Medically reviewed by Drugs.com. Last updated on Feb 15, 2019.
(sil DEN a fil)
- Sildenafil Citrate
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Revatio: 10 mg/12.5 mL (12.5 mL)
Generic: 10 mg/12.5 mL (12.5 mL)
Suspension Reconstituted, Oral:
Revatio: 10 mg/mL (112 mL) [contains sodium benzoate]
Revatio: 20 mg
Viagra: 25 mg, 50 mg, 100 mg [contains fd&c blue #2 aluminum lake]
Generic: 20 mg, 25 mg, 50 mg, 100 mg
Brand Names: U.S.
- Phosphodiesterase-5 Enzyme Inhibitor
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.
Rapid; slower with a high-fat meal; tablet and suspension are bioequivalent
Vd total: Neonates: 22.4 L (or 456 L/70 kg) (Mukherjee 2009)
Vdss: Adults: 105 L
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 activity as sildenafil
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.
Onset of Action
Onset: Erectile dysfunction: ~60 minutes; Peak effect: Decrease blood pressure: Oral: 1 to 2 hours
Time to Peak
Oral: Fasting: 30 to 120 minutes (median 60 minutes); delayed by 60 minutes with a high-fat meal
Duration of Action
Erectile dysfunction: 2 to 4 hours; Decrease blood pressure: <8 hours
Neonates: PNA 1 day: 55.9 hours (Mukherjee 2009)
Neonates: PNA 7 days: 47.7 hours (Mukherjee 2009)
Adults: 4 hours
Active N-desmethyl metabolite: Terminal:
Neonates: 11.9 hours (Mukherjee 2009)
Adults: 4 hours
Neonates: Sildenafil: 93.9% ± 2.5%; N-desmethyl metabolite: 92% ± 3% (Mukherjee 2009)
Adults: Sildenafil and N-desmethyl metabolite: ~96%
Special Populations: Renal Function Impairment
Severe renal impairment is associated with increased plasma levels.
Special Populations: Hepatic Function Impairment
Hepatic impairment is associated with increased plasma levels.
Special Populations: Elderly
Age 65 years or older is associated with increased plasma levels.
Use: Labeled Indications
Erectile dysfunction: Viagra: Treatment of erectile dysfunction (ED)
Pulmonary arterial hypertension: Revatio: Treatment of pulmonary arterial hypertension (PAH) (WHO Group I; efficacy established predominately in patients with WHO/NYHA functional class II and III) in adults to improve exercise ability and delay clinical worsening.
Off Label Uses
Achalasia/Esophageal motility disorders
Initial trials in healthy adults indicate that sildenafil affects lower esophageal sphincter pressure and amplitude, suggesting potential beneficial activity for patients with certain types of esophageal motility disorders. Limited data available from controlled trials evaluating the use of sildenafil in the treatment of achalasia and other esophageal motility disorders also suggest beneficial results. American College of Gastroenterology clinical guidelines regarding the management of achalasia consider pharmacological therapy, including sildenafil, to be a third-line option for patients who have not received surgical/mechanical therapy and who have failed botulinum toxin therapy. Larger, controlled trials evaluating efficacy and safety are needed.
Persistent pulmonary hypertension after recent left ventricular assist device placement
A systematic review of the available data (two retrospective case series, one prospective open-label study, and one case report) found that sildenafil significantly improved mPAP in patients with recent LVAD placement and persistent pulmonary hypertension. Data also showed that PVR, CVP, and CI were improved. Some patients also had improved clinical outcomes, such as transplant eligibility and the ability to wean off of nitric oxide [Baker 2016], [Hamden 2014], [Klodell 2017], [Mychaskiw 2001], [Tedford 2008]. Specific dosing, at this time, cannot be recommended. Additional data may be necessary to further define the role of sildenafil in this setting.
Based on the International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support (MCS), PDE inhibitors may be considered for the management of RV dysfunction associated with pulmonary hypertension following MCS.
Data from 2 small controlled trials support the use of sildenafil for Raynaud phenomenon. Additional trials may be necessary to further define the role of sildenafil in this condition.
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 (eg, Revatio).
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.
Erectile dysfunction (Viagra): Oral: Usual dose: 50 mg once daily 1 hour (range: 30 minutes to 4 hours) before sexual activity as needed; dosing range: 25 to 100 mg once daily; maximum dose: 100 mg once daily.
Pulmonary arterial hypertension (PAH) (Revatio):
IV: 2.5 mg or 10 mg 3 times daily
Oral: 20 mg to 40 mg 3 times daily; may increase to a maximum of 80 mg 3 times daily in patients who do not achieve an adequate response (ACCP [Taichman 2014]; Galiè 2005)
Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice. 5 mg or 20 mg 3 times daily, administered 4 to 6 hours apart; maximum dose: 20 mg 3 times daily
Raynaud phenomenon (off-label use): Oral: 50 mg twice daily. Clinical trials were up to 4 weeks. (Fries 2005; Roustit 2013)
Dosage considerations for patients stable on alpha-blockers: Viagra: Initial: 25 mg
Dosage adjustment for concomitant use of potent CYP34A inhibitors: Viagra:
Strong CYP3A inhibitors (eg, itraconazole, ketoconazole, saquinavir) or erythromycin: Starting dose of 25 mg should be considered
Protease inhibitors: Maximum sildenafil dose: 25 mg every 48 hours
Elderly >65 years: Use with caution.
Erectile dysfunction (Viagra): Oral: Starting dose of 25 mg should be considered.
PAH (Revatio): Refer to adult dosing.
Note: In pediatric patients (1 to 17 years of age) with PAH, an increased mortality risk was associated with long-term use (>2 years) at dosage levels of 0.88 to 2.5 mg/kg/dose administered three times daily (Barst, 2012; Barst, 2012a); use of Revatio, especially chronic use, is not recommended in pediatric patients due to a dose-dependent increased mortality risk observed in trials; however, situations may exist in which the benefit-risk profile of Revatio may make its use, with close monitoring, acceptable in individual pediatric patients, for example, when other treatment options are limited. 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.
Pulmonary hypertension: Limited data available; dose and duration of therapy not established; interpatient variability has been reported; Oral:
Infants: 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 (Humpl, 2011; Mourani, 2009).
An open-label, prospective trial of 25 pediatric patients <5 years of age (median age: 6 months; age range: 10 days to 4.9 years) reported statistically significant improvement in echocardiography outcome measures; in 15 patients, sildenafil abolished rebound pulmonary hypertension following NO withdrawal; the initial dose of 0.25 mg/kg/dose four times daily was titrated as tolerated to a target of 1 mg/kg/dose four times daily; the reported median dose was 0.7 mg/kg/dose four times daily (range: 0.5 to 2.25 mg/kg/dose); reported duration of therapy was 9 days to 4.3 years (n=25); 11 patients were discontinued on sildenafil therapy due to clinical resolution; nine deaths were reported [severe lung hypoplasia (n=3); veno-occlusive disease post-chemotherapy (n=1); severe BPD (n=1); cause of death unrelated to pulmonary vascular disease (n=4)] (Humpl, 2011).
A retrospective trial of 25 pediatric patients <2 years of age (which included at least 16 infants) evaluated long-term safety and efficacy in patients with chronic lung disease (72% with BPD); at therapy initiation, the subject ages ranged from 14 days to 96 weeks (median: ~6 months); the initial dose of 0.5 mg/kg/dose every 8 hours was titrated as tolerated; the majority of patients were treated with 8 mg/kg/day (2 mg/kg/dose four times daily); echocardiogram showed clinical improvement in 88% of patients; reported duration of therapy was 28 to 950 days (median: 241 days); five deaths were reported during therapy (day 25 to 241 of therapy; median: 135 days); causes of death included sepsis, meningitis, and refractory respiratory disease (Mourani, 2009).
Children and Adolescents <18 years of age: Note: Dosage should not be increased; higher doses and long-term use are associated with an increased mortality risk (Barst, 2012; Barst, 2012a).
8 to 20 kg: 10 mg three times daily
>20 kg to 45 kg: 20 mg three times daily
>45 kg: 40 mg three times daily
Dosing based on the STARTS-1 and 2 trial, a randomized, double-blind, placebo-controlled study in 235 pediatric patients (1 to 17 years of age) which evaluated short-term and long-term safety and efficacy of 3 dose levels (low, medium, and high-dose); results suggested that the medium dose level (shown above) is efficacious at improving exercise capacity, functional class and hemodynamic status in the short-term (16 weeks duration); the low dosage level was not shown to be efficacious. The long-term safety and efficacy data showed a dose-dependent increased risk of mortality which was highest among the high-dose group. It was estimated that the dosing presented will produce serum concentration of 140 ng/mL and would be expected to inhibit 77% of phosphodiesterase type 5 activity in vitro (Barst, 2012; Barst, 2012a).
Pulmonary hypertension, congenital heart surgery (postoperative): Limited data available; dosing regimens variable:
Oral (or nasogastric tube): Infants, Children, and Adolescents: Initial: 0.5 mg/kg/dose upon admission to ICU; 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; dosing based on a retrospective report of 100 pediatric patients (including neonates through >10 years of age) which showed reduction in pulmonary arterial pressures and/or prevention of severe pulmonary hypertension (Nemoto, 2010). A lower dose of 0.35 mg/kg/dose every 4 hours for 1 week postoperatively was used in a retrospective, case-controlled trial of 38 pediatric patients (age range: 5 to 33 months) (Palma, 2011). In another retrospective report (n=45, median age: 32.6 months; range: 6 days to 17 years), a mean dose of 0.9 ± 0.3 mg/kg/dose four times daily was reported (Uhm, 2010). Note: Use of preoperative sildenafil therapy for the prevention of pulmonary hypertension following congenital heart surgery has produced variable efficacy results (Palma, 2011); a double-blind, placebo-controlled trial showed a negative impact on oxygenation and ventricular function (Vassalos, 2011).
IV: Infants >60 days and Children: 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 was used for pulmonary hypertension occurring within 48 hours of the end of cardiac surgery in a multicenter, randomized, double-blind, placebo-controlled dose-finding trial (n=17; median age: 5 months; age range: 3 months to 14 years; neonates and infants <60 days were excluded from the trial); dosages were either low, medium, or high dose (n=4 each treatment group; n=5 placebo) designed to attain serum concentrations of 40, 120, and 360 ng/mL, respectively; patients receiving sildenafil at all dosages were found to have lower pulmonary artery pressure and when compared to placebo, shorter duration of mechanical ventilation (median: 3 days vs 8 days), shorter ICU stay (median: 6 days vs 15 days), and shorter hospitalization (median: 12 days vs 21 days); study closed early due to slow patient accrual leading to underpowered results; no conclusions about dosage were able to be determined (Fraisse, 2011).
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: Single dose: 0.4 mg/kg/dose (range: 0.3 to 0.5 mg/kg/dose) given once 60 minutes prior to iNO discontinuation; dosing based on a randomized, double-blind, placebo-controlled trial in 29 infants and young children (median age: 5.6 months; age range: 1 to 15 months; n=15 treatment arm) (Namachivayam, 2006).
Dosage considerations for patients taking alpha blockers: There are no pediatric-specific recommendations; in adult patients, dosing adjustment suggested.
Dosage adjustment for concomitant use of potent CYP34A inhibitors: There are no pediatric-specific recommendations; in adult patients receiving Revatio, the following dosing adjustment suggested:
Strong CYP3A inhibitors (eg, itraconazole, ketoconazole): Not recommended
Protease inhibitors: Concurrent use is contraindicated
Note: Commercial oral suspension is available (10 mg/mL)
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.Nahata MC, Morosco RS, and Brady MT, “Extemporaneous Sildenafil Citrate Oral Suspensions for the Treatment of Pulmonary Hypertension in Children,” Am J Health-Syst Pharm, 2006, 63(3):254-7.16434784
Revatio: Administer doses at least 4 to 6 hours apart with or without food. Shake oral suspension well for ≥10 seconds before administering dose; do not mix with any other medication or additional flavoring agent.
Viagra: Administer with or without food 30 minutes to 4 hours before sexual activity
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).
Oral suspension: 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 Revatio oral suspension after 60 days.
Alcohol (Ethyl): May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Monitor therapy
Alpha1-Blockers (Nonselective): Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect 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. Consider therapy modification
Alpha1-Blockers (Uroselective): May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Monitor therapy
Alprostadil: Phosphodiesterase 5 Inhibitors may enhance the adverse/toxic effect of Alprostadil. Avoid combination
Amyl Nitrite: Phosphodiesterase 5 Inhibitors may enhance the vasodilatory effect of Amyl Nitrite. Avoid combination
Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Blood Pressure Lowering Agents: Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Bosentan: May decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Phosphodiesterase 5 Inhibitors may increase the serum concentration of Bosentan. Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Clarithromycin: May increase the serum concentration of Sildenafil. Consider therapy modification
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Sildenafil. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Sildenafil. Management: Use of sildenafil for pulmonary hypertension should be avoided with strong CYP3A4 inhibitors. When used for erectile dysfunction, starting adult dose should be reduced to 25 mg. Maximum adult dose with ritonavir or cobicistat is 25 mg per 48 hours. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dapoxetine: May enhance the orthostatic hypotensive effect of Phosphodiesterase 5 Inhibitors. Avoid combination
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Erythromycin (Systemic): May increase the serum concentration of Sildenafil. Management: For pulmonary arterial hypertension, US label recommends no dose adjustment and Canadian label recommends reducing to 20mg twice/day. For erectile dysfunction, consider using a lower starting dose of 25mg in patients who are also taking erythromycin. Consider therapy modification
Etravirine: May decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Management: No empiric dosage adjustments are recommended with concomitant therapy; however, dose of the phosphodiesterase inhibitor may need to be altered based on clinical response. Monitor therapy
Fluconazole: May increase the serum concentration of Sildenafil. Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Grapefruit Juice: May increase the serum concentration of Sildenafil. Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Itraconazole: May increase the serum concentration of Sildenafil. Management: Concurrent itraconazole is not recommended when sildenafil is used for treatment of pulmonary arterial hypertension. If sildenafil is used to treat erectile dysfunction, an initial dose of 25 mg is recommended with concurrent itraconazole. Consider therapy modification
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Ketoconazole (Systemic): May increase the serum concentration of Sildenafil. Management: Concurrent ketoconazole is not recommended when sildenafil is used for treatment of pulmonary arterial hypertension. If sildenafil is used to treat erectile dysfunction, an initial dose of 25 mg is recommended with concurrent ketoconazole. Consider therapy modification
Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Lorcaserin: May enhance the adverse/toxic effect of Phosphodiesterase 5 Inhibitors. Specifically, the risk of developing priapism may be increased. Monitor therapy
Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Molsidomine: May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Avoid combination
Nefazodone: May increase the serum concentration of Sildenafil. Consider therapy modification
Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Nitroprusside: Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Nitroprusside. Avoid combination
Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the adverse/toxic effect of other Phosphodiesterase 5 Inhibitors. Avoid combination
Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification
Posaconazole: May increase the serum concentration of Sildenafil. Management: Concurrent posaconazole is not recommended when sildenafil is used for treatment of pulmonary arterial hypertension. If sildenafil is used to treat erectile dysfunction, an initial dose of 25 mg is recommended with concurrent posaconazole. Consider therapy modification
Protease Inhibitors: May increase the serum concentration of Sildenafil. Management: Erectile dysfunction: sildenafil max = 25 mg/48 hrs with ritonavir, atazanavir, or darunavir; starting dose = 25 mg with other protease inhibitors (adult doses). Contraindicated if sildenafil being used for pulmonary arterial hypertension. Consider therapy modification
Riociguat: Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Riociguat. Avoid combination
Sapropterin: May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Monitor therapy
Saquinavir: May increase the serum concentration of Sildenafil. Management: Used for PAH: no dose adjustment recommended per US label, Canadian label recommends decrease to 20 mg twice/day. Used for ED: consider a lower starting dose of 25 mg with concurrent saquinavir. Consider therapy modification
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Simeprevir: May increase the serum concentration of Phosphodiesterase 5 Inhibitors. Monitor therapy
St John's Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Telithromycin: May increase the serum concentration of Sildenafil. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Vasodilators (Organic Nitrates): Phosphodiesterase 5 Inhibitors may enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Avoid combination
Voriconazole: May increase the serum concentration of Sildenafil. Management: Concurrent voriconazole is not recommended when sildenafil is used for treatment of pulmonary arterial hypertension. If sildenafil is used to treat erectile dysfunction, an initial dose of 25 mg is recommended with concurrent voriconazole. Consider therapy modification
Based upon normal doses for either indication or route. (Adverse effects such as flushing, diarrhea, myalgia, and visual disturbances may be increased with adult doses >100 mg/24 hours.)
Cardiovascular: Flushing (10% to 19%)
Central nervous system: Headache (16% to 46%)
Gastrointestinal: Dyspepsia (3% to 17%; dose-related)
Ophthalmic: Visual disturbance (2% to 11%; including vision color changes, blurred vision, and photophobia; dose-related)
Respiratory: Epistaxis (9% to 13%)
2% to 10%:
Central nervous system: Insomnia (≤7%), dizziness (2% to 4%), paresthesia (≤3%)
Dermatologic: Erythema (6%), skin rash (1% to 3%)
Gastrointestinal: Diarrhea (3% to 9%), gastritis (≤3%), nausea (2% to 3%)
Genitourinary: Urinary tract infection (3%)
Hepatic: Increased liver enzymes (2% to 10%)
Neuromuscular & skeletal: Myalgia (2% to 7%), back pain (3% to 4%)
Respiratory: Nasal congestion (4% to 9%), exacerbation of dyspnea (≤7%), nasal congestion (4%), rhinitis (4%), sinusitis (3%)
Miscellaneous: Fever (6%)
<2%, postmarketing, and/or case reports (limited to important or life-threatening): Abdominal pain, abnormal dreams, abnormal hepatic function tests, absent reflexes, accidental injury, amnesia (transient global), anemia, angina pectoris, anorgasmia, anterior chamber eye hemorrhage, anterior ischemic optic neuropathy, anxiety, arthritis, asthma, ataxia, atrioventricular block, auditory impairment, basal cell carcinoma (Loeb 2015), bone pain, breast hypertrophy, bronchitis, burning sensation of eyes, cardiac arrest, cardiac failure, cardiomyopathy, cataract, cerebral hemorrhage, cerebral thrombosis, cerebrovascular hemorrhage, chest pain, chills, colitis, conjunctivitis, contact dermatitis, cystitis, depression, dermal ulcer, diaphoresis, diplopia, drowsiness, dry eye syndrome, dysphagia, ECG abnormality, edema, ejaculatory disorder, esophagitis, exfoliative dermatitis, eye pain, eye redness, facial edema, falling, gastroenteritis, genital edema, gingivitis, glossitis, gout, hearing loss, hematuria, hemorrhage, herpes simplex infection, hyperglycemia, hypernatremia, hypersensitivity reaction, hypertension, hypertonia, hyperuricemia, hypoesthesia, hypoglycemia, hypotension, increased bronchial secretions, increased cough, increased intraocular pressure, increased thirst, ischemic heart disease, leukopenia, laryngitis, malignant melanoma (Li 2014; Loeb 2015), migraine, myasthenia, mydriasis, myocardial infarction, neuralgia, neuropathy, nocturia, orthostatic hypotension, ostealgia, osteoarthritis, otalgia, pain, palpitations, peripheral edema, pharyngitis, photophobia, priapism, prolonged erection, pruritus, pulmonary hemorrhage, rectal hemorrhage, retinal edema, retinal hemorrhage, retinal vascular disease, rupture of tendon, seizure, severe sickle cell crisis (vaso-occlusive crisis in patients with pulmonary hypertension associated with sickle cell disease), shock, skin photosensitivity, stomatitis, subarachnoid hemorrhage, swelling of eye, syncope, synovitis, tachycardia, temporary vision loss, tenosynovitis, tinnitus, transient ischemic attacks, tremor, unstable diabetes, urinary frequency, urinary incontinence, urticaria, ventricular arrhythmia, vertigo, visual field loss, vitreous detachment, vitreous traction, vomiting, weakness, xerostomia
Concerns related to adverse effects:
• Color discrimination: May cause dose-related impairment of color discrimination. Use caution in patients with retinitis pigmentosa; a minority have genetic disorders of retinal phosphodiesterases (no safety information available).
• Hearing loss: Sudden decrease or loss of hearing has been reported; hearing changes may be accompanied by tinnitus and dizziness. A direct relationship between therapy and hearing loss has not been determined.
• Hypersensitivity: Hypersensitivity reactions, including rash, urticaria, anaphylactic reaction, and anaphylactic shock, have been reported.
• Hypotension: Decreases in blood pressure may occur due to vasodilator effects; use with caution in patients with left ventricular outflow obstruction (aortic stenosis, hypertrophic obstructive cardiomyopathy), those on antihypertensive therapy, with resting hypotension (BP <90/50 mm Hg), fluid depletion, or autonomic dysfunction; may be more sensitive to hypotensive actions. Patients should be hemodynamically stable prior to initiating therapy at the lowest possible dose. Monitor blood pressure when combining with medications that lower blood pressure. Substantial consumption of ethanol may increase the risk of hypotension and orthostasis. Lower ethanol consumption has not been associated with significant changes in blood pressure or increase in orthostatic symptoms. Have patients avoid or limit ethanol consumption.
• Priapism: Painful erection >6 hours in duration has been reported rarely. Educate patient to seek medical assistance for erection lasting >4 hours.
• Vision loss: Sudden loss of vision in one or both eyes, including permanent loss of vision, may occur and be a sign of nonarteritic anterior ischemic optic neuropathy (NAION). Risk may be increased with history of vision loss. Other risk factors for NAION include low cup-to-disc ratio (“crowded disc”), coronary artery disease, diabetes, hypertension, hyperlipidemia, smoking, and >50 years of age. Patients suffering sudden vision loss should discontinue therapy and consult health care provider immediately. A direct relationship between therapy and vision loss has not been determined.
• 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 (eg, aortic stenosis). 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.
• Hepatic impairment: Use Viagra with caution in patients with hepatic impairment; use lowest starting dose (25 mg).
• Peptic ulcer disease: Use with caution in patients with active peptic ulcer disease; safety has not been established.
• PAH: Sudden cessation of sildenafil monotherapy could result in an exacerbation of PAH. Efficacy in adult patients determined through short-term (12-16 week) studies; safety of longer-term use is unclear. A long-term use trial in pediatric patients showed increased mortality in the higher dose groups (20-80 mg [depending upon weight] 3 times/day) after 2 years of use (Barst 2012a; Barst 2012b).
• 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 pulmonary arterial hypertension (PAH), consider the possibility of PVOD.
• Renal impairment: Use Viagra with caution in patients with renal impairment; dose adjustment may be needed; use lowest starting dose (25 mg) in severe dysfunction (CrCl <30 mL/minute).
• 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.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Nitrates: Use of sildenafil is contraindicated in patients currently taking nitrate preparations. However, when nitrate administration becomes medically necessary, the ACCF/AHA 2013 guidelines on treatment of ST-segment elevation MI and the ACCF/AHA 2012 guidelines on treatment of unstable angina/non ST-segment elevation MI support administration of nitrates only if 24 hours have elapsed after use of sildenafil (ACCF/AHA [Anderson 2013]; ACCF/AHA [O'Gara 2013]).
• Pediatric: Use of Revatio, especially chronic use, is not recommended in children. After 2 years of treatment, increased mortality was seen in a long-term (median treatment exposure: 4.6 years) study at higher doses (20 to 80 mg [depending upon weight] 3 times/day) (Barst 2012a; Barst 2012b).
• Elderly: Use with caution; dose adjustment may be required.
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. The 2 mL oral syringe provided by the manufacturer 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 will need to be dispensed.
• Appropriate use: In the treatment of erectile dysfunction potential underlying causes of erectile dysfunction should be evaluated prior to initiating sildenafil treatment.
• Limitations of use: In the treatment of pulmonary arterial hypertension the addition of sildenafil to bosentan therapy does not result in any beneficial effect on exercise capacity.
Monitor blood pressure and pulse when used concurrently with medications that lower blood pressure; monitor for pulmonary edema
Information related to the use of sildenafil for the treatment of pulmonary arterial hypertension (PAH) in pregnant women is limited (Cartago 2014; Hsu 2011; Wollein 2016). Women with pulmonary arterial hypertension are encouraged to avoid pregnancy (McLaughlin 2009; Taichman 2014). Because sildenafil causes vasodilation in the uterus, it is currently under study for various obstetric uses (Dunn 2016; Dunn 2017; Pels 2017). However, due to adverse events in the newborn observed using preliminary data from a study evaluating sildenafil for fetal growth restriction, use of sildenafil in pregnant women outside of a controlled clinical study is not currently recommended (Groom 2018).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience diarrhea, flushing, redness, heartburn, muscle pain, nosebleed, rhinitis, rhinorrhea, back pain, or insomnia. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), angina, tachycardia, abnormal heartbeat, dizziness, passing out, severe headache, severe nausea, vomiting, vision changes, blindness, hearing impairment, tinnitus, difficulty breathing, swelling of arms or legs, bruising, bleeding, or priapism (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
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