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Adverse events occurring in ≥3% of patients treated with Tracleer
and more frequently than the placebo group1
| Adverse event | Tracleer
(n=258) | Placebo
(n=172) |
| Respiratory tract infection | 56 (22%) | 30 (17%) |
| Headache | 39 (15%) | 25 (14%) |
| Edema | 28 (11%) | 16 (9%) |
| Chest pain | 13 (5%) | 8 (5%) |
| Syncope | 12 (5%) | 7 (4%) |
| Flushing | 10 (4%) | 5 (3%) |
|
| Adverse event | Tracleer
(n=258) | Placebo
(n=172) |
| Hypotension | 10 (4%) | 3 (2%) |
| Sinusitis | 9 (4%) | 4 (2%) |
| Arthralgia | 9 (4%) | 3 (2%) |
| Liver function test abnormal | 9 (4%) | 3 (2%) |
| Palpitations | 9 (4%) | 3 (2%) |
| Anemia | 8 (3%) | — |
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Safety profile when administered with other standard medication in pivotal trials
 | Patients receiving Tracleer continued other medications, including anticoagulants, digoxin, diuretics, and vasodilators such as calcium channel blockers and ACE inhibitors.2,3 |
| | Patients receiving epoprostenol within 3 months of study screening were ineligible for participation.2,3 |
| | In the EARLY trial, both the Tracleer group and the placebo group included some patients on sildenafil at baseline (Tracleer, n=14; placebo, n=15).4 |
Drug-drug interactions1
Tracleer's DDI profile is well-studied, meeting all postapproval commitments from the FDA
| | Tracleer is contraindicated for use with cyclosporine A and glyburide. |
| | Tracleer is metabolized by CYP2C9 and CYP3A. |
| — | Co-administration with agents that are metabolized by these pathways may affect plasma concentrations of one or both agents. |
| — | When initiating lopinavir/ritonavir and other ritonavir-containing HIV regimens, dosage adjustment of Tracleer is necessary. |
| — | When co-administered with simvastatin, or other statins that are CYP3A substrates, dosage adjustment of such statins may need to be considered. |
| — | When co-administered with rifampicin, a CYP3A inducer, liver function should be monitored weekly for the first 4 weeks before reverting to normal (monthly) monitoring. |
| — | Co-administration of tacrolimus and bosentan resulted in markedly increased plasma concentrations of bosentan in animals; caution should be exercised if they are used together. |
| — | When co-administered with ketoconazole, a potent CYP3A inhibitor, no dose adjustment of bosentan is necessary, but increased effects of Tracleer may need to be considered. |
| | There are no clinically relevant interactions between Tracleer and warfarin, digoxin, nimodipine, losartan, or sildenafil. |
| | Tracleer has no significant interaction with iloprost. |
Tracleer is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in
patients with WHO Class II-IV symptoms, to improve exercise ability and decrease the rate of
clinical worsening. Patients with WHO Class II symptoms showed reduction in the rate of clinical
deterioration and a trend for improvement in walk distance. Physicians should consider whether
these potential benefits are sufficient to offset liver injury in WHO Class II patients, which may
preclude future use as their disease progresses.
Important safety information
Because of the associated risks, Tracleer may be prescribed only through the Tracleer Access Program.
Potential for serious liver injury (including, after prolonged treatment, rare cases of liver failure
and unexplained hepatic cirrhosis in a setting of close monitoring)—Liver monitoring of all patients
is essential prior to initiation of treatment and monthly thereafter.
High potential for major birth defects—Pregnancy must be excluded and prevented through the use of
reliable forms of birth control; monthly pregnancy tests should be obtained.
Contraindicated for use with cyclosporine A and glyburide.
Please see full prescribing information including BOXED WARNING.
- Tracleer (bosentan) full prescribing information. Actelion Pharmaceuticals US, Inc. August 2009.
- Channick RN, Simonneau G, Sitbon O, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet. 2001;358:1119-1123.
- Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002;346:896-903.
- Galiè N, Rubin LJ, Hoeper MM, et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet. 2008;371:2093-2100.
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