Other drugs that reduce blood pressure Alpha blockers. In drug-drug interaction
studies, sildenafil (25 mg, 50 mg, or 100 mg) and the alpha-blocker doxazosin (4 mg or
8 mg) were administered simultaneously to patients with benign prostatic hyperplasia
(BPH) stabilized on doxazosin therapy. In these study populations, mean additional
reductions of supine systolic and diastolic blood pressure of 7/7 mmHg, 9/5 mmHg, and
8/4 mmHg, respectively, were observed. Mean additional reductions of standing blood
pressure of 6/6 mmHg, 11/4 mmHg, and 4/5 mmHg, respectively, were also observed.
There were infrequent reports of patients who experienced symptomatic postural
hypotension. These reports included dizziness and light-headedness, but not syncope.
Amlodipine. When sildenafil 100 mg oral was co-administered with amlodipine, 5 mg
or 10 mg oral, to hypertensive patients, the mean additional reduction on supine blood
pressure was 8 mmHg systolic and 7 mmHg diastolic.
Monitor blood pressure when co-administering blood pressure lowering drugs with
USE IN SPECIFIC POPULATIONS
Pregnancy Category B There are no adequate and well-controlled studies of sildenafil
in pregnant women. No evidence of teratogenicity, embryotoxicity, or fetotoxicity
was observed in pregnant rats or rabbits dosed with sildenafil 200 mg/kg/day during
organogenesis, a level that is, on a mg/m2 basis, 32- and 68-times, respectively, the
recommended human dose (RHD) of 20 mg three times a day. In a rat pre- and postnatal
development study, the no-observed-adverse-effect dose was 30 mg/kg/day (equivalent
to 5-times the RHD on a mg/m2 basis).
Labor and Delivery The safety and efficacy of REVATIO during labor and delivery have
not been studied.
Nursing Mothers It is not known if sildenafil or its metabolites are excreted in human
breast milk. Because many drugs are excreted in human milk, caution should be exercised
when REVATIO is administered to a nursing woman.
Pediatric Use In a randomized, double-blind, multi-center, placebo-controlled, parallelgroup, dose-ranging study, 234 patients with PAH, aged 1 to 17 years, body weight
greater than or equal to 8 kg, were randomized, on the basis of body weight, to three
dose levels of REVATIO, or placebo, for 16 weeks of treatment. Most patients had mild to
moderate symptoms at baseline: WHO Functional Class I (32%), II (51%), III (15%), or IV
(0.4%). One-third of patients had primary PAH; two-thirds had secondary PAH (systemicto-pulmonary shunt in 37%; surgical repair in 30%). Sixty-two percent of patients were
female. Drug or placebo was administered three times a day.
The primary objective of the study was to assess the effect of REVATIO on exercise
capacity as measured by cardiopulmonary exercise testing in pediatric patients
developmentally able to perform the test (n=115). Administration of REVATIO did not
result in a statistically significant improvement in exercise capacity in those patients. No
patients died during the 16-week controlled study.
After completing the 16-week controlled study, a patient originally randomized to
REVATIO remained on his/her dose of REVATIO or, if originally randomized to placebo,
was randomized to low-, medium-, or high-dose REVATIO. After all patients completed
16 weeks of follow-up in the controlled study, the blind was broken and doses were
adjusted as clinically indicated. Patients treated with sildenafil were followed for a
median of 4.6 years (range 2 days to 8.6 years). During the study, there were 42 reported
deaths, with 37 of these deaths reported prior to a decision to titrate subjects to a lower
dosage because of a finding of increased mortality with increasing REVATIO doses. For
the survival analysis which included 37 deaths, the hazard ratio for high dose compared
to low dose was 3.9, p=0.007. Causes of death were typical of patients with PAH. Use of
REVATIO, particularly chronic use, is not recommended in children.
Geriatric Use Clinical studies of REVATIO did not include sufficient numbers of subjects
aged 65 and over to determine whether they respond differently from younger subjects.
Other reported clinical experience has not identified differences in responses between
the elderly and younger patients. In general, dose selection for an elderly patient should
be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac
function, and of concomitant disease or other drug therapy.
Patients with Hepatic Impairment No dose adjustment for mild to moderate
impairment is required. Severe impairment has not been studied.
Patients with Renal Impairment No dose adjustment is required (including severe
impairment CLcr <30 mL/min).
PATIENT COUNSELING INFORMATION
• Inform patients of contraindication of REVATIO with regular and/or intermittent use of
• Inform patients that sildenafil is also marketed as VIAGRA for erectile dysfunction.
Advise patients taking REVATIO not to take VIAGRA or other PDE-5 inhibitors.
• Advise patients to seek immediate medical attention for a sudden loss of vision in one
or both eyes while taking REVATIO. Such an event may be a sign of NAION.
• Advise patients to seek prompt medical attention in the event of sudden decrease or
loss of hearing while taking REVATIO. These events may be accompanied by tinnitus