Ambrisan5 mg

Ambrisan is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to improve exercise capacity and delay clinical worsening. Indications below are classified by strength of evidence.

Established / Approved Use

• Treatment of PAH in adults, including idiopathic and heritable PAH and PAH associated with connective tissue disease, to improve exercise capacity and delay clinical worsening.

Guideline-Supported Combination Therapy

• Ambrisan combined with a phosphodiesterase-5 (PDE5) inhibitor such as tadalafil is supported by clinical trial evidence for reducing the risk of clinical failure events and is recommended for appropriate patients in pulmonary hypertension treatment guidelines.

Not Indicated / Off-Label Caution

• Ambrisan is not indicated for, and is contraindicated in, pulmonary hypertension associated with idiopathic pulmonary fibrosis (see Contraindications).
• Use for other forms of pulmonary hypertension (WHO Groups II–V) is not supported by evidence and is not recommended outside specialist evaluation.

Each film-coated tablet contains Ambrisentan 5 mg or 10 mg as the active pharmaceutical ingredient, together with pharmaceutically acceptable excipients.

Ambrisan is an orally administered, propanoic-acid class endothelin receptor antagonist (ERA) that is selective for the endothelin type A (ET_A) receptor. It is used in the long-term management of pulmonary arterial hypertension (PAH) and is supplied as film-coated tablets for once-daily oral use.

Ambrisan belongs to the therapeutic class of Endothelin Receptor Antagonists (ERAs), a group of pulmonary vasodilators used specifically in the management of pulmonary arterial hypertension.

Ambrisentan selectively blocks the endothelin type A (ET_A) receptor on vascular smooth muscle, inhibiting the vasoconstrictive and proliferative effects of endothelin-1 and thereby reducing pulmonary vascular resistance in patients with PAH.

Pharmacokinetics

• Protein binding: approximately 99%
• Metabolism: primarily glucuronidation and oxidative pathways
• Elimination half-life: approximately 15 hours
• Excretion: predominantly via bile/feces

Ambrisan tablets should be swallowed whole with or without food, at approximately the same time each day. Tablets should not be split, crushed, or chewed.

Clinically significant interactions with Ambrisan include:

• Cyclosporine: Increases Ambrisan plasma exposure; limit dose to 5 mg once daily and monitor closely.
• Rifampin: May transiently increase Ambrisan exposure when therapy is initiated together; monitor closely during the first weeks of co-administration.
• Other PAH therapies (e.g., PDE5 inhibitors such as tadalafil or sildenafil): Deliberate combination use is supported by clinical evidence, but patients should be monitored for additive hypotension and fluid-related effects.
• Hormonal contraceptives: Because Ambrisan is contraindicated in pregnancy, use of a reliable non-hormonal or combined contraceptive method is advised.

Side effects reported with Ambrisan:

Common

• Peripheral edema/fluid retention
• Headache
• Flushing
• Nasal congestion, sinusitis, rhinitis
• Palpitations
• Dizziness
• Constipation

Less Common but Clinically Important

• Decreased hemoglobin/anemia (see Precautions)
• Liver enzyme elevation/hepatic injury (see Precautions)
• Decreased sperm count (see Precautions)
• Pulmonary edema in patients with underlying pulmonary veno-occlusive disease (see Precautions)

Ambrisan carries a boxed warning for embryo-fetal toxicity and is contraindicated in pregnancy; animal studies have shown teratogenic effects. Females of reproductive potential should have a negative pregnancy test before starting Ambrisan, use reliable contraception throughout treatment, and undergo monthly pregnancy testing per product labeling. If pregnancy occurs during treatment, Ambrisan should be stopped immediately and the prescribing physician contacted.

It is not known whether Ambrisan passes into breast milk. Because of the potential for serious adverse effects in a nursing infant, the decision to discontinue breastfeeding or discontinue the drug should be made with the physician, weighing the importance of treatment to the mother.

Ambrisan should be initiated and monitored only by a physician experienced in managing pulmonary arterial hypertension. Key precautions:

• Embryo-fetal toxicity: Boxed warning; see Contraindications and Pregnancy and Lactation.
• Hepatotoxicity: Liver injury has been reported with endothelin receptor antagonists as a class; periodic clinical assessment for signs/symptoms of liver injury (fatigue, nausea, jaundice, right upper-quadrant pain) is reasonable, with liver function testing if symptoms occur.
• Fluid retention/peripheral edema: Can occur, particularly in the first weeks of treatment; monitor closely in patients with underlying heart failure and manage (e.g., with diuretics) if significant.
• Decreased hemoglobin/anemia: Monitor hemoglobin/hematocrit, particularly early in treatment.
• Decreased sperm count: Reported with endothelin receptor antagonists as a class; counsel male patients on potential fertility effects.
• Pulmonary veno-occlusive disease (PVOD): If pulmonary edema develops after starting Ambrisan, evaluate for underlying PVOD before continuing therapy.
• Specialist management required: Given the need for pregnancy risk management and specialized monitoring, Ambrisan should not be initiated or managed in general-practice settings.

Clinical experience with Ambrisan overdose is limited; based on its mechanism, overdose may be expected to cause hypotension. If overdose is suspected, seek immediate medical attention or contact emergency services/poison control. Management is supportive and symptomatic; there is no specific antidote, and hemodialysis is not expected to be effective due to high protein binding.

Store Ambrisan tablets at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Renal Impairment

No dosage adjustment generally required in mild-to-moderate impairment; data in severe impairment are limited, so use with caution.

Hepatic Impairment

Not recommended in moderate-to-severe hepatic impairment; use with caution and monitoring in mild impairment.

Elderly

No overall differences in safety/effectiveness observed in patients over 65 years, but caution is warranted given greater frequency of concomitant disease and other drug therapy.

Pediatric

Safety and efficacy of Ambrisan have not been established in pediatric patients.

Ambrisan is used as a long-term, ongoing therapy for pulmonary arterial hypertension; duration is determined by the treating specialist based on clinical response and tolerability. Treatment should not be stopped abruptly without medical advice, as discontinuation may be associated with worsening of PAH symptoms.

Endothelin Receptor Antagonist (ERA) — propanoic-acid derivative class.

Ambrisentan selectively antagonizes the endothelin type A (ET_A) receptor on vascular smooth muscle, blocking the vasoconstrictive and proliferative effects of endothelin-1, thereby reducing pulmonary vascular resistance and improving hemodynamics in PAH.

X (contraindicated in pregnancy under the legacy FDA pregnancy category system)

Safety and efficacy of Ambrisan have not been established in pediatric patients; use in children is not recommended outside specialized clinical settings.