CardioSource WorldNews August 2015 | Page 27

USE IN SPECIFIC POPULATIONS

Pregnancy
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%). Onethird of patients had primary PAH; two-thirds had secondary PAH (systemic-to-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).

CLINICAL

NEWS JOURNAL WRAP
Continued from page 22

seem to be more sensitive than men
to the toxic effects of alcohol on cardiac function, developing alcohol cardiomyopathy with lower total lifetime
dose of alcohol compared with men.”
In an accompanying editorial,
Kihei Yoneyama, MD, PhD, and
João A.C. Lima, MD, write that
these findings add interesting new
evidence to how the effects of alcohol
on the heart differ between sexes.
They speculate that “light to moderate alcohol consumption may counteract the effect of traditional risk
factor burden that commonly lead to
concentric remodeling.” They recommend further longitudinal research
addressing “whether mild to moderate alcohol consumption specifically
protects against the development of
heart failure with preserved ejection
fraction through preventing concentric LV remodeling in the general
population.”
Gonçalves A, Jhund PS, Claggett B, et al. Circ
Cardiovasc Imaging. 2015;8:e002846.

PATIENT COUNSELING INFORMATION

• Inform patients of contraindication of REVATIO with regular and/or intermittent use of organic
nitrates.
• 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 and dizziness.
Rx only
RVU763901-04

ACC.org/CSWN

Rev. June 2015
©2015 Pfizer Inc.

All rights reserved.

July 2015

Bariatric Surgery
Superior to Lifestyle
Intervention for
Type 2 Diabetes
Bariatric surgery and healthy lifestyle
changes resulted in better disease
remission in patients with type 2 diabetes mellitus (T2DM) than healthy
lifestyle changes alone, according to a
new stud