Tracleer

Trade name

Tracleer^®

International non-proprietary name

Bosentan

Pharmaceutical form

Film-coated tablets

Composition

One tablets contains:

• Active substance – bosentan 62,5 mg or 125 mg(in form of monohydrate)
• Excipients: corn starch, pre-gelatinized starch, sodium starch glycolate, povidone K90, glyceryl behenate, magnesium stearate
• Film-coat: hydroxypropylmethylcellulose, triacetin, talc, titanium dioxide (E 171), iron (III) oxide yellow E172, iron (III) oxide red E 172, ethylcellulose aqueous dispersion (solid part).

Description

• Orange white, round, biconvex
• film-coated tablets embossed with “62,5” on one  side.
• Orange white, oval, biconvex
• film-coated tablets embossed with “125” on one  side

Pharmacotherapeutic group

• Hypotensives
• Other antihypertensives. BosentanATX Code С02КХ01

Pharmacodynamics

• Bosentan is a dual endothelin receptor antagonist (ERA) with affinity for both endothelin A and B (ET_A and ET_B)
• Bosentan decreases both pulmonary and systemic vascular resistance, resulting in increased cardiac output without increasing heart rate. The neurohormone endothelin-1 (ET-1) is one of the most potent vasoconstrictors known and can also promote fibrosis, cell proliferation, cardiac hypertrophy, and remodeling and is pro-inflammatory.
• These effects are mediated by ET-1binding to ET_A and ET_B receptors located in the endothelium and vascular smooth muscle cells. ET-1 concentrations in tissues and plasma are increased in several cardiovascular disorders and connective tissue diseases, including pulmonary arterial hypertension, scleroderma, acute and chronic heart failure, myocardial ischemia, systemic hypertension and atherosclerosis, suggesting a pathogenic role of ET-1 in these diseases.
• In PAH and heart failure, in the absence of endothelin receptor antagonism, elevated ET-1 concentrations are strongly correlated with the severity and prognosis of these diseases.
• Bosentan competes with the binding of ET-1 and other ET peptides to both ET_A and ET_B receptors, with a slightly higher affinity for ET_A receptors (K_i = 4.1–43 nM) than for ET_B receptors (K_i = 38‑730 nM). Bosentan specifically antagonizes ET receptors and does not bind to other receptors.

Therapeutic indications

Treatment of pulmonary arterial hypertension (PAH).

Efficacy has been shown in:

• Primary (idiopathic and familial) PAH
• PAH secondary to scleroderma without significant interstitial pulmonary disease
• PAH associated with congenital systemic-to-pulmonary shunts and Eisenmenger’s physiology
• Tracleer is also indicated to reduce the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease.

 Posology and method of administration

• Tablets are to be taken orally morning and evening, with or without food. The film-coated tablets are to be swallowed with water.
• Pulmonary arterial hypertension
• In adult patients, Tracleer® treatment should be initiated at a dose of 62.5 mg twice daily for 4 weeks and then increased to the maintenance dose of 125 mg twice daily.
• Some patients not responding well to 125 mg twice daily of Tracleer may slightly improve their exercise capacity when the dose is increased to 250 mg twice daily. A careful benefit/risk assessment should be made, taking into consideration that the liver toxicity is dose dependent
• Systemic sclerosis with ongoing digital ulcer disease
• Treatment should only be initiated and monitored by a physician experienced in the treatment of systemic sclerosis.
• The treatment should be initiated at a dose of 62.5 mg twice daily for 4 weeks and then increased to the maintenance dose of 125 mg twice daily.
• The patient’s response to treatment and need for continued therapy should be re‑evaluated on a regular basis.A careful risk/benefit assessment should be made, taking into consideration the liver toxicity of bosentan.

Adverse reactions

• The most commonly reported adverse drug reactions are headache, edema/fluid retention, abnormal liver function test and anemia/hemoglobin decrease.
• Treatment with bosentan has been associated with dose-dependent elevations in liver aminotransferases and decreases in hemoglobin concentration.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients
• Concomitant use of of cyclosporine A
• Pregnancy
• Women of child-bearing potential who are not using reliable methods of contraception