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.
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).
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.
• Aminotransferase elevations more than 3 × upper limit of normal
• Concurrent use of lopinavir/ritonavir
• Hypersensitivity to drug
• Patients receiving concurrent cyclosporine or glyburide
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).
• Give tablets in morning and evening, with or without food.
• Consider gradual dosage reduction when discontinuing drug.
CNS: headache, fatigue
CV: edema, hypotension, palpitations
Hepatic: hepatic dysfunction, hepatic injury, hepatotoxicity
Skin: pruritus, flushing
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
• 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.
☞ 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.
• 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.
Pharmacologic: endothelin receptor antagonists
Time/action profile (blood levels)
Adverse Reactions/Side Effects
Central nervous system
- headache (most frequent)
Ear, Eye, Nose, Throat
- nasopharyngitis (most frequent)
- hepatotoxicity (life-threatening)
- ↓ sperm counts
- anemia (most frequent)
Drug-Drug interactionBosentan is metabolized by and induces the CYP3A4 and 2C9 enzyme systems.May ↓ effectiveness of hormonal contraceptives (additional method of contraception recommended).Significantly ↓ cyclosporine levels; cyclosporine significantly ↑ bosentan levels (concurrent use contraindicated).↑ risk of hepatotoxicity with glyburide (concurrent use contraindicated).Lopinavir/ritonavir or other ritonavir —containing regimens significantly ↑ levels (initiate bosentan at 62.5 mg once daily or every other day if receiving ritonavir-containing regimen for ≥10 days) (if initiating ritonavir in patient already receiving bosentan, discontinue bosentan for ≥36 hr before initiating ritonavir; can resume bosentan after ≥10 days at 62.5 mg once daily or every other day).Ketoconazole ↑ levels.↓ levels of simvastatin, lovastatin, and atorvastatin.↓ levels of warfarin.May ↓ levels of tacrolimus and sirolimus.
- Assess for signs and symptoms of primary pulmonary hypertension (dyspnea, exercise intolerance) prior to and periodically during therapy.
- Lab Test Considerations: Monitor serum AST, ALT, and bilirubin prior to and monthly during treatment. If AST and ALT are ↑ >3 and ≤5 times the upper limit of normal, confirm level with a second test. If confirmed, reduce dose or interrupt therapy and monitor AST and ALT every 2 wk. If AST and ALT return to pretreatment levels, continue therapy or resume therapy the starting dose and recheck AST and ALT within 3 days.If AST and ALT are >5 and ≤8 times the upper limit of normal, confirm level with a second test. If confirmed, stop therapy and monitor AST and ALT every 2 wk. Once AST and ALT return to normal levels, reintroduce therapy at starting dose and recheck AST and ALT levels within 3 days. If AST and ALT levels are >8 times the upper limit of normal if clinical symptoms of liver injury (nausea, vomiting, fever, abdominal pain, jaundice, unusual lethargy or fatigue) occur, or if bilirubin levels are ≥2 times the upper limit of normal, discontinue therapy permanently.
- Monitor hemoglobin and hematocrit levels 1 and 3 mo after initiation of therapy and every 3 mo thereafter. May cause ↓ in hemoglobin.
Potential Nursing DiagnosesImpaired gas exchange (Indications)
- Do not confuse Tracleer with Tricor.
- Oral: Administer in the morning and evening without regard to food.
- Bosentan can only be prescribed through the TRACLEER Access Program (T.A.P.) by calling 1–866–228–3546. It is not available at local pharmacies or wholesalers.
- Instruct patient to take bosentan as directed. Take missed doses as soon as remembered unless almost time for next dose; do not double doses. Do not stop taking bosentan without consulting health care professional; may cause an increase in symptoms. Explain the requirements of the TRACLEER Access Program.
- Advise patient to notify health care professional immediately if nausea, vomiting, fever, abdominal pain, unusual tiredness, stomach pain, or jaundice occurs or if swelling of ankles or legs or difficulty breathing occurs.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any Rx, OTC, or herbal products.
- Advise patient of the requirement of monthly lab tests to monitor for liver dysfunction.
- Caution premenopausal women about the importance of effective contraception, the interaction of bosentan with hormonal contraceptives, and the need for monthly serum or urine pregnancy tests. Crushed or broken tablets should not be handled by pregnant women. Inform men that bosentan may cause decreased sperm count.
- Improved exercise capacity and decreased rate of clinical progression in patients with primary pulmonary hypertension.
bosentanA competitive mixed endothelin-A and endothelin-B receptor antagonist used to manage pulmonary arterial hypertension.
Headache, flushing, hepatotoxicity, leg oedema, anaemia.