VOLIBRIS FILM-COATED TABLET 10 MG

TABLET, FILM COATED

**4\. POSOLOGY AND METHOD OF ADMINISTRATION** **4.1. General** Ambrisentan is for oral use and can be administered with or without food. Treatment should only be initiated by a physician experienced in the treatment of PAH. **4.2. Recommended adult dosage** Ambrisentan treatment should be initiated at a dose of 5 mg once daily and may be increased to 10 mg once daily depending upon clinical response and tolerability. When used in combination with tadalafil, the ambrisentan starting dose of 5 mg should be titrated to 10 mg once daily, as tolerated (see _section 12.1.2.2_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Limited data suggest that the abrupt discontinuation of ambrisentan is not associated with rebound worsening of PAH. **4.3. Use with cyclosporine A** 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 _Interactions with Other Medicinal Products and Other Forms of Interaction; Pharmacokinetic Properties, Metabolism_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). **4.4. Recommended pediatric and adolescent dosage** Safety and efficacy of ambrisentan have not been established in patients under 18 years of age; therefore, the use of ambrisentan in these patients is not recommended (see _Non-clinical Information_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). **4.5. Dosage instructions in special populations** **4.5.1. Elderly** No dose adjustment is required in patients aged 65 years and over (see _Pharmacokinetics in Special Populations_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). **4.5.2. Renal Impairment** No dose adjustment is required in patients with renal impairment (see _Pharmacokinetics_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). There is limited experience of VOLIBRIS in individuals with severe renal impairment (creatinine clearance <30 mL/min); initiate treatment cautiously in this subgroup and take particular care if the dose is increased to 10 mg. **4.5.3. Hepatic Impairment** VOLIBRIS has not been studied in individuals with severe hepatic impairment or with clinically significant elevated hepatic transaminases. Since the main routes of metabolism of ambrisentan are glucuronidation and oxidation with subsequent elimination in the bile, hepatic impairment would be expected to increase exposure (Cmax and AUC) of ambrisentan. Therefore, VOLIBRIS is not recommended in patients with moderate impairment, is contraindicated in patients with severe hepatic impairment (with or without cirrhosis) or with clinically significant elevated hepatic transaminases (see _Contraindications, Special Warnings and Special Precautions for Use_ and _Pharmacokinetics_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Use caution when administering VOLIBRIS in patients with mild pre-existing impaired liver function who may require reduced doses of VOLIBRIS (see _Special Warnings and Special Precautions for Use_ and _Pharmacokinetics in Special Populations_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). **4.6. Method of Administration** 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.