VOLIBRIS Film-coated tablet Ref.[6154] Active ingredients: Ambrisentan

Treatment must be initiated by a physician experienced in the treatment of PAH.

Posology

Adults

Ambrisentan monotherapy

Volibris is to be taken orally to begin at a dose of 5 mg once daily and may be increased to 10 mg daily depending upon clinical response and tolerability.

Ambrisentan in combination with tadalafil

When used in combination with tadalafil, Volibris should be titrated to 10 mg once daily.

In the AMBITION study, patients received 5 mg ambrisentan daily for the first 8 weeks before up titrating to 10 mg, dependent on tolerability (see section 5.1). When used in combination with tadalafil, patients were initiated with 5 mg ambrisentan and 20 mg tadalafil. Dependent on tolerability the dose of tadalafil was increased to 40 mg after 4 weeks and the dose of ambrisentan was increased to 10 mg after 8 weeks. More than 90% of patients achieved this. Doses could also be decreased depending on tolerability.

Limited data suggest that the abrupt discontinuation of ambrisentan is not associated with rebound worsening of PAH.

Ambrisentan in combination with cyclosporine A

In adults, when co-administered with cyclosporine A, the dose of ambrisentan should be limited to 5 mg once daily and the patient should be carefully monitored (see sections 4.5 and 5.2).

Paediatric patients aged 8 to less than 18 years

Ambrisentan monotherapy or in combination with other PAH therapies

Volibris is to be taken orally based on the dose regimen described below:

a = dependent on clinical response and tolerability (see section 5.1)

Ambrisentan in combination with cyclosporine A In paediatric patients, when co-administered with cyclosporine A, the dose of ambrisentan for patients ≥50 kg should be limited to 5 mg once daily, or for patients ≥20 to <50 kg should be limited to 2.5 mg once daily. The patient should be carefully monitored (see sections 4.5 and 5.2).

Special populations

Elderly patients

No dose adjustment is required in patients over the age of 65 (see section 5.2).

Patients with renal impairment

No dose adjustment is required in patients with renal impairment (see section 5.2). There is limited experience with ambrisentan in individuals with severe renal impairment (creatinine clearance <30 ml/min); therapy should be initiated cautiously in this subgroup and particular care taken if the dose is increased to 10 mg ambrisentan.

Patients with hepatic impairment

Ambrisentan has not been studied in individuals with hepatic impairment (with or without cirrhosis). Since the main routes of metabolism of ambrisentan are glucuronidation and oxidation with subsequent elimination in the bile, hepatic impairment might be expected to increase exposure (Cmax and AUC) to ambrisentan. Therefore, ambrisentan must not be initiated in patients with severe hepatic impairment, or clinically significant elevated hepatic aminotransferases (greater than 3 times the Upper Limit of Normal (>3xULN); see sections 4.3 and 4.4).

Paediatric population

The safety and efficacy of ambrisentan in children below 8 years of age have not been established. No clinical data are available (see section 5.3 regarding data available in juvenile animals).

Method of administration

Volibris is for oral use. It is recommended that the tablet is swallowed whole and it can be taken with or without food. It is recommended that the tablet should not be split, crushed or chewed.

There is no experience in PAH patients of ambrisentan at daily doses greater than 10 mg. In healthy volunteers, single doses of 50 and 100 mg (5 to 10 times the maximum recommended dose) were associated with headache, flushing, dizziness, nausea and nasal congestion.

Due to the mechanism of action, an overdose of ambrisentan could potentially result in hypotension (see section 5.3). In the case of pronounced hypotension, active cardiovascular support may be required. No specific antidote is available.

Volibris 2.5 mg film-coated tablets:

2 years.

Volibris 5 mg and 10 mg film-coated tablets:

5 years.

This medicinal product does not require any special storage conditions.

Volibris 2.5 mg film-coated tablets:

Opaque, white high density polyethylene (HDPE) bottles closed with polypropylene child-resistant closures with a polyethylene faced induction heat seal liner.

The bottles contain 30 film-coated tablets.

Volibris 5 mg and 10 mg film-coated tablets:

PVC/PVDC/aluminium foil blisters.

Pack sizes with unit dose blisters of 10 × 1 or 30 × 1 film-coated tablets.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.