Bosentas

Bosentan (Bosentan) Instructions
Common name: Bosentan
Trade name: Quankeli
Full names: Bosentan, Quanli, Bosentan, Bosentas

Indications:
Quanli is suitable for the treatment of patients with pulmonary arterial hypertension (PAH) (WHO group 1) of WHO functional classification II-IV, as well as the patient's exercise capacity and reduction of clinical deterioration. Studies supporting Tancoli mainly include patients with idiopathic or hereditary PAH (60%) in WHO functional class II-IV, PAH associated with connective tissue diseases (21%), and PAH associated with left-to-right shunting congenital heart disease (18%).

Usage and Dosage:
The initial dose of Quankeli is 62.5 mg twice a day for 4 weeks, and then increased to the recommended maintenance dose of 125 mg twice a day. Doses higher than 125 mg twice daily do not confer additional benefit sufficient to offset the increased risk of hepatotoxicity. Quanqili should be taken before or after meals in the morning and evening.

Adverse reactions:
The most common adverse drug reactions (the incidence rate in the bosentan treatment group is more than 1%, and its incidence rate is 0.5% higher than the incidence rate in the placebo group) include headache (11 .5% and 9.8%), edema/fluid retention (13.2% and 10.9%), abnormal liver function tests (10.9% and 4.6%), and anemia/reduced hemoglobin (9.9% and 4.9%).

Contraindications:
The following patients are contraindicated in taking Tricolli:
1. Those who are allergic to any component of Tricolli;
2. Pregnant women or women of childbearing age who have not taken adequate contraceptive measures (at least 2 reliable contraceptive measures). Fetal malformations have been reported in animals;
3. Patients with moderate or severe liver function impairment and/or the baseline values ​​of liver transaminase, namely aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT), are higher than 3 times the upper limit of normal (ULN), especially patients with an increase in total bilirubin exceeding 2 times the upper limit of normal;
4. Those who use cyclosporine A concomitantly;
5. Those who use glibenclamide concomitantly.

Notes:
If the patient's systemic systolic blood pressure is lower than 85mmHg, Quankeli must be used with caution.
Hematological changes: Treatment with Quancoli is accompanied by a dose-related decrease in hemoglobin concentration (average 0.9g/dl), which may be due to blood dilution. Most are observed within a few weeks of starting treatment with Quancoli. They stabilize after 4-12 weeks of treatment and generally do not require blood transfusion. It is recommended to check the hemoglobin concentration before starting treatment, 1 month and 3 months after treatment, and then every 3 months. If there is a significant decrease in hemoglobin, further evaluation is required to determine the cause and whether special treatment is needed.
Fluid Retention: Treatment of patients with severe chronic heart failure who are treated with Trancor is associated with an increased rate of hospitalization because chronic heart failure worsens during the first 4-8 weeks of Trancor treatment, possibly as a result of fluid retention. It is recommended to monitor patients for symptoms of fluid retention (such as weight gain). When symptoms appear, it is recommended to start diuretics or increase the dose of diuretics currently being used. It is recommended to treat patients with symptoms of fluid retention with diuretics before starting treatment with Trancuril.
Management of patients with elevated liver transaminases: ALT/AST levels >3 and ≤5ULN, treatment and monitoring recommendations are as follows: do another liver function test to confirm, if confirmed, reduce the daily dose or stop treatment, and monitor transaminase levels at least every 2 weeks. If transaminases return to pretreatment levels, consider continuing or reinstating bosentan (see Retreatment).
ALT/AST level > 5 and ≤ 8 ULN, the recommendations for treatment and monitoring are as follows: do another liver function test to confirm, if confirmed, reduce the daily dose or stop treatment, and monitor transaminase levels at least every 2 weeks. Once transaminases have returned to pretreatment levels, consider continuing or reinstating bosentan (see Retreatment).
ALT/AST level>8ULN, treatment and monitoring recommendations are as follows: treatment must be discontinued, and bosentan should not be considered again. When transaminase elevations are accompanied by clinical signs of liver damage (e.g. nausea, vomiting, fever, abdominal pain, jaundice, or rarely somnolence or fatigue) or when bilirubin rises more than 2 times the upper limit of normal, treatment must be discontinued and the use of bosentan is not considered.
Re-treatment: Re-treatment with bosentan should only be considered if the potential benefits of trancorib treatment outweigh the risks and the transaminases are within normal values. Bosentan should be re-administered at the initial dose. Transaminases must be tested within 3 days of re-use and again after 2 weeks, and then proceed according to the above recommendations.

Storage:
Film-coated and dispersible tablets: Store at 20-25ºC (68-77ºF).
Excursions allowed between 15-30°C (59-86°F).
Separate dispersible tablets should be stored under the same conditions and used within 7 days.
And store out of the reach of children.

Mechanism of action:
Quankeli is a dual endothelin receptor antagonist with affinity for both ETA (endothelin receptor A) and ETB (endothelin receptor B). Bosentan reduces pulmonary and systemic vascular resistance, thereby increasing cardiac output without increasing heart rate. The neurohormone endothelin is a potent vasoconstrictor that can promote fibrosis, cell proliferation and tissue remodeling. Both plasma and tissue endothelin concentrations are increased in many cardiovascular diseases, including pulmonary hypertension, suggesting a pathological role for endothelin in these diseases. In pulmonary hypertension, plasma endothelin concentration is strongly associated with poor prognosis. Bosentan is specific for endothelin receptors. Bosentan competes with endothelin to bind to ETA and ETB receptors, and its affinity for ETA receptors is slightly higher than for ETB receptors. In animal models of pulmonary hypertension, long-term oral administration of bosentan can reduce pulmonary vascular resistance, remodel pulmonary vessels, and reverse right ventricular hypertrophy. Bosentan reduces collagen deposition in animal models of pulmonary fibrosis.

Efficacy and safety:
Thirty-two patients with primary pulmonary hypertension (PPH) or pulmonary arterial hypertension due to scleroderma (SSc/PAH), WHO stage III or IV, were randomized to receive double-blind bosentan or placebo. Study drugs (oral vasodilators, anticoagulants, diuretics, cardiac glycosides and/or oxygen inhalation) are added to the treatment of existing PPH or SSc/PAH, but prostacyclin treatment is not allowed 3 months before the study or during the study). Patients received 62.5 mg of bosentan or an equivalent amount of placebo twice daily for 4 weeks and then 125 mg of bosentan or an equivalent amount of placebo twice daily for the remainder of the trial. The primary assessment was performed at 12 weeks, and patients were followed until 28 weeks. Treatment with this product is closely associated with a significant increase in walking distance. The main efficacy parameter was the 6-minute walking distance test. At 12 weeks, the mean gain from baseline was 70.1 ± 12.3 m (95% confidence interval [CL] = 44.5, 95.6) in the bosentan group and the mean decrease was 5.8 ± 36.3 m (95% CI = -86.6, 75.2) in the placebo group. As a result of bosentan treatment, the mean increase in walking distance was 75.9 ± 31.0 m (95% CL = 12.5, 139.2; t-test, P = 0.0205). From baseline to 12 weeks, pulmonary artery pressure (PAP), cardiac index (CI), pulmonary vascular resistance (PVR), right atrial pressure (RAP), and pulmonary capillary wedge pressure (PCWP) were significantly improved in the bosentan group compared with the placebo group. Changes in hemodynamic parameters from baseline to 12 weeks, values ​​are mean±SD *p＜0.05 **p＜0.001 In 9 patients (42.8%) treated with this product, the WH0 stage of pulmonary hypertension improved from stage III to stage II. In the placebo group, 1 patient (9.1%) improved from stage III to stage II, and 2 patients (18.1%) worsened from stage III to stage IV. In the study, there was no worsening of functional stage in patients treated with this product. In this study, an additional pre-clinical deterioration analysis was performed (endpoint defined as death, lung transplantation, or withdrawal due to clinical deterioration). Three patients in the placebo group dropped out due to clinical deterioration (not necessarily a change in WHO stage), while no patients in the bosentan group dropped out. The mean maximum dyspnea score measured during the walking test showed improvement in the bosentan group compared with the placebo group. The average patient score decreased by 0.19 in the bosentan group but increased by 1.36 in the placebo group. All bosentan-treated patients and eight placebo-treated patients in the double-blind study entered the open-label expansion study. After one year of treatment, patients who were first treated with bosentan maintained their efficacy; patients who were first treated with placebo showed improvements in exercise capacity after receiving bosentan.