Silatio

White, round, biconvex, film coated tablet with engraved 20 on one side and scored on the other side.
Each film coated tablet contains Sildenafil 20 mg.

Pharmacology: Pharmacodynamics: Sildenafil inhibits phosphodiesterase type 5 (PDE-5) in smooth muscle of pulmonary vasculature where PDE-5 is responsible for the degradation of cyclic guanosine monophosphate (cGMP). Increased cGMP concentration results in pulmonary vasculature relaxation; vasodilation in the pulmonary bed and the systemic circulation (to a lesser degree) may occur.
Pharmacokinetics: Duration: Decrease blood pressure: <8 hours.
Absorption: Rapid; slower with a high-fat meal.
Distribution: V_dss: 105 L.
Protein binding, plasma: ~96% (Sildenafil and N-desmethyl metabolite).
Metabolism: Hepatic via CYP 3A4 (major) and CYP 2C9 (minor route): forms N-desmethyl metabolite (active).
Bioavailability: 41% (25 to 63%).
Half-life elimination: 4 hours.
Time to peak: 30-120 minutes; delayed by 60 minutes with a high-fat meal.
Excretion: Feces (~80%, as metabolites), urine (~13%).

Treatment of pulmonary arterial hypertension (PAH) (WHO Group I; efficacy established predominantly in patients with WHO/NYHA functional class II and III) in adults to improve exercise ability and delay clinical worsening.

Oral, Adults: Administer with or without food.
20 mg 3 times daily administered 4 to 6 hours apart; may increase to a maximum of 80 mg 3 times daily in patients who do not achieve an adequate response.
Elderly >65 years: Use with caution.
Dosage adjustment in renal impairment: No dosage adjustment necessary.
Dosage adjustment in hepatic impairment: Child-Pugh class A and B: No dosage adjustment necessary; has not been studied in severe impairment (Child-Pugh class C).

In single dose volunteer studies of doses up to 800 mg, adverse reactions were similar to those seen at lower doses, but the incidence rates and severities were increased. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and not eliminated in the urine.

Hypersensitivity to sildenafil or any component of the formulation.
Concurrent use (regularly/intermittently) of organic nitrates in any form (eg, nitroglycerin, isosorbide dinitrate).
Concurrent use of riociguat (a guanylate cyclase stimulator).

Warnings as the Ministry of Public Health Notification: Use for patients diagnosed with pulmonary arterial hypertension only.

Decreases in blood pressure may occur due to vasodilator effects; use with caution in patients with left ventricular outflow obstruction (aortic stenosis or hypertrophic obstructive cardiomyopathy), those on antihypertensive therapy, with resting hypotension (BP<90/50 mmHg), fluid depletion, or autonomic dysfunction; may be more sensitive to hypotensive actions.
Use with caution in patients with uncontrolled hypertension (>170/110 mmHg); life-threatening arrhythmias, stroke or MI within the last 6 months; cardiac failure or coronary artery disease causing unstable angina; safety and efficacy have not been studied in these patients.
Use in patients with pulmonary veno-occlusive disease (PVOD) is not recommended (has not been studied); If pulmonary edema occurs when treating pulmonary arterial hypertension, consider the possibility of PVOD.
Vision loss, including permanent loss of vision, may occur and be a sign of nonarteritic anterior ischemia optic neuropathy (NAION). Risk may be increased with history of vision loss. Other risk factors for NAION include low cup-to-disc ratio ("crowded disc"), coronary artery disease, diabetes, hypertension, hyperlipidemia, smoking, and age >50 years. Patients suffering sudden vision loss should discontinue therapy and consult health care provider immediately.
May cause dose-related impairment of color discrimination.
Use caution in patients with retinitis pigmentosa; a minority have genetic disorders of retinal phosphodiesterase (no safety information available).
Sudden decrease or loss of hearing has been reported; hearing changes maybe accompanied by tinnitus and dizziness.
A direct relationship between therapy and vision or hearing loss has not been determined.
Use of sildenafil is contraindicated in patients currently taking nitrate preparations.
Avoid abrupt discontinuation, especially if used as monotherapy in pulmonary arterial hypertension as exacerbation may occur.
Use caution in patients with bleeding disorders or with active peptic ulcer disease; safety has not been established.
Efficacy has not been established for treatment of pulmonary hypertension associated with sickle cell disease.
Use with caution in the elderly, or patients with renal or hepatic dysfunction; dose adjustment may be needed.

Adverse events were not observed in animal reproduction studies. Information related to the use of sildenafil for the treatment of pulmonary arterial hypertension (PAH) in pregnant women is limited.
Less than 0.001% appears in the semen.
It is not known if sildenafil is excreted in breast milk. Caution should be exercised when administering sildenafil to nursing women.

Based upon normal doses for either indication or route. (Adverse effects such as flushing, diarrhea, myalgia, and visual disturbances may be increased with dose >100 mg/24 hours.)
Cardiovascular: Flushing.
Central nervous system: Dizziness, headache, insomnia, paresthesia.
Dermatologic: Erythema, skin rash.
Gastrointestinal: Diarrhea, dyspepsia, gastritis, nausea.
Genitourinary: Urinary tract infection.
Hepatic: Increased liver enzymes.
Neuromuscular & skeletal: Back pain, Myalgia.
Ocular: Visual disturbance (including vision color change, blurred vision, and photophobia).
Respiratory: Epistaxis, exacerbation of dyspnea, nasal congestion, rhinitis, sinusitis.
Miscellaneous: Fever.
Rare but important or life-threatening: Abnormal hepatic function tests, absent reflexes, amnesia (transient global),anemia, anorgasmia, anterior chamber eye hemorrhage, anterior ischemic optic neuropathy, arthritis, auditory impairment, basal cell carcinoma, breast hypertrophy, burning sensation of eyes, cardiac failure, cataract, cerebrovascular hemorrhage, colitis, cystitis, depression, diaphoresis, diplopia, dry eye syndrome, dysphagia, ECG abnormality, ejaculatory disorder, exfoliative dermatitis, falling, gastroenteritis, genital edema, gingivitis, glossitis, gout, herpes simplex infection, hyperglycemia, hypernatremia, hypersensitivity reaction, hypertension, hypertonia, hypoglycemia, increased bronchial secretions, increased intraocular pressure, ischemic heart disease, laryngitis, leukopenia, malignant melanoma, migraine, myasthenia, mydriasis, myocardial infarction, neuralgia, neuropathy, orthostatic hypotension, otalgia, peripheral edema, pharyngitis, photophobia, priapism, prolonged erection, pulmonary hemorrhage, rectal hemorrhage, retinal edema, retina hemorrhage, retinal vascular disease, rupture of tendon, seizure, severe sickle cell crisis (vaso-occlusive crisis in patients with pulmonary hypertension associated with sickle cell disease), skin photosensitivity, stomatitis, syncope, synovitis, tachycardia, transient ischemic attacks, unstable diabetes, urinary incontinence, ventricular arrhythmia, vitreous detachment, vitreous traction.

Avoid concomitant use of Sildenafil with any of the following: Alprostadil, Amyl nitrate; Boceprevir; Conivaptan; Dapoxetine; Fusidic acid (Systemic); Idelalisib; Molsidomine; Phosphodiesterase 5 Inhibitors; Riociguat; Telaprevir; Vasodilators (organic nitrates).
Sildenafil may increase the levels/effects of Alpha1-Blockers, Alprostadil, Amyl Nitrile; Blood Pressure Lowering Agents; Bosentan; Phosphodiesterase-5 inhibitors, Riociguat, Vasodilators (organic nitrates).
The levels/effects of Sildenafil may be increased by: Alcohol (Ethyl); Aprepitant; Boceprevir; Clarithromycin; Conivaptan; CYP3A4 Inhibitors (Moderate); CYP3A4 Inhibitors (Strong); Dapoxetine; Dasatinib; Erythromycin (Systemic); Fluconazole; Fosaprepitant; Fusidic acid (Systemic); Idelalisib; Itraconazole; Ivacaftor; Ketoconazole (Systemic); Lorcaserin; Mifepristone; Molsidomine; Nefazodone; Netupitant; Palbociclib; Posaconazole; Protease Inhibitors; Sapropterin; Saquinavir; Simeprevir; Stiripentol; Telaprevir; Telithromycin; Voriconazole.
The levels/effects of Sildenafil may be decreased by: Bosentan; CYP3A4 Inducers (Moderate); CYP3A4 Inducers (Strong); Dabrafenib; Deferasirox; Enzalutamide; Etravirine; Mitotane; Siltuximab; St. John's Wort, Tocilizumab.
Grapefruit juice may increase serum levels/toxicity of sildenafil; avoid grapefruit juice.

Store below 30°C.

Other Antihypertensives

G04BE03 - sildenafil ; Belongs to the class of drugs used in erectile dysfunction.
C02KX - Antihypertensives for pulmonary arterial hypertension ; Used in the treatment of pulmonary arterial hypertension.

S