bosentan

Tracleer

Pharmacologic class: Endothelin-receptor antagonist, vasodilator

Therapeutic class: Antihypertensive

Pregnancy risk category X

FDA Box Warning

• Drug causes at least 3 × 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 × 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 × 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

➣ Patients with pulmonary arterial hypertension (World Health Organization Group 1) to improve exercise ability and to decrease clinical worsening

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

• Aminotransferase elevations more than 3 × upper limit of normal

• Concurrent use of lopinavir/ritonavir

Contraindications

• Hypersensitivity to drug

• Patients receiving concurrent cyclosporine or glyburide

• Pregnancy

Precautions

Use cautiously in:

• moderate to severe hepatic impairment (avoid use)

• mild hepatic impairment

• mitral stenosis, pulmonary veno-occlusive disease

• fluid retention, decreased sperm count, decreased hemoglobin level and hematocrit

• concurrent use of a CYP2C9 inhibitor and a strong or moderate CYP3A inhibitor (not recommended)

• concurrent use of tacrolimus

• elderly patients

• breastfeeding patients

• children younger than age 12 (safety and efficacy not established).

Administration

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

• Consider gradual dosage reduction when discontinuing drug.

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

CYP2C9 inhibitors (such as amiodarone, fluconazole), moderate CYP3A inhibitors (such as amprenavir, diltiazem, erythromycin, fluconazole), strong CYP3A inhibitors (such as itraconazole, ketoconazole): largely increased bosentan plasma concentration

Drugs metabolized by CYP2C9 and CYP3A: decreased plasma concentrations of these drugs

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

Hormonal contraceptives: decreased bosentan efficacy

Lopinavir/ritonavir combination: increased bosentan trough concentration

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.

See If signs of pulmonary edema occur, consider the possibility of underlying pulmonary venoocclusive disease and discontinue treatment if necessary.

• 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.

• Because of the potential for adverse effects in the breastfeeding infant, a decision should be made to discontinue breastfeeding or discontinue drug, taking into account the importance of drug to the mother.

• 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.

bosentan

A competitive mixed endothelin-A and endothelin-B receptor antagonist used to manage pulmonary arterial hypertension.

Adverse effects
Headache, flushing, hepatotoxicity, leg oedema, anaemia.

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.

bosentan

An ENDOTHELIN-1 receptor antagonist drug used to treat pulmonary hypertension. A brand name is Tracleer.

单词	bosentan
释义	bosentan bosentan Tracleer *Pharmacologic class:* Endothelin-receptor antagonist, vasodilator *Therapeutic class:* Antihypertensive *Pregnancy risk category X* FDA Box Warning • Drug causes at least 3 × 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 × 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 × 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 ➣ Patients with pulmonary arterial hypertension (World Health Organization Group 1) to improve exercise ability and to decrease clinical worsening 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 • Aminotransferase elevations more than 3 × upper limit of normal • Concurrent use of lopinavir/ritonavir Contraindications • Hypersensitivity to drug • Patients receiving concurrent cyclosporine or glyburide • Pregnancy Precautions Use cautiously in: • moderate to severe hepatic impairment (avoid use) • mild hepatic impairment • mitral stenosis, pulmonary veno-occlusive disease • fluid retention, decreased sperm count, decreased hemoglobin level and hematocrit • concurrent use of a CYP2C9 inhibitor and a strong or moderate CYP3A inhibitor (not recommended) • concurrent use of tacrolimus • elderly patients • breastfeeding patients • children younger than age 12 (safety and efficacy not established). Administration • Give tablets in morning and evening, with or without food. • Consider gradual dosage reduction when discontinuing drug. 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 CYP2C9 inhibitors (such as amiodarone, fluconazole), moderate CYP3A inhibitors (such as amprenavir, diltiazem, erythromycin, fluconazole), strong CYP3A inhibitors (such as itraconazole, ketoconazole): largely increased bosentan plasma concentration Drugs metabolized by CYP2C9 and CYP3A: decreased plasma concentrations of these drugs Glyburide: decreased blood levels of both drugs, increased risk of hepatic damage Hormonal contraceptives: decreased bosentan efficacy Lopinavir/ritonavir combination: increased bosentan trough concentration 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. See If signs of pulmonary edema occur, consider the possibility of underlying pulmonary venoocclusive disease and discontinue treatment if necessary. • 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. • Because of the potential for adverse effects in the breastfeeding infant, a decision should be made to discontinue breastfeeding or discontinue drug, taking into account the importance of drug to the mother. • 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. bosentan A competitive mixed endothelin-A and endothelin-B receptor antagonist used to manage pulmonary arterial hypertension. Adverse effects Headache, flushing, hepatotoxicity, leg oedema, anaemia. 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. bosentan An ENDOTHELIN-1 receptor antagonist drug used to treat pulmonary hypertension. A brand name is Tracleer.
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