP3A4 and greatly raises sildenafil levels. ED: 25 mg starting dose every 48h; PH: contraindicated.
Ritonavir (a CYP3A4 inhibitor) markedly reduces first-pass metabolism of Sildenafil, greatly increasing its systemic exposure.
Monitor blood pressure, orthostatic hypotension and abnormally prolonged erection.
Severe symptomatic hypotension or an erection lasting more than 4 hours requires urgent medical evaluation.
Sildenafil for erectile dysfunction should be started low (max 25 mg every 48 h) with Ritonavir; for pulmonary hypertension the combination is contraindicated in many regimens.
DailyMed/FDA (NIH/NLM) — approved Ritonavir label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2849298e-de6e-47bb-8194-56e075b33fc3 ; approved Sildenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00ee09dd-2de0-4dc4-85f6-b51ed6eabd5b — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining sildenafil with doxazosin can lower blood pressure too much, especially on standing (orthostatic hypotension), with dizziness and a risk of fainting.
Both classes cause vasodilation; together they can produce symptomatic orthostatic hypotension, especially when the alpha-blocker is started or at high doses. In studies, sildenafil and tadalafil increased the hypotensive effect of doxazosin. The patient should be stabilised on the alpha-blocker before starting the PDE5, with a low starting dose and tolerability assessment.
PDE5 + alpha-blocker: additive vasodilator effect. Stabilise the alpha-blocker before starting the PDE5 and use the lowest starting dose; doxazosin has a greater haemodynamic interaction than tamsulosin.
Additive vasodilator effect between PDE5 and alpha-1 blocker.
Orthostatic blood pressure and symptoms when starting the combination.
Dizziness on standing, syncope, symptomatic hypotension.
Stabilise the alpha-blocker before starting the PDE5; start with the lowest PDE5 dose; advise standing up slowly.
DailyMed/FDA (NIH/NLM) — approved Doxazosin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e1f5e49-2da1-43ab-9795-228a8bcc5a82 ; PubMed — https://pubmed.ncbi.nlm.nih.gov/16387566/ ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Combining sildenafil with tamsulosin can lower blood pressure and cause dizziness or fainting, especially on standing.
Co-administration of PDE5 inhibitors with tamsulosin can cause symptomatic hypotension in some patients, due to the combined vasodilator effect. Although tamsulosin is more selective and has less haemodynamic interaction than other alpha-blockers (doxazosin, for example, showed a greater additive effect in studies), the tamsulosin label advises caution.
PDE5 + tamsulosin: risk of symptomatic hypotension documented in labels. Tamsulosin has less haemodynamic interaction than other alpha-blockers, but caution remains; stabilise and use a low starting dose.
Additive vasodilator effect (PDE5 + alpha-1 antagonist).
Orthostatic blood pressure and symptoms when starting the combination.
Dizziness on standing, syncope.
Stabilise tamsulosin before starting the PDE5; start low and assess tolerability.
DailyMed/FDA (NIH/NLM) — approved Tamsulosin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ed219aa-cf65-457f-8570-d26b48edb240 ; PubMed — https://pubmed.ncbi.nlm.nih.gov/16387566/ ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Potentially fatal severe hypotension. Never combine PDE-5 inhibitors with nitrates.
Sildenafil inhibits PDE5 and markedly potentiates the vasodilating and hypotensive effect of nitrates (nitric oxide donors): the combination can cause severe hypotension, syncope, myocardial infarction and death. The approved sildenafil label formally contraindicates use with nitrates, in any form (sublingual, oral, topical, transdermal) and at any time. If the patient took sildenafil, at least 24 hours should elapse before giving a nitrate (48 hours for tadalafil, which has a longer half-life); in the event of angina after sildenafil, the emergency department should be contacted immediately.
Absolute contraindication: nitrates + PDE5 inhibitors cause severe, potentially fatal hypotension. Do not combine; after sildenafil, do not give nitrates within the following 24 hours.
Both raise cGMP — extreme vasodilation and marked blood pressure drop.
Immediate BP monitoring; seek emergency care on syncope or chest pain.
Syncope, severe dizziness, chest pain, tachycardia.
Absolute contraindication. If the patient took Sildenafil, wait at least 24 hours before any nitrate.
DailyMed/FDA (NIH/NLM) — approved Sildenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00ee09dd-2de0-4dc4-85f6-b51ed6eabd5b ; approved Nitroglycerin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3c11c1c2-8e62-4f63-8293-2f8b8d845f7e
Ketoconazole raises Sildenafil concentrations, with a risk of hypotension and intensified adverse effects.
Sildenafil is a CYP3A4 substrate, and ketoconazole, a potent inhibitor of this enzyme, can markedly raise its concentrations, potentiating vasodilation (hypotension, headache, flushing, nasal congestion) and the risk of priapism. The sildenafil label recommends considering a starting dose of 25 mg in patients treated with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole). Alert the patient to alarm signs (priapism, chest pain) and avoid the simultaneous use of nitrates.
Ketoconazole + sildenafil: the azole greatly raises sildenafil levels (CYP3A4), with a risk of hypotension, priapism and toxicity. Consider a starting dose of 25 mg.
CYP3A4 inhibition — the main sildenafil metabolic pathway — increases its plasma exposure.
Blood pressure, headache, facial flushing, palpitations.
Severe hypotension, syncope, chest pain, priapism.
Limit the sildenafil dose (max 25 mg) during ketoconazole therapy; avoid use in unstable cardiovascular disease.
DailyMed/FDA (NIH/NLM) — approved Ketoconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f162e616-21b4-49b1-b437-15e21001a6f0 ; approved Sildenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00ee09dd-2de0-4dc4-85f6-b51ed6eabd5b
Itraconazole raises Sildenafil concentrations, with a risk of hypotension and adverse effects.
Sildenafil is metabolised by CYP3A4, and the sildenafil label recommends "considering a starting dose of 25 mg in patients treated with strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, saquinavir) or erythromycin"; the itraconazole label distinguishes the indications: for pulmonary hypertension, sildenafil is "not recommended during and 2 weeks after treatment with itraconazole", while for erectile dysfunction it recommends "monitoring for adverse reactions". Raised sildenafil levels potentiate the risk of hypotension, headache, flushing, dyspepsia and, rarely, priapism or visual disturbances. For erectile dysfunction, use the lowest effective dose (never exceeding 25 mg) and space the doses; for pulmonary hypertension, avoid the combination and seek an alternative.
Itraconazole + sildenafil: itraconazole inhibits CYP3A4 and raises sildenafil levels. Consider a 25 mg starting dose; PH: not recommended during and 2 weeks after itraconazole.
CYP3A4 inhibition — the main sildenafil metabolic pathway — increases its exposure.
Blood pressure, headache, flushing, palpitations.
Hypotension, syncope, priapism.
Limit the sildenafil dose (max 25 mg) during itraconazole therapy.
DailyMed/FDA (NIH/NLM) — approved Itraconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a4d555fa-787c-40fb-bb7d-b0d4f7318fd0 ; approved Sildenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00ee09dd-2de0-4dc4-85f6-b51ed6eabd5b
A high-fat meal delays the onset of sildenafil effect (lower and later peak concentration).
If rapid onset is desired, take sildenafil on an empty stomach.
DailyMed/FDA (NIH/NLM) — approved Sildenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00ee09dd-2de0-4dc4-85f6-b51ed6eabd5b ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Substantial alcohol intake with sildenafil can potentiate the blood pressure fall and vasodilator effects.
Avoid substantial alcohol intake during the sildenafil effect period.
DailyMed/FDA (NIH/NLM) — approved Sildenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00ee09dd-2de0-4dc4-85f6-b51ed6eabd5b
Contraindicated in patients in whom sexual activity is inadvisable due to cardiovascular risk (severe heart disease, unstable angina, recent stroke or myocardial infarction).
Do not use; assess cardiovascular risk before starting treatment.
DailyMed/FDA (NIH/NLM) — approved Sildenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00ee09dd-2de0-4dc4-85f6-b51ed6eabd5b ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Contraindicated in patients with hypotension (<90/50 mmHg) due to the risk of an additional blood pressure fall.
Do not use; correct hypotension before considering treatment.
DailyMed/FDA (NIH/NLM) — approved Sildenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00ee09dd-2de0-4dc4-85f6-b51ed6eabd5b ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Sildenafil is contraindicated in patients with hereditary degenerative retinal disorders, such as retinitis pigmentosa, due to a lack of safety data.
Do not use in these patients.
DailyMed/FDA (NIH/NLM) — approved Sildenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00ee09dd-2de0-4dc4-85f6-b51ed6eabd5b ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Sildenafil is not indicated for use in women; no adequate studies in pregnant women are available.
Not indicated in women; no adequate data in pregnancy.
Not indicated in women; no data on milk excretion.
Not applicable (male-only drug).
DailyMed/FDA (NIH/NLM) — approved Sildenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00ee09dd-2de0-4dc4-85f6-b51ed6eabd5b ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
PDE5 inhibitor used in erectile dysfunction. It improves erections during sexual stimulation (assessed objectively), with an effect for up to about 4 hours after dosing. It produces a slight blood pressure reduction (mean maximum decrease of 8.3/5.3 mmHg); it potentiates the hypotensive effect of nitrates, so the combination is contraindicated.
Selectively inhibits phosphodiesterase type 5 (PDE5), responsible for cGMP degradation in the corpus cavernosum; increased cGMP produces smooth muscle relaxation and blood inflow. Without sexual stimulation (nitric oxide release) it has no effect. It is about 4,000-fold more selective for PDE5 than for PDE3.
Rapidly absorbed, with peak plasma concentrations 30 to 120 minutes after dosing (median 60 minutes when fasted). Absolute bioavailability is about 41%. A high-fat meal reduces the rate of absorption. It is about 96% bound to plasma proteins.
Metabolised in the liver, mainly by CYP3A4 (main pathway) and, to a lesser extent, by CYP2C9. The main metabolite, N-desmethylsildenafil, has about 50% of the potency of the parent compound. About 80% of the dose is excreted in faeces and 13% in urine.
The elimination half-life is about 3 to 5 hours (4 hours); 24 hours after a 100 mg dose, plasma concentrations are approximately 2 ng/ml.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
