Ambrisan5 mg

Ambrisan 5 mg is indicated for the treatment of Pulmonary Arterial Hypertension (PAH) (WHO Group 1) to improve exercise ability and delay clinical worsening.

Anti-hypertensive, Endothelin receptor antagonist

Endothelin-1 (ET-1) is a potent autocrine and paracrine peptide. Two receptor subtypes, ETA and ETB, mediate the effects of ET-1 in the vascular smooth muscle and endothelium. The primary actions of ETA are vasoconstriction and cell proliferation, while the predominant actions of ETB are vasodilation, antiproliferation, and ET-1 clearance.In patients with PAH, plasma ET-1 concentrations are increased as much as 10-fold and correlate with increased mean right atrial pressure and disease severity. ET-1 and ET-1 mRNA concentrations are increased as much as 9-fold in the lung tissue of patients with PAH, primarily in the endothelium of pulmonary arteries. These findings suggest that ET-1 may play a critical role in the pathogenesis and progression of PAH.Ambrisan 5 mg is a high-affinity (Ki=0.011 nM) ETA receptor antagonist with a high selectivity for the ETA versus ETB receptor ( > 4000-fold). The clinical impact of high selectivity for ETA is not known.

Initial treatment is 5 mg once daily, and can be increased to 10 mg once daily if 5 mg is tolerated. Ambrisan 5 mg may be administered with or without food.

Adult dose: Initial treatment is 5 mg once daily, and can be increased to 10 mg once daily if 5 mg is tolerated. Ambrisan 5 mg may be administered with or without food.Pediatric patients: The safety and effectiveness of Ambrisan 5 mg in pediatric patients have not been established.

Multiple dose co-administration of Ambrisan 5 mg and Cyclosporine resulted in an approximately 2-fold increase in Ambrisan 5 mg exposure in healthy volunteers; therefore, limit the dose of Ambrisan 5 mg to 5 mg once daily when co-administered with Cyclosporine.

Ambrisan 5 mg may cause fetal harm when administered to a pregnant woman. Ambrisan 5 mg is contraindicated in women who are or may become pregnant. 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. Pregnancy must be excluded before the initiation of treatment with Ambrisan 5 mg and prevented during treatment and for one month after stopping treatment. Ambrisan 5 mg is contraindicated in patients with Idiopathic Pulmonary Fibrosis (IPF) including IPF patients with pulmonary hypertension (WHO Group 3).

Decreases in hemoglobin concentration and hematocrit have followed administration of other endothelin receptor antagonists and were observed in clinical studies with Ambrisan 5 mg

Pregnancy Category X. It is not known whether Ambrisan 5 mg is excreted in human milk. Breastfeeding while receiving Ambrisan 5 mg is not recommended.

Fluid Retention: Peripheral edema is a known class effect of endothelin receptor antagonists, and is also a clinical consequence of PAH and worsening PAH. Pulmonary Veno-occlusive Disease: If patients develop acute pulmonary edema during initiation of therapy with vasodilating agents such as Ambrisan 5 mg, the possibility of pulmonary veno-occlusive disease should be considered, and if con_rmed. Ambrisan 5 mg should be discontinued. Hematological Changes: Decreases in hemoglobin concentration and hematocrit have followed administration of other endothelin receptor antagonists and were observed in clinical studies with Ambrisan 5 mg.Hepatic impairment: Ambrisan 5 mg is not recommended in patients with moderate or severe hepatic impairment.

Store in a cool and dry place, below 30°C. Protect from light and moisture.

Pediatric patients: Safety and effectiveness of Ambrisan 5 mg in pediatric patients have not been established.Hepatic impaired patient: Ambrisan 5 mg is not recommended in patients with moderate or severe hepatic impairment.

Anti-hypertensive, Endothelin receptor antagonist

Endothelin-1 (ET-1) is a potent autocrine and paracrine peptide. Two receptor subtypes, ETA and ETB, mediate the effects of ET-1 in the vascular smooth muscle and endothelium. The primary actions of ETA are vasoconstriction and cell proliferation, while the predominant actions of ETB are vasodilation, antiproliferation, and ET-1 clearance. Ambrisan 5 mg is a high-affinity ETA receptor antagonist with a high selectivity for the ETA versus ETB receptor (>4000-fold). The clinical impact of high selectivity for ETA is not known.The pharmacokinetics of Ambrisan 5 mg (S-Ambrisan 5 mg) in healthy subjects are dose proportional. The absolute bioavailability of Ambrisan 5 mg is not known. Ambrisan 5 mg is absorbed with peak concentrations occurring approximately 2 hours after oral administration in healthy subjects and PAH patients. Food does not affect its bioavailability. In vitro studies indicate that Ambrisan 5 mg is a substrate of P-gp. Ambrisan 5 mg is highly bound to plasma proteins (99%). The elimination of Ambrisan 5 mg is predominantly by non-renal pathways, but the relative contributions of metabolism and biliary elimination have not been well characterized. In plasma, the AUC of 4-hydroxymethyl Ambrisan 5 mg accounts for approximately 4% relative to parent Ambrisan 5 mg AUC. Thein vivo inversion of S-Ambrisan 5 mg to R-Ambrisan 5 mg is negligible. The mean oral clearance of Ambrisan 5 mg is 38 mL/min and 19 mL/min in healthy subjects and in PAH patients, respectively. Although Ambrisan 5 mg has a 15-hour terminal half-life, the mean trough concentration of Ambrisan 5 mg at steady-state is about 15% of the mean peak concentration and the accumulation factor is about 1.2 after long-term daily dosing, indicating that the effective half-life of Ambrisan 5 mg is about 9 hours.

Pregnancy Category X. It is not known whether Ambrisan 5 mg is excreted in human milk. Breastfeeding while receiving Ambrisan 5 mg is not recommended.