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PDE5 Inhibitor — Pulmonary Arterial Hypertension / Raynaud's Phenomenon Pregnancy: UK SPC §4.6 verbatim. WOMEN OF CHILDBEARING POTENTIAL: 'Due to lack of data on effects of Revatio in pregnant women, Revatio is not recommended for women of childbearing potential unless also using appropriate contraceptive measures.' PREGNANCY: 'There are no data from the use of sildenafil in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy and embryonal/foetal development. Studies in animals have shown toxicity with respect to postnatal development (see section 5.3). Due to lack of data, Revatio should not be used in pregnant women unless strictly necessary.' BREAST-FEEDING: 'There are no adequate and well controlled studies in lactating women. Data from one lactating woman indicate that sildenafil and its active metabolite N-desmethylsildenafil are excreted into breast milk at very low levels. No clinical data are available regarding adverse events in breast-fed infants, but amounts ingested would not be expected to cause any adverse effects. Prescribers should carefully assess the mother's clinical need for sildenafil and any potential adverse effects on the breast-fed child.' FERTILITY: 'Non-clinical data revealed no special hazard for humans based on conventional studies of fertility.'

Sildenafil

Brand names: Revatio (PAH), Viagra (ED)

In the vascular setting sildenafil is used as a pulmonary vasodilator for pulmonary arterial hypertension (under the brand Revatio), distinct from its erectile dysfunction indication.

Adult dose

Dose: 20 mg three times a day (TID) — PAH
Route: Oral. The sourced product is a powder for oral suspension reconstituted to 10 mg/ml, and §4.2 expresses the doses as volumes of that suspension ('20 mg (2 ml of reconstituted suspension)'); the SPCs of other Revatio presentations are not in this bundle, so confirm the strength of the preparation in hand. With or without food.
Frequency: Three times a day (TID) — §4.2: doses 'should be taken approximately 6 to 8 hours apart with or without food'.
⚠️ SCOPE — PAH ONLY; NO RAYNAUD'S DOSE IS PUBLISHED. This page's category is 'PDE5 Inhibitor — Pulmonary Arterial Hypertension / Raynaud's Phenomenon' and PAH leads it; the sourced UK SPC is the licensed PAH product and doses that indication exactly. THE BUNDLE CONTAINS NO RAYNAUD'S PHENOMENON OR DIGITAL-ULCER POSOLOGY OF ANY KIND — that use is off-label and neither provider doses it, so it is left unsourced rather than filled from the erectile-dysfunction label (50 mg as needed / 25–100 mg), which is a different indication. || VERBATIM, UK SPC §4.2: 'Treatment should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension. In case of clinical deterioration in spite of Revatio treatment, alternative therapies should be considered.' 'Adults — The recommended dose is 20 mg three times a day (TID).' || METHOD OF ADMINISTRATION (§4.2): 'Revatio powder for oral suspension is for oral use only. The reconstituted oral suspension (a white, grape flavoured oral suspension) should be taken approximately 6 to 8 hours apart with or without food. Before withdrawing the required dose, shake the bottle vigorously for a minimum of 10 seconds.' || MISSED DOSE (§4.2): 'Physicians should advise patients who forget to take Revatio to take a dose as soon as possible and then continue with the normal dose. Patients should not take a double dose to compensate for the missed dose.' || CO-ADMINISTERED CYP3A4 INHIBITORS (§4.2): 'A downward dose adjustment to 20 mg twice daily should be considered when sildenafil is co-administered to patients already receiving CYP3A4 inhibitors like erythromycin or saquinavir. A downward dose adjustment to 20 mg once daily is recommended in case of co-administration with more potent CYP3A4 inhibitors clarithromycin, telithromycin and nefazodone.' The MOST potent CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) are a CONTRAINDICATION, not a dose reduction (§4.3). §4.2 adds: 'Dose adjustments for sildenafil may be required when co-administered with CYP3A4 inducers.' || ELDERLY (§4.2): 'Dose adjustments are not required in elderly patients. Clinical efficacy as measured by 6-minute walk distance could be less in elderly patients.' || STOPPING (§4.2): 'Limited data suggest that the abrupt discontinuation of Revatio is not associated with rebound worsening of pulmonary arterial hypertension. However to avoid the possible occurrence of sudden clinical deterioration during withdrawal, a gradual dose reduction should be considered. Intensified monitoring is recommended during the discontinuation period.' || WHICH FORMS OF PAH (§4.4): 'Studies with sildenafil have been performed in forms of pulmonary arterial hypertension related to primary (idiopathic), connective tissue disease associated or congenital heart disease associated forms of PAH. The use of sildenafil in other forms of PAH is not recommended.' §4.4 also states efficacy 'has not been established in patients with severe pulmonary arterial hypertension (functional class IV)' and that the benefit-risk balance 'has not been established in patients assessed to be at WHO functional class I pulmonary arterial hypertension'. || MAX DOSE LEFT EMPTY DELIBERATELY: the SPC states no adult ceiling with any explicit maximum cue. The '100 mg' maximum in the bundle's other provider belongs to the ERECTILE-DYSFUNCTION tablet label and must never be applied to PAH. §4.8 records that 40 mg and 80 mg TID were given in the trials ('Doses up to 80 mg three times a day (4 times the recommended dose of 20 mg three times a day) were administered') — that is trial exposure, not a licensed ceiling, and discontinuation for adverse events rose with dose (2.9% at 20 mg TID vs 8.5% at 80 mg TID).

Paediatric dose

Route: Oral. §4.2: 'Revatio powder for oral suspension is for oral use only.' The sourced product reconstitutes to 10 mg/ml and §4.2 expresses each band as a volume of that suspension.
Frequency: Three times a day — doses 'should be taken approximately 6 to 8 hours apart with or without food' (§4.2).
Max: 20 mg three times a day — the highest recommended band (body weight over 20 kg). §4.2: 'Higher than recommended doses should not be used in paediatric patients with PAH.'
Concentration: 10 mg/ml
PAEDIATRIC PAH, 1 to 17 years — the PAH half of this page. The SPC gives no paediatric regimen for Raynaud's phenomenon or digital ulcers. || ⚠️ WEIGHT-BANDED, NOT PER-KG: dosePerKg is deliberately null so the weight calculator does not run — a band is not a mg/kg figure and must not be interpolated between bands. || VERBATIM, UK SPC §4.2, paediatric population (1 year to 17 years): 'For paediatric patients aged 1 year to 17 years old, the recommended dose in patients ≤ 20 kg is 10 mg (1 ml of reconstituted suspension) three times a day and for patients > 20 kg is 20 mg (2 ml of reconstituted suspension) three times a day. Higher than recommended doses should not be used in paediatric patients with PAH (see also sections 4.4 and 5.1).' Note the boundary: 20 kg itself falls in the 10 mg band. || ⚠️ MORTALITY SIGNAL ABOVE THE RECOMMENDED DOSE — §4.4: 'In the long term paediatric extension study, an increase in deaths was observed in patients administered doses higher than the recommended dose. Therefore, doses higher than the recommended doses should not be used in paediatric patients with PAH.' || ⚠️ NEONATES / PPHN — §4.2: 'Outside its authorised indications, sildenafil should not be used in neonates with persistent pulmonary hypertension of the newborn as risks outweigh the benefits (see section 5.1).' || UNDER 1 YEAR — §4.2: 'The safety and efficacy of Revatio in other conditions in children below 1 year of age has not been established. No data are available.' || CONCENTRATION 10 mg/ml is the strength of the sourced product (Revatio 10 mg/ml powder for oral suspension), confirmed by the SPC's own '10 mg (1 ml of reconstituted suspension)'; confirm the strength of the preparation in hand. Shake the bottle vigorously for a minimum of 10 seconds before withdrawing the dose.

Dose adjustments

Renal

UK SPC §4.2 verbatim: 'Initial dose adjustments are not required in patients with renal impairment, including severe renal impairment (creatinine clearance < 30 ml/min). A downward dose adjustment to 20 mg twice daily should be considered after a careful benefit-risk assessment only if therapy is not well-tolerated.' No separate paediatric renal statement appears in the bundle.

Hepatic

UK SPC §4.2 verbatim: 'Initial dose adjustments are not required in patients with hepatic impairment (Child-Pugh class A and B). A downward dose adjustment to 20 mg twice daily should be considered after a careful benefit-risk assessment only if therapy is not well-tolerated. Revatio is contraindicated in patients with severe hepatic impairment (Child-Pugh class C), (see section 4.3).'

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 (§4.3).
  • Co-administration with nitric oxide donors (such as amyl nitrite) or nitrates in any form, 'due to the hypotensive effects of nitrates' (§4.3).
  • Co-administration with guanylate cyclase stimulators such as riociguat — §4.3: 'The co-administration of PDE5 inhibitors, including sildenafil, with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic hypotension.'
  • Combination with the most potent of the CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir) (§4.3).
  • Loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy (NAION), 'regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure' (§4.3).
  • Severe hepatic impairment — one of the sub-groups in which 'the safety of sildenafil has not been studied and its use is therefore contraindicated' (§4.3).
  • Recent history of stroke or myocardial infarction — same §4.3 sub-group list.
  • Severe hypotension (blood pressure < 90/50 mmHg) at initiation — same §4.3 sub-group list.
  • Not a contraindication but 'not recommended' (§4.4): known hereditary degenerative retinal disorders such as retinitis pigmentosa — 'The safety of sildenafil has not been studied in patients with known hereditary degenerative retinal disorders ... and therefore its use is not recommended.'
  • Not a contraindication but 'not recommended' (§4.4): forms of PAH other than primary (idiopathic), connective tissue disease associated or congenital heart disease associated PAH.
  • Not a contraindication but a caution (§4.4): 'patients with hypotension, patients with fluid depletion, severe left ventricular outflow obstruction or autonomic dysfunction' may be adversely affected by sildenafil's vasodilatory effects.

Side effects

  • Most commonly reported adverse reactions in the two placebo-controlled PAH studies (≥ 10% on Revatio vs placebo), §4.8: headache, flushing, dyspepsia, diarrhoea and pain in extremity.
  • In the epoprostenol add-on study, §4.8: 'Newly reported adverse reactions, which occurred more frequently in the sildenafil/epoprostenol group, were ocular hyperaemia, vision blurred, nasal congestion, night sweats, back pain and dry mouth. The known adverse reactions headache, flushing, pain in extremity and oedema were noted in a higher frequency in sildenafil/epoprostenol treated patients.'
  • §4.8: 'In the two placebo-controlled studies adverse events were generally mild to moderate in severity.' Discontinuation for adverse events was 2.9% at 20 mg TID, 3.0% at 40 mg TID and 8.5% at 80 mg TID (vs 2.9% placebo).
  • Prolonged erections and priapism — §4.4: 'Prolonged erections and priapism have been reported with sildenafil in post-marketing experience. In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance.' Caution in anatomical deformation of the penis and in conditions predisposing to priapism (sickle cell anaemia, multiple myeloma, leukaemia).
  • Non-arteritic anterior ischaemic optic neuropathy (NAION) — §4.3 makes a previous episode causing loss of vision in one eye an absolute contraindication.
  • Serious cardiovascular events — §4.4: 'In post-marketing experience with sildenafil for male erectile dysfunction, serious cardiovascular events, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular haemorrhage, transient ischaemic attack, hypertension and hypotension have been reported in temporal association with the use of sildenafil. Most, but not all, of these patients had pre-existing cardiovascular risk factors.'
  • This side-effect list may be incomplete — check the full SPC.

Monitoring

  • §4.2: 'Treatment should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension.'
  • Clinical response — §4.2: 'In case of clinical deterioration in spite of Revatio treatment, alternative therapies should be considered.'
  • Blood pressure and vasodilatory effect — §4.4: 'physicians should carefully consider whether patients with certain underlying conditions could be adversely affected by sildenafil's mild to moderate vasodilatory effects, for example patients with hypotension, patients with fluid depletion, severe left ventricular outflow obstruction or autonomic dysfunction'; severe hypotension (< 90/50 mmHg) at initiation is a contraindication (§4.3).
  • Vision — a previous NAION episode with loss of vision in one eye is a contraindication (§4.3), and use is 'not recommended' in known hereditary degenerative retinal disorders such as retinitis pigmentosa (§4.4).
  • Paediatric dosing — §4.4 requires that doses higher than the recommended dose are not used in children with PAH, after 'an increase in deaths was observed in patients administered doses higher than the recommended dose' in the long-term paediatric extension study.
  • Withdrawal — §4.2: 'a gradual dose reduction should be considered. Intensified monitoring is recommended during the discontinuation period.'
  • Erection persisting longer than 4 hours — §4.4: 'the patient should seek immediate medical assistance.'
  • Concomitant medicines — §4.2: 'In general, any dose adjustment should be administered only after a careful benefit-risk assessment' when co-administering CYP3A4 inhibitors or inducers.

Clinical monograph

How it works

It selectively inhibits phosphodiesterase type 5, preventing breakdown of cyclic GMP in vascular smooth muscle and so enhancing nitric-oxide-mediated pulmonary vasodilatation.

Prescribing in practice

  • It is absolutely contraindicated with nitrates and nitric oxide donors because of life-threatening hypotension, and should not be combined with riociguat for the same reason.
  • Avoid co-administration with potent CYP3A4 inhibitors without dose review, and use cautiously in patients on alpha-blockers or with resting hypotension.
  • Caution is needed in left ventricular outflow obstruction and in conditions predisposing to priapism, and it should not be used purely to improve outcome in pulmonary hypertension associated with sickle cell disease.

Monitoring

Monitor blood pressure, symptomatic response and exercise capacity, and review vision and hearing if sudden disturbances are reported.

Counselling the patient

  • Never take with nitrate heart medicines or recreational nitrates ('poppers').
  • Report sudden loss of vision or hearing, or a painful prolonged erection.
  • Headache, flushing and indigestion are common and usually settle.

Evidence & guidelines

Its pulmonary arterial hypertension licence is supported by the SUPER-1 trial and reflected in the SPC and specialist guidance.

Reference: SUPER-1 Trial; STARTS-2 Trial; NICE TA235 (Sildenafil for PAH); ESC/ERS PAH Guidelines 2022; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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