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Lojuxta is a brand name for Lomitapide. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 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…
Verbatim from this product's EMA label. Tap a section to expand.
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. 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. 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. 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.
2). Patients with mild hepatic impairment (Child-Pugh A) should not exceed 40 mg daily. 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. 4).
4). The most common adverse reactions were gastrointestinal effects. Gastrointestinal adverse reactions were reported by 27 (93%) of 29 patients in the Phase 3 clinical study. Diarrhoea occurred in 79% of patients, nausea in 65%, dyspepsia in 38%, and vomiting in 34%.
Other reactions reported by at least 20% of patients include abdominal pain, abdominal discomfort, abdominal distension, constipation, and flatulence. Gastrointestinal adverse reactions occurred more frequently during the dose escalation phase of the study and decreased once patients established the maximum tolerated dose of lomitapide.
Gastrointestinal adverse reactions of severe intensity were reported by 6 (21%) of 29 patients in the Phase 3 clinical study, with the most common being diarrhoea (4 patients, 14%); vomiting (3 patients, 10%); and abdominal pain, distension, and/or discomfort (2 patients, 7%).
Gastrointestinal reactions contributed to the reasons for early discontinuation from the study for 4 (14%) patients. The most commonly reported adverse reactions of severe intensity were diarrhoea (4 subjects, 14%), vomiting (3 patients, 10%), and abdominal distension and ALT increased (2 subjects each, 7%).
13 Tabulated list of adverse reactions The adverse reactions are listed below by SOC (System Organ Class) and by frequency, most frequent reactions first. Frequency of the adverse reactions is defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
Table 3 lists all adverse reactions reported across the 35 patients treated in the Phase 2 Study UP1001 and in the Phase 3 Study UP1002/AEGR-733-005 or its extension study AEGR-733-012.
Table 3:
1). There have been no concomitant or subsequent clinically meaningful elevations in serum bilirubin, International Normalised Ratio (INR), or alkaline phosphatase. The extent to which lomitapide-associated hepatic steatosis promotes the elevations in aminotransferase is unknown.
The liver enzyme changes can occur at any time during therapy, but occur most often during dose escalation. Although cases of hepatic dysfunction (elevated aminotransferase with increase in bilirubin or INR) or hepatic failure have not been reported, there is concern that lomitapide could induce steatohepatitis, which can progress to cirrhosis over several years.
The clinical studies supporting the safety and efficacy of lomitapide in HoFH would have been unlikely to detect this adverse outcome given their size and duration. Monitoring of liver function tests Measure ALT, AST, alkaline phosphatase, total bilirubin, gamma-glutamyl transferase (gamma-GT) and serum albumin before initiation of treatment with Lojuxta.
The medicinal product is contraindicated in patients with moderate or severe hepatic impairment and those with unexplained persistent abnormal liver function tests. 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.
6 During the first year, measure liver-related tests (ALT and AST, at a minimum) prior to each increase in dose or monthly, whichever occurs first. After the first year, do these tests at least every 3 months and before any increase in dose.
Decrease the dose of Lojuxta if elevations of aminotransferase are observed and discontinue treatment for persistent or clinically significant elevations (see Table 1). Dose modification based on elevated hepatic aminotransferases Table 1 summarises recommendations for dose adjustment and monitoring for patients who develop elevated aminotransferase during therapy with Lojuxta.
1. 2). • Patients with a known significant or chronic bowel disease such as inflammatory bowel disease or malabsorption. 5). 5]). 6).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Frequency of adverse reactions in HoFH patients System Organ Class Frequency Adverse reaction Infections and infestations Common Gastroenteritis Metabolism and nutrition disorders Very common Decreased appetite Not known Dehydration Nervous system disorders Common Dizziness Headache Migraine Gastrointestinal disorders Very common Diarrhoea Nausea Vomiting Abdominal discomfort Dyspepsia Abdominal pain Abdominal pain upper Flatulence Abdominal distension Constipation Common Gastritis Rectal tenesmus Aerophagia Defaecation urgency Eructation Frequent bowel movements Gastric dilatation Gastric disorder Gastro-oesophageal reflux disease Haemorrhoidal haemorrhage Regurgitation Hepatobiliary disorders Common Hepatic steatosis Hepatotoxicity Hepatomegaly Skin and subcutaneous tissue disorders Common Ecchymosis Papule Rash erythematous Xanthoma Not known Alopecia Musculoskeletal and connective tissue disorders Not known Myalgia General disorders and administration site conditions Common Fatigue 14 System Organ Class Frequency Adverse reaction Investigations Very common Alanine aminotransferase increased Aspartate aminotransferase increased Weight decreased Common International normalised ratio increased Blood alkaline phosphatase increased Blood potassium decreased Carotene decreased International normalised ratio abnormal Liver function test abnormal Prothrombin time prolonged Transaminases increased Vitamin E decreased Vitamin K decreased Table 4 lists all adverse reactions for subjects who received lomitapide monotherapy (N = 291) treated in Phase 2 studies in subjects with elevated LDL-C (N = 462).
Table 4:
Frequency of adverse reactions in elevated LDL-C patients System Organ Class Frequency Adverse reaction Infections and infestations Uncommon Gastroenteritis Gastrointestinal infection Influenza Nasopharyngitis Sinusitis Blood and lymphatic system disorders Uncommon Anaemia Metabolism and nutrition disorders Common Decreased appetite Uncommon Dehydration Increased appetite Nervous system disorders Uncommon Paraesthesia Somnolence Eye disorders Uncommon Eye swelling Ear and labyrinth disorders Uncommon Vertigo Respiratory, thoracic and mediastinal disorders Uncommon Pharyngeal lesion Upper-airway cough syndrome 15 System Organ Class Frequency Adverse reaction Gastrointestinal disorders Very common Diarrhoea Nausea Flatulence Common Abdominal pain upper Abdominal distension Abdominal pain Vomiting Abdominal discomfort Dyspepsia Eructation Abdominal pain lower Frequent bowel movements Uncommon Dry mouth Faeces hard Gastro-oeosophageal reflux disease Abdominal tenderness Epigastric discomfort Gastric dilatation Haematemesis Lower gastrointestinal haemorrhage Reflux oesophagitis Hepatobiliary disorders Uncommon Hepatomegaly Skin and subcutaneous tissue disorders Uncommon Blister Dry skin Hyperhidrosis Musculoskeletal and connective tissue disorders Common Muscle spasms Uncommon Arthralgia Myalgia Pain in extremity Joint swelling Muscle twitching Renal and urinary disorders Uncommon Haematuria General disorders and administrative site conditions Common Fatigue Asthenia Uncommon Chest pain Chills Early satiety Gait disturbance Malaise Pyrexia Investigations Common Alanine aminotransferase increased Aspartate aminotransferase increased Hepatic enzyme increased Liver function test abnormal Neutrophil count decreased White blood cell count decreased Uncommon Weight decreased Blood bilirubin increased Gamma-glutamyltransferase increased Neutrophil percentage increased Protein urine Prothrombin time prolonged Pulmonary function test abnormal White blood cell count increased 16 Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Table 1:
Dose adjustment and monitoring for patients with elevated aminotransferases ALT or AST Treatment and monitoring recommendations* ≥ 3x and < 5x Upper Limit of Normal (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 (such as alkaline phosphatase, total bilirubin, and INR). • Repeat tests weekly and withhold dosing if there are signs of abnormal liver function (increase in bilirubin or INR), if aminotransferase levels rise above 5 x ULN, or if aminotransferase levels do not fall below 3x ULN within approximately 4 weeks.
Refer patients with persistent elevations in aminotransferase > 3x ULN to a hepatologist for further investigation. • If resuming Lojuxta after aminotransferase levels resolve to < 3x ULN, consider reducing the dose and monitor liver-related tests more frequently.
≥5x ULN • Withhold dosing and obtain additional liver-related tests if not already measured (such as alkaline phosphatase, total bilirubin, and INR). If aminotransferase levels do not fall below 3x ULN within approximately 4 weeks refer the patient to a hepatologist for further investigation.
• If resuming Lojuxta after aminotransferase levels resolve to < 3x ULN, reduce the dose and monitor liver-related tests more frequently. *Recommendations based on an ULN of approximately 30-40 international units/L. If aminotransferase elevations are accompanied by clinical symptoms of liver injury (such as nausea, vomiting, abdominal pain, fever, jaundice, lethargy, flu-like symptoms), increases in bilirubin ≥ 2x ULN, or active liver disease, discontinue treatment with Lojuxta and refer the patient to a hepatologist for further investigation.
Reintroduction of treatment may be considered if the benefits are considered to outweigh the risks associated with potential liver disease. Hepatic steatosis and risk of progressive liver disease Consistent with the mechanism of action of lomitapide, most treated patients exhibited increases in hepatic fat content.
1). The median absolute increase in hepatic fat was 6% after both 26 weeks and 78 weeks of treatment, from 1% at baseline, measured by MRS. Hepatic steatosis is a risk factor for progressive liver disease including steatohepatitis and cirrhosis.
The long term consequences of hepatic steatosis associated with lomitapide treatment are unknown. Clinical data suggest that hepatic fat accumulation is reversible after stopping treatment with Lojuxta, but whether histological sequelae remain is unknown, especially after long-term use.
7 Monitoring for evidence of progressive liver disease. g. Fibroscan, acoustic radiation force impulse (ARFI), or magnetic resonance (MR) 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 (ESR), CK-18 Fragment, NashTest (liver inflammation) • Enhanced Liver Fibrosis (ELF) panel, Fibrometer, AST/ALT ratio, Fib-4 score, Fibrotest (liver fibrosis) 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 […]