Tracleer (bosentan)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Pulmonary arterial hypertension
General Information
Tracleer tablets have been approved by the FDA for the treatment
of pulmonary arterial hypertension (PAH). This drug is indicated
for use in improving exercise ability and decreasing the rate of
clinical worsening in patients with WHO Class III or IV symptoms.
Tracleer 125 mg (taken twice a day) is the first approved oral
treatment for patients with PAH.
Tracleer belongs to a class of drugs known as endothelin
receptor antagonists (ERAs). Patients with PAH have elevated levels
of endothelin, a potent blood vessel constrictor, in their plasma
and lung tissue. Tracleer blocks the binding of endothelin to its
receptors, thereby negating endothelin's deleterious
effects.
Clinical Results
Results of a pivotal trial known as BREATHE-1 (Bosentan:
Randomized Trial of Endothelin Receptor Antagonist THErapy)
supported the approval of Tracleer. In the 213-subject trial,
Tracleer (125 mg b.i.d. and 250 mg b.i.d.) was administered on a
twice-daily basis. For both primary and secondary PAH, results
showed statistically significant improvements versus placebo in the
primary efficacy endpoint, exercise capacity. The overall treatment
effect for both doses of Tracleer combined was a 44-meter
improvement in walking distance compared to placebo (as measured by
a six-minute walk test). Tracleer also produced a significant delay
in time to clinical worsening, defined as death, hospitalization,
worsening PAH or initiation of intravenous therapy. Lastly,
treatment with Tracleer resulted in significant improvement in
functional status and breathlessness.
Side Effects
Adverse reactions reported in clinical testing of Tracleer
include (but are not limited to) the following:
- Headache
- Nasopharyngitis (inflammation of the nose and pharynx)
- Flushing
- Edema, lower limb
- Hypotension
- Palpitations
Women who are pregnant, or who may become pregnant, should not
take Tracleer due to the risk of birth defects. Additionally,
patients receiving Tracleer should undergo monthly liver monitoring
to ensure that proper enzyme levels are maintained.
Mechanism of Action
Endothelin-1 (ET-1) is a neurohormone, the effects of which are
mediated by binding to ETA and ETB receptors in the endothelium and
vascular smooth muscle. ET-1 concentrations are elevated in plasma
and lung tissue of patients with pulmonary arterial hypertension,
suggesting a pathogenic role for ET-1 in this disease. Bosentan is
a specific and competitive antagonist at endothelin receptor types
ETA and ETB . Bosentan has a slightly higher affinity for ETA
receptors than for ETB receptors (from Tracleer Prescribing
Information).
Additional Information
