In a placebo-controlled trial, was associated with more adverse drug events (ADEs) in 3% or more of patients taking the recommended daily dose (20 mg three times daily) than in subjects taking placebo. These ADEs were characterized as mild to moderate.

At the placebo dose, the incidence of retinal hemorrhage was 1%; at the recommended sildenafil dose, 1.4%; and at all sildenafil doses, 1.9%. However, these patients tended to have other risk factors for hemorrhage, including the simultaneous use of anticoagulant therapy. Commonly reported ADEs in patients taking citrate are listed in Table 5.

Table 5 Adverse Drug Events Reported by 3% or More of Patients Taking Sildenafil or Placebo for Pulmonary Arterial Hypertension

Placebo (n = 70) Sildenafil 20 mg Three Times Daily (n = 60)
Headache

39

46

Dyspepsia

7

13

Flushing

4

10

Epistaxis

1

9

Diarrhea

6

9

Insomnia

1

7

Dyspnea exacerbated

3

7

Myalgia

4

7

CONTRAINDICATIONS

Sildenafil drug potentiates the hypotensive effects of nitrates, and its use is thus contraindicated for patients who are using organic nitrates in any form, either regularly or intermittently. Patients with a known hypersensitivity to any component of the tablet should not use the product.

DRUG INTERACTIONS

Sildenafil is extensively metabolized by CYP450 3A4 and, to a lesser degree, by CYP 2C9. Substrates of CYP 3A4 that are coadministered with this drug, or in combination with CYP 3A4 substrates and beta blockers, can either increase or decrease serum levels of sildenafil.

Drugs that inhibit the CYP 3A4 iso-enzyme include, cimetidine, and saquinavir (Fortovase, Roche), whereas bosentan decreases serum concentrations of sildenafil.

Concurrent administration of sildenafil and the alpha blocker doxazosin mesy-late (Pfizer) infrequently resulted in symptomatic postural hypotension, including dizziness and light-headedness. The use of vitamin K with sildenafil medication resulted in a higher incidence of bleeding, predominantly associated with epistaxis.

DOSAGE AND ADMINISTRATION

Revatio is administered as a 20-mg tablet, to be taken orally three times a day, four to six hours apart, with or without regard to food.

It is available as a white, film-coated, round tablet to distinguish it from Viagra, which is blue and oval-shaped. Viagra is available as 25-, 50-, and 100-mg tablets.

CONCLUSION

Treatment options for the management of PAH are continuously evolving. The use of vasodilator agents to decrease PVR by reducing inflammatory mediators, remodeling of pulmonary vessel walls, vasoconstriction, and thrombosis has vastly improved the poor prognosis associated with PAH. Because the rapid progression of this disease is associated with right-sided heart failure and ultimately death, adjunctive or augmentation therapies can aid in decreasing the high risk of premature morbidity and mortality, improving survival rates, and enhancing patient compliance.

Citrate is the first oral selective cGMP-specific PDE5 inhibitor indicated for the treatment of PAH and is designed to improve exercise capacity. It shows remarkable short-term hemodynamic effects in patients already receiving therapy for PAH. However, more studies of its long-term use are warranted.