sildenafil citrate
Viagra

Available forms
Available by prescription only
Tablets: 25 mg, 50 mg, 100 mg

Indications and dosages
 Treatment of erectile dysfunction. Adults: 50 mg P.O. as a single dose, p.r.n., 1 hour before sexual activity. However, patient may take drug 30 minutes to 4 hours before sexual activity. Based on effectiveness and tolerance by patient, may increase dose to maximum single dose of 100 mg or decrease dose to 25 mg. A maximum recommended dosing frequency is once daily.
≡ Dosage adjustment. For elderly patients with hepatic impairment or severe renal impairment, and for those concurrently taking potent cytochrome P-450 3A4 inhibitors, consider a starting dose of 25 mg.

Pharmacodynamics
Erectile action: Sildenafil has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum.

Pharmacokinetics
Absorption: Rapidly absorbed after oral administration. A high-fat meal delays the rate of absorption by about 1 hour and reduces peak levels by one-third. Absolute bioavailability of sildenafil is about 40%.
Distribution: Widely distributed to body tissues with a mean steady state volume of distribution of 105 L. Both drug and its major active metabolite are 96% bound to plasma proteins. Protein-binding is independent of drug levels.
Metabolism: The primary pathway for sildenafil elimination is metabolism by the CYP 3A4 and CYP 2C9 hepatic microsomal isoenzymes. N-desmethylation converts sildenafil into the major circulating metabolite, which accounts for about 20% of the pharmacologic effects of sildenafil.
Excretion: About 80% of an oral dose is metabolized and excreted in the feces, and about 13% is excreted in the urine.

Contraindications and precautions
Contraindicated in patients using organic nitrates and in those hypersensitive to drug or its components. Use cautiously in patients who have had an MI, CVA, or life-threatening arrhythmias within the past 6 months; those with a history of cardiac failure, coronary artery disease, or uncontrolled high or low blood pressure; those with anatomic deformation of the penis; and those predisposed to priapism (sickle cell anemia, multiple myeloma, leukemia), retinitis pigmentosa, bleeding disorders, or active peptic ulcers.

Interactions
Drug-drug. Delavirdine, protease inhibitors: Increases sildenafil levels, which may increase sildenafil-related adverse reactions, including hypotension, vision changes, and priapism. Sildenafil dose shouldn’t exceed 25 mg in a 48-hour period.
Inhibitors of cytochrome P-450 isoforms 3A4, such as cimetidine, erythromycin, itraconazole, and ketoconazole: May reduce sildenafil clearance. Avoid use together.
Nitrates: Enhances hypotensive effects of nitrates. Don’t use together.
Protease inhibitors, delavirdine: Increases plasma sildenafil levels, which may cause an increase in sildenafil-associated adverse events, including hypotension, visual changes, and priapism. Don’t exceed 25 mg in a 48-hour period.
Rifampin: May reduce sildenafil levels. Monitor effect closely.
Drug-food. High-fat meals: Can delay absorption of drug and onset of action by 1 hour. Separate administration time from meals.

Adverse reactions
CNS: headache, dizziness.
CV: flushing.
EENT: nasal congestion, abnormal vision (photophobia, color blindness).
GI: dyspepsia, diarrhea.
GU: urinary tract infection.
Skin: rash.

Effects on lab test results
None reported.

Overdose and treatment
In healthy volunteers, doses up to 800 mg produced adverse events similar to those seen at lower doses but at an increased rate.
 Use standard supportive measures to treat overdose. Renal dialysis isn’t expected to increase clearance.

Special considerations
• Because sexual activity may increase cardiac risk, evaluate patient’s CV status before starting therapy.
Pregnant patients
• Drug seems to have favorable teratogenic, embryotoxic, and fetotoxic profiles, and it isn’t readily distributed into semen. It isn’t expected to be harmful to pregnant partners of men receiving therapy.
Breast-feeding patients
• Drug isn’t indicated for use in women.
Pediatric patients
• Drug shouldn’t be used in children or neonates.
Geriatric patients
• Healthy people age 65 and older have reduced drug clearance, which results in plasma drug levels about 40% higher than those in younger subjects.

Patient education
• Tell patient that drug doesn’t protect against sexually transmitted diseases and that he should use protective measures to prevent infection.
• Advise patient that drug is most rapidly absorbed if taken on an empty stomach.
• Tell patient to report visual changes.
• Urge patient to seek medical attention if erection persists for longer than 4 hours.
• Advise patient that drug has no effect in the absence of sexual stimulation.
• Advise patient receiving HIV medications that there is an increased risk of sildenafil-associated adverse events, including hypotension, visual changes, and priapism. Tell him to promptly report adverse events and not to exceed 25 mg of sildenafil in a 48-hour period.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use