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Medication Safety Issues
Sound-alike/look-alike issues:
Revatio® may be confused with ReVia®
Sildenafil may be confused with tadalafil, vardenafil
Viagra® may be confused with Allegra®, Vaniqa™
Pronunciation
(sil DEN a fil)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Revatio®: Treatment of pulmonary arterial hypertension (WHO Group I)
Viagra®: Treatment of erectile dysfunction (ED)
Use: Unlabeled/Investigational
Pulmonary arterial hypertension in children
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Less than 0.001% appears in the semen.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to sildenafil or any component of the formulation; concurrent use (regularly/intermittently) of organic nitrates in any form (eg, nitroglycerin, isosorbide dinitrate)
Warnings/Precautions
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 rarely; hearing changes may be accompanied by tinnitus and dizziness. A direct relationship between therapy and hearing loss has not been determined.
• Hypotension: Decreases in blood pressure may occur due to vasodilator effects; use with caution in patients with left ventricular outflow obstruction (aortic stenosis or hypertrophic obstructive cardiomyopathy); may be more sensitive to hypotensive actions. Concurrent use with alpha-adrenergic antagonist therapy or substantial alcohol consumption may cause symptomatic hypotension; patients should be hemodynamically stable prior to initiating therapy at the lowest possible dose.
• Vision loss: Vision loss may occur rarely 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. Safety and efficacy were not studied in patients with known degenerative retinal disorders (eg, retinitis pigmentosa); use is not recommended. A direct relationship between therapy and vision loss has not been determined.
•Priapism: Painful erection >6 hours in duration; rare. Educate patient to seek medical assistance for erection lasting >4 hours.
Disease-related concerns:
• Anatomical penis deformation: Use with caution in patients with anatomical deformation of the penis (angulation, cavernosal fibrosis, or Peyronie's disease).
• Bleeding disorders: Use with caution in patients with bleeding disorders; safety and efficacy have 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, physicians should consider the cardiovascular status of their patients prior to initiating any treatment for erectile dysfunction.
• Cardiovascular disease: Use is not recommended in patients with hypotension (<90/50 mm Hg); uncontrolled hypertension (>170/100 mm Hg); unstable angina or angina during intercourse; 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, physicians may wish to 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 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 and efficacy have not been established.
• Renal impairment: Use with caution in patients with renal impairment; dose adjustment may be needed; use lowest starting dose (25 mg) in severe dysfunction (Clcr <30 mL/minute).
Concurrent drug therapy issues:
• Alpha-blockers: Use with caution in patients taking alpha-blockers; may cause symptomatic hypotension. Safety of this combination may be affected by other antihypertensives and intravascular volume depletion. Patients should be hemodynamically stable prior to initiating therapy. Initiate sildenafil at the lowest recommended dose. Alpha-blockers should be initiated at the lowest recommended dose in patients currently receiving sildenafil.
• High potential for interactions: Use with caution in patients taking strong CYP3A4 inhibitors (eg, ritonavir can increase sildenafil levels, initiate sildenafil at decreased dose; see Drug Interactions); consider alternative agents that avoid or lessen the potential for CYP-mediated interactions.
• Nitrates: Concomitant (regularly/intermittently) use with all forms of nitrates is contraindicated. If nitrate administration is medically necessary, it is not known when nitrates can be safely administered following the use of sildenafil (per manufacturer); the ACC/AHA 2007 guidelines supports administration of nitrates only if 24 hours have elapsed.
• Other treatments for erectile dysfunction: Safety and efficacy with other treatments for erectile dysfunction have not been established; use is not recommended.
•Pulmonary arterial hypertension: Efficacy with concurrent bosentan therapy has not been evaluated; use with caution.
Special populations:
• Elderly: Use with caution; dose adjustment may be required.
Other warnings/precautions:
• Appropriate use: Potential underlying causes of erectile dysfunction should be evaluated prior to treatment.
Adverse Reactions
Based upon normal doses for either indication. (Adverse effects such as flushing, diarrhea, myalgia, and visual disturbances may be increased with doses >100 mg/24 hours.)
>10%:
Central nervous system: Headache (16% to 46%)
Gastrointestinal: Dyspepsia (7% to 17%; dose related)
2% to 10%:
Cardiovascular: Flushing (10%)
Central nervous system: Insomnia (?7%), pyrexia (6%), dizziness (2%)
Dermatologic: Erythema (6%), rash (2%)
Gastrointestinal: Diarrhea (3% to 9%), gastritis (?3%)
Genitourinary: Urinary tract infection (3%)
Hepatic: LFTs increased
Neuromuscular & skeletal: Myalgia (?7%), paresthesia (?3%)
Ocular: Abnormal vision (color changes, blurred vision, or increased sensitivity to light 3% to 11%; dose related)
Respiratory: Epistaxis (9% to 13%), dyspnea exacerbated (?7%), nasal congestion (4%), rhinitis (4%), sinusitis (3%)
<2%, postmarketing, and/or case reports (limited to important or life-threatening): Allergic reaction, amnesia (transient global), anemia, angina pectoris, anorgasmia, asthma, AV block, cardiac arrest, cardiomyopathy, cataract, cerebral thrombosis, cerebrovascular hemorrhage, colitis, cystitis, depression, dysphagia, edema, exfoliative dermatitis, eye hemorrhage, gout, hearing decreased, hearing loss, heart failure, hematuria, hemorrhage, hyper-/hypoglycemia, hypernatremia, hyper-/hypotension, hyperuricemia, intracerebral hemorrhage, intraocular pressure increased, leukopenia, migraine, myocardial ischemia, MI, myasthenia, mydriasis, neuralgia, nonarteritic ischemic optic neuropathy (NAION), palpitation, postural hypotension, priapism, pulmonary hemorrhage, rectal hemorrhage, retinal vascular disease or bleeding, seizure, shock, stomatitis, subarachnoid hemorrhage, syncope, tachycardia, tendon rupture, TIA, urinary incontinence, ventricular arrhythmia, vertigo, visual field loss, vitreous detachment/traction, vomiting
Metabolism/Transport Effects
Substrate of CYP2C9 (minor), 3A4 (major); Inhibits CYP1A2 (weak), 2C9 (weak), 2C19 (weak), 2D6 (weak), 2E1 (weak), 3A4 (weak)
Drug Interactions
Alpha1-Blockers: Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Alpha1-Blockers. Exceptions: Dapiprazole [Off Market}. Risk D: Consider therapy modification
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Phosphodiesterase 5 Inhibitors. Risk D: Consider therapy modification
Bosentan: May increase the metabolism of Sildenafil. Sildenafil may increase the serum concentration of Bosentan. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: 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. Risk C: Monitor therapy
HMG-CoA Reductase Inhibitors: Sildenafil may decrease the metabolism of HMG-CoA Reductase Inhibitors. Exceptions: Fluvastatin; Pravastatin; Rosuvastatin. Risk D: Consider therapy modification
Macrolide Antibiotics: May decrease the metabolism of Phosphodiesterase 5 Inhibitors. Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification
Protease Inhibitors: May decrease the metabolism of Phosphodiesterase 5 Inhibitors. Management: Dose restrictions for tadalafil, and/or sildenafil and vardenafil are recommended in combination with ritonavir, atazanavir, indinavir, darunavir and saquinavir. Consult specific prescribing information for detailed recommendations. Risk D: Consider therapy modification
Sapropterin: May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Risk C: Monitor therapy
Vasodilators (Organic Nitrates): Phosphodiesterase 5 Inhibitors may enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Food: 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.
Storage
Store tablets at controlled room temperature of 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Mechanism of Action
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.
Pharmacodynamics/Kinetics
Onset of action: ~60 minutes
Duration: 2-4 hours
Absorption: Rapid; slower with a high-fat meal
Distribution: Vdss: 105 L
Protein binding, plasma: ~96%
Metabolism: Hepatic via CYP3A4 (major) and CYP2C9 (minor route); forms metabolite (active)
Bioavailability: 40%
Half-life elimination: 4 hours
Time to peak: 30-120 minutes; delayed by 60 minutes with a high-fat meal
Excretion: Feces (80%); urine (13%)
Dosage
Oral:
Children ?1 month: Pulmonary arterial hypertension (unlabeled use): 0.25-2 mg/kg/dose every 4-6 hours. Most reports used 0.5 mg/kg/dose and titrated up to 2 mg/kg/dose
Adults:
Erectile dysfunction (Viagra®): Usual dose: 50 mg once daily 1 hour (range: 30 minutes to 4 hours) before sexual activity; dosing range: 25-100 mg once daily
Pulmonary arterial hypertension (Revatio®): Pulmonary arterial hypertension (Revatio®): 20 mg 3 times/day, taken 4-6 hours apart
Elderly >65 years: Use with caution
Revatio®: Refer to adult dosing.
Viagra®: Starting dose of 25 mg should be considered.
Dosage considerations for patients stable on alpha-blockers: Viagra®: Initial 25 mg
Dosage adjustment for concomitant use of potent CYP34A inhibitors:
Revatio®:
Erythromycin, saquinavir: No dosage adjustment
Itraconazole, ketoconazole, ritonavir: Not recommended
Viagra®:
Erythromycin, itraconazole, ketoconazole, saquinavir: Starting dose of 25 mg should be considered
Ritonavir: Maximum: 25 mg every 48 hours
Dosage adjustment in renal impairment:
Revatio®: Dose adjustment not necessary
Viagra®: Clcr <30 mL/minute: Starting dose of 25 mg should be considered
Dosage adjustment in hepatic impairment:
Revatio®: Child-Pugh class A and B: Dose adjustment not necessary
Viagra®: Child-Pugh class A and B: Starting dose of 25 mg should be considered; not studied in severe impairment (Child-Pugh class C)
Administration: Oral
Revatio®: Administer tablets at least 4-6 hours apart
Viagra®: Administer orally 30 minutes to 4 hours before sexual activity
Patient Education
Inform prescriber of all other medications you are taking; serious side effects can result when sildenafil is used with nitrates and some other medications. Avoid grapefruit juice. 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; change in vision; change in hearing or ringing in the ears; genital swelling; or other adverse reactions. If erection lasts longer than 4 hours, contact prescriber immediately; permanent damage to the penis can occur.
Geriatric Considerations
Since the elderly often have concomitant diseases, many of which may contraindicate the use of sildenafil, a thorough knowledge of diseases and medications used must be assessed. Adjust dose for renal/hepatic function.
Additional Information
Sildenafil 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 Considerations
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 CYP3A4, such as HMG-CoA reductase inhibitors, protease inhibitors, certain macrolide antibiotics, imidazole antibiotics)
Cardiovascular Considerations
Sildenafil, 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 PDE-5 inhibitors 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 PDE-5 inhibitors alone 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 (Cheitlin, 1999). 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)
• heart failure and with borderline low blood pressure and borderline 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)
Additional guidelines for the treatment of ED in patients with cardiovascular disease have also been published (Jackson, 2006). These guidelines, referred to as the Princeton II Guidelines, support the use of PDE-5 inhibition only in patients with asymptomatic coronary disease and <3 of the following risk factors: Controlled hypertension, mild stable angina, successful coronary revascularization, previous uncomplicated MI (>6-8 weeks), mild valvular disease, and left ventricular dysfunction (with or without NYHA Class I limitations).
When nitrate administration becomes medically necessary, the ACC/AHA 2004 guidelines on treatment of ST-segment elevation MI and the ACC/AHA 2007 guidelines on treatment of unstable angina/non ST-segment elevation MI supports administration of nitrates only if 24 hours have elapsed after use of sildenafil and 48 hours after use of tadalafil. The appropriate delay for the use of nitrates after vardenafil has not been determined.
Sildenafil is selective for PDE-5 and has limited effect on PDE-3, which controls cardiac contractility.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness
Mental Health: Effects on Psychiatric Treatment
Useful for psychotropic-induced sexual dysfunction
Nursing: Physical Assessment/Monitoring
Monitor other medications patient may be taking for effectiveness and interactions. Instruct patient on appropriate use and cautions, possible side effects, and symptoms to report
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Revatio®: 20 mg
Viagra®: 25 mg, 50 mg, 100 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Revatio)
20 mg (30): $448.07
Tablets (Viagra)
25 mg (10): $133.99
50 mg (10): $133.99
100 mg (10): $133.99
Extemporaneously Prepared
A stable suspension of sildenafil citrate (2.5 mg/mL) may be prepared as follows: Triturate thirty (30) sildenafil 25 mg tablets (Viagra®) to a fine powder in a mortar and pestle. Create a uniform paste by stirring in a small volume of suspending agent (1:1 mixture of methylcellulose 1% and simple syrup NF or a 1:1 mixture of Ora-Sweet® and Ora-Plus®). Continue adding vehicle to the paste in a geometric manner, with mixing, until near the desired volume. Transfer suspension to a graduated cylinder and QS to 300 mL with vehicle. Final suspension should be transferred to amber plastic bottles, labeled with “shake well” and dated for 90-day expiration at room temperature (25°C) or under refrigeration (4°C).
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, 63:254-7.
References
Abrams D, Schulze-Neick I, and Magee AG, “Sildenafil as a Selective Pulmonary Vasodilator in Childhood Primary Pulmonary Hypertension,” Heart, 2000, 84(2):E4.
Anderson JL, Adams CD, Antman EM, et al, “ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction: Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients with Unstable Angina/Non ST-Elevation Myocardial Infarction) Developed in Collaboration With the American College of Emergency Physicians, The Society of Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons,” J Am Coll Cardiol, 2007, 50(7):1-157. Available at http://content.onlinejacc.org/cgi/reprint/50/7/e1
Antman EM, Anbe DT, Armstrong PW, et al, “ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction),” Circulation, 2004, 110(9):e82-292.
Baquero H, Soliz A, Neira F, et al. “Oral Sildenafil in Infants With Persistent Pulmonary Hypertension of the Newborn: A Pilot Randomized Blinded Study,” Pediatrics, 2006, 117(4):1077-83.
Carroll WD and Dhillon R, “Sildenafil as a Treatment for Pulmonary Hypertension,” Arch Dis Child, 2003, 88(9):827-8.
Chaudhari M, Vogel M, Wright C,et al. “Sildenafil in Neonatal Pulmonary Hypertension Due to Impaired Alveolarisation and Plexiform Pulmonary Arteriopathy,”Arch Dis Child Fetal Neonatal Ed, 2005, 90(6):F527-8.
Cheitlin 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.
Galie N, Ghofrani HA, Torbicki A, et al, “Sildenafil Citrate Therapy for Pulmonary Arterial Hypertension,” N Engl J Med, 2005, 353(20):2148-57.
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.
Humpl T, Reyes JT, Holtby H, et al, “Beneficial Effect of Oral Sildenafil Therapy in Childhood Pulmonary Arterial Hypertension: Twelve-Month Clinical Trial of a Single-Drug, Open-Label, Pilot Study,” Circulation, 2005, 111(24):3274-80.
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.
Jackson G, Rosen RC, Kloner RA, et al, “The Second Princeton Consensus on Sexual Dysfunction and Cardiac Risk: New Guidelines for Sexual Medicine,” J Sex Med, 2006, 3(1):28-36.
Juliana AE and Abbad FC. “Severe Persistent Pulmonary Hypertension of the Newborn in a Setting Where Limited Resources Exclude the Use of Inhaled Nitric Oxide: Successful Treatment With Sildenafil,”Eur J Pediatr, 2005, 164(10):626-9.
Karatza AA, Bush A, and Magee AG, “Safety and Efficacy of Sildenafil Therapy in Children With Pulmonary Hypertension,” Int J Cardiol, 2005, 100(2):267-73.
Karatza AA, Narang I, Rosenthal M, et al, “Treatment of Primary Pulmonary Hypertension With Oral Sildenafil,” Respiration, 2004, 71(2):192-4.
Knoderer CA, Ebenroth ES, Brown JW. “Chronic Outpatient Sildenafil Therapy for Pulmonary Hypertension in a Child After Cardiac Surgery,” Pediatr Cardiol, 2005, 26(6):859-61.
McVary KT, “Clinical Practice. Erectile Dysfunction,” N Engl J Med, 2007, 357(24):2472-81.
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.
International Brand Names
Lexi-Comp.com
Last full review/revision September 2008
Content last modified September 2008
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