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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REVATIO (REVATIO).
| Breastfeeding | Sildenafil is excreted in human breast milk in low concentrations. The milk-to-plasma ratio is approximately 0.3. Due to limited data, caution is advised. Consider the benefits of breastfeeding, the risk of potential infant exposure, and the mother's need for the drug. If used, monitor the infant for adverse effects such as hypotension or priapism. |
| 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. |
■ 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 any form of nitrate (organic nitrates or organic nitrites).","Concomitant use with riociguat, a guanylate cyclase stimulator.","Hypersensitivity to sildenafil or any component of the formulation.","Pediatric patients (due to increased mortality)."]
| 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."] |
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| 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. |