sil-DEN-a-fil

Therapeutic Classification:erectile dysfunction agents, vasodilators

Pharmacologic Classification: phosphodiesterase type 5 inhibitors

Viagra:

• Erectile dysfunction (ED).

Revatio and Liqrev:

• Pulmonary arterial hypertension (PAH) (WHO Group I).

• Viagra: Enhances effects of nitric oxide released during sexual stimulation. Nitric oxide activates guanylate cyclase, which produces increased levels of cyclic guanosine monophosphate (cGMP). cGMP produces smooth muscle relaxation of the corpus cavernosum, which promotes increased blood flow and subsequent erection. cGMP also leads to vasodilation of the pulmonary vasculature. Sildenafil inhibits the enzyme phosphodiesterase type 5 (PDE5), PDE5 inactivates cGMP.
• Revatio and Liqrev: Produces vasodilation of the pulmonary vascular bed.

• Viagra: Enhanced blood flow to the corpus cavernosum and erection sufficient to allow sexual intercourse.
• Requires sexual stimulation.
• Revatio and Liqrev: Improved exercise tolerance (or pulmonary hemodynamics) and delayed worsening of disease.

Absorption: Rapidly absorbed (41%) after oral administration; IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues; negligible amount in semen.

Protein Binding: 96%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme; one metabolite is active and accounts for 20% or more of drug effect. Metabolites excreted mostly (80%) in feces; 13% excreted in urine.

Half-life: 4 hr (for sildenafil and active metabolite).

(vasodilation, ability to produce erection)

Contraindicated in:

• Hypersensitivity
• Concurrent use of nitrates or riociguat
• Pulmonary veno-occlusive disease.

Use Cautiously in:

• Serious underlying cardiovascular disease (including history of MI, stroke, or serious arrhythmia within 6 mo), cardiac failure, or coronary artery disease with unstable angina
• History of HF, coronary artery disease, uncontrolled hypertension (BP >170/110 mm Hg) or hypotension (BP <90/50 mm Hg), dehydration, autonomic dysfunction, or severe left ventricular outflow obstruction
• Pulmonary hypertension secondary to sickle cell anemia (may ↑ risk of vaso-occlusive crises)
• Concurrent treatment with antihypertensives or glipizide
• Renal impairment (CCr <30 mL/min, hepatic impairment; all result in ↑ blood levels; ↓ dose required with Viagra)
• Anatomic penile deformity (angulation, cavernosal fibrosis, Peyronie disease)
• Conditions associated with priapism (sickle cell anemia, multiple myeloma, leukemia)
• Bleeding disorders or active peptic ulceration
• History of sudden severe vision loss or at risk for non-arteritic ischemic optic neuropathy (low cup-to-disc ratio in eye, age >50 yr, diabetes, hypertension, coronary artery disease, hyperlipidemia, and smoking); may ↑ risk of recurrence
• Retinitis pigmentosa
• Alpha adrenergic blockers (patients should be on stable dose of alpha blockers before starting sildenafil)
• OB: Revatio and Liqrev: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Lactation: Revatio and Liqrev: Safety not established
• Pedi: Revatio and Liqrev: Safety and effectiveness not established in children <18 yr (Liqrev) or <1 yr (Revatio)
• Geri: Older adults may have ↑ levels and may require lower doses.

CV: hypotension, MI, SUDDEN DEATH, vaso-occlusive crises.

Derm: flushing, rash.

EENT: epistaxis, hearing loss, nasal congestion, vision loss.

GI: dyspepsia, diarrhea.

GU: priapism, urinary tract infection.

MS: myalgia.

Neuro: headache, dizziness, insomnia, paresthesia.
Misc: (INCLUDING ANAPHYLAXIS)HYPERSENSITIVITY REACTIONS .

Drug-Drug:

• Concurrent use of nitrates may cause serious, life-threatening hypotension and is contraindicated.
• Concurrent use of riociguat may result in severe hypotension; concurrent use contraindicated.
• CYP3A4 inhibitors, including cimetidine, erythromycin, tacrolimus, ketoconazole, itraconazole, and protease inhibitor antiretrovirals, including nelfinavir and ritonavir, may ↑ levels and the risk of toxicity, including hypotension (initial dose of sildenafil for ED should be ↓ to 25 mg) (concurrent use of strong CYP3A inhibitors not recommended with oral Revatio).
• ↑risk of hypotension with alpha adrenergic blockers and acute ingestion of alcohol.
• CYP3A4 inducers, including rifampin, bosentan, barbiturates, carbamazepine, phenytoin, efavirenz, nevirapine, rifampin, or rifabutin, may ↓ levels and effectiveness; dose adjustments may be necessary in the treatment of PAH.
• May ↑ levels and the risk of toxicity of bosentan.
• Use cautiously with glipizide.
• May ↑ the risk of bleeding with warfarin.

Erectile Dysfunction

• PO (Adults): Viagra: 50 mg taken 1 hr before sexual activity (range 25–100 mg taken 30 min–4 hr before sexual activity); not more than once daily; Concurrent use of Viagra with alpha-blocker antihypertensives: do not use 50–100 mg dose within 4 hr of alpha blocker, 25-mg dose may be taken anytime.
• PO (Geriatric Patients 65 yr or with concurrent enzyme inhibitors): Viagra: 25 mg taken 1 hr before sexual activity (range 25–100 mg taken 30 min–4 hr before sexual activity); not more than once daily.

Pulmonary Arterial Hypertension

• PO (Adults): Revatio or Liqrev: 20 mg 3 times daily; may ↑ in 20-mg increments to 80 mg 3 times daily based on clinical response and tolerability.
• PO (Children 1 yr and >45 kg): Revatio: 20 mg 3 times daily; may ↑ to 40 mg 3 times daily based on clinical response and tolerability.
• PO (Children 1 yr and 21–45 kg): Revatio: 20 mg 3 times daily.
• PO (Children 1 yr and 20 kg): Revatio: 10 mg 3 times daily.
• IV (Adults): Revatio: 10 mg 3 times daily.

(Generic available)

• Tablets (Revatio): 20 mg;
• Tablets (Viagra): 25 mg; 50 mg; 100 mg;
• Oral suspension (Revatio) (grape flavor): 10 mg/mL;
• Oral suspension (Liqrev) (strawberry flavor): 10 mg/mL;
• Solution for injection (Revatio): 0.8 mg/mL;

• Viagra: Determine the presence of ED before administration. Sildenafil has no effect in the absence of sexual stimulation.
• Revatio: Monitor hemodynamic parameters and exercise tolerance prior to and periodically during therapy.

• Do not confuse Viagra with Allegra.
• PO: Dose for ED is usually administered 1 hr before sexual activity. May be administered 30 min–4 hr before sexual activity.
  • Dose for PAH is administered 3 times daily without regard to food. Doses should be spaced 4–6 hr apart.
  • Use syringe provided for accurate dosing of oral suspension. Shake well before using. Revatio oral suspension is stable for 60 days from date of reconstitution; Liqrev oral suspension is stable for 90 days after opening the bottle.

IV Administration:

• Administer undiluted. Solution is clear and colorless; do not administer solutions that are cloudy, discolored, or contain a precipitate.
• Rate: Administer as a bolus three times daily.

• Instruct patient to take sildenafil as directed. For ED, take approximately 1 hr before sexual activity and not more than once per day. If taking sildenafil for PAH, take missed doses as soon as remembered unless almost time for next dose; do not double doses.
• Advise patient that Viagra is not indicated for use in women.
• Caution patient not to take sildenafil concurrently with alpha-adrenergic blockers (unless on a stable dose of nitrates). If chest pain occurs after taking sildenafil, instruct patient to seek immediate medical attention. Advise patient taking sildenafil for PAH to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Instruct patient to notify health care professional promptly if erection lasts longer than 4 hr or if experiencing sudden or decreased vision loss in 1 or both eyes or loss or decrease in hearing, ringing in the ears, or dizziness.
• Inform patient that sildenafil offers no protection against sexually transmitted diseases. Counsel patient that protection against sexually transmitted diseases and HIV infection should be considered.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

• Male erection sufficient to allow intercourse.
• Increased exercise tolerance.

Liqrev, Revatio, Viagra