Sildenafil

The original erectile-dysfunction drug — shorter-acting than tadalafil (~4-hour window vs ~36); also prescribed for pulmonary hypertension.

Sildenafil blocks PDE5, the enzyme that breaks down cGMP — the signalling molecule that keeps blood-vessel smooth muscle relaxed. Blocking it lets cGMP persist, so vessels stay dilated wherever nitric-oxide signalling is already active. That conditional is the whole drug: it amplifies an existing arousal signal rather than creating one. The same mechanism in the lung vasculature is why a separate sildenafil product is approved for pulmonary arterial hypertension. Its practical difference from tadalafil is duration — hours rather than more than a day.

Among the best-evidenced drugs in this file — large RCTs, decades of use. The effect on erectile function is robust. Off-label cosmetic or training uses have no suitable trial evidence.

• STRONG for erectile dysfunction, on decades of large randomised trials. Among the best-evidenced compounds in this catalogue.
• STRONG for pulmonary arterial hypertension, but under a SEPARATE approved product at different strengths — that indication does not transfer to an ED tablet.
• NONE SHOWN for gym performance or general vascular health in healthy people. For altitude specifically the evidence is LIMITED and MIXED rather than absent: a 14-mountaineer crossover trial found increased maximum workload under hypoxia, while a 62-person randomised trial found no pulmonary-pressure benefit and a worse altitude-sickness score on one day. Nothing there supports routine use or prevention of altitude illness.
• FDA has repeatedly found undeclared PDE5 drugs in products marketed as sexual-enhancement supplements — that is a documented enforcement problem, and it is distinct from legitimate state-licensed online pharmacies, which FDA says do operate lawfully.
• Sudden hearing loss and non-arteritic anterior ischaemic optic neuropathy appear as post-marketing reports. The label is careful about causation — for NAION the observational association does not establish it, and for hearing loss neither frequency nor causality can be determined. Either way, any sudden vision or hearing change means stopping and being seen.

Shorter-acting than tadalafil. It is metabolised by CYP3A4, which underlies its significant interactions. Vision changes with a blue tinge are a recognised effect of its weak activity at a related enzyme in the retina.

Headache, flushing, congestion, visual tinting; serious interactions with nitrates (dangerous blood-pressure drops) and caution with alpha-blockers. Rare but real: priapism, sudden hearing/vision events. Counterfeit tablets are a well-documented problem and often contain unlisted doses of the real drug.

• Anyone taking nitrates in any form, including recreational nitrites
• Anyone taking riociguat or another guanylate cyclase stimulator
• Anyone whose cardiovascular condition makes sexual activity inadvisable
• Anyone with a history of non-arteritic anterior ischaemic optic neuropathy, or significant kidney or liver impairment — these are precautions requiring individual prescriber assessment rather than absolute bars

• Nitrates in any form — an absolute contraindication, including recreational nitrites. The combination can drop blood pressure catastrophically.
• Guanylate cyclase stimulators such as riociguat — the second absolute contraindication.
• Alpha-blockers and other antihypertensives, which can cause clinically important hypotension.
• Ritonavir, which raises sildenafil exposure roughly elevenfold and has been associated at high exposure with fainting, low blood pressure and prolonged erection.
• Other sildenafil-containing products (including those for pulmonary hypertension), other PDE5 inhibitors, and other erectile-dysfunction treatments — the label says combining them may further lower blood pressure and is not recommended.
• Heavy drinking independently worsens dizziness, blood pressure and erectile function; the label's interaction study found no potentiation at a moderate blood-alcohol level and heavier exposure was not studied.
• Strong CYP3A4 inhibitors and inducers, which raise or lower its levels significantly.
• Products bought outside licensed pharmacies, a common vehicle for undeclared analogs.

• Whether your heart can tolerate sexual activity at all — a cardiovascular assessment that belongs before the prescription, not after.
• Blood pressure, especially for anyone on alpha-blockers or other antihypertensives.
• Any sudden vision or hearing change, which means stopping and seeking prompt assessment.
• An erection lasting more than four hours needs immediate emergency care.
• Conditions the label says need prescriber assessment first: penile deformity, sickle-cell disease, multiple myeloma, leukaemia, retinitis pigmentosa, bleeding disorders and active peptic ulceration.

No withdrawal syndrome and no rebound. Effects fade within hours. Erectile function returns to whatever it was, since the drug treats a symptom rather than a cause — and that cause is frequently cardiovascular, which is why erectile dysfunction is worth investigating rather than only medicating.

US: prescription-only.

Papers about this compound, not proof of the claims above. A title says what was studied, which is sometimes a negative result or a different question entirely.

• Sildenafil for idiopathic pulmonary fibrosis: A systematic review and meta-analysis
  Pulm Pharmacol Ther, 2022
• Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction: a systematic review and meta-analysis
  Int Urol Nephrol, 2017
• Use of sildenafil for pulmonary hypertension in neonates
  Bol Med Hosp Infant Mex, 2020

• Sildenafil/Viagra in the treatment of premature ejaculationInt J Impot Res · 2019
• Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction: a systematic review and meta-analysisInt Urol Nephrol · 2017
• Sildenafil in Combination Therapy against Cancer: A Literature ReviewCurr Med Chem · 2021
• Sildenafil's impact on male infertility: what has changed in 20 years?Int J Impot Res · 2019
• Sildenafil does not reliably improve exercise performance in hypoxia: a systematic reviewBMJ Open Sport Exerc Med · 2019
• A Systematic Review of Sildenafil Mortality Through the YearsCureus · 2022
• Sildenafil beyond erectile dysfunction and pulmonary arterial hypertension: Thinking about new indicationsFundam Clin Pharmacol · 2021
• Sildenafil-associated hepatoxicity: a review of the literatureEur Rev Med Pharmacol Sci · 2017
• Sildenafil in dialysis patientsInt J Artif Organs · 2006
• Exploring the Multifaceted Potential of Sildenafil in MedicineMedicina (Kaunas) · 2023
• Sildenafil in Term and Premature Infants: A Systematic ReviewClin Ther · 2015
• Viagra (sildenafil citrate) and ophthalmologyProg Retin Eye Res · 2002