TRACLEER for ORAL SUSPENSION Dosage & Rx Info

Tracleer For Oral Suspension Generic Name & Formulations

Legal Class

General Description

Bosentan 32mg; dispersible tabs for oral susp; tutti frutti flavor; contains phenylalanine.

Pharmacological Class

Endothelin receptor antagonist.

How Supplied

Tabs—30, 60; Tabs for oral susp—14, 56

Manufacturer

Actelion Pharmaceuticals

Generic Availability

Tabs (YES); Tabs for oral susp (NO)

Mechanism of Action

Bosentan is a specific and competitive antagonist at endothelin receptor types ET_A and ET_B. Endothelin-1 (ET-1) is a neurohormone, the effects of which are mediated by binding to ET_A and ET_B receptors in the endothelium and vascular smooth muscle. ET-1 concentrations are elevated in plasma and lung tissue of patients with PAH, suggesting a pathogenic role for ET-1 in this disease.

Tracleer For Oral Suspension Indications

Indications

Pulmonary arterial hypertension (PAH) (WHO Group I) in adults with WHO Class II–IV symptoms to improve exercise ability and decrease clinical worsening. Idiopathic or congenital PAH to improve pulmonary vascular resistance (expected to improve exercise ability) in pediatrics ≥3yrs.

Tracleer For Oral Suspension Dosage and Administration

Adults and Children

Must register patient in the Tracleer REMS Program (see full labeling). Take in the AM and PM. ≤12yrs (≥4–8kg): 16mg twice daily; (>8–16kg): 32mg twice daily; (>16–24kg): 48mg twice daily; (>24–40kg): 64mg twice daily. >12yrs (<40kg): 62.5mg twice daily; (>40kg): initially 62.5mg twice daily for 4 weeks, then 125mg twice daily. Concomitant ritonavir (for at least 10 days): start bosentan at the recommended initial dose once daily or every other day based on tolerability; discontinue bosentan at least 36 hours before starting ritonavir. Dose adjustments for ALT/AST elevations (confirm with another test): see full labeling.

Tracleer For Oral Suspension Contraindications

Contraindications

Pregnancy. Concomitant cyclosporine A, glyburide.

Tracleer For Oral Suspension Boxed Warnings

Boxed Warning

Risks of hepatotoxicity. Embryo-fetal toxicity.

Tracleer For Oral Suspension Warnings/Precautions

Warnings/Precautions

Moderate or severe hepatic impairment or baseline ALT/AST >3×ULN: not recommended. Monitor ALT/AST levels prior to initiating therapy and then monthly; discontinue if elevations are accompanied by clinical symptoms of hepatotoxicity or increases in bilirubin ≥2×ULN. Reduce dose or interrupt treatment, and monitor if ALT/AST >3×ULN (see full labeling); permanently discontinue if ALT/AST >8×ULN. Embryo-fetal toxicity. Obtain (–) pregnancy test and use 2 effective methods of contraception prior to initiation, monthly during treatment, and for 1 month after last dose (see full labeling). 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.

REMS

YES

Tracleer For Oral Suspension Pharmacokinetics

Absorption

Absolute bioavailability: ~50%.

Distribution

Volume of distribution: ~18 L. Plasma protein bound: >98%.

Metabolism

Hepatic.

Elimination

Fecal. Half-life: ~5 hours.

Tracleer For Oral Suspension Interactions

Interactions

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

Tracleer For Oral Suspension Adverse Reactions

Adverse Reactions

Respiratory tract infection, headache, edema, chest pain, syncope, flushing, hypotension, sinusitis, arthralgia, elevated liver enzymes, palpitations, anemia, pyrexia; hepatotoxicity, fluid retention, decreased sperm counts.

Tracleer For Oral Suspension Clinical Trials

See Literature

Tracleer For Oral Suspension Note

Notes

Only prescribers and pharmacies registered with Bosentan REMS Program may prescribe or dispense Tracleer. Patients must be enrolled and meet all conditions of Bosentan REMS Program. To register call (866) 359-2612.

Tracleer For Oral Suspension Patient Counseling