• Pulmonary arterial hypertension (PAH) (WHO Group 1).
• Idiopathic or congenital PAH.

Contraindicated in:

• Hypersensitivity
• Concurrent use of cyclosporine or glyburide
• Concurrent use with a CYP2C9 inhibitor and a strong or moderate CYP3A4 inhibitor
• Moderate to severe liver impairment or patients with ↑ liver enzymes (>3x ULN)
• OB: Pregnancy (may cause fetal harm); Lactation: Lactation.

Use Cautiously in:

• Women of reproductive potential
• Pedi: Children <3 yr (safety and effectiveness not established).

CV: edema, hypotension, palpitations.

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), flushing, pruritus, rash.

EENT: nasopharyngitis.

GI: HEPATOTOXICITY, dyspepsia.

GU: ↓sperm counts.

Hemat: anemia.

Neuro: headache, fatigue.
Misc: ANAPHYLAXIS, ANGIOEDEMA.

Drug-Drug:

• Bosentan 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.
• May ↓ levels of atorvastatin, lovastatin, sildenafil, simvastatin, sirolimus, tacrolimus, tadalafil, and warfarin..

(Generic available)

• Tablets: 62.5 mg; 125 mg;
• Tablets for oral suspension: 32 mg;

• PO (Adults and Children >12 yr and >40 kg): 62.5 mg twice daily for 4 wk initially, then ↑ to maintenance dose of 125 mg twice daily.
• PO (Adults and Children >12 yr and <40 kg): 62.5 mg twice daily as initial and maintenance dose.
• PO (Children 3–12 yr and 24.1–40 kg): 64 mg twice daily as initial and maintenance dose.
• PO (Children 3–12 yr and 16.1–24 kg): 48 mg twice daily as initial and maintenance dose.
• PO (Children 3–12 yr and 8.1–16 kg): 32 mg twice daily as initial and maintenance dose.
• PO (Children 3–12 yr and 4–8 kg): 16 mg twice daily as initial and maintenance dose.

Tracleer

• Antagonizes the effects of the neurohormone endothelin by binding to its receptor sites in endothelium and vascular smooth muscle.

• Improved exercise capacity and decreased clinical deterioration.

Therapeutic Classification: vasodilators

Pharmacologic Classification: endothelin receptor antagonists

Absorption: 50% absorbed following oral administration in normal patients.

Distribution: 18 L.

Protein Binding: >98%.

Metabolism/Excretion: Highly metabolized; one metabolite contributes to pharmacologic activity. Eliminated via biliary excretion; <3% excreted in urine.

Half-life: 5 hr.

(blood levels)

• 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 Bosentan REMS 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.
• Instruct female patients with reproductive potential to use acceptable methods of contraception (1 highly effective form of contraception — intrauterine device [IUD] or tubal sterilization, or a combination of methods — hormonal method with a barrier method or two barrier methods) during and for 1 mo after therapy is completed. Hormonal contraceptives alone should not be used for contraception. If partner's vasectomy is the chosen method, a hormonal or barrier method must be used in addition to the vasectomy. May be teratogenic. Counsel patient on pregnancy prevention and emergency contraception. Patient should discontinue medication and inform health care professional immediately if pregnancy is suspected. Inform men that bosentan may cause decreased sperm count.

BOE-sen-tan