Sildenafil
Generic: SILDENAFIL
Basic Information
Manufacturer
Torrent Pharmaceuticals Limited
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
1bc081f2-399d-43fa-9e0f-9f8df0118e99
Indications & Usage
1 INDICATIONS AND USAGE Adults Sildenafil citrate 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 ) Adults Sildenafil tablets are 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 use information is approved for Viatris Specialty LLC's, REVATIO (sildenafil) tablets.
However, due to Viatris Specialty LLC's marketing exclusivity rights, this drug product is not labeled with that information.
( 1 ) Adults Sildenafil tablets are 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 use information is approved for Viatris Specialty LLC's, REVATIO (sildenafil) tablets.
However, due to Viatris Specialty LLC's marketing exclusivity rights, this drug product is not labeled with that information.
Adverse Reactions
6 ADVERSE REACTIONS Adults: Headache, dyspepsia, flushing, pain in limb, myalgia, back pain and diarrhea.
( 6.1 , 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc.
at 1-800-912-9561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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 ) ] 6.1 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.
In a 12-week, placebo-controlled clinical study and an open-label extension study (SUPER-1) in 277 sildenafil citrate-treated adults with PAH (WHO Group I) [see Clinical Studies (14)] the adverse reactions that were reported by at least 10% of sildenafil citrate-treated patients in any dosing group, and were more frequent in sildenafil citrate-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 sildenafil citrate-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 sildenafil tablets 20 mg, 40 mg, 80 mg and Placebo three times per day in SUPER-1 (More Frequent in sildenafil-Treated Patients than Placebo-Treated Patients) Sildenafil tablets 20 mg (n = 69) Sildenafil tablets 40 mg (n = 67) Sildenafil tablets 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 sildenafil citrate (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 sildenafil citrate + 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 sildenafil tablets 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 use information is approved for Viatris Specialty LLC's, REVATIO (sildenafil) tablets.
However, due to Viatris Specialty LLC's marketing exclusivity rights, this drug product is not labeled with that information.
6.2 Postmarketing 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 ) ].
( 6.1 , 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc.
at 1-800-912-9561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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 ) ] 6.1 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.
In a 12-week, placebo-controlled clinical study and an open-label extension study (SUPER-1) in 277 sildenafil citrate-treated adults with PAH (WHO Group I) [see Clinical Studies (14)] the adverse reactions that were reported by at least 10% of sildenafil citrate-treated patients in any dosing group, and were more frequent in sildenafil citrate-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 sildenafil citrate-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 sildenafil tablets 20 mg, 40 mg, 80 mg and Placebo three times per day in SUPER-1 (More Frequent in sildenafil-Treated Patients than Placebo-Treated Patients) Sildenafil tablets 20 mg (n = 69) Sildenafil tablets 40 mg (n = 67) Sildenafil tablets 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 sildenafil citrate (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 sildenafil citrate + 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 sildenafil tablets 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 use information is approved for Viatris Specialty LLC's, REVATIO (sildenafil) tablets.
However, due to Viatris Specialty LLC's marketing exclusivity rights, this drug product is not labeled with that information.
6.2 Postmarketing 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 ) ].