FDA

Revatio

Approved 30 Aug 2012OralFor suspension

The FDA lists this product in 3 strengths and forms.

Indications

Adults REVATIO is indicated for the treatment of pulmonary arterial hypertension (PAH) (World Health Organization [WHO] Group I) in adults to improve exercise ability and delay clinical worsening [see Clinical Studies (14) ] . Pediatric Patients (1 to 17 Years Old) REVATIO is indicated in pediatric patients 1 to 17 years old for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) to improve exercise ability and, in pediatric patients too young to perform standardized exercise testing, pulmonary hemodynamics thought to underlie improvements in exercise [see Clinical Studies (14) ] .

Adults REVATIO is a phosphodiesterase-5 (PDE-5) inhibitor indicated for the treatment of pulmonary arterial hypertension (PAH) (World Health Organization [WHO] Group I) in adults to improve exercise ability and delay clinical worsening. ( 1 ) Pediatric Patients (1 to 17 years old) REVATIO is indicated in pediatric patients 1 to 17 years old for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) to improve exercise ability and, in pediatric patients too young to perform standard exercise testing, pulmonary hemodynamics thought to underlie improvements in exercise ( 1 , 14 )

Contraindications

REVATIO is contraindicated in patients with:

Concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension [see Warnings and Precautions (5.1) ] .
Concomitant use of riociguat, a guanylate cyclase stimulator. Phosphodiesterase-5 (PDE-5) inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat.
Known hypersensitivity to sildenafil or any component of the tablet, injection, or oral suspension. Hypersensitivity, including anaphylactic reaction, anaphylactic shock and anaphylactoid reaction, has been reported in association with the use of sildenafil.
Use with organic nitrates or riociguat. ( 4 )
History of hypersensitivity reaction to sildenafil or any component of the tablet, injection, or oral suspension. ( 4 )

Warnings and precautions

Vasodilation effects may be more common in patients with hypotension or on antihypertensive therapy. ( 5.1 )
Use in pulmonary veno-occlusive disease (PVOD) may cause pulmonary edema and is not recommended. ( 5.2 )
Hearing or visual impairment: Seek medical attention if sudden decrease or loss of vision or hearing occurs. ( 5.4 , 5.5 )

At a glance

Brand name: Revatio
Active substance: sildenafil citrate
Route: Oral
Dosage form: For suspension
Applicant: Viatris
Status: Discontinued
FDA approval: 30 Aug 2012
Application: NDA203109-001

Indications

Contraindications

REVATIO is contraindicated in patients with:

Concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension [see Warnings and Precautions (5.1) ] .
Concomitant use of riociguat, a guanylate cyclase stimulator. Phosphodiesterase-5 (PDE-5) inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat.
Known hypersensitivity to sildenafil or any component of the tablet, injection, or oral suspension. Hypersensitivity, including anaphylactic reaction, anaphylactic shock and anaphylactoid reaction, has been reported in association with the use of sildenafil.
Use with organic nitrates or riociguat. ( 4 )
History of hypersensitivity reaction to sildenafil or any component of the tablet, injection, or oral suspension. ( 4 )

Warnings and precautions

Vasodilation effects may be more common in patients with hypotension or on antihypertensive therapy. ( 5.1 )
Use in pulmonary veno-occlusive disease (PVOD) may cause pulmonary edema and is not recommended. ( 5.2 )
Hearing or visual impairment: Seek medical attention if sudden decrease or loss of vision or hearing occurs. ( 5.4 , 5.5 )

Adverse reactions

The following serious adverse events are discussed elsewhere in the labeling:

Hypotension [see Warnings and Precautions (5.1) ]
Vision Loss [see Warnings and Precautions (5.4) ]
Hearing Loss [see Warnings and Precautions (5.5) ]
Priapism [see Warnings and Precautions (5.7) ]
Vaso-occlusive Crisis in Patients with Pulmonary Hypertension Secondary to Sickle Cell Disease [see Warnings and Precautions (5.8) ] Adults: Headache, dyspepsia, flushing, pain in limb, myalgia, back pain and diarrhea. ( 6.1 , 6.2 ) Children: Priapism. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Viatris at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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. In a 12-week, placebo-controlled clinical study and an open-label extension study (SUPER-1) in 277 REVATIO-treated adults with PAH (WHO Group I) [see Clinical Studies (14) ] the adverse reactions that were reported by at least 10% of REVATIO-treated patients in any dosing group, 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. The overall frequency of discontinuation in REVATIO-treated patients was 3% (20 mg and 40 mg three times a day) and 8% (80 mg three times a day). The overall frequency of discontinuation for placebo was 3%. Table 1. Most Common Adverse Reactions in Patients Treated with REVATIO 20 mg, 40 mg, 80 mg and Placebo Three Times Per Day in SUPER-1 (More Frequent in REVATIO-Treated Patients than Placebo-Treated Patients) REVATIO 20 mg (n = 69) REVATIO 40 mg (n = 67) REVATIO 80 mg (n = 71) Placebo (n = 70) Headache 46% 42% 49% 39% Flushing 10% 9% 16% 4% Pain in Limb 7% 15% 9% 6% Myalgia 7% 6% 14% 4% Back Pain 13% 13% 9% 11% Dyspepsia 13% 8% 13% 7% Diarrhea 9% 12% 10% 6% In a placebo-controlled fixed dose titration study (PACES-1) 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, no new safety issues were identified except for edema, which occurred in 25% of subjects in the combined REVATIO + epoprostenol group compared with 13% of subjects in the epoprostenol group [see Clinical Studies (14) ] .

In a study to assess the effects of multiple doses of REVATIO on mortality in adults with PAH (StudyA1481324), the lower dose 5 mg TID group showed a higher observed number of deaths (all related to underlying disease/disease under study), serious adverse events, and severe adverse events than the 20 mg and 80 mg TID groups [see Clinical Studies (14) ] . Overall, the safety data for sildenafil 80 mg TID dose in Study A1481324 was consistent with the established safety profile of sildenafil in previous adult PAH studies.

Pediatric Patients REVATIO was studied in a total of 234 PAH pediatric patients 1 to 17 years of age in a 16‑week, double-blind placebo‑controlled study (STARTS-1); 220 patients continued in a long-term extension study (STARTS-2). Erection increased was observed in 9% of patients treated with sildenafil in STARTS-1. No other new adverse reactions were identified in pediatric patients [see Use in Specific Populations (8.4) ] .

REVATIO Injection Adverse events with REVATIO injection were similar to those seen with oral tablets.

6.2Postmarketing Experience

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. Cardiovascular Events 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.

Nervous System Seizure, seizure recurrence Ophthalmologic NAION [see Warnings and Precautions (5.4) , Patient Counseling Information (17) ] .

Revatio

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Revatio

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.1Hypotension

5.2Worsening Pulmonary Vascular Occlusive Disease

5.3Epistaxis

5.4Visual Loss

5.5Hearing Loss Cases

5.6Combination with Other PDE-5 Inhibitors

5.7Priapism Use

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information