Posology : מינונים

4.2 Posology and method of administration

Treatment with Lojuxta should be initiated and monitored by a physician experienced in the treatment of lipid disorders.

Posology

The recommended starting dose is 5 mg once daily. After 2 weeks the dose may be increased, according to LDL-C response and based on acceptable safety and tolerability, to 10 mg and then, at a minimum of 4-week intervals, to 20 mg, 40 mg, and to the maximum recommended dose of 60 mg (see section 4.4).

The dose should be escalated gradually to minimise the incidence and severity of gastrointestinal adverse reactions and aminotransferase elevations.

The occurrence and severity of gastrointestinal adverse reactions associated with the use of Lojuxta decreases in the presence of a low fat diet. Patients should follow a diet supplying less than 20% of energy from fat prior to initiating treatment, and should continue this diet during treatment. Dietary counselling should be provided.

Patients should avoid consumption of grapefruit juice and alcohol (see sections 4.4 and 4.5).

For patients on a stable maintenance dose of Lojuxta who receive atorvastatin either: • Separate the dose of the medicinal products by 12 hours
OR
• Decrease the dose of Lojuxta by half.

Patients on 5 mg should remain on 5 mg.
Careful titration may then be considered according to LDL-C response and safety/tolerability.
Upon discontinuation of atorvastatin the dose of Lojuxta should be up-titrated according to LDL-C response and safety/tolerability.

For patients on a stable maintenance dose of Lojuxta who receive any other weak cytochrome P450 (CYP) 3A4 inhibitor, separate the dose of the medicinal products (Lojuxta and the weak CYP3A4 inhibitor) by 12 hours.

Exercise additional caution if administering more than 1 weak CYP3A4 inhibitor with Lojuxta.
Consider limiting the maximum dose of Lojuxta according to desired LDL-C response.

Based on observations of decreased essential fatty acid and vitamin E levels in clinical studies, patients should take daily dietary supplements that provide 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) per day, throughout treatment with Lojuxta (see section 4.4).

Special populations

Elderly population
There is limited experience with lomitapide in patients aged 65 years or older. Therefore, particular caution should be exercised in these patients.

Since the recommended dose regimen involves starting at the low end of the dosing range and escalating cautiously according to individual patient tolerability, no adjustment to the dosing regimen is recommended for the elderly.

Hepatic impairment
Lomitapide is contraindicated in patients with moderate or severe hepatic impairment including patients with unexplained persistent abnormal liver function tests (see sections 4.3 and 5.2).
Patients with mild hepatic impairment (Child-Pugh A) should not exceed 40 mg daily.
Renal impairment
Patients with end-stage renal disease receiving dialysis should not exceed 40 mg daily (see section 5.2).

Paediatric population
The safety and efficacy of lomitapide in children <18 years have not been established and the use of this medicinal product in children is therefore not recommended. No data are available.

Method of administration

Oral use.
Administration with food may increase exposure to lomitapide. It should be taken on an empty stomach, at least 2 hours after the evening meal because the fat content of a recent meal may adversely impact gastrointestinal tolerability (see section 4.4).