Lojuxta (Lomitapide)
MTP Inhibitor for Homozygous Familial Hypercholesterolemia
Quick Facts About Lojuxta
Key Takeaways About Lojuxta
- Lojuxta (lomitapide) is specifically approved for homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder causing extremely high cholesterol from birth.
- It works by blocking microsomal triglyceride transfer protein (MTP), reducing the liver's production of LDL cholesterol-containing particles.
- Regular liver function monitoring is mandatory because lomitapide can cause hepatotoxicity and hepatic steatosis (fatty liver).
- Numerous serious drug interactions exist, particularly with strong CYP3A4 inhibitors such as azole antifungals, macrolide antibiotics, and HIV protease inhibitors.
- Lojuxta must not be used during pregnancy and requires strict adherence to a low-fat diet (less than 20% of energy from fat) to minimize gastrointestinal side effects.
What Is Lojuxta and What Is It Used For?
Lojuxta contains the active substance lomitapide, a lipid-regulating agent that belongs to a unique pharmacological class known as microsomal triglyceride transfer protein (MTP) inhibitors. MTP is an intracellular enzyme found in the endoplasmic reticulum of hepatocytes (liver cells) and enterocytes (intestinal cells). It plays a critical role in assembling very-low-density lipoproteins (VLDL) in the liver and chylomicrons in the intestine. By inhibiting MTP, lomitapide prevents the assembly and secretion of these apolipoprotein B-containing lipoproteins into the bloodstream, thereby reducing circulating levels of harmful lipids.
Lomitapide is specifically indicated for the treatment of adult patients with homozygous familial hypercholesterolemia (HoFH), an extremely rare autosomal codominant genetic disorder affecting approximately 1 in 160,000 to 1 in 1,000,000 individuals worldwide. Patients with HoFH inherit defective genes from both parents, resulting in severely impaired LDL receptor function and extraordinarily high levels of LDL cholesterol from birth. Without treatment, LDL cholesterol levels often exceed 13 mmol/L (500 mg/dL), leading to accelerated atherosclerosis, premature coronary heart disease, aortic stenosis, and cardiovascular death in early adulthood.
Traditional lipid-lowering therapies such as statins, ezetimibe, and PCSK9 inhibitors frequently provide inadequate cholesterol reduction in HoFH patients because these treatments rely at least partially on functional LDL receptors. Lojuxta offers an LDL receptor-independent mechanism of action, making it effective even in patients with minimal or absent receptor activity. In the pivotal clinical trial, lomitapide reduced LDL cholesterol by approximately 50% when added to existing maximally tolerated lipid-lowering therapy, including LDL apheresis where available.
Lojuxta can lower blood levels of:
- LDL cholesterol ("bad" cholesterol) – the primary driver of atherosclerotic cardiovascular disease
- Total cholesterol – the sum of all cholesterol fractions in the blood
- Apolipoprotein B (ApoB) – the structural protein of atherogenic lipoproteins
- Triglycerides – fats carried in the blood that contribute to cardiovascular risk
It is important to understand that Lojuxta is not a first-line treatment for common high cholesterol. It is reserved exclusively for HoFH and must be prescribed and supervised by a physician experienced in the management of lipid disorders. The drug was approved by the European Medicines Agency (EMA) under "exceptional circumstances" due to the extreme rarity of HoFH, meaning that comprehensive data are limited and are reviewed annually.
What Should You Know Before Taking Lojuxta?
Contraindications
Lojuxta must not be taken in the following circumstances, as doing so could cause serious or life-threatening harm:
- You are allergic to lomitapide or any of the other ingredients (pregelatinised starch, sodium starch glycolate, microcrystalline cellulose, lactose monohydrate, colloidal anhydrous silica, magnesium stearate)
- You have liver problems or unexplained abnormal liver function tests (elevated transaminases)
- You have significant or chronic bowel disease, or cannot absorb food from the gut properly (chronic malabsorption syndromes)
- You are taking more than 40 mg simvastatin daily
- You are taking any strong CYP3A4 inhibitors (see Drug Interactions section)
- You are pregnant, trying to become pregnant, or think you may be pregnant
The contraindication with strong CYP3A4 inhibitors is particularly important because these drugs dramatically increase lomitapide blood levels, amplifying the risk of serious adverse effects including severe hepatotoxicity. Strong CYP3A4 inhibitors that are absolutely contraindicated with Lojuxta include:
- Azole antifungals: itraconazole, ketoconazole, fluconazole, voriconazole, posaconazole
- Macrolide antibiotics: telithromycin, clarithromycin, erythromycin
- HIV protease inhibitors: indinavir, nelfinavir, saquinavir, ritonavir
- Calcium channel blockers/antiarrhythmics: diltiazem, verapamil, dronedarone
Warnings and Precautions
Speak to your doctor or pharmacist before taking Lojuxta if you have a history of liver problems, including liver problems while taking other medications. Lomitapide capsules can cause side effects that may also be symptoms of liver damage. These are listed in the side effects section, and you must immediately tell your doctor if you experience any signs or symptoms of liver injury, as they may be caused by hepatic damage.
Your doctor will perform blood tests to check your liver function before starting Lojuxta, whenever the dose is increased, and regularly throughout treatment (at minimum every 3 months during the first year, then at least twice yearly thereafter). These tests help your doctor adjust your dose appropriately. If blood tests reveal liver abnormalities, your doctor may reduce the dose or discontinue treatment.
Lomitapide is known to cause hepatic steatosis (fatty liver), which is an expected pharmacological effect of MTP inhibition. The clinical significance of long-term hepatic fat accumulation is not fully understood, but it may progress to steatohepatitis, fibrosis, or cirrhosis in some patients. For this reason, long-term hepatic monitoring beyond standard liver function tests may be considered by your treating physician.
You may experience fluid loss and dehydration due to gastrointestinal side effects such as vomiting, nausea, and diarrhea. It is important to prevent dehydration by drinking sufficient fluids. Severe or persistent gastrointestinal symptoms should prompt medical evaluation, as dehydration can lead to serious complications.
Children and adolescents: No studies have been conducted in children and adolescents under 18 years of age. The use of Lojuxta in this population is therefore not recommended.
Pregnancy and Breastfeeding
Do not take Lojuxta if you are pregnant, planning to become pregnant, or think you may be pregnant, as lomitapide may cause harm to the unborn baby. Before starting treatment, you must confirm that you are not pregnant and that you are using effective contraception as advised by your doctor. If you become pregnant while taking Lojuxta, stop taking the capsules immediately and contact your doctor.
If you use oral contraceptives (birth control pills) and experience diarrhea and/or vomiting lasting more than 2 days, you must use an additional barrier method of contraception (such as condoms or a diaphragm) for 7 days after symptoms resolve, as the effectiveness of oral contraceptives may be reduced by gastrointestinal disturbance.
It is not known whether lomitapide passes into breast milk. If you are breastfeeding or planning to breastfeed, discuss with your doctor whether you should stop taking Lojuxta or discontinue breastfeeding.
Driving and using machines: Your treatment may affect your ability to drive or operate machinery. If you experience dizziness during treatment, do not drive or use machines until you feel better.
Excipients: Lojuxta capsules contain lactose and a small amount of sodium. If you have been told by your doctor that you have an intolerance to certain sugars, speak with your doctor before taking this medicine. The sodium content is less than 1 mmol (23 mg) per capsule, meaning the product is essentially sodium-free.
How Does Lojuxta Interact with Other Drugs?
Drug interactions with lomitapide are extensive and clinically important. Lomitapide is primarily metabolized by cytochrome P450 3A4 (CYP3A4) in the liver, and it also inhibits P-glycoprotein (P-gp). This dual pharmacokinetic profile means that many commonly used medications can either increase lomitapide exposure (increasing toxicity risk) or have their own blood levels altered by lomitapide (changing their efficacy or safety profile).
Always tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take. This includes over-the-counter medicines, herbal remedies, and dietary supplements.
Major Interactions (Contraindicated)
The following drugs must never be taken together with Lojuxta because they dramatically increase lomitapide blood levels through CYP3A4 inhibition:
| Drug Category | Examples | Risk |
|---|---|---|
| Azole antifungals | Itraconazole, ketoconazole, fluconazole, voriconazole, posaconazole | Severely increased lomitapide levels; hepatotoxicity risk |
| Macrolide antibiotics | Telithromycin, clarithromycin, erythromycin | Severely increased lomitapide levels |
| HIV protease inhibitors | Indinavir, nelfinavir, saquinavir, ritonavir | Severely increased lomitapide levels |
| Calcium channel blockers / antiarrhythmics | Diltiazem, verapamil, dronedarone | Significantly increased lomitapide levels |
Moderate Interactions (Dose Adjustment Required)
The following medications may require dose adjustment of Lojuxta or enhanced monitoring when used concurrently. Your doctor will determine the appropriate dose based on the specific combination:
| Drug Category | Examples | Effect |
|---|---|---|
| Cholesterol-lowering agents | Atorvastatin, simvastatin (max 40 mg) | Increased risk of liver damage and myopathy |
| Oral contraceptives | Ethinylestradiol, norgestimate | Reduced contraceptive efficacy possible |
| Glucocorticoids | Beclometasone, prednisolone | May alter lomitapide metabolism |
| Immunosuppressants | Ciclosporin, tacrolimus | Altered metabolism; monitoring required |
| Anticoagulants | Warfarin (coumarins) | Increased warfarin effect; INR monitoring needed |
| Antiepileptics (CYP3A4 inducers) | Phenobarbital, carbamazepine, phenytoin | May reduce lomitapide effectiveness |
| Anti-tuberculosis agents | Rifampicin, isoniazid | May reduce lomitapide levels (CYP3A4 induction) |
| Cancer treatments | Bicalutamide, lapatinib, methotrexate, nilotinib, tamoxifen | Altered metabolism of either drug |
| Herbal remedies | St. John's wort, ginkgo biloba | St. John's wort may reduce lomitapide levels |
Food and Beverage Interactions
- Grapefruit juice: Must be completely avoided as it inhibits CYP3A4 and can dramatically increase lomitapide blood levels
- Alcohol: Not recommended during Lojuxta treatment due to added liver stress
- Peppermint oil and Seville oranges (bitter oranges): Your Lojuxta dose may need adjustment if you consume these
- Low-fat diet: Essential – fat intake should be less than 20% of total energy to minimize gastrointestinal side effects. Consult a dietitian for specific guidance.
If you are also taking a bile acid sequestrant such as colesevelam or cholestyramine, you should take the bile acid sequestrant at least 4 hours before or 4 hours after taking Lojuxta to avoid reduced absorption.
What Is the Correct Dosage of Lojuxta?
Always take Lojuxta exactly as your doctor or pharmacist has instructed. This medicine should only be prescribed by a doctor with specialist experience in treating lipid disorders. Your doctor will monitor you regularly with blood tests and clinical assessments throughout treatment.
Adults
Starting Dose
The recommended starting dose is 5 mg once daily. Your doctor may slowly increase your dose over time according to the following titration schedule, up to a maximum of 60 mg once daily.
| Titration Step | Daily Dose | Minimum Duration Before Next Increase |
|---|---|---|
| Step 1 (Starting dose) | 5 mg | At least 2 weeks |
| Step 2 | 10 mg | At least 4 weeks |
| Step 3 | 20 mg | At least 4 weeks |
| Step 4 | 40 mg | At least 4 weeks |
| Step 5 (Maximum dose) | 60 mg | Maintenance |
Do not change your dose yourself. Your doctor will determine the appropriate dose and duration based on your cholesterol response and liver function test results. Dose increases will only occur if liver enzymes remain within acceptable limits.
Take Lojuxta with a glass of water once daily at bedtime, at least 2 hours after your evening meal. Do not take it with food, as this significantly increases the likelihood and severity of gastrointestinal side effects. Swallow the capsule whole – do not open, crush, or chew.
Required Nutritional Supplements
While taking Lojuxta, you must also take daily nutritional supplements because the drug can reduce absorption of fat-soluble vitamins and essential fatty acids. Your doctor or dietitian will advise you on obtaining these supplements:
| Supplement | Daily Amount |
|---|---|
| Vitamin E | 400 IU |
| Omega-3 EPA | Approximately 110 mg |
| Omega-3 DHA | Approximately 80 mg |
| Omega-3 ALA | Approximately 210 mg |
| Omega-6 (Linoleic acid) | Approximately 200 mg |
Children and Adolescents
Lojuxta has not been studied in patients under 18 years of age. Its use in children and adolescents is not recommended due to insufficient safety and efficacy data.
Elderly Patients
No specific dose adjustment is required for elderly patients. However, as with all patients, dose titration should be guided by tolerability and liver function monitoring. Elderly patients may be more susceptible to gastrointestinal side effects and dehydration.
Missed Dose
If you forget to take a dose, simply take your normal dose at the usual time the next day. Do not take a double dose to make up for a missed dose. Skipping a single dose will not significantly affect your treatment, but try to take the medicine consistently.
Overdose
If you take more Lojuxta than you should, contact your doctor or pharmacist immediately. There is no specific antidote for lomitapide overdose, and treatment would be supportive and symptomatic, focusing on managing gastrointestinal symptoms and monitoring liver function.
If you stop taking Lojuxta, your cholesterol levels will likely rise again. Do not stop treatment without consulting your doctor, even if you feel well, as high cholesterol does not cause noticeable symptoms until serious cardiovascular damage has occurred.
What Are the Side Effects of Lojuxta?
Like all medicines, Lojuxta can cause side effects, although not everybody gets them. Most side effects are related to the gastrointestinal tract and are a consequence of the drug's mechanism of action – by reducing fat absorption and lipoprotein secretion, unabsorbed fat in the intestine causes digestive discomfort. Adhering strictly to a low-fat diet (less than 20% of daily calories from fat) is the single most effective strategy to minimize these symptoms.
Abnormal liver function test results have been commonly reported (up to 1 in 10 patients). Signs and symptoms of liver problems include nausea, vomiting, stomach pain, muscle aches and pains, fever, yellowing of the skin or eyes (jaundice), unusual tiredness, and flu-like symptoms. Tell your doctor immediately if you experience any of these symptoms, as treatment may need to be stopped.
Very Common
May affect more than 1 in 10 people
- Diarrhea
- Nausea and vomiting
- Abdominal pain, discomfort, or bloating
- Decreased appetite
- Indigestion (dyspepsia)
- Flatulence (gas)
- Constipation
- Weight loss
Common
May affect up to 1 in 10 people
- Gastroenteritis (stomach and bowel inflammation)
- Regurgitation (food coming back up)
- Belching (burping)
- Incomplete bowel emptying, urgency to defecate
- Rectal bleeding or blood in stool
- Dizziness, headache, migraine
- Fatigue, lack of energy, general weakness
- Enlarged or damaged liver, fatty liver
- Purple skin discolouration, hard skin lumps, rash, yellow skin lumps
- Altered blood coagulation tests
- Changed blood cell counts
- Lowered levels of potassium, carotene, vitamin E, and vitamin K
- Muscle cramps
Uncommon
May affect up to 1 in 100 people
- Flu or cold, fever, sinusitis, cough
- Low red blood cell count (anaemia)
- Dehydration, dry mouth
- Increased appetite
- Burning or tingling skin sensation
- Swollen eyes
- Sore throat
- Bloody vomit, dry skin, blisters
- Excessive sweating
- Joint pain or swelling, pain in hands or feet
- Muscle pain
- Blood or protein in urine
- Chest pain
- Gait changes
- Abnormal lung function tests
Not Known
Frequency cannot be estimated from available data
- Hair loss (alopecia)
- Muscle pain (myalgia)
- Fluid loss causing headache, dry mouth, dizziness, fatigue, or loss of consciousness (dehydration)
The gastrointestinal side effects tend to be most pronounced during the early phases of treatment and when the dose is increased. Many patients find that symptoms gradually improve over time as the body adjusts. Splitting fat intake evenly throughout the day and avoiding large fatty meals can also help. Your doctor may temporarily reduce your dose if gastrointestinal symptoms become severe.
If you experience unexplained muscle pain, tenderness, or weakness while taking Lojuxta together with a statin (such as simvastatin), contact your doctor immediately. The combination of lomitapide with statins may increase the risk of myopathy (muscle disease) and potentially rhabdomyolysis (severe muscle breakdown).
How Should You Store Lojuxta?
Proper storage of Lojuxta is essential to maintain the medication's effectiveness and safety. Follow these storage guidelines:
- Temperature: Store at or below 30°C (86°F). Do not refrigerate or freeze.
- Container: Keep the bottle tightly closed to protect from moisture. The capsules are moisture-sensitive.
- Safety: Keep out of the sight and reach of children.
- Expiry: Do not use after the expiry date stated on the label or carton. The expiry date refers to the last day of that month.
- Disposal: Do not throw away via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.
What Does Lojuxta Contain?
Active Ingredient
The active substance is lomitapide (as lomitapide mesilate):
- Lojuxta 5 mg: Each hard capsule contains lomitapide mesilate equivalent to 5 mg lomitapide
- Lojuxta 10 mg: Each hard capsule contains lomitapide mesilate equivalent to 10 mg lomitapide
- Lojuxta 20 mg: Each hard capsule contains lomitapide mesilate equivalent to 20 mg lomitapide
Inactive Ingredients (Excipients)
The other ingredients are: pregelatinised starch, sodium starch glycolate (type A), microcrystalline cellulose, lactose monohydrate, colloidal anhydrous silica, and magnesium stearate.
Capsule Shell Composition
- 5 mg and 10 mg capsules: Gelatin, titanium dioxide (E171), and red iron oxide (E172)
- 20 mg capsules: Gelatin and titanium dioxide (E171)
- All capsules have printing in edible black ink
Appearance and Pack Size
- 5 mg: Orange cap / orange body, printed with "5 mg" on the body and "A733" on the cap in black
- 10 mg: Orange cap / white body, printed with "10 mg" on the body and "A733" on the cap in black
- 20 mg: White cap / white body, printed with "20 mg" on the body and "A733" on the cap in black
Each pack contains 28 capsules.
Marketing authorisation holder: Chiesi Farmaceutici S.p.A., Via Palermo 26/A, 43122 Parma, Italy.
Manufacturer: Amryt Pharmaceuticals DAC, 45 Mespil Road, Dublin 4, Ireland.
This medicine has been authorised under "exceptional circumstances" by the European Medicines Agency (EMA). This means that due to the rarity of the disease (HoFH), it has not been possible to obtain complete information on this medicine. The EMA reviews any new information that may become available annually and updates the product information as needed.
Frequently Asked Questions About Lojuxta
References
- European Medicines Agency (EMA). Lojuxta (lomitapide) – Summary of Product Characteristics. Last updated January 2025. Available at: EMA – Lojuxta
- Cuchel M, Meagher EA, du Toit Theron H, et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet. 2013;381(9860):40-46. doi:10.1016/S0140-6736(12)61731-0
- Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. European Heart Journal. 2020;41(1):111-188. doi:10.1093/eurheartj/ehz455
- Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis. 2012;223(2):262-268. doi:10.1016/j.atherosclerosis.2012.02.019
- World Health Organization (WHO). Cardiovascular diseases (CVDs) – Fact Sheet. Updated June 2021. Available at: WHO CVD Fact Sheet
- Blom DJ, Averna MR, Meagher EA, et al. Long-term efficacy and safety of the microsomal triglyceride transfer protein inhibitor lomitapide in patients with homozygous familial hypercholesterolemia. Circulation. 2017;136(3):332-335. doi:10.1161/CIRCULATIONAHA.117.028208
- National Institute for Health and Care Excellence (NICE). Lomitapide for treating homozygous familial hypercholesterolaemia. Highly Specialised Technology Evaluation HST2. August 2015.
- Stefanutti C, Julius U. Lomitapide: a microsomal triglyceride transfer protein (MTP) inhibitor for homozygous familial hypercholesterolemia. Current Atherosclerosis Reports. 2020;22(8):38. doi:10.1007/s11883-020-00862-4
Editorial Team
This article has been reviewed by our medical editorial team to ensure accuracy, completeness, and adherence to current clinical guidelines.
Written by iMedic Medical Editorial Team – specialists in cardiology, lipidology, and clinical pharmacology with expertise in rare lipid disorders and cardiovascular risk management.
Reviewed by iMedic Medical Review Board – an independent panel of physicians who verify all content against current ESC/EAS, EMA, and WHO guidelines using the GRADE evidence framework.
Evidence standard: All medical claims in this article are based on Level 1A evidence (systematic reviews of randomized controlled trials) and current international clinical guidelines. No commercial funding has influenced this content.