Ambrisentan

1 INDICATIONS AND USAGE Ambrisentan tablets are indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) in adult patients: To improve exercise ability and delay clinical worsening. Studies establishing effectiveness included predominantly patients with WHO Functional Class II–III symptoms and etiologies of idiopathic or heritable PAH (60%) or PAH associated with connective tissue diseases (34%). Ambrisentan tablets are an endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) in adult patients: To improve exercise ability and delay clinical worsening.

6 ADVERSE REACTIONS Clinically significant adverse reactions that appear in other sections of the labeling include: Embryo-fetal Toxicity [see Warnings and Precautions (5.1) , Use in Specific Populations (8.1) ] Fluid Retention [see Warnings and Precautions (5.2) ] Pulmonary Edema with PVOD [see Warnings and Precautions (5.3) ] Decreased Sperm Count [see Warnings and Precautions (5.4) ] Hematologic Changes [see Warnings and Precautions (5.5) ] Most common adverse reactions (>3% compared to placebo) are peripheral edema, nasal congestion, sinusitis, and flushing ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp . at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

4.1 Pregnancy Ambrisentan tablets may cause fetal harm when administered to a pregnant female. Ambrisentan tablets are contraindicated in females who are pregnant. Ambrisentan was consistently shown to have teratogenic effects when administered to animals. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Dosage and Administration (2.2), Warnings and Precautions (5.1), and Use in Specific Populations (8.1)].

WARNING: EMBRYO-FETAL TOXICITY Ambrisentan tablets are contraindicat ed for use during pregnancy because it may cause major birth defects if used by pregnant patients, based on studies in animals [see Contraindications (4.1), Warnings and Precautions (5.1), and Use in Specific Populations (8.1)]. Therefore, for females of reproductive potential, exclude pregnancy before the initiation of treatment must use acceptable methods of contraception during treatment with ambrisentan tablets. 5 WARNINGS AND PRECAUTIONS Fluid retention may require intervention ( 5.2 ). If patients develop acute pulmonary edema during initiation of therapy with ambrisentan tablets, consider underlying pulmonary veno-occlusive disease and discontinue treatment if necessary ( 5.3 ). Decreases in sperm count have been observed in patients taking endothelin receptor antagonists ( 5.4 ). Decreases in hemoglobin have been observed within the first few weeks; measure hemoglobin at initiation, at 1 month, and periodically thereafter ( 5.5 ). 5.1 Embryo-fetal Toxicity Based on data from animal reproduction studies, ambrisentan tablets may cause fetal harm when administered during pregnancy and is contraindicated during pregnancy. 4 CONTRAINDICATIONS Pregnancy ( 4.1 ) Idiopathic Pulmonary Fibrosis ( 4.2 ) 4.1 Pregnancy Ambrisentan tablets may cause fetal harm when administered to a pregnant female. Ambrisentan tablets are contraindicated in females who are pregnant. Ambrisentan was consistently shown to have teratogenic effects when administered to animals.