sildenafil

Action

Inhibits PDE5, enhancing the effects of nitric oxide released during sexual stimulation. This action inactivates cyclic guanosine monophosphate (cGMP), which then increases cGMP levels in corpus cavernosum. Resulting smooth muscle relaxation promotes increased blood flow and subsequent erection. Also relaxes pulmonary vascular smooth muscle cells and, to a lesser degree, vasodilation in systemic circulation.

Availability

Injection (Revatio): 10 mg in 12.5-ml single-use vial

Tablets: 20 mg (Revatio); 25 mg, 50 mg, 100 mg (Viagra)

Indications and dosages

➣ Erectile dysfunction

Adults: 50 mg P.O., preferably 1 hour before anticipated sexual activity. Range is 25 to 100 mg taken 30 minutes to 4 hours before sexual activity, not to exceed one dose daily.

➣ Pulmonary hypertension (Revatio only)

Adults: 20 mg P.O. t.i.d. approximately 4 to 6 hours apart, with or without food. Higher doses not recommended. Or, 10 mg by I.V. bolus t.i.d.

Dosage adjustment

• Hepatic or renal impairment (Viagra)

• Concurrent use of hepatic isoenzyme inhibitors (such as cimetidine, erythromycin, itraconazole, ketoconazole) (Viagra)

• Elderly patients (Viagra)

Contraindications

• Hypersensitivity to drug

• Concurrent use of nitrates (nitroglycerin, isosorbide mononitrate or dinitrate)

Precautions

Use cautiously in:

• serious cardiovascular disease (such as history of myocardial infarction, cerebrovascular accident, or serious arrhythmia within past 6 months); coronary artery disease (current or previous) with unstable angina; resting blood pressure below 90/50 mm Hg or above 170/110 mm Hg (current or previous); heart failure (current or previous); renal or hepatic impairment (current or previous); bleeding disorder; active peptic ulcer; anatomic penile deformity; retinitis pigmentosa; conditions associated with priapism (sickle cell anemia, multiple myeloma, leukemia); pulmonary veno-occlusive disease; use not recommended for any of these conditions

• history of uncontrolled hypertension or hypotension

• concurrent use of alpha blockers and antihypertensives (particularly bosentan)

• concurrent use of potent CYP3A inhibitors such as erythromycin, ketoconazole, itraconazole, ritonavir, or saquinavir (use not recommended)

• patients older than age 65

• pregnant or breastfeeding patients

• children (safety and efficacy not established).

Administration

☞ Don't give concurrently with nitrates.

• Administer Viagra 30 minutes to 4 hours before sexual activity.

• If administering Revatio I.V., give by bolus injection only.

Adverse reactions

CNS: headache, dizziness, anxiety, drowsiness, vertigo, transient global amnesia, insomnia, paresthesia, seizures, cerebrovascular hemorrhage, transient ischemic attack

CV: hypertension, hypotension, myocardial infarction (MI), cardiovascular collapse, ventricular arrhythmias, sudden death

EENT: transient vision loss, blurred or color-tinged vision, increased light sensitivity, ocular redness, retinal bleeding, vitreous detachment or traction, photophobia, hearing loss, epistaxis, rhinitis, sinusitis nasal congestion

GI: diarrhea, dyspepsia, gastritis

Musculoskeletal: myalgia

Respiratory: exacerbation of dyspnea

GU: hematuria, urinary tract infection, priapism

Skin: flushing, rash, erythema, pyrexia

Other: hypersensitivity including anaphylactic reactions (rare)

Interactions

Drug-drug. Alpha blockers, Antihypertensives, nitrates: increased risk of hypotension

Enzyme inducers, rifampin: reduced sildenafil blood level

Hepatic isoenzyme inhibitors (such as cimetidine, erythromycin, itraconazole, ketoconazole), protease inhibitors (such as indinavir, nelfinavir, ritonavir, saquinavir): increased sildenafil blood level and effects

Drug-food. High-fat diet: reduced drug absorption, decreased peak level

Patient monitoring

• Monitor cardiovascular status carefully.

• Evaluate patient's vision and hearing.

• Assess for drug efficacy.

Patient teaching

• Advise patient taking drug for erectile dysfunction to take 30 minutes to 4 hours before sexual activity.

• Tell patient not to exceed prescribed dosage or take more than one dose daily.

☞ Instruct patient to stop sexual activity and contact prescriber immediately if chest pain, dizziness, or nausea occurs.

☞ Teach patient to recognize and immediately report serious cardiac and vision problems and sudden decrease in or loss of hearing.

• Inform patient that drug can cause serious interactions with many common drugs. Instruct him to tell all prescribers he's taking it.

☞ Caution patient never to take drug with nitrates, because of risk of potentially fatal hypotension.

• Instruct patient not to take other PDE5 inhibitors.

• Instruct patient to report priapism (persistent, painful erection) or erections lasting more than 4 hours.

• Tell patient that high-fat diet may interfere with drug efficacy.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and foods mentioned above.