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Pronunciation(sil DEN a fil)
U.S. Brand NamesViagra®
SynonymsUK92480
Generic AvailableNo
Canadian Brand NamesViagra®
UseTreatment of erectile dysfunction
Use - Unlabeled/InvestigationalPsychotropic-induced sexual dysfunction; primary pulmonary hypertension
Pregnancy Risk FactorB
Pregnancy ImplicationsSildenafil is not indicated for use in women.
ContraindicationsHypersensitivity to sildenafil or any component of the formulation; concurrent use of organic nitrates (nitroglycerin) in any form (potentiates the hypotensive effects)
Warnings/PrecautionsThere is a degree of cardiac risk associated with sexual activity; therefore, physicians may wish to consider the cardiovascular status of their patients prior to initiating any treatment for erectile dysfunction. Agents for the treatment of erectile dysfunction should be used with caution in patients with anatomical deformation of the penis (angulation, cavernosal fibrosis, or Peyronie's disease), or in patients who have conditions which may predispose them to priapism (sickle cell anemia, multiple myeloma, leukemia). The safety and efficacy of sildenafil with other treatments for erectile dysfunction have not been studied and are, therefore, not recommended as combination therapy.
A minority of patients with retinitis pigmentosa have generic disorders of retinal phosphodiesterases. There is no safety information on the administration of sildenafil to these patients and sildenafil should be administered with caution.
Adverse Reactions>10%: Central nervous system: Headache
Note: Dyspepsia and abnormal vision (color changes, blurred or increased sensitivity to light) occurred at an incidence of >10% with doses of 100 mg.
1% to 10%:
Cardiovascular: Flushing
Central nervous system: Dizziness
Dermatologic: Rash
Genitourinary: Urinary tract infection
Ophthalmic: Abnormal vision (color changes, blurred or increased sensitivity to light)
Respiratory: Nasal congestion
<2% (Limited to important of life-threatening): Allergic reaction, angina pectoris anorgasmia, asthma, AV block, cardiac arrest, cardiomyopathy, cataract, cerebral thrombosis, colitis, dyspnea, edema, exfoliative dermatitis, eye hemorrhage, gout, heart failure, hyperglycemia, hypotension, migraine, myocardial ischemia, neuralgia, photosensitivity, postural hypotension, priapism, rectal hemorrhage, seizure, shock, syncope, vertigo
Overdosage/ToxicologyIn studies with healthy volunteers of single doses up to 800 mg, adverse events were similar to those seen at lower doses but incidence rates were increased
Drug InteractionsSubstrate of CYP2C8/9 (minor), 3A4 (major); Inhibits CYP1A2 (weak), 2C8/9 (weak), 2C19 (weak), 2D6 (weak), 2E1 (weak), 3A4 (weak) Azole antifungals: May increase the serum concentrations of sildenafil; reduce starting dose to 25 mg.
Alpha-blockers (doxazosin): Concomitant use may lead to symptomatic hypotension in some patients. Sildenafil in doses >25 mg should not be given within 4 hours of administering an alpha-blocker.
CYP3A4 inhibitors: May increase the levels/effects of sildenafil. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.
Macrolide antibiotics: May increase serum concentrations of sildenafil; reduce starting dose to 25 mg if used with clarithromycin, erythromycin, telithromycin or troleandomycin.
Nitroglycerin (other nitrates): Concurrent use with sildenafil is contraindicated due to the potential for severe, potentially fatal, hypotensive responses.
Protease inhibitors: May increase the serum concentrations of sildenafil; reduce dose to 25 mg/24 hours.
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Ethanol/Nutrition/Herb InteractionsFood: Amount and rate of absorption of sildenafil is reduced when taken with a high-fat meal. Serum concentrations/toxicity may be increased with grapefruit juice; avoid concurrent use.
Herb/Nutraceutical: St John's wort may decrease sildenafil levels.
StabilityStore tablets at controlled room temperature of 15°C to 30°C (59°F to 86°F).
Mechanism of ActionDoes 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.
Pharmacodynamics/KineticsOnset of action: ~60 minutes
Duration: 2-4 hours
Absorption: Rapid
Protein binding, plasma: ~96%
Metabolism: Hepatic via CYP3A4 (major) and CYP2C9 (minor route)
Bioavailability: 40%
Half-life elimination: 4 hours
Time to peak: 30-120 minutes
Excretion: Feces (80%); urine (13%)
DosageAdults: Oral: Erectile dysfunction: For most patients, the recommended dose is 50 mg taken as needed, approximately 1 hour before sexual activity. However, sildenafil may be taken anywhere from 30 minutes to 4 hours before sexual activity. Based on effectiveness and tolerance, the dose may be increased to a maximum recommended dose of 100 mg or decreased to 25 mg. The maximum recommended dosing frequency is once daily.
Primary pulmonary hypertension (unlabeled use): 25 mg twice daily, titrated based on response. Dosages up to 100 mg 5 times/day have been used (limited data).
Dosage adjustment for patients >65 years of age, hepatic impairment (cirrhosis), severe renal impairment (creatinine clearance <30 mL/minute), or concomitant use of potent cytochrome P450 3A4 inhibitors (erythromycin, ketoconazole, itraconazole, ritonavir, amprenavir): Higher plasma levels have been associated which may result in increase in efficacy and adverse effects and a starting dose of 25 mg should be considered
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AdministrationAdminister orally ~1 hour before sexual activity (may be used anytime from 4 hours to 30 minutes before).
Patient EducationInform prescriber of all other medications you are taking; serious side effects can result when sildenafil is used with nitrates and some other medications. Do not combine sildenafil with other approaches to treating erectile dysfunction without consulting prescriber. Note: Sildenafil provides no protection against sexually-transmitted diseases, including HIV. You may experience headache, flushing, or abnormal vision (color changes, blurred or increased sensitivity to light); use caution when driving at night or in poorly lit environments. Report immediately acute allergic reactions; chest pain or palpitations; persistent dizziness; sign of urinary tract infection; skin rash; respiratory difficulty; genital swelling; or other adverse reactions. If erection lasts longer than 4 hours, contact prescriber immediately; permanent damage to the penis can occur.
Additional InformationSildenafil is ~10 times more selective for PDE-5 as compared to PDE6. This enzyme is found in the retina and is involved in phototransduction. At higher plasma levels, interference with PDE6 is believed to be the basis for changes in color vision noted in some patients.
Anesthesia and Critical Care Concerns/Other ConsiderationsUse of sildenafil is contraindicated in patients currently taking nitrate preparations.
Cardiovascular effects of sildenafil may be potentially hazardous in patients with:
 active coronary ischemia (not on nitrates)
congestive heart failure and with low blood pressure and low volume status
complicated, multidrug antihypertensive regimens
potential for drug-drug interactions that may prolong sildenafil half-life (eg, drugs that predominantly inhibit CYP3A4, such as HMG-CoA reductase inhibitors, protease inhibitors, certain macrolide antibiotics, imidazole antibiotics)
Cardiovascular ConsiderationsSildenafil, when used in conjunction with nitrates, may be associated with severe hypotension, myocardial infarction, and possibly death. While there are no clear significant increased cardiovascular events with sildenafil therapy alone, this drug should be absolutely avoided in conjunction with nitrates and may also induce significant and possibly fatal hypotension in patients with heart failure. Hemodynamic effects of sildenafil include a very slight drop in blood pressure without significant changes in heart rate. The most recent guidelines on the use of sildenafil in patients with cardiovascular disease are outlined in detail (J Am Coll Cardiol, 1999, 33:273-82). The general clinical recommendations are as follows. Use of sildenafil is contraindicated in patients currently taking nitrate preparations.
Cardiovascular effects of sildenafil may be potentially hazardous in patients with:
active coronary ischemia (not on nitrates)
congestive heart failure and with low blood pressure and low volume status
complicated, multidrug antihypertensive regimens
potential for drug-drug interactions that may prolong sildenafil half-life (eg, drugs that predominantly inhibit cytochrome P450 3A4 - HMG-CoA reductase inhibitors, calcium channel blockers, ketoconazole, erythromycin etc)
Sildenafil is selective for PDE-5 and has limited effect on PDE3, which controls cardiac contractility.
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Dental Health: Effects on Dental TreatmentNo significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic PrecautionsNo information available to require special precautions
Mental Health: Effects on Mental StatusMay cause dizziness
Mental Health: Effects on Psychiatric TreatmentUseful for psychotropic-induced sexual dysfunction
Dosage FormsTablet, as citrate: 25 mg, 50 mg, 100 mg
ReferencesCheitlin MD, Hutter AM Jr, Brindis RG, et al, "Use of Sildenafil (Viagra®) in Patients With Cardiovascular Disease,"J Am Coll Cardiol, 1999, 33(1):273-82.
"Erythromycin (E-Mycin®) and Sildenafil (Viagra®)," in Hansten and Horn's Drug Interactions Analysis and Management, Seattle, WA: Applied Therapeutics, Inc, 1998, 2:3N109.
Geelen P, Drolet B, Rail J, et al, "Sildenafil (Viagra) Prolongs Cardiac Repolarization by Blocking the Rapid Component of the Delayed Rectifier Potassium Current,"Circulation, 2000, 102(3):275-7.
Goldstein I, Lue TF, Padma-Nathan H, et al, "Oral Sildenafil in the Treatment of Erectile Dysfunction. Sildenafil Study Group,"N Engl J Med, 1998, 338(20):1397-404.
Ishikura F, Beppu S, Hamada T, et al, "Effects of Sildenafil Citrate (Viagra) Combined With Nitrate on the Heart,"Circulation, 2000, 102(20):2516-21.
Jackson G and Chambers J, "Sildenafil for Primary Pulmonary Hypertension: Short and Long-Term Symptomatic Benefit,"Int J Clin Pract, 2002 56(5):397-8.
Phillips BG, Kato M, Pesek CA, et al, "Sympathetic Activation by Sildenafil,"Circulation, 2000, 102(25):3068-73.
Prasad S, Wilkinson J, and Gatzoulis MA, "Sildenafil in Primary Pulmonary Hypertension,"N Engl J Med, 2000, 343(18):1342.
Rendell MS, Rajfer J, Wicker PA, et al, "Sildenafil for Treatment of Erectile Dysfunction in Men With Diabetes: A Randomized Controlled Trial. Sildenafil Diabetes Study Group,"JAMA, 1999, 281(5):421-6.
Traverse JH, Chen YJ, Du R, et al, "Cyclic Nucleotide Phosphodiesterase Type 5 Activity Limits Blood Flow to Hypoperfused Myocardium During Exercise,"Circulation, 2000, 102(24):2997-3002.
Watanabe H, Ohashi K, Takeuchi K, et al, "Sildenafil for Primary and Secondary Pulmonary Hypertension,"Clin Pharmacol Ther, 2002, 71(5):398-402.
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International Brand NamesAnaus® (AR); Aphrodil® (HK, JO, KW, LB, MT, MY, RO); Bifort® (AR); Caverta® (IN); Diserec® (CO); Ejertol® (CO); Elebra® (CO); Erilin® (CO); Eroxim® (CO); Firmel® (AR); Hormotone® (CO); Lumix® (AR); Penegra® (IN); Segurex® (AR); Sildefil® (AR); Sildegra® (TR); Sildenafil® (CO); Sildenafil MK® (CO); Tranky® (CO); Viagra® (AT, AU, BE, CA, CH, CL, CO, CZ, DE, DK, ES, FI, FR, GB, HR, HU, ID, IE, IL, IT, MX, NL, NO, NZ, PL, PT, RO, RU, SE, SG, SI, TH, TR, YU, ZA); Vigradina® (CO); Vigrande® (TR); Vimax® (AR); Vorst® (AR)
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