Embelin 5(Ambrisentan)

Therapeutic Group: Endothelin receptor antagonist

Presentation

EmbelinTM 5: Each film coated tablet contains Ambrisentan INN 5 mg

Description

Ambrisentan is an endothelin receptor antagonist that is selective for the endothelin type-A (ETA) receptor. 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. Ambrisentan is a high-affinity ETA receptor antagonist with a high selectivity for the ETA versus ETB receptor

Indications

Ambrisentan is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1)

• To improve exercise ability and delay clinical worsening

• In combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability

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%).

Dosage & Administration

Initiate treatment at 5 mg once daily, with or without tadalafil 20 mg once daily. At 4-week intervals, either the dose of Ambrisentan or tadalafil can be increased, as needed and tolerated, to Ambrisentan 10 mg or tadalafil 40 mg. Do not split, crush, or chew tablets.

Side Effects

Most common adverse reactions (>3% compared to placebo) are peripheral edema, nasal congestion, sinusitis, and flushing. When used in combination with tadalafil, most common adverse reactions (>5% compared with either monotherapy) are peripheral edema, headache, nasal congestion, cough, anemia, dyspepsia, and bronchitis

Precautions

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 Ambrisentan, the possibility of pulmonary veno-occlusive disease should be considered, and if confirmed.
Ambrisentan 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 Ambrisentan

Use in Pregnancy & Lactation

Pediatric patients: Safety and effectiveness of Ambrisentan in pediatric patients have not been established.
Hepatic impaired patient: Ambrisentan is not recommended in patients with moderate or severe hepatic impairment.
Pregnancy and Lactation: Pregnancy Category X. It is not known whether Ambrisentan is excreted in human milk. Breastfeeding while receiving Ambrisentan is not recommended.

Drug Interaction

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

Over Dose

There is no experience with overdosage of Ambrisentan. The highest single dose of Ambrisentan administered to healthy
volunteers was 100 mg, and the highest daily dose administered to patients with PAH was 10 mg once daily

Storage

Do not store above 30 0c. Keep away from light and out of the reach of children

Commercial Pack

EmbelinTM 5: Each box contains 2 blister strips of 10 tablets