Version July 2025
Dosage guidance:
Dosage form information: Oral suspensions may be available in multiple concentrations (commercially available: 10 mg/mL; extemporaneous preparation: 2.5 mg/mL); dosing should be presented in mg of sildenafil; use extra precaution when verifying product formulation and calculation of dose volumes. The 2 mL oral syringe included with the 10 mg/mL oral suspension only provides measurements for fixed doses of 5 mg and 20 mg; for patients not receiving either of these fixed doses, an appropriate-size calibrated oral syringe should be dispensed.
Pulmonary hypertension: Limited data available:
Persistent pulmonary hypertension in the neonate (PPHN): Note: Optimal dose and duration of therapy not established; interpatient variability has been reported.
GA >34 weeks:
Oral: Note: Guidelines suggest sildenafil may be used as adjunctive therapy in PPHN refractory to inhaled nitric oxide especially when oxygenation index (OI) >25 (Ref).
Initial: Oral: 0.5 to 1 mg/kg/dose every 6 to 8 hours; titrate as needed; usual reported range: 0.5 to 2 mg/kg/dose every 6 to 8 hours (Ref); doses as high as 3 mg/kg/dose every 6 hours have been reported for short-term treatment; however, chronic treatment with doses >2 mg/kg/dose are not recommended in children and adolescents due to a dose-dependent increased mortality risk observed in trials (Ref).
IV:
Continuous IV infusion: Loading dose: IV: 0.4 mg/kg loading dose administered over 3 hours followed by continuous IV infusion of 1.6 mg/kg/day (~0.07 mg/kg/hour) (Ref). Note: This regimen is recommended in neonates with congenital diaphragmatic hernia (CDH) (Ref).
Intermittent IV infusion: IV: Initial dose: 0.125 to 0.5 mg/kg/dose every 6 to 8 hours; titrate doses as necessary; doses have been increased in increments of 0.125 to 0.5 mg/kg/dose; usual maximum dose: 1 mg/kg/dose up to 10 mg/dose; maximum reported dose: 2 mg/kg/dose (Ref).
Bronchopulmonary dysplasia (BPD) associated pulmonary hypertension:
PMA ≥36 weeks:
Oral: 0.25 to 0.5 mg/kg/dose every 6 to 8 hours; titrate gradually as tolerated up to 1 mg/kg/dose; maximum reported dose: 8 mg/kg/day (Ref).
IV: Initial: 0.25 to 0.5 mg/kg/dose every 6 to 8 hours (Ref).
Pulmonary hypertension, facilitation of inhaled nitric oxide (iNO) wean (in patients who previously failed iNO wean): Note: Limited information exists; a wide range of doses and interpatient variability has been reported; careful dose titration is necessary; most literature consists of case reports or small studies.
Full-term neonates:
One-time dose:
Oral: 0.25 to 0.3 mg/kg/dose administered 60 to 70 minutes prior to iNO discontinuation; if initial sildenafil dose does not result in successful iNO weaning, sildenafil may be repeated in 12 hours at a dose of 0.4 mg/kg/dose administered 60 minutes prior to iNO discontinuation (Ref).
IV: 0.125 mg/kg/dose administered 60 minutes prior to iNO discontinuation; if initial sildenafil dose does not result in successful iNO weaning, sildenafil may be repeated in 12 hours at a dose of 0.2 mg/kg/dose administered 60 minutes prior to iNO discontinuation (Ref).
Multiple dose: Oral: Initial: 0.3 mg/kg/dose (range: 0.22 to 0.47 mg/kg/dose) every 6 hours (average duration: 28 days) was used in seven patients (median age: 12 months; range: 3 days to 21 months); optimal duration of treatment not established (Ref).
Dosage guidance:
Dosage form information: Oral suspensions may be available in multiple concentrations (commercially available: 10 mg/mL; extemporaneous preparation: 2.5 mg/mL); dosing should be presented in mg of sildenafil; use extra precaution when verifying product formulation and calculation of dose volumes. The 2 mL oral syringe included with the 10 mg/mL oral suspension only provides measurements for fixed doses of 5 mg and 20 mg; for patients not receiving either of these fixed doses, an appropriate-size calibrated oral syringe should be dispensed.
Pulmonary arterial hypertension:
Infants: Limited data available; duration of therapy not established; interpatient variability has been reported: Oral: Initial: 0.25 mg/kg/dose every 6 hours or 0.5 mg/kg/dose every 8 hours; titrate as needed; maximum reported dose range: 1 to 2 mg/kg/dose every 6 to 8 hours (Ref). Note: May consider lower initial doses (eg, 0.25 mg/kg/dose every 8 hours) in critically ill patients receiving concomitant vasoactive agents, especially infants <4 months of age (Ref).
Children and Adolescents <18 years:
≤20 kg: Oral: 10 mg three times daily.
>20 to 45 kg: Oral: 20 mg three times daily.
>45 kg: Oral: 20 mg three times daily; titrate as needed; maximum dose: 40 mg/dose.
Pulmonary hypertension, congenital heart disease (postoperative): Limited data available:
Oral (or nasogastric tube): Dosing regimens variable (Ref):
Infants, Children, and Adolescents: Oral (or nasogastric tube): Initial: 0.5 mg/kg/dose increase in 0.5 mg/kg/dose increments every 4 to 6 hours up to a maximum dose of 2 mg/kg/dose as tolerated; upon discontinuation of mechanical ventilation, sildenafil therapy can be tapered over 5 to 7 days (Ref). Note: Use of preoperative sildenafil therapy for the prevention of pulmonary hypertension following congenital heart surgery has been reported and has produced variable efficacy results (Ref).
IV: Dosing regimens variable (Ref):
Infants >60 days and Children: IV: Loading dose: Range: 0.04 to 0.35 mg/kg administered over 5 minutes, followed by a maintenance infusion: Reported range: 0.015 to 0.4 mg/kg/hour continued for 24 to 72 hours (Ref).
Pulmonary hypertension, facilitation of inhaled nitric oxide (iNO) wean (in patients who have not previously failed iNO wean): Limited data available:
Infants and Children ≤15 months: Oral (nasogastric): Single dose: 0.4 mg/kg/dose (range: 0.3 to 0.5 mg/kg/dose) given once 60 minutes prior to iNO discontinuation (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Revatio: Children and Adolescents: Oral, IV: Mild, moderate, and severe impairment: No dosage adjustment necessary.
Revatio: Children and Adolescents: Oral, IV:
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: There are no dosage recommendations in the manufacturer's labeling (has not been studied).
(For additional information see "Sildenafil: Drug information")
Dosage guidance:
Safety: Do not administer in patients who regularly take nitrates due to risk for severe hypotension. After intermittent nitrate use, delay sildenafil administration for ≥24 hours (Ref). If a patient taking sildenafil develops chest pain, delay nitrate administration for ≥24 hours. For patients taking a non-uroselective alpha-1 blocking antihypertensive agent, use sildenafil with caution and consider a lower starting dose, as sildenafil can potentiate hypotensive effects (Ref); some experts recommend against routinely using these drugs together, particularly in patients with cardiovascular disease (Ref). Use of a uroselective alpha-1 blocker in combination with sildenafil is acceptable when both agents are used at low doses (Ref).
Erectile dysfunction:
Oral: 50 mg once daily as needed 1 hour before sexual activity; may be taken up to 4 hours before sexual activity. Reduce to 25 mg once daily if side effects occur. May increase to a maximum dose of 100 mg once daily if there is incomplete response.
High-altitude pulmonary edema (adjunctive therapy) (alternative agent) (off-label use):
Prevention: Note: May use as an adjunct to gradual ascent in high-risk individuals (eg, history of high-altitude pulmonary edema) who cannot take nifedipine (Ref).
Oral: 50 mg every 8 hours starting the day of ascent; continue for 3 to 5 days after reaching maximal altitude (Ref); can extend for up to 7 days in individuals who ascend faster than recommended (Ref).
Treatment: Note: Alternative agent when nifedipine is not available. Adjunctive to nonpharmacologic measures (eg, oxygen supplementation, portable hyperbaric chamber, gradual descent) or as monotherapy if nonpharmacologic measures are not possible (Ref).
Oral: 50 mg every 8 hours; continue until descent is complete, symptoms resolve, and oxygenation is normal for the altitude (Ref).
Pulmonary arterial hypertension: Note: Consult a pulmonary arterial hypertension specialist for all management decisions; choice of therapy is dependent on etiology, risk stratification, and cardiopulmonary comorbidities. Sildenafil is contraindicated in patients taking riociguat due to potentially severe hypotension (Ref).
Oral: 20 mg 3 times daily; some do not recommend titration to higher doses (Ref). However, in patients who fail to demonstrate or maintain an adequate clinical response, others consider slowly increasing the dose in 20 mg increments to a maximum dose of 80 mg 3 times daily (Ref).
IV: 10 mg 3 times daily.
Raynaud phenomenon (alternative agent) (off-label use):
Oral: Initial: 20 mg once or twice daily; based on response and tolerability, may increase to 20 mg 3 times daily as needed; if lower doses are ineffective, may increase further to 40 mg 3 times daily if tolerated (Ref); others have reported using 50 mg 2 to 3 times daily as tolerated (Ref).
Sexual dysfunction associated with selective serotonin reuptake inhibitors, mild to moderate (adjunctive agent) (off-label use):
Note: May add-on for mitigating mild to moderate sexual adverse effects; benefit reported in both men and women (Ref). Prior to adding sildenafil, may trial watchful waiting for limited time (eg, 2 to 8 weeks), as treatment-onset sexual dysfunction may remit spontaneously (Ref).
Oral: 50 mg once daily as needed taken 1 to 4 hours before sexual activity. May increase based on response and tolerability to a maximum dose of 100 mg once daily as needed 1 to 4 hours before sexual activity. Not to be taken more than once daily (Ref).
Conversion between oral sildenafil and IV sildenafil: A 10 mg IV sildenafil dose is expected to provide similar effects as a 20 mg oral dose (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Although only 13% of sildenafil is excreted in the urine, the AUC is approximately doubled in patients with CrCl <30 mL/minute, most likely due to a decrease in hepatic function associated with uremia (Ref); use with caution when initiating therapy or with any increase in dose in these patients, including patients on renal replacement therapies. Additionally, although there are no specific dosage adjustments recommended for off-label indications (has not been studied), the same general dosing principles may apply for these indications in patients with altered kidney function or on renal replacement therapies (Ref).
Altered kidney function: Oral, IV:
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute:
Pulmonary arterial hypertension: No dosage adjustment necessary; use with caution (Ref).
Erectile dysfunction: Initial: 25 mg once daily as needed 1 hour before sexual activity; may be taken up to 4 hours before sexual activity (Ref). May cautiously increase dose based on tolerability and response. Maximum dose: 100 mg once daily.
Hemodialysis, intermittent (thrice weekly): Oral, IV: Not dialyzable (Ref):
Pulmonary arterial hypertension: No dosage adjustment necessary; use with caution (Ref).
Erectile dysfunction: Initial: 25 mg once daily as needed 1 hour before sexual activity; may be taken up to 4 hours before sexual activity (Ref). May cautiously increase dose based on tolerability and response. Maximum dose: 100 mg once daily (Ref).
Peritoneal dialysis: Oral, IV: Unlikely to be significantly dialyzable (highly protein bound) (Ref):
Pulmonary arterial hypertension: No dosage adjustment necessary; use with caution (Ref).
Erectile dysfunction: Initial: 25 mg once daily as needed 1 hour before sexual activity; may be taken up to 4 hours before sexual activity (Ref). May cautiously increase dose based on tolerability and response. Maximum dose: 100 mg once daily (Ref).
CRRT: Oral, IV:
Pulmonary arterial hypertension: There are no specific dosage adjustments recommended (has not been studied); however, dosage adjustment is likely unnecessary; use with caution (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Oral, IV:
Pulmonary arterial hypertension: There are no specific dosage adjustments recommended (has not been studied); however, dosage adjustment is likely unnecessary; use with caution (Ref).
Mild to moderate impairment (Child-Pugh classes A and B):
Revatio, Liqrev: No dosage adjustment necessary.
Viagra: Starting dose of 25 mg should be considered.
Severe impairment (Child-Pugh class C):
Revatio, Liqrev: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Viagra: Starting dose of 25 mg should be considered.
Sudden auditory impairment and hearing loss have occurred. Hearing changes are generally unilateral and may be accompanied by tinnitus and dizziness. A direct relationship between therapy and hearing loss has not been determined (Ref). The potential hearing loss affects high frequencies and is reversible (Ref).
Mechanism: Not clearly established; several proposed mechanisms. May be related to elevated middle inner ear pressure which results from congestion of nasal erectile tissue. Intensification of effects of nitric oxide and/or activation of intracellular cyclic guanosine monophosphate (cGMP) may also contribute (Ref).
Onset: Rapid; most cases occur within 12 to 24 hours (Ref).
Modest decreases in blood pressure (ie, reductions of 7 to 10 mmHg in systolic and 7 mm Hg in diastolic pressure) may occur (Ref). Blood pressure generally normalizes within 6 hours of administration (Ref). Concurrent organic nitrate or guanylate cyclase stimulator therapy may potentiate the vasodilatory effects of sildenafil and produce severe hypotension; use is contraindicated (Ref).
Mechanism: Related to the pharmacologic action; inhibition of phosphodiesterase-5 (PDE-5) activity in the vascular smooth muscle results in vasodilation, which can lead to hypotension (Ref).
Onset: Rapid; decreases in blood pressure generally occur within 1 to 2 hours after administration (Ref).
Risk factors:
• Concurrent medications that either potentiate the vasodilatory effects of sildenafil (eg, alpha-adrenergic antagonists) or increase sildenafil serum concentrations (eg, ritonavir) (Ref)
• Concurrent antihypertensives
• Left ventricular outflow obstruction (eg, aortic stenosis, hypertrophic cardiomyopathy [HCM] with left ventricular outflow tract obstruction [LVOTO])
• Resting hypotension (BP <90/50 mm Hg)
• Fluid depletion
• Autonomic dysfunction
• Hemodynamic instability
Painful priapism lasting >4 hours in duration has been reported rarely (Ref).
Mechanism: Related to pharmacologic action; inhibition of phosphodiesterase-5 (PDE-5) activity, which leads to increased accumulation of cyclic guanosine monophosphate (cGMP) in response to release of nitric oxide (Ref).
Onset: Rapid; has occurred shortly after orgasm (Ref).
Risk factors:
• Sildenafil overdose (Ref)
• Concurrent medications that may cause priapism (eg, amitriptyline, nortriptyline, second-generation antipsychotics, trazodone) (Ref)
Visual disturbance (including vision color changes, transient impairment of color discrimination [blue/green], and cyanopsia [blue-tinged vision]; photophobia; and blurred vision) may occur (Ref). Sudden vision loss in one or both eyes may occur and represent a sign of nonarteritic anterior ischemic optic neuropathy (NAION); however, a direct relationship has not been determined (Ref). Most visual disturbances are transient (Ref). Cyanopsia, photophobia, and blurred vision typically resolve within 5 hours after discontinuation (Ref). Complete resolution of NAION may be delayed (weeks to a year) (Ref). Anterior uveitis, macular edema, and retinal artery occlusion have also been reported (Ref).
Mechanism:
• Impaired color discrimination: Dose-related; related to the pharmacologic action. May be a result of minor inhibition of phosphodiesterase-6 (PDE-6).
• Cyanopsia, photophobia, blurred vision: Dose-related; related to the pharmacologic action. May be a result of minor inhibition of phosphodiesterase-6 (PDE-6) which is expressed in rod and cone photoreceptor cells in the retina (Ref).
• NAION: Not clearly established; may be due to hypoperfusion of ciliary arteries resulting from hypotension (Ref).
Onset: Cyanopsia, photophobia, blurred vision: Rapid; generally occur within 1 to 2 hours after ingestion (Ref). NAION: Varied; hours to months after ingestion (Ref).
Risk factors:
General:
• Retinitis pigmentosa (possible risk factor) (no safety information available)
Impaired color discrimination:
• Higher dose
NAION:
• Low cup-to-disc ratio ("crowded disc") (Ref)
• Older patients (>50 years of age) (Ref)
• Coronary heart disease (Ref)
• Diabetes (Ref)
• Hypertension (Ref)
• Hyperlipidemia (Ref)
• Smoking (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Flushing (9% to 19%)
Gastrointestinal: Diarrhea (9% to 12%), dyspepsia (3% to 17%)
Nervous system: Headache (16% to 49%)
Neuromuscular & skeletal: Back pain (3% to 13%), limb pain (7% to 15%), myalgia (2% to 14%)
Ophthalmic: Visual disturbance (2% to 11%; including vision color changes, blurred vision, photophobia)
Respiratory: Epistaxis (2% to 3%; patients with pulmonary arterial hypertension secondary to connective tissue disorder: 13%)
1% to 10%:
Cardiovascular: Angina pectoris (<2%), atrioventricular block (<2%), cardiomyopathy (<2%), chest pain (<2%), ECG abnormality (<2%), edema (<2%), heart failure (<2%), hypotension (<2%), ischemic heart disease (<2%), orthostatic hypotension (<2%), palpitations (<2%), peripheral edema (<2%), shock (<2%), syncope (<2%), tachycardia (<2%)
Dermatologic: Contact dermatitis (<2%), dermal ulcer (<2%), diaphoresis (<2%), exfoliative dermatitis (<2%), pruritus (<2%), skin photosensitivity (<2%), skin rash (2% to 3%), urticaria (<2%)
Endocrine & metabolic: Hyperglycemia (<2%), hypernatremia (<2%), hyperuricemia (<2%), hypoglycemia (<2%), increased thirst (<2%), unstable diabetes (<2%)
Gastrointestinal: Abdominal pain (<2%), colitis (<2%), dysphagia (<2%), esophagitis (<2%), gastroenteritis (<2%), gingivitis (<2%), glossitis (<2%), nausea (2% to 3%), rectal hemorrhage (<2%), stomatitis (<2%), vomiting (<2%), xerostomia (<2%)
Genitourinary: Anorgasmia (<2%), breast hypertrophy (<2%), cystitis (<2%), ejaculatory disorder (<2%), genital edema (<2%), nocturia (<2%), urinary frequency (<2%), urinary incontinence (<2%)
Hematologic & oncologic: Anemia (<2%), leukopenia (<2%)
Hepatic: Abnormal hepatic function tests (<2%)
Hypersensitivity: Facial edema (<2%), hypersensitivity reaction (<2%)
Infection: Herpes simplex infection (<2%)
Nervous system: Abnormal dreams (<2%), absent reflexes (<2%), asthenia (<2%), ataxia (<2%), cerebral thrombosis (<2%), chills (<2%), depression (<2%), dizziness (2% to 4%) (table 1), drowsiness (<2%), falling (<2%), hypertonia (<2%), hypoesthesia (<2%), migraine (<2%), myasthenia (<2%), neuralgia (<2%), neuropathy (<2%), pain (<2%), tremor (<2%), vertigo (<2%)
|
Drug (Sildenafil) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Sildenafil) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
4% |
2% |
50 mg |
Tablets |
Erectile dysfunction |
511 |
607 |
|
3% |
2% |
100 mg |
Tablets |
Erectile dysfunction |
506 |
607 |
|
3% |
2% |
25 mg |
Tablets |
Erectile dysfunction |
312 |
607 |
|
2% |
1% |
N/A |
Tablets |
Erectile dysfunction |
734 |
725 |
Neuromuscular & skeletal: Arthritis (<2%), gout (<2%), ostealgia (<2%), osteoarthritis (<2%), rupture of tendon (<2%), synovitis (<2%), tenosynovitis (<2%)
Ophthalmic: Anterior chamber eye hemorrhage (<2%), cataract (<2%), conjunctivitis (<2%), dry eye syndrome (<2%), eye pain (<2%), mydriasis (<2%)
Otic: Auditory impairment (<2%), hearing loss (<2%), otalgia (<2%), tinnitus (<2%)
Respiratory: Asthma (<2%), bronchitis (<2%), dyspnea (<2%), increased bronchial secretions (<2%), increased cough (<2%), laryngitis (<2%), nasal congestion (4% to 9%), pharyngitis (<2%)
Postmarketing:
Cardiovascular: Acute myocardial infarction (Ref), hypertension, ventricular arrhythmia
Dermatologic: Basal cell carcinoma of skin (Ref), malignant melanoma (Ref)
Genitourinary: Hematuria, priapism (Ref)
Hematologic & oncologic: Hemorrhage, sickle cell crisis (vaso-occlusive crisis in patients with pulmonary hypertension associated with sickle cell disease) (Ref)
Hepatic: Hepatic failure (Ref)
Nervous system: Amnesia (transient global), anxiety, cerebral hemorrhage, cerebrovascular hemorrhage, cranial nerve palsy (Ref), psychosis (Ref), seizure (including recurrent seizures), subarachnoid hemorrhage (Ref), transient ischemic attacks (Ref)
Ophthalmic: Anterior ischemic optic neuropathy (nonarteritic; NAION) (Ref), anterior uveitis (Ref), burning sensation of eyes, diplopia, eye redness, increased intraocular pressure, macular edema (Ref), retinal artery occlusion (Ref), retinal edema, retinal vascular disease, swelling of eye, vision loss, vitreous detachment, vitreous traction
Respiratory: Pulmonary hemorrhage
Hypersensitivity to sildenafil or any component of the formulation; concurrent use (regularly/intermittently) of organic nitrates in any form (eg, nitroglycerin, isosorbide dinitrate); concomitant use of riociguat (a guanylate cyclase stimulator).
According to the manufacturers of protease inhibitors (atazanavir, darunavir, fosamprenavir, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, saquinavir, tipranavir): Concurrent use with a protease inhibitor regimen when sildenafil is used for pulmonary artery hypertension.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling):
Viagra: Prior episode of non-arteritic anterior ischemic optic neuropathy (NAION).
Revatio: Prior episode of non-arteritic anterior ischemic optic neuropathy (NAION); concurrent use with potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir); pulmonary hypertension secondary to sickle cell anemia; severe hepatic impairment; recent history of stroke or MI, or life-threatening arrhythmia; coronary artery disease causing unstable angina; severe hypotension (<90/50 mm Hg) at initiation.
Disease-related concerns:
• Anatomical penis deformation: Use with caution in patients with anatomical deformation of the penis (angulation, cavernosal fibrosis, or Peyronie disease).
• Bleeding disorders: Use with caution in patients with bleeding disorders; safety has not been established. In vitro studies have suggested a decreased effect on platelet aggregation.
• Cardiovascular disease: Use with caution in patients with hypotension (<90/50 mm Hg); uncontrolled hypertension (>170/110 mm Hg); life-threatening arrhythmias, stroke or MI within the last 6 months; cardiac failure or coronary artery disease causing unstable angina; safety and efficacy have not been studied in these patients. Use caution in patients with left ventricular outflow obstruction. Patients should be hemodynamically stable prior to initiating therapy. There is a degree of cardiac risk associated with sexual activity; therefore, health care providers should consider the cardiovascular status of their patients prior to initiating any treatment for erectile dysfunction.
• Conditions predisposing to priapism: Use with caution in patients who have conditions which may predispose them to priapism (sickle cell anemia, multiple myeloma, leukemia). All patients should be instructed to seek immediate medical attention if erection persists >4 hours.
• Peptic ulcer disease: Use with caution in patients with active peptic ulcer disease; safety has not been established.
• Pulmonary arterial hypertension: Sudden cessation of sildenafil monotherapy could result in an exacerbation of pulmonary arterial hypertension (PAH). Efficacy in adult patients determined through short-term (12 to 16 week) studies. A long-term use trial in pediatric patients showed increased mortality in the higher dose groups (20 to 80 mg [depending upon weight] 3 times per day) after 2 years of use, which was related to disease progression (Barst 2012; Barst 2014; manufacturer's labeling).
• Pulmonary veno-occlusive disease: Use in patients with pulmonary veno-occlusive disease (PVOD) is not recommended (has not been studied); if pulmonary edema occurs when treating PAH, consider the possibility of PVOD.
• Sickle cell anemia: Treatment of pulmonary hypertension with sildenafil in this patient population may lead to more hospitalizations for management of vaso-occlusive crises. The effectiveness and safety of sildenafil have not been established in pulmonary hypertension secondary to sickle cell disease.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Suspension: Oral suspensions may be available in multiple concentrations (commercially available: 10 mg/mL; extemporaneous preparation: 2.5 mg/mL); dosing should be presented in mg of sildenafil; use extra precaution when verifying product formulation and calculation of dose volumes.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Revatio: 10 mg/12.5 mL (12.5 mL)
Generic: 10 mg/12.5 mL (12.5 mL)
Suspension, Oral, as citrate:
Liqrev: 10 mg/mL (122 mL [DSC]) [contains sodium benzoate]
Suspension Reconstituted, Oral:
Revatio: 10 mg/mL (112 mL [DSC]) [contains sodium benzoate; grape flavor]
Generic: 10 mg/mL (112 mL)
Tablet, Oral:
Revatio: 20 mg
Viagra: 25 mg, 50 mg, 100 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Generic: 20 mg, 25 mg, 50 mg, 100 mg
May be product dependent
Solution (Revatio Intravenous)
10 mg/12.5 mL (per mL): $26.07
Solution (Sildenafil Citrate Intravenous)
10 mg/12.5 mL (per mL): $17.60
Suspension (reconstituted) (Sildenafil Citrate Oral)
10 mg/mL (per mL): $1.07 - $87.94
Tablets (Revatio Oral)
20 mg (per each): $74.23
Tablets (Sildenafil Citrate Oral)
20 mg (per each): $19.00 - $22.05
25 mg (per each): $0.11 - $66.46
50 mg (per each): $0.11 - $66.46
100 mg (per each): $0.11 - $66.46
Tablets (Viagra Oral)
25 mg (per each): $104.91
50 mg (per each): $99.92
100 mg (per each): $104.91
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Film, Oral:
Viagra: 50 mg (2 ea, 4 ea) [contains levomenthol]
Solution, Intravenous:
Revatio: 10 mg/12.5 mL (12.5 mL)
Tablet, Oral:
Revatio: 20 mg
Viagra: 25 mg, 50 mg, 100 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Generic: 20 mg, 25 mg, 50 mg, 100 mg
Note: Commercial oral suspension is available (10 mg/mL).
2.5 mg/mL oral suspension
A 2.5 mg/mL sildenafil citrate oral suspension may be made with tablets and either a 1:1 mixture of methylcellulose 1% and simple syrup NF or a 1:1 mixture of Ora-Sweet and Ora-Plus. Crush thirty sildenafil 25 mg tablets (Viagra) in a mortar and reduce to a fine powder. Add small portions of chosen vehicle and mix to a uniform paste; mix while adding vehicle in incremental proportions to almost 300 mL; transfer to a graduated cylinder, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 300 mL. Store in amber plastic bottles and label "shake well". Stable for 90 days at room temperature or refrigerated.
Oral: Revatio: Note: Oral suspensions may be available in multiple concentrations (commercially available: 10 mg/mL; extemporaneous preparation: 2.5 mg/mL); use extra precaution when verifying product formulation and calculation of dose volumes. The 2 mL oral syringe included with the 10 mg/mL oral suspension only provides measurements for fixed doses of 5 mg and 20 mg; for patients not receiving either of these fixed doses, an appropriate-size calibrated oral syringe should be dispensed.
Administer doses at least 4 to 6 hours apart; may be administered without regard to meals; shake oral suspension well prior to use.
IV: Revatio:
Neonates:
Continuous IV infusion:
Loading dose: Usually administered over 3 hours (Ref).
Continuous IV infusion: Administer as a continuous IV infusion with the use of an infusion pump.
Intermittent IV infusions: Infusion time variable; infuse over 1 hour, longer infusion times are commonly used to minimize risk of hypotension; reported infusion times range: 15 minutes to 3 hours (Ref).
Infant, Children, and Adolescents: In clinical trials, loading dose was administered as a bolus over 5 minutes, followed by a continuous IV infusion (Ref).
Oral:
Revatio, Liqrev: Administer doses with or without food. Shake oral suspension well for ≥10 seconds before administering each dose; do not mix with any other medication or additional flavoring agent. Administer with an accurate measuring device (eg, calibrated oral syringe).
Viagra: Administer with or without food 30 minutes to 4 hours before sexual activity.
Orodispersible film (Canadian product): Place on tongue and allow to disintegrate completely prior to swallowing with or without water. Allow first film to fully dissolve before administering a second film if needed.
IV: Revatio: Administer as an IV bolus.
Tablets/injection: Store at 20°C to 25°C (68°F to 77°F); excursions are permitted to 15°C to 30°C (59°F to 86°F). Discard any unused injection.
Oral suspension:
Revatio: Store unreconstituted powder below 30°C (86°F); protect from moisture. Store reconstituted oral suspension below 30°C (86°F) or at 2°C to 8°C (36°F to 46°F). Do not freeze. Discard unused product 60 days after reconstitution.
Liqrev: Store at 20°C to 25°C (68°F to 77°F); excursions are permitted to 15°C to 30°C (59°F to 86°F). Discard unused product 90 days after opening bottle.
Treatment of WHO Group I pulmonary arterial hypertension (PAH) (Revatio: FDA approved in ages ≥1 year and adults; Liqrev: FDA approved in adults); treatment of erectile dysfunction (Viagra: FDA approved in male adults). Has also been used for treatment of persistent pulmonary hypertension of the newborn (PPHN), treatment of bronchopulmonary dysplasia (BPD) associated pulmonary hypertension, facilitation of weaning from nitric oxide (ie, to attenuate rebound effects after discontinuing inhaled nitric oxide), and secondary pulmonary hypertension following cardiac surgery.
Revatio may be confused with ReVia, Revonto
Sildenafil may be confused with silodosin, tadalafil, vardenafil
Viagra may be confused with Allegra, Vaniqa
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (pediatric liquid medications requiring measurement) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
Sildenafil is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) with severe heart failure with hypotension or concurrent use of nitrates for angina (O’Mahony 2023).
Oral suspension is supplied with a 2 mL oral syringe with only 0.5 mL and 2 mL dose markings; when administering a 10 mg (1 mL) dose measure to the 0.5 mL marking two times. In cases when the dose is <0.5 mL, remove the supplied syringe and provide the most appropriate device to measure the prescribed dose. (ISMP Community/Ambulatory Care Newsletter March 2024)
Substrate of CYP1A2 (Minor), CYP2C19 (Minor), CYP2C9 (Minor), CYP2D6 (Minor), CYP2E1 (Minor), CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Alcohol (Ethyl): May increase hypotensive effects of Phosphodiesterase 5 Inhibitors. Risk C: Monitor
Alpha1-Blockers (Nonselective): Phosphodiesterase 5 Inhibitors may increase hypotensive effects of Alpha1-Blockers (Nonselective). Management: Ensure patient is stable on one agent prior to initiating the other, and always initiate combination using the lowest possible dose of the drug being added. When tadalafil is used for treatment of BPH, concurrent alpha 1-blockers are not recommended. Risk D: Consider Therapy Modification
Alpha1-Blockers (Uroselective): May increase hypotensive effects of Phosphodiesterase 5 Inhibitors. Risk C: Monitor
Alprostadil: Phosphodiesterase 5 Inhibitors may increase adverse/toxic effects of Alprostadil. Risk X: Avoid
Amyl Nitrite: Phosphodiesterase 5 Inhibitors may increase vasodilatory effects of Amyl Nitrite. Risk X: Avoid
Blood Pressure Lowering Agents: Phosphodiesterase 5 Inhibitors may increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bosentan: May decrease serum concentration of Sildenafil. Sildenafil may increase serum concentration of Bosentan. Management: When sildenafil is used for treatment of pulmonary arterial hypertension (PAH), coadministration of sildenafil and bosentan is not recommended. Otherwise, monitor for reduced sildenafil efficacy if combined with bosentan. Risk D: Consider Therapy Modification
Ciprofloxacin (Systemic): May increase serum concentration of Sildenafil. Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
Cobicistat: May increase serum concentration of Sildenafil. Management: Use of cobicistat and sildenafil for the treatment of PAH is contraindicated. If using sildenafil for the treatment of erectile dysfunction, limit the sildenafil dose to 25 mg and do not use more frequently than every 48 hours. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Moderate): May decrease serum concentration of Sildenafil. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Sildenafil. Risk C: Monitor
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Sildenafil. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Sildenafil. Management: Use of sildenafil for pulmonary arterial hypertension (PAH) should be avoided with strong CYP3A4 inhibitors. When used for erectile dysfunction, consider using a lower starting dose of 25 mg and monitor patients for sildenafil toxicities. Risk D: Consider Therapy Modification
Dapoxetine: May increase orthostatic hypotensive effects of Phosphodiesterase 5 Inhibitors. Risk X: Avoid
Erythromycin (Systemic): May increase serum concentration of Sildenafil. Management: For pulmonary arterial hypertension, no dose adjustment required. For erectile dysfunction, consider using a lower starting dose of 25 mg in patients who are also taking erythromycin. Monitor patients for sildenafil toxicities when combined. Risk D: Consider Therapy Modification
Etravirine: May decrease serum concentration of Phosphodiesterase 5 Inhibitors. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Grapefruit Juice: May increase serum concentration of Sildenafil. Risk C: Monitor
Lenacapavir: May increase serum concentration of Sildenafil. Management: For pulmonary arterial hypertension, no dose adjustment required. For erectile dysfunction, use a lower starting dose of 25 mg in patients who are also taking lenacapavir. Monitor patients for sildenafil toxicities when combined. Risk D: Consider Therapy Modification
Molsidomine: May increase hypotensive effects of Phosphodiesterase 5 Inhibitors. Risk X: Avoid
Nitroprusside: Phosphodiesterase 5 Inhibitors may increase hypotensive effects of Nitroprusside. Risk X: Avoid
Phosphodiesterase 5 Inhibitors: May increase adverse/toxic effects of Phosphodiesterase 5 Inhibitors. Risk X: Avoid
Pomelo: May decrease serum concentration of Sildenafil. Risk C: Monitor
Protease Inhibitors: May increase serum concentration of Sildenafil. Management: Use of protease inhibitors and sildenafil for the treatment of PAH is contraindicated. If using sildenafil for the treatment of erectile dysfunction, limit the sildenafil dose to 25 mg and do not use more frequently than every 48 hours. Risk D: Consider Therapy Modification
Riociguat: Phosphodiesterase 5 Inhibitors may increase hypotensive effects of Riociguat. Risk X: Avoid
Sapropterin: May increase hypotensive effects of Phosphodiesterase 5 Inhibitors. Risk C: Monitor
Simeprevir: May increase serum concentration of Phosphodiesterase 5 Inhibitors. Risk C: Monitor
Vasodilators (Organic Nitrates): Phosphodiesterase 5 Inhibitors may increase vasodilatory effects of Vasodilators (Organic Nitrates). Risk X: Avoid
Vericiguat: May increase hypotensive effects of Phosphodiesterase 5 Inhibitors. Risk X: Avoid
Grapefruit juice may increase serum levels/toxicity of orally administered sildenafil. Management: Monitor for increased effects/toxicity with concomitant oral use.
Sildenafil was shown to cross the placenta in ex vivo placenta perfusion studies (Hitzerd 2019; Russo 2018).
Outcome data following maternal use of sildenafil during pregnancy are available (Cesta 2021; Dunn 2016; Groom 2019; McKinlay 2024; Pels 2020; Pels 2022; Rakhanova 2023; Sharp 2018; Sharp 2024; Terstappen 2020; Turner 2021).
Untreated pulmonary arterial hypertension (PAH) during pregnancy increases the risk for heart failure, stroke, preterm delivery, and maternal/fetal death. Patients with PAH are encouraged to avoid becoming pregnant (ESC/ERS [Humbert 2022]). Manage PAH during pregnancy as part of a patient-specific multidisciplinary team. Phosphodiesterase 5 inhibitors may be considered to treat PAH during pregnancy and most data are available for sildenafil. Monitor patients closely during pregnancy and postpartum (ESC/ERS [Humbert 2022]; Hemnes 2015).
Because sildenafil causes vasodilation in the uterus, it has been studied for various obstetric indications (De Bie 2022; Dunn 2017; Ferreira 2019). Based on available data, sildenafil should not be used to treat fetal growth restriction (SMFM [Martins 2020]).
Heart rate, blood pressure, oxygen saturation, PaO2, oxygenation index.
Erectile dysfunction: Does not directly cause penile erections but affects the response to sexual stimulation. The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation and inflow of blood to the corpus cavernosum. Sildenafil enhances the effect of NO by inhibiting phosphodiesterase type 5 (PDE-5), which is responsible for degradation of cGMP in the corpus cavernosum; when sexual stimulation causes local release of NO, inhibition of PDE-5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum; at recommended doses, it has no effect in the absence of sexual stimulation.
Pulmonary arterial hypertension (PAH): Inhibits phosphodiesterase type 5 (PDE-5) in smooth muscle of pulmonary vasculature where PDE-5 is responsible for the degradation of cyclic guanosine monophosphate (cGMP). Increased cGMP concentration results in pulmonary vasculature relaxation; vasodilation in the pulmonary bed and the systemic circulation (to a lesser degree) may occur.
Onset of action: Erectile dysfunction: ~60 minutes.
Peak effect: Decrease blood pressure: Oral: 1 to 2 hours.
Duration: Erectile dysfunction: 2 to 4 hours; Decrease blood pressure: <8 hours.
Absorption: Rapid; slower with a high-fat meal; tablet and suspension are bioequivalent.
Distribution: Distributes into tissues.
Vd total:
Term neonates: 19.8 to 22.4 L (Mukherjee 2009; Rhee 2022).
Vdss: Adults: 105 L.
Protein binding, plasma:
Term neonates: Sildenafil: 93.9% ± 2.5%; N-desmethyl metabolite: 92% ± 3% (Mukherjee 2009).
Adults: Sildenafil and N-desmethyl metabolite: ~96%.
Metabolism: Hepatic via CYP3A4 (major) and CYP2C9 (minor route); major metabolite (UK-103320 or desmethylsildenafil) is formed via N-desmethylation pathway and has 50% of the potency of sildenafil.
Bioavailability: Oral: Mean: 41%; range: 25% to 63%; may be higher in patients with PAH compared to healthy volunteers; Note: A 10 mg dose of the injection is predicted to have an effect equal to a 20 mg oral dose taking into consideration the parent drug and active metabolite.
Half-life elimination:
Sildenafil: Terminal:
Term neonates (Mukherjee 2009):
PNA 1 day: 55.9 hours.
PNA 7 days: 47.7 hours.
Adults: 4 hours.
Active N-desmethyl metabolite: Terminal:
Neonates: 11.9 hours (Mukherjee 2009).
Adults: 4 hours.
Time to peak: Oral: Fasting: 30 to 120 minutes (median 60 minutes); delayed by 60 minutes with a high-fat meal.
Excretion: Feces (~80%, as metabolites); urine (~13%).
Clearance: Decreased in patients with hepatic cirrhosis or severe renal impairment; clearance may be lower in patients with PAH compared to normal volunteers. Sildenafil clearance in newborns is significantly decreased compared to adults, but approaches adult (allometrically scaled) values by the first week of life (Mukherjee 2009). Clearance of N-desmethyl active metabolite is decreased in patients with severe renal impairment.
Altered kidney function: Severe renal impairment is associated with increased plasma levels.
Hepatic function impairment: Hepatic impairment is associated with increased plasma levels.
Older adult: Age 65 years or older is associated with increased plasma levels.
