Bosentan

 

Introduction

Bosentan is a dual endothelin receptor antagonist used in the treatment of pulmonary artery hypertension (PAH). It is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Tracleer. Bosentan is used to treat pulmonary hypertension by blocking the action of endothelin molecules that would otherwise promote narrowing of the blood vessels and lead to high blood pressure. Bosentan is a competitive antagonist of endothelin-1 at the endothelin-A (ET-A) and endothelin-B (ET-B) receptors. Under normal conditions, endothelin-1 binding of ET-A or ET-B receptors causes constriction of the pulmonary blood vessels. By blocking this interaction, bosentan decreases pulmonary vascular resistance. Bosentan has a slightly higher affinity for ET-A than ET-B.
Classification of PAH (updated 2015):

Indication

Bosentan is indicated mainly for the treatment of pulmonary hypertension (WHO Group I), in patients with WHO Class II-IV symptoms,use to improve exercise capacity and decrease the rate of clinical worsening
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Pharmacokinetics



Pharmacodynamics

Contra-indications:

  • Intolerance to bosentan
  • Pregnancy

Cautions:

This product should be used with caution if the patients:
  • are planning to become pregnant, or are breast-feeding
  • are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
  • have allergies to medicines, foods, or other substances
  • have a history of liver problems
  • in mild liver impairment: no dose adjustment required and
  • in moderate or severe: avoid use
  • abnormal liver function tests( monthly monitoring of liver function tests while taking Bosentan is required)
  • have heart problems (e. g, congestive heart failure),
  • blood problems (e. g, anemia)
  • hematocrit and hemoglobin have been observed in patients treated with bosentan. Hemoglobin levels should be monitored after 1 and 3 months of treatment and then every 3 months.
  • have fluid retention (e. g, unusual swelling of the arms, hands, legs, or feet)
  • drink alcohol or take medicines that may harm the liver (e. g, acetaminophen, methotrexate, isoniazid, certain medicines for HIV infection)

Drug interactions:

Some medicines may interact with bosentan, especially any of the following:
  • Amiodarone, azole antifungals (eg, fluconazole, itraconazole, ketoconazole, voriconazole), cobicistat, cyclosporine, diltiazem, HIV protease inhibitors (eg, ritonavir), macrolide antibiotics (eg, erythromycin), or tacrolimus because they may increase the risk of bosentan's side effects
  • Glyburide or rifampin because the risk of liver problems may be increased
  • Anticoagulants (eg, warfarin), axitinib, bosutinib, cabazitaxel, HMG-CoA reductase inhibitors (statins) (eg, simvastatin), hormonal contraceptives (eg, oral, injected, patch, implanted birth control), or ulipristal because their effectiveness may be decreased by bosentan

Side-effects:

  • Flushing
  • headache
  • nose or throat irritation
  • symptoms of respiratory tract infection (eg, cough, runny or stuffy nose, sneezing)

Dosage:


F.C tablet: 125 mg


  • Discontinuation of treatment: Consider a reduction in dosage to 62.5 mg PO twice daily for 3-7 days