bosentan (redirected from Tracleer)

bosentan,

a vasodilator used to treat pulmonary arterial hypertension.

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bosentan

Tracleer

Pharmacologic class: Endothelin-receptor antagonist, vasodilator

Therapeutic class: Antihypertensive

Pregnancy risk category X

FDA Boxed Warning

• Drug causes at least 3 x ULN (upper limit of normal) of alanine aminotransferase and aspartate aminotransferase levels in about 11% of patients (along with elevated bilirubin in a few cases). These changes indicate potentially serious hepatic injury. Obtain serum transaminase levels before therapy begins and then monthly.
• Transaminase elevations warrant close attention. Avoid giving drug to patients with baseline transaminase levels more than 3 x ULN, because monitoring for hepatic injury may be more difficult. Stop therapy if transaminase elevations are accompanied by indications of hepatic injury or if bilirubin level is 2 x ULN or higher.
• Rare postmarketing cases of unexplained hepatic cirrhosis occurred after prolonged therapy in patients with multiple comorbidities and drug therapies.
• Drug is contraindicated in pregnancy because it's likely to cause major birth defects. Exclude pregnancy before therapy starts, and instruct patient to use reliable contraceptive method. Caution patient not to use hormonal contraceptives alone, because drug may render these ineffective; instruct her to use additional forms of contraception. Obtain monthly pregnancy tests.
• Because of potential hepatic injury and to reduce risk of fetal exposure, drug may be prescribed only through Tracleer Access Program.

Action

Binds to and blocks receptor sites for endothelin A and B in endothelium and vascular smooth muscle. This action reduces elevated endothelin levels in patients with pulmonary arterial hypertension, and inhibits vasoconstriction resulting from endothelin-1 (ET-1).

Availability

Tablets: 62.5 mg, 125 mg

⊘Indications and dosages

➣ To improve exercise ability and slow clinical deterioration in patients with pulmonary arterial hypertension who have World Health Organization class III or class IV symptoms

Adults: Initially, 62.5 mg P.O. b.i.d. for 4 weeks; increase to maintenance dosage of 125 mg P.O. b.i.d. In patients older than age 12 who weigh less than 40 kg (88 lb), initial and maintenance dosages are 62.5 mg b.i.d.

Dosage adjustment

• Moderate to severe hepatic dysfunction
• Hepatic injury in patients with alanine aminotransferase or aspartate aminotransferase elevations

Contraindications

• Hypersensitivity to drug
• Severe hepatic impairment
• Patients receiving concurrent cyclosporine or glyburide
• Pregnancy or breastfeeding
• Children younger than age 12 (safety and efficacy not established)

Precautions

Use cautiously in:
• mitral stenosis
• elderly patients.

Administration

• Give tablets in morning and evening, with or without food.

Route	Onset	Peak	Duration
P.O.	Variable	3-5 hr	Unknown

Adverse reactions

CNS: headache, fatigue

CV: edema, hypotension, palpitations

EENT: nasopharyngitis

GI: dyspepsia

Hepatic: hepatic dysfunction, hepatic injury, hepatotoxicity

Skin: pruritus, flushing

Interactions

Drug-drug. Cyclosporine: decreased cyclosporine blood level, increased bosentan blood level

Glyburide: decreased blood levels of both drugs, increased risk of hepatic damage

Hormonal contraceptives: decreased bosentan efficacy

Ketoconazole: increased bosentan blood level and effects

Simvastatin and other statins: decreased effects of these drugs

Drug-diagnostic tests. Hematocrit, hemoglobin: decreased values

Transaminases: increased values

Patient monitoring

• Assess serum transaminase levels within first 3 days of therapy and then monthly.
• Evaluate hemoglobin level 1 month after therapy and then every 3 months.
• Assess female patient for pregnancy every month during therapy.

Patient teaching

• Tell patient to take drug with or without food in morning and evening.
• Caution female patient to avoid pregnancy, and discuss reliable contraceptive methods. Instruct her to contact prescriber immediately if she thinks she may be pregnant.
• Inform patient that he'll undergo CBC measurement and liver function testing regularly during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

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bosentan

Vascular disease A mixed ET_A–endothelin and ET_B receptor antagonist, used as a long-term antihypertensive, which ↓ BP without reflex neurohormonal activation. See Endothelin ET_A receptor, Endothelin ET_B receptor.