"The U.S. Food and Drug Administration today approved Opsumit (macitentan), a new drug to treat adults with pulmonary arterial hypertension (PAH), a chronic, progressive and debilitating disease that can lead to death or the need for lung transpla"...
The following serious adverse events are discussed elsewhere in the labeling:
- Mortality with pediatric use [see WARNINGS AND PRECAUTIONS and Use In Specific Populations]
- Hypotension [see WARNINGS AND PRECAUTIONS]
- Vision loss [see WARNINGS AND PRECAUTIONS]
- Hearing loss [see WARNINGS AND PRECAUTIONS]
- Priapism [see WARNINGS AND PRECAUTIONS]
- Vaso-occlusive crisis [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Safety data of REVATIO in adults were obtained from the 12-week, placebo-controlled clinical study (Study 1) and an open-label extension study in 277 REVATIO-treated patients with PAH, WHO Group I [see Clinical Studies].
The overall frequency of discontinuation in REVATIO-treated patients on 20 mg three times a day was 3% and was the same for the placebo group.
In Study 1, the adverse reactions that were reported by at least 3% of REVATIO-treated patients (20 mg three times a day) and were more frequent in REVATIO-treated patients than in placebo-treated patients are shown in Table 1. Adverse reactions were generally transient and mild to moderate in nature.
Table 1: Most Common Adverse Reactions in Patients
with PAH in Study 1 (More Frequent in REVATIO-Treated Patients than
Placebo-Treated Patients and Incidence ≥ 3% in REVATIO-Treated
(n = 70)
|REVATIO 20 mg three times a day, %
(n = 69)
At doses higher than the recommended 20 mg three times a day, there was a greater incidence of some adverse reactions including flushing, diarrhea, myalgia and visual disturbances. Visual disturbances were identified as mild and transient, and were predominately color-tinge to vision, but also increased sensitivity to light or blurred vision.
The incidence of retinal hemorrhage with REVATIO 20 mg three times a day was 1.4% versus 0% placebo and for all REVATIO doses studied was 1.9% versus 0% placebo. The incidence of eye hemorrhage at both 20 mg three times a day and at all doses studied was 1.4% for REVATIO versus 1.4% for placebo. The patients experiencing these reactions had risk factors for hemorrhage including concurrent anticoagulant therapy.
In a placebo-controlled fixed dose titration study (Study 2) of REVATIO (starting with recommended dose of 20 mg and increased to 40 mg and then 80 mg all three times a day) as an adjunct to intravenous epoprostenol in patients with PAH, the adverse reactions that were more frequent in the REVATIO + epoprostenol group than in the epoprostenol group (greater than 6% difference) are shown in Table 2 [see Clinical Studies].
Table 2: Adverse Reactions
(%) in patients with PAH in Study 2 (incidence in REVATIO + Epoprostenol group
at least 6% greater than Epoprostenol group)
|REVATIO + Epoprostenol
(n = 134)
(n = 131)
|(REVATIO + Epoprostenol) minus Epoprostenol|
|Pain in extremity||17||6||11|
|^includes peripheral edema|
REVATIO injection was studied in a 66-patient, placebo-controlled study in patients with PAH at doses targeting plasma concentrations between 10 and 500 ng/mL (up to 8 times the exposure of the recommended dose). Adverse events with REVATIO injection were similar to those seen with oral tablets.
The following adverse reactions have been identified during post approval use of sildenafil (marketed for both PAH and erectile dysfunction). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
In postmarketing experience with sildenafil at doses indicated for erectile dysfunction, serious cardiovascular, cerebrovascular, and vascular events, including myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, pulmonary hemorrhage, and subarachnoid and intracerebral hemorrhages have been reported in temporal association with the use of the drug. Most, but not all, of these patients had preexisting cardiovascular risk factors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of sildenafil without sexual activity. Others were reported to have occurred hours to days after use concurrent with sexual activity. It is not possible to determine whether these events are related directly to sildenafil, to sexual activity, to the patient's underlying cardiovascular disease, or to a combination of these or other factors.
Seizure, seizure recurrence
Read the Revatio (sildenafil citrate) Side Effects Center for a complete guide to possible side effects
Concomitant use of REVATIO with nitrates in any form is contraindicated [see CONTRAINDICATIONS].
Ritonavir and other Potent CYP3A Inhibitors
Concomitant use of REVATIO with ritonavir and other potent CYP3A inhibitors is not recommended [see CLINICAL PHARMACOLOGY].
Other Drugs That Reduce Blood Pressure
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.
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 REVATIO [see WARNINGS AND PRECAUTIONS].
Read the Revatio Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 9/15/2015
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