Lomitapide oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of lomitapide.
Drugs List
Therapeutic Indications
Uses
Homozygous familial hypercholesterolaemia: Adjunct to diet
Lomitapide 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).
Dosage
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.
Adults
Initial dose: 5mg once daily. After 2 weeks the dose may be increased, based on acceptable safety and tolerability, to 10mg and then, at a minimum of 4 week intervals, to 20mg, 40mg, and to the maximum recommended dose of 60mg once daily.
The dose should be escalated gradually to minimise the incidence and severity of gastrointestinal side effects and aminotransferase elevations.
Patients with Renal Impairment
Patients with end stage renal disease receiving dialysis should not exceed 40mg daily.
Patients with Hepatic Impairment
Patients with mild hepatic impairment (Child-Pugh A) should not exceed 40mg daily.
Additional Dosage Information
Lomitapide 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 lomitapide treatment. A low-fat diet should continue during treatment. Dietary counselling should be provided.
The manufacturer states that concurrent use with a moderate or strong CYP3A4 inhibitor is contraindicated. Patients receiving any other weak CYP3A4 inhibitor and a stable maintenance dose of lomitapide should space the dose of the medications by 12 hours.
For patients on a stable dose of lomitapide who receive atorvastatin either:
Separate the dose of the medications by 12 hours.
or
Decrease the dose of lomitapide by half.
Patients on 5mg should remain on 5mg.
Careful titration may then be considered according to LDL-C response and safety/tolerability.
Dose adjustment and monitoring for patients with elevated aminotransferases
ALT or AST of 3 to less than 5 times ULN
Confirm elevation with a repeat measurement within one week.
If confirmed, reduce the dose and obtain additional liver-related tests if not already measured.
Repeat tests weekly and withhold dosing if there are signs of abnormal liver function, if aminotransferase levels rise above 5x ULN, or if aminotransferase levels do not fall below 3x ULN within approximately 4 weeks. Refer patients with persistent elevations in aminotransferase greater than 3x ULN to a hepatologist for further investigation.
If resuming lomitapide after aminotransferase levels resolve to less than less than 3x ULN, consider reducing the dose and monitor liver-related tests more frequently.
ALT or AST of 5 or more times ULN
Withhold dosing and obtain additional liver-related tests if not already measured. If aminotransferase levels do not fall below 3x ULN within approximately 4 weeks refer the patient to a hepatologist for further investigation.
If resuming lomitapide after aminotransferase levels resolve to less than 3x ULN, reduce the dose and monitor liver-related tests more frequently.
Clinical symptoms of hepatic injury
If aminotransferase elevations are accompanied by clinical symptoms of liver injury, increases in bilirubin greater than 2x ULN, or active liver disease, discontinue treatment with lomitapide and refer the patient to a hepatologist for further investigation.
Reintroduction of treatment may be considered if the benefits outweigh the risks associated with potential liver disease.
Contraindications
Children under 18 years
Elevated serum transaminases - greater than 5 times upper limit of normal
Abnormal liver function test
Breastfeeding
Chronic inflammatory bowel disease
Galactosaemia
Moderate hepatic impairment
Pregnancy
Severe inflammatory bowel disease
Precautions and Warnings
Females of childbearing potential
Patients over 65 years
Glucose-galactose malabsorption syndrome
Lactose intolerance
Mild hepatic impairment
Severe renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Exclude other causes of hyperlipoproteinaemia
Treatment to be initiated and supervised by a specialist
Contains lactose
Reduce dose if ALT or AST 3-5 x ULN, on repeat test
Exclude pregnancy prior to initiation of treatment
Perform liver function tests before commencing therapy
After 1st year of therapy monitor LFTs 3 monthly or before dose increase
During 1st year of therapy perform LFTs monthly or before dose increase
Monitor for steatohepatitis/fibrosis at baseline and annually
Advise patient of potential risk of dehydration
Advise patient to seek advice at first indications of pregnancy
Discontinue if bilirubin > 2 x ULN and refer to hepatologist
Interrupt treatment if ALT or AST > 5 x ULN
Pregnancy confirmed: Advise patient to discontinue and consult doctor
Discontinue if active liver disease occurs and refer to hepatologist
Careful dose titration may minimise incidence of side effects
Advise patient not to take St John's wort concurrently
Advise patient peppermint oil products may increase plasma level
Advise patient to avoid alcohol during treatment
Advise patient Seville (sour) orange products may increase plasma level
Advise patient that blueberry products may increase plasma level
Advise patient that cranberry products may increase plasma level
Advise patient to avoid grapefruit products
Dietary restrictions should be maintained
Female: Ensure adequate contraception during treatment
Advise patient how to prevent dehydration
Advise patient to take vitamin E and saturated fatty acid supplements
Take once daily at least 2 hours after last meal of the day
Perform liver function tests prior to commencing treatment. If the baseline liver-related tests are abnormal, consider initiating the medicinal product after appropriate investigation by a hepatologist and the baseline abnormalities are explained or resolved.
Screening
Regular screening for steatohepatitis/fibrosis should be performed at baseline and on an annual basis using the following imaging and biomarker evaluations:
Imaging for tissue elasticity (e.g. fibroscan, acoustic radiation force impulse or magnetic resonance elastography).
Gamma-GT and serum albumin to detect possible liver injury.
At least one marker from each of the following categories:
High sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate, CK-18 fragment, NASH test.
Enhanced liver fibrosis (ELF) panel, fibrometer, AST/ALT ratio, Fib-4 score, Fibrotest.
The performance of these tests and their interpretation should involve collaboration between the treating physician and the hepatologist. Patients with results suggesting the presence of steatohepatitis or fibrosis should be considered for liver biopsy.
If a patient has biopsy-proven steatohepatitis or fibrosis, the risk/benefit ratio should be reassessed and treatment stopped if necessary.
Caution should be exercised when lomitapide is used with other medicinal products known to have potential for hepatotoxicity.
Prescribe daily supplements that contain 400 units of vitamin E and at least 200mg linoleic acid, 210mg alpha linolenic acid, 110mg eicosapentaenoic acid, and 80mg docosahexaenoic acid.
Pregnancy and Lactation
Pregnancy
Lomitapide is contraindicated during pregnancy.
The manufacturer contraindicates use of lomitapide during pregnancy. Animal studies have shown developmental toxicity (teratogenicity, embryotoxicity). As there is limited published information regarding use in human pregnancy the risks are unknown.
Lactation
Lomitapide is contraindicated during breastfeeding.
The manufacturer advises that the patient either discontinues lomitapide or discontinues breastfeeding. The presence of lomitapide in human breast milk is unknown and therefore the effects on exposed infants are also unknown.
Side Effects
Abdominal discomfort
Abdominal distension
Abdominal pain
Abnormal INR
Abnormal liver function tests
Aerophagia
Alanine aminotransferase increased
Alopecia
Anaemia
Arthralgia
Aspartate aminotransferase increased
Asthenia
Blistering
Carotene decreased
Chest pain
Chills
Constipation
Decreased appetite
Dehydration
Diarrhoea
Disturbances of appetite
Dizziness
Dry mouth
Dry skin
Dyspepsia
Early satiety
Ecchymosis
Epigastric discomfort
Eructation
Erythematous rash
Eye swelling
Faecal urgency
Fatigue
Flatulence
Gait abnormality
Gamma glutamyl transferase (GGT) increased
Gastric dilatation
Gastric disorders
Gastritis
Gastro-enteritis
Gastro-intestinal haemorrhage
Gastro-intestinal infection
Gastroesophageal reflux disease
Haematemesis
Haematuria
Haemorrhoidal haemorrhage
Hard faeces
Headache
Hepatic steatosis
Hepatomegaly
Hepatotoxicity
Hyperhidrosis
Increase in alkaline phosphatase
Increase in serum transaminases
Increased bowel action
Influenza
Joint swelling
Malaise
Migraine
Muscle spasm
Muscle twitch
Myalgia
Nasopharyngitis
Nausea
Neutrophil percentage increased
Painful extremities
Papules
Paraesthesia
Pharyngeal lesion
Proteinuria
Prothrombin time increased
Pulmonary function test abnormal
Pyrexia
Reduced neutrophil count
Reduced plasma potassium levels
Regurgitation
Serum bilirubin increased
Sinusitis
Somnolence
Tenesmus
Upper-airway cough syndrome
Vertigo
Vitamin E decreased
Vitamin K decreased
Vomiting
Weight loss
White blood cell count decreased
White blood cell count raised
Xanthoma
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: May 2019.
Reference Sources
Summary of Product Characteristics: Lojuxta hard capsules. Aegerion Pharmaceuticals Ltd. Revised August 2019.
The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 May 2019.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Lomitapide Last revised: 03 December 2018
Last accessed: 22 May 2019.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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