REVATIO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REVATIO (REVATIO).
REVATIO (sildenafil) is a phosphodiesterase type 5 (PDE5) inhibitor. By inhibiting PDE5, it increases cyclic guanosine monophosphate (cGMP) levels in pulmonary vascular smooth muscle, leading to vasodilation and reduced pulmonary vascular resistance.
| Metabolism | Metabolized primarily by CYP3A4 (major) and CYP2C9 (minor) to active N-desmethyl metabolite. |
| Excretion | Primarily hepatic metabolism (CYP3A4) to N-desmethyl sildenafil (active). Renal excretion accounts for ~80% as metabolites; ~13% fecal. |
| Half-life | Terminal elimination half-life ~4 hours (range 3-5 hours) in steady state; similar in pulmonary arterial hypertension patients. |
| Protein binding | ~96% bound to plasma proteins (albumin and alpha1-acid glycoprotein). |
| Volume of Distribution | Vd ~1.0 L/kg (range 0.8-1.5 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral absolute bioavailability ~41% (range 25-63%) due to first-pass metabolism; IV bioavailability 100%. |
| Onset of Action | Oral: Rapid absorption, onset within 30-60 minutes; IV: Within 5-20 minutes; no inhaled formulation. |
| Duration of Action | Clinical hemodynamic effects persist 4-6 hours; peak vasodilation at 1-2 hours post oral dose. |
| Molecular Weight | 474.6 |
20 mg orally three times daily, administered 4-6 hours apart.
| Dosage form | FOR SUSPENSION |
| Renal impairment | For GFR <30 mL/min: not recommended. For GFR 30-80 mL/min: no dose adjustment needed. |
| Liver impairment | Child-Pugh A and B: no dose adjustment recommended. Child-Pugh C: no data available; use with caution. |
| Pediatric use | For pulmonary arterial hypertension: 10 mg orally three times daily for patients weighing 20-40 kg; 20 mg orally three times daily for >40 kg. Not recommended for weight <20 kg. |
| Geriatric use | No specific dose adjustment required but consider age-related renal impairment; start at lowest dose and monitor closely. |
| 1st trimester | Limited human data; animal studies show adverse effects (fetotoxicity, increased mortality). Use only if potential benefit justifies risk. |
| 2nd trimester | Limited human data; animal studies show adverse effects. Use only if clearly needed. |
| 3rd trimester | May cause hypotension in neonate; use not recommended. |
Clinical note
Comprehensive clinical and safety monograph for REVATIO (REVATIO).
| Placental transfer | Crosses placenta in animals; limited human data suggests transfer. |
| Breastfeeding | Excreted into breast milk in low amounts; unlikely to cause adverse effects in infant. Consider alternative if concern. |
| Lactation Rating |
■ FDA Black Box Warning
Not approved for use in pediatric patients; increased risk of mortality seen in pediatric patients with pulmonary hypertension. Use is contraindicated in pediatric patients.
| Serious Effects |
Concomitant use with nitrates or nitric oxide donorsConcomitant use with riociguatHypersensitivity to sildenafil or any component
| Precautions | Use with nitrates in any form is contraindicated due to risk of severe hypotension., Use with potent CYP3A4 inhibitors (e.g., ritonavir) is not recommended., Not recommended for use in patients with pulmonary hypertension secondary to sickle cell anemia., May cause hearing loss or sudden decrease or loss of hearing., Priapism risk in patients with anatomical deformation of penis or conditions predisposing to priapism., Use with alpha-blockers may cause symptomatic hypotension. |
| Food/Dietary | Avoid grapefruit juice as it inhibits CYP3A4, increasing sildenafil concentration. High-fat meals may delay absorption but do not reduce total exposure; administer consistently relative to meals. |
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| Teratogenic Risk | Revatio (sildenafil) is classified as FDA Pregnancy Category B. Animal studies have not shown teratogenic effects, but there are no adequate and well-controlled studies in pregnant women. It should be used during pregnancy only if clearly needed. Potential fetal risks include possible decreased uterine blood flow and fetal distress, particularly in cases of preeclampsia. However, sildenafil is under investigation for preventing fetal growth restriction. Trimester-specific risks are not definitively established, but caution is advised in all trimesters. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate during therapy, especially in pregnant women with preeclampsia or other hypertensive disorders. Fetal monitoring (non-stress test or biophysical profile) may be considered in late pregnancy due to potential effects on uterine blood flow. Additionally, monitor for signs of fetal distress if used near term. |
| Fertility Effects | Sildenafil does not appear to impair fertility in animal studies. In humans, there is no evidence of adverse effects on fertility in men or women. However, sildenafil is sometimes used off-label for female sexual dysfunction and may theoretically improve fertility by increasing uterine blood flow, but this is not established. |
| Clinical Pearls | REVATIO (sildenafil) is a PDE5 inhibitor used for pulmonary arterial hypertension (PAH). It is dosed at 20 mg three times daily, 4-6 hours apart. Monitor for hypotension, especially when co-administered with antihypertensives or nitrates (absolute contraindication). Caution in hepatic impairment (Child-Pugh A/B) and severe renal impairment (CrCl <30 mL/min). Avoid use with potent CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) – reduce dose to 20 mg BID if co-administered. Risk of non-arteritic anterior ischemic optic neuropathy (NAION), especially in patients with underlying anatomical risk factors. For pediatric patients, dose based on weight: 10 mg TID for 8-20 kg, 20 mg TID for >20 kg. |
| Patient Advice | Take REVATIO exactly as prescribed, three times daily, about 4-6 hours apart, with or without food. · Do not take REVATIO if you are taking any nitrates (e.g., nitroglycerin) or recreational drugs called 'poppers' (amyl nitrate) as this can cause a dangerous drop in blood pressure. · Contact your doctor immediately if you experience sudden vision loss, hearing loss, or an erection lasting more than 4 hours (priapism). · Avoid grapefruit juice as it may increase sildenafil levels and side effects. · Do not use REVATIO for erectile dysfunction; it is a different formulation and dose. |