BOSENTAN
(bo-sen'tan)
Tracleer
Classifications: cardiovascular agent; vasodilator; endothelin receptor a antagonist
Pregnancy Category: X
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62.5 mg, 125 mg tablets
Bosentan is a potent endothelin A receptor antagonist. Endothelin is a peptide with potent vasoconstrictor activity implicated
in the pathogenesis of hypertension, CHF, and renal failure. Bosentan is a potent dilator of pulmonary vascular beds in patients
with primary pulmonary hypertension, although it is not selective for pulmonary vasculature alone.
Bosentan vasodilates the pulmonary vasculature thus reducing pulmonary hypertension.
Treatment of pulmonary arterial hypertension (PAH).
Hypersensitivity to bosentan; pregnancy (category X), lactation; concomitant administration with cyclosporine or glyburide.
Safety and efficacy in pediatric patients have not been established.
Liver disease or reduces hepatic blood flow; severe hypertension.
Pulmonary Arterial Hypertension
Adult: PO 62.5 mg b.i.d., may titrate up to 125 mg b.i.d.
Hepatic Impairment
If LFTs >3 and  5 x upper limit of normal (ULN) reduce dose
and monitor LFTs q2wk. If LFTs return to normal may continue treatments. If LFTs >5 and 8
x ULN, discontinue and monitor LFTs q2wk. If LFTs return to normal, may restart drug cautiously. If LFTs >8
x ULN, discontinue and do not restart.
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Oral
- Do not administer unless liver function tests have been performed and the patient has been determined to have adequate liver
function.
- Give in the morning and evening with or without food.
- Do not administer to anyone also receiving glyburide or cyclosporine.
- Store in a tightly closed container at 15°–30° C (59°–86° F).
Body as a Whole: Flushing, lower limb edema, fatigue. CNS:
Headache.
CV: Hypotension, palpitations, edema. GI:
Abnormal AST, ALT, dyspepsia. Respiratory:
Nasopharyngitis. Skin: Pruritus.
Drug:
macrolide antibiotics, cimetidine,
cyclosporine,
fluoxetine,
ketoconazole may increase bosentan levels; may decrease concentrations of simvastatin,
tacrolimus;
carbamazepine,
oral contraceptives, phenytoin,
rifampin may decrease bosentan levels; glyburide may cause increase LFTs and lack of hypoglycemic effects. Herbal:
Ephedra,
Ma Huang may antagonize antihypertensive effects.
Absorption: 50% bioavailability. Peak: 3–5 h. Distribution: 98% protein bound. Metabolism: Extensively metabolized by CYP3A4 and CYP2C9 to 3 metabolites, one is active. Elimination: Primarily excreted in bile. Half-Life: 5 h.
Assessment & Drug Effects
- Lab tests: Monitor LFT (ALT, AST, bilirubin) within 3 d of initiating treatment and q2wk thereafter. Use same monitoring schedule
following discontinuation and reintroduction of bosentan. Monitor Hgb at periodic intervals.
- Report immediately ALT & AST elevations accompanied by S&S of liver injury (jaundice, nausea, vomiting, fever, abdominal pain,
lethargy or fatigue) or bilirubin
2 x ULN.
- Concurrent drugs: Monitor lipid profile in patients receiving lipid-lowering statin drugs; the dose of the statin drug may
need to be adjusted. Monitor PT/INR in patients receiving oral anticoagulants, especially when bosentan is added or withdrawn
and periodically during concurrent therapy; adjustments in the anticoagulant may be necessary.
Patient & Family Education
- Use a barrier form of birth control in addition to oral, injected, or implanted contraceptives while taking bosentan.
- Contact physician immediately if you think you are pregnant.
- Do not breast feed while using this drug without consulting physician.
- Do not take glyburide while receiving bosentan. Contact your physician for an alternative drug for control of blood glucose.
- Do not use any OTC medications, vitamins, or herbal supplements without clearance from your physician.
- Notify physician immediately if you experience any of the following: dark-colored urine, pale stools, nausea and vomiting,
loss of appetite, stomach pain, yellow skin or eyes, fast or pounding heartbeat, swelling in your ankles or feet.
Canadian drug name; 
Prototype drug