At the 2015 ESC congress in London UK, Aegerion Pharmaceuticals organized a satellite symposium in which three expert witnesses were cross examined on their views on the prevalence, presentation and treatment homozygous familial hypercholesterolaemia (HoFH) as a precursor to premature myocardial infarction (MI).
The symposium contains a discussion of current treatment options for HoFH, including Lojuxta® (lomitapide) capsules. Click here to view the Aegerion ESC symposium summary video.
PRESCRIBING INFORMATION
Lojuxta® (lomitapide) hard capsules
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See below for how to report adverse reactions.
Before prescribing Lojuxta, please refer to the full Summary of Product Characteristics (SPC)[i].
Presentations: Hard capsules containing 5 mg, 10 mg or 20 mg lomitapide (as lomitapide mesylate).
Indication: Lojuxta is indicated as an adjunct to a low‑fat diet and other lipid‑lowering medicinal products with or without low density lipoprotein (LDL) apheresis in adult patients with homozygous familial hypercholesterolaemia (HoFH). Genetic confirmation of HoFH should be obtained whenever possible. Other forms of primary hyperlipoproteinaemia and secondary causes of hypercholesterolaemia (e.g., nephrotic syndrome, hypothyroidism) must be excluded.
Dosage and Administration: Treatment should be administered and monitored by a physician experienced in the treatment of lipid disorders. The recommended starting dose is 5 mg once daily to be taken orally. After 2 weeks the dose may be increased, 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. The dose should be escalated gradually to minimise the incidence and severity of gastrointestinal side effects and aminotransferase elevations. Lojuxta 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. Patients should follow a diet supplying less than 20% of energy from fat prior to initiating Lojuxta treatment, and should continue this diet during treatment. Dietary counselling should be provided. 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. Dose modifications: Prescribers should consult the SPC for full details of dose adjustments for patients with hepatic impairment, renal impairment or receiving weak CYP3A4 inhibitors. When administered with atorvastatin, the dose of Lojuxta should either be taken 12 hours apart or be decreased by half. Careful titration may then be considered according to LDL‑C response and safety/tolerability. The dose of Lojuxta should be taken 12 hours apart from any other weak CYP3A4 inhibitor. The safety and efficacy of use in children (<18 years) has not been established and therefore the use of Lojuxta in children is not recommended. Contraindications: Hypersensitivity to lomitapide or to any of the excipients. Patients with the following conditions: moderate to severe hepatic impairment; unexplained persistent abnormal liver function tests; and significant or chronic bowel disease. Concomitant administration of >40 mg simvastatin or strong or moderate CYP3A4 inhibitors. Pregnancy.
Warnings and precautions: Liver enzyme abnormalities – Lomitapide can cause elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and hepatic steatosis. There is a concern that lomitapide could induce steatohepatitis. Liver function tests should be monitored closely before initiating treatment with Lojuxta. If baseline liver tests are abnormal, consider initiating treatment of Lojuxta after appropriate investigation by a hepatologist. In the first year, liver-related tests should be measured before each increase in dose or monthly, whichever occurs first. After the first year, tests should be performed at least every three months and before any increase in dose. Refer to the SPC for full details of dose modifications in the event of elevated hepatic aminotransferases. Hepatic Steatosis – Consistent with the mechanism of action of lomitapide, most treated patients exhibited increases in hepatic fat content. Regular screening for steatohepatitis/fibrosis should be performed at baseline and on an annual basis. The performance and interpretation of these tests should involve collaboration with a hepatologist. If results of these tests suggest the presence of steatohepatitis or fibrosis, a liver biopsy should be considered and if the condition is proven, the benefit‑risk should be reassessed and treatment stopped if necessary. Use of alcohol – Alcohol is not recommended during Lojuxta treatment. Lactose – Lojuxta contains lactose, so should not be given to patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption. Effects on ability to drive and use machines – Adverse reactions such as dizziness and fatigue have been associated with Lojuxta.
Interactions: Prescribers should consult the SPC for full details of interactions. Weak CYP3A4 inhibitors are expected to increase the exposure of lomitapide (See Dosage and administration).
Co-administration of a CYP3A4 inducer is expected to reduce the effect of Lojuxta and the use of St. John’s Wort should be avoided with Lojuxta. Lomitapide increases plasma concentrations of HMG-CoA reductase inhibitors (‘statins’). Patients using statins in addition to Lojuxta should be advised of the potential increased risk of myopathy and told to report any unexplained muscle pain, tenderness or weakness. In rare cases, myopathy may take the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and can lead to fatality. Lomitapide increases the plasma concentrations of warfarin. Patients taking warfarin should undergo regular monitoring of the INR, and the dose of warfarin should be adjusted as clinically indicated.
Caution should be exercised when Lojuxta is used with other medicinal products known to have potential for hepatotoxicity, such as isotretinoin, amiodarone, acetaminophen (paracetamol) (>4g/day for ≥3days/week), methotrexate, tetracyclines and tamoxifen. Bile acid sequestrants can interfere with the absorption of oral medicines and should be taken at least 4 hours before or after Lojuxta. Coadministration of Lojuxta with P‑gp substrates may increase the absorption of P‑gp substrates. Patients should avoid grapefruit juice.
Pregnancy and Breastfeeding: The absence of pregnancy should be confirmed before initiating treatment in women of childbearing age and effective contraception should be initiated. Patients taking oestrogen‑based oral contraceptives should be advised about possible loss of effectiveness due to diarrhoea and/or vomiting. Additional contraceptive measures should be used for 7 days after resolution of symptoms. Oestrogen‑containing oral contraceptives are weak CYP3A4 inhibitors (see Interactions above). There are no reliable data on the use of Lojuxta in pregnant women. Animal studies have shown reproductive toxicity. It is not known whether lomitapide is excreted into human milk. A decision should be made whether to discontinue breast-feeding or discontinue Lojuxta, taking into account the importance of treatment with Lojuxta to the mother.
Undesirable effects: Prescribers should consult the SPC for full details of adverse reaction (ADRs). The most serious ADRs during treatment were liver aminotransferase abnormalities, as described herein. The most common ADRs were gastrointestinal effects including diarrhoea, nausea, dyspepsia and vomiting. Gastrointestinal ADRs occurred more frequently during the dose escalation phase of the study and decreased once patients established the maximum tolerated dose of lomitapide. Adverse reactions reported in the HoFH clinical trials: Very common serious ADRs (≥1/10) – increased ALT or AST, weight decrease, decreased appetite, diarrhoea, nausea, vomiting, abdominal discomfort, abdominal pain, abdominal distension, dyspepsia, flatulence and constipation. Common serious ADRs (>1/100) – hepatic steatosis, hepatoxicity, hepatomegaly. Common ADRs (≥1/100 to <1/10) include gastroenteritis, dizziness, headache, migraine, dyspepsia, gastritis, rectal tenesmus, aerophagia, defaecation urgency, eructation, frequent bowel movements, gastric dilatation, gastric disorder, gastroesophageal reflux disease, haemorrhoidal haemorrhage, regurgitation, hepatic steatosis, ecchymosis, papule, rash erythematous, xanthoma, fatigue, INR increase or abnormal, blood alkaline phosphatase increase, blood potassium decrease, carotene decrease, liver function test abnormal, transaminase increase, prothrombin time prolonged, Vitamin E decrease and Vitamin K decrease.
Legal category: POM.
Package quantities: High density polyethylene (HDPE) bottles with polypropylene screw cap containing 28 capsules.
Cost: NHS list prices (excluding VAT): Bottle of 28 x 5mg capsules £17,765, Bottle of 28 x 10mg capsules £17,765, Bottle of 28 x 20mg capsules £17,765.
Marketing Authorisation Numbers: EU/1/13/851/001, EU/1/13/851/002, EU/1/13/851/003
Marketing Authorisation Holder: Aegerion Pharmaceuticals Limited, Lakeside House, 1 Furzeground Way, Stockley Park East, Uxbridge, UB11 1BD. Tel 00800 234 37466. Email [email protected].
Date of preparation/date last revised: April 2015.
Adverse events should be reported. Reporting forms and information can be found at:
UK: www.mhra.gov.uk/yellowcard.
Ireland: HPRA Pharmacovigilance, Earlsfort Terrace, Dublin 2
www.hpra.ie e-mail: [email protected]
tel: 01 6764971, Fax: 01 6762517
Adverse events should also be reported to Aegerion by email to [email protected] or by telephoning the freephone number 00800 234 37466.
[i] Lojuxta® (lomitapide) hard capsules Summary of Product Characteristics. Available from http://www.medicines.org.uk/emc.
