Lomitapide

eMC source: Lojuxta 10 mg hard capsules (homozygous familial hypercholesterolaemia). Treatment should be initiated and monitored by a physician experienced in the treatment of lipid disorders. The dose should be escalated gradually to minimise the incidence and severity of gastrointestinal adverse reactions and aminotransferase elevations. Administration with food may increase exposure, and the fat content of a recent meal may adversely affect gastrointestinal tolerability; patients should follow a diet supplying less than 20% of energy from fat before and during treatment, with dietary counselling, and should avoid grapefruit juice. Based on decreased essential fatty acid and vitamin E levels in clinical studies, patients should take daily dietary supplements providing 400 IU vitamin E and approximately 200 mg linoleic acid, 110 mg eicosapentaenoic acid (EPA), 210 mg alpha-linolenic acid (ALA) and 80 mg docosahexaenoic acid (DHA) throughout treatment. For patients on a stable maintenance dose who receive atorvastatin, either separate the two medicinal products by 12 hours or decrease the lomitapide dose by half (patients on 5 mg remain on 5 mg), with careful re-titration afterwards according to LDL-C response and tolerability; on discontinuation of atorvastatin, up-titrate again. For any other weak CYP3A4 inhibitor, separate the doses by 12 hours and consider limiting the maximum lomitapide dose. Liver monitoring: measure ALT, AST, alkaline phosphatase, total bilirubin, gamma-GT and serum albumin before initiation; during the first year measure liver-related tests (at minimum ALT and AST) before each dose increase or monthly, whichever occurs first, then at least every 3 months and before any dose increase. Reduce the dose if aminotransferase elevations are observed and discontinue for persistent or clinically significant elevations (ALT or AST >=3x and <5x ULN: confirm within one week, then reduce the dose, add further liver tests and repeat weekly; withhold dosing if there are signs of abnormal liver function, if levels rise above 5x ULN, or if they do not fall below 3x ULN within approximately 4 weeks). Hepatic impairment: contraindicated in moderate or severe impairment; patients with mild impairment (Child-Pugh A) should not exceed 40 mg daily. Elderly: there is limited experience in patients aged 65 or older and particular caution should be exercised, but no adjustment to the dosing regimen is recommended since the regimen already starts at the low end and escalates cautiously. Paediatric population: safety and efficacy in children under 18 years have not been established and use is not recommended; no data are available.