SILDENAFIL CITRATE

SILDENAFIL CITRATE- sildenafil citrate tablet
Torrent Pharmaceuticals Limited

1 INDICATIONS AND USAGE

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 Patients (1 to 17 Years old)

​ Sildenafil tablets are 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 underly improvements in exercise [see Clinical Studies (14) ].

2 DOSAGE AND ADMINISTRATION

2.1 ​Recommended Dosage in Adults

Oral Dosage

​ The recommended dosage of sildenafil tablets are 20 mg three times a day. Dose may be titrated to a maximum of 80 mg three times a day, if required, based on symptoms and tolerability [see Clinical Studies (14) ].

​ Although dose-response improvement in exercise ability was not observed in short-term studies in adults with PAH, the delay in clinical worsening with long-term use of sildenafil in Study A1481324 supports dosing up to a maximum of 80 mg three times a day [see Clinical Studies (14) ].

​ 2.2 Recommended Dosage in Pediatric Patients

​ Oral Dosage

​ The recommended dosage in patients ≤20 kg is 10 mg three times a day.

​ For pediatric patients 20 kg to 45 kg, the recommended dosage is 20 mg three times a day.

​ For pediatric patients 45 kg and greater, the recommended dosage is 20 mg three times a day. A maximum dose in pediatric patients has not been identified. Based on the experience in adults, dose may be titrated to a maximum of 40 mg three times a day for pediatric patients >45 kg, if required, based on symptoms and tolerability [see Clinical Studies (14) ].

3 DOSAGE FORMS AND STRENGTHS

Sildenafil Tablets, USP

Sildenafil tablets, USP are supplied as white to off-white, round, biconvex, film-coated tablets debossed with ’85’ on one side and plain on other side containing sildenafil citrate equivalent to 20 mg of sildenafil.

4 CONTRAINDICATIONS

Sildenafil citrate 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 (PDE5) inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat.
• Known hypersensitivity to sildenafil or any component of the tablet. Hypersensitivity, including anaphylactic reaction, anaphylactic shock and anaphylactoid reaction, has been reported in association with the use of sildenafil.

5 WARNINGS AND PRECAUTIONS

5.1 Hypotension

Sildenafil citrate has vasodilatory properties, resulting in mild and transient decreases in blood pressure. Before prescribing sildenafil tablets, carefully consider whether patients with certain underlying conditions could be adversely affected by such vasodilatory effects (e.g., patients on antihypertensive therapy or with resting hypotension [blood pressure less than 90/50], fluid depletion, severe left ventricular outflow obstruction, or autonomic dysfunction). Monitor blood pressure when co-administering blood pressure lowering drugs with sildenafil citrate.

5.2 Worsening Pulmonary Vascular Occlusive Disease

Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD). Since there are no clinical data on administration of sildenafil citrate to patients with veno-occlusive disease, administration of sildenafil citrate to such patients is not recommended. Should signs of pulmonary edema occur when sildenafil citrate is administered, consider the possibility of associated PVOD.

5.3 Epistaxis

The incidence of epistaxis was 13% in patients taking sildenafil citrate with PAH secondary to CTD. This effect was not seen in idiopathic PAH (sildenafil 3%, placebo 2%) patients. The incidence of epistaxis was also higher in sildenafil-treated patients with a concomitant oral vitamin K antagonist (9% versus 2% in those not treated with concomitant vitamin K antagonist).

The safety of sildenafil citrate is unknown in patients with bleeding disorders or active peptic ulceration.

5.4 Visual Loss

When used to treat erectile dysfunction, non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported postmarketing in temporal association with the use of PDE-5 inhibitors, including sildenafil. Most patients had underlying anatomic or vascular risk factors for developing NAION, including low cup to disc ratio (“crowded disc”).

Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking sildenafil citrate.

There are no controlled clinical data on the safety or efficacy of sildenafil citrate in patients with retinitis pigmentosa, a minority of whom have genetic disorders of retinal phosphodiesterases. Therefore, use of sildenafil citrate in patients with retinitis pigmentosa is not recommended.

5.5 Hearing Loss

Cases of sudden decrease or loss of hearing, which may be accompanied by tinnitus and dizziness, have been reported in temporal association with the use of PDE-5 inhibitors, including sildenafil citrate. In some of the cases, medical conditions and other factors were reported that may have played a role. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of sildenafil citrate, to the patient’s underlying risk factors for hearing loss, a combination of these factors, or to other factors.

Advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking PDE-5 inhibitors, including sildenafil tablets.

5.6 Combination with Other PDE-5 inhibitors

Sildenafil is also marketed as VIAGRA^®. The safety and efficacy of combinations of sildenafil tablets with VIAGRA or other PDE-5 inhibitors have not been studied. Inform patients taking sildenafil tablets not to take VIAGRA or other PDE-5 inhibitors.

5.7 Priapism

Use sildenafil citrate with caution in patients with anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, or Peyronie’s disease) or in patients who have conditions, which may predispose them to priapism (e.g., sickle cell anemia, multiple myeloma, or leukemia). In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism (painful erection greater than 6 hours in duration) is not treated immediately, penile tissue damage and permanent loss of potency could result.

5.8 Vaso-occlusive Crisis in Patients with Pulmonary Hypertension Secondary to Sickle Cell Disease

In a small, prematurely terminated study of patients with pulmonary hypertension (PH) secondary to sickle cell disease, vaso-occlusive crises requiring hospitalization were more commonly reported by patients who received sildenafil citrate than by those randomized to placebo. The effectiveness and safety of sildenafil citrate in the treatment of PH secondary to sickle cell disease has not been established.