Ambrisentan

Source: UK SPC (eMC) for Ambrisentan 10 mg film-coated Tablets, §4.2 (https://www.medicines.org.uk/emc/product/11697/smpc). Indication context: pulmonary arterial hypertension (PAH). Treatment must be initiated by a physician experienced in the treatment of PAH. IN COMBINATION WITH TADALAFIL: ambrisentan 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; patients were initiated on ambrisentan 5 mg plus tadalafil 20 mg, tadalafil was increased to 40 mg after 4 weeks and ambrisentan to 10 mg after 8 weeks, and more than 90% of patients achieved this. Doses could also be decreased depending on tolerability. WITH CICLOSPORIN A: in adults, limit the dose of ambrisentan to 5 mg once daily and monitor the patient carefully. DISCONTINUATION: limited data suggest that abrupt discontinuation of ambrisentan is not associated with rebound worsening of PAH. ELDERLY: no dose adjustment is required over the age of 65. HEPATIC IMPAIRMENT: ambrisentan has not been studied in individuals with hepatic impairment; it must not be initiated in patients with severe hepatic impairment or with clinically significant elevated hepatic aminotransferases (>3xULN). HAEMOGLOBIN: initiation is not recommended in patients with clinically significant anaemia; the incidence of anaemia was increased when ambrisentan was dosed in combination with tadalafil (15%) compared with ambrisentan (7%) or tadalafil (11%) monotherapy. METHOD OF ADMINISTRATION: swallow the tablet whole, with or without food; it should not be split, crushed or chewed. No openFDA record was fetched for this drug and §4.5 was not retrieved — the single interaction listed comes from the §4.2 ciclosporin A paragraph; verify the full §4.5 before use.

NOT A PER-KG DOSE — dosePerKg is deliberately null; do not compute a weight-based dose from this entry. UK SPC §4.2 gives a fixed dose within a weight band: paediatric patients aged 8 to less than 18 years weighing 50 kg or more, as monotherapy or in combination with other PAH therapies, take an initial once-daily dose of 5 mg with subsequent once-daily titration to 10 mg dependent on clinical response and tolerability. 'The safety and efficacy of ambrisentan in children below 8 years of age have not been established. No clinical data are available.' No regimen is given in this SPC for paediatric patients weighing less than 50 kg. Verify any under-18 use against a children's formulary.