Generic Name and Formulations:
Bosentan 62.5mg, 125mg; tabs.

Company:
Actelion Pharmaceuticals

Indications for TRACLEER:
Pulmonary arterial hypertension (PAH) (WHO Group I) in patients with WHO Class II–IV symptoms to improve exercise ability and decrease rate of clinical worsening.

Adult:
Must register patient in T.A.P. program (see full labeling for restrictions and stipulations on use). Take in the AM and PM. <40kg: 62.5mg twice daily. >40kg: Initially 62.5mg twice daily for 4 weeks, then 125mg twice daily. Dose adjustments for developing ALT/AST elevations (confirm with another test): ALT/AST >3 and ≤5 x ULN: reduce daily dose to 62.5mg twice daily; if levels return to pretreatment values, continue or reintoduce treatment as appropriate. ALT/AST >5 and ≤8 x ULN: stop treatment and monitor at least every 2 weeks; if levels return to pretreament values, consider reintroduction. ALT/AST >8 x ULN: stop treatment, do not reintroduce. Concomitant ritonavir (for at least 10 days): start bosentan at 62.5mg once daily or every other day based on tolerability. Discontinue bosentan at least 36 hours before starting ritonavir.

Children:
Not established.

Pharmacological Class:
Endothelin receptor antagonist.

Contraindications:
Concomitant cyclosporine A, glyburide. Pregnancy (Cat.X).

Warnings/Precautions:
Moderate to severe hepatic impairment or ALT/AST >3 x ULN at baseline: not recommended. Monitor ALT/AST levels prior to initiating therapy and then monthly; if liver injury occurs, discontinue therapy. Counsel patient about need for contraception; obtain a negative pregnancy test prior to initiation of drug and monthly thereafter; use 2 effective methods of contraception (see literature). Monitor hemoglobin and hematocrit at 1 and 3 months, then every 3 months thereafter. Monitor for significant fluid retention and pulmonary edema; discontinue if pulmonary veno-occlusive disease develops. Avoid abrupt cessation. Nursing mothers: not recommended.

Interactions:
See Contraindications. Potentiated by CYP2C9 (eg, fluconazole amiodarone) or strong or moderate CYP3A inhibitors (eg, ketoconazole, itraconazole, amprenavir, erythromycin, diltiazem); concomitant CYP2C9 inhibitor/moderate or strong CYP3A inhibitor combinations: not recommended. Potentiated by ritonavir. Rifampin alters bosentan levels (monitor hepatic function weekly for 4 weeks, followed by normal monitoring). Caution with tacrolimus. Antagonizes CYP2C9 or CYP3A substrates (eg, simvastatin). May interfere with hormonal contraceptives; use additional forms of contraception. May antagonize warfarin.

Adverse Reactions:
Respiratory tract infection, headache, edema, chest pain, syncope, flushing, hypotension, sinusitis, arthralgia, elevated liver enzymes, palpitations, anemia; decreased sperm counts.

Note:
Only prescribers and pharmacies registered with Tracleer Access Program (T.A.P.) may prescribe Tracleer. Patients must be enrolled and meet all conditions of T.A.P. To register call (866) 228-3546.

REMS:
YES

How Supplied:
Tabs—30, 60