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Continuing Education Activity

Homozygous familial hypercholesterolemia (HoFH) medications comprise mipomersen and lomitapide. Lomitapide is an FDA-approved in addition to a diet low in fats, and other drugs used to reduce lipids, to decrease low-density lipoprotein (LDL) cholesterol, apolipoprotein B, and other lipoproteins, in patients suffering from HoFH.


  • Outline the mechanism of action of lomitapide.
  • Review the potential side effects of lomitapide.
  • Identify the needed monitoring of lomitapide.
  • Summerize the plans of the interprofessional team to enhance communication and coordinating care to improve lomitapide and promote outcomes.


Homozygous familial hypercholesterolemia: Added to a diet with low fats and other drugs to reduce lipids, involving LDL apheresis to decrease low-density lipoprotein cholesterol (LDL-C), total cholesterol, apolipoprotein B (apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) in patients suffering from HoFH.[1][2]

Patients who suffer from HoFH might have arcus corneae, tendinous xanthomas, and xanthelasma and planar or tuberous xanthomas. Planar xanthomas are flat or somewhat elevated yellowish patches. Tuberous xanthomas are painless, hard nodules usually on the extensor joints’ surfaces.

Guidelines: Lomitapide might be beneficial in patients suffering from HoFH with inadequate responsiveness to the inhibitors of PCSK9 treatment.[3][4] Also, lomitapide might be useful in patients suffering from atherosclerotic cardiovascular disease (ASCVD) and baseline LDL-C ≥190 mg/dL who lack proper responding to statins (with or without inhibitors of PCSK9 or ezetimibe).[5][6][7][8]

Mechanism of Action

Lomitapide binds instantly to and suppresses microsomal triglyceride transfer protein (MTP) inside the endoplasmic reticulum lumen. Suppressing MTP hinders producing lipoproteins that contain apo-B in the hepatocytes and the enterocytes and leads to a decrease in generating very-low-density lipoprotein (VLDL) and chylomicrons and hence decreases the levels of LDL-C in plasma.[9]


Lomitapide is taken once per day; administered with water and without food minimally 2 hours following the night meal because taking it with food might raise the danger of gastrointestinal side effects; and wallowed as the entire capsules without opening, crushing, dissolving, or chewing.

Starting dose is 5 mg once per day; following 2 weeks or more of treatment, might be raised to 10 mg once per day, based on tolerance; next at periods of 4-weeks or greater, may be increased to 20 mg once per day, then to 40 mg once per day, and lastly to the highest dose of 60 mg per day based on tolerance.

Adverse Effects

The most frequently reported adverse effects include the following: 

  • Cardiovascular: Chest pain

  • Central nervous system: Fatigue 

  • Gastrointestinal: Severe diarrhea and vomiting, nausea, dyspepsia, weight loss, severe abdominal pain, discomfort and distension, constipation, flatulence, and gastroenteritis.

  • Hepatic: Elevated transaminases levels in serum and liver steatosis

  • Infection: Influenza

  • Neuromuscular and skeletal: Back pain

  • Respiratory: Pharyngolaryngeal pain and nasopharyngitis[10]


Pregnancy; concomitant administration with moderate or potent inhibitors of CYP3A4; moderately or seriously deteriorated liver (Child-Pugh class B or C) and patients suffering from active hepatic disorders, involving unjustified lasting increases of transaminases in the serum.[11]

Hypersensitivity to lomitapide or other formula elements; identified critical, chronic disorders of the bowel such as malabsorption or inflammatory bowel disease; co-administration of daily simvastatin greater than 20 mg (co-administration with daily simvastatin of 40 mg daily is allowed for patients initially tolerant to daily simvastatin of 80 mg for a year or more with no indication of myotoxicity); intolerance to galactose, deficiency in Lapp-lactase, or malabsorption of glucose-galactose.[12]


Ask for hepatic and renal function tests (baseline alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin).

Before starting treatment, pregnancy test in females of child-bearing age.

In the first year, assess transaminases every month or before any rise in the dosage (whichever happens first), and afterward every three months minimally and before increasing the dose.

Check other medications that patients might be administering; adjusting doses or alternative treatments might be required. 

Check signs of severe diarrhea or hepatic toxicity.

For Nurses

Assess abnormalities in the ordered labs and reports. 

Monitor for and inform the patient to report severe diarrhea or any signs of hepatic toxicity, for example, loss of appetite, serious abdominal pain, jaundice, dark urine, or light-colored feces.


Lomitapide could elevate transaminases. In a clinical trial, 34% of patients showed an elevation in ALT or AST about three times the upper limit of normal (ULN), or even more. There were no significant clinically relevant elevations in alkaline phosphatase, total bilirubin, or the international normalized ratio (INR).[13][14]

Lomitapide can elevate liver fats. This can occur with or without related transaminases elevations. Following 26 and 78 weeks of therapy, the median absolute rise in liver fats, from a baseline of 1%, was 6% assessed through magnetic resonance spectroscopy (MRS). Lomitapide therapy-associated liver steatosis could be a risk factor for advanced liver disease, involving both steatohepatitis or cirrhosis.

Before starting therapy, assess AST, ALT, alkaline phosphatase, and total bilirubin and routinely AST and ALT as required afterward. During treatment, modify lomitapide dosage if the AST or  ALT is three times the ULN or more. Stop lomitapide in case of clinically meaningful hepatic toxicity.

For the risk of liver toxicity, lomitapide is prescribed only via a controlled program below policy for assessing and mitigating risk. Prescribe lomitapide only to patients who are confirmed either clinically or by laboratory results to have HoFH. Lomitapide efficacy and safety remain unconfirmed in patients diagnosed with hypercholesterolemia other than HoFH.[15]

Enhancing Healthcare Team Outcomes

Dyslipidemia is a risk factor for atherosclerosis and could cause asymptomatic coronary artery or peripheral arterial diseases.

  • Causes of dyslipidemia include sedentary living with diets rich in calories, saturated and trans fats, cholesterol, and/or familial (genetic) abnormalities in metabolizing fats.
  • Diagnosis is by measuring serum lipid levels (assessing total cholesterol, TGs, and HDL cholesterol and quantified LDL cholesterol and VLDL).
  • Screening exams should take place at 9 to 11 years old, then at 17 to 21 years old and 2 to 8 years old (for a significant family history of serious hyperlipidemia, premature coronary artery disease, or other risk factors); adults should have screening starting at 20 years of age, and then every five years.
  • Total and HDL cholesterol are assessable while not fasting; however, most patients should have all lipids assessed during fasting, often for 12 hours, for optimal validity and precision.
  • The American Heart Association and the American College of Cardiology recommend treatment for all patients in the four key risk groups and those who have raised lipid profiles and other risk factors combinations to decrease atherosclerotic cardiovascular disease risk. 
  • Management relies on the particular abnormalities in the lipid profile. However, it should always cover optimizing compliance, changing lifestyle (diet modification and physical activity), controlling diabetes and hypertension, quitting smoking, and sometimes in cases with an elevated risk of myocardial infarction or death because of coronary artery disease, low-dose of daily aspirin.
  • Lomitapide is a microsomal triglyceride transfer protein inhibitor, which affects secreting TG-rich lipoproteins in the intestine and the liver. The dose starts low and step-by-step, raised almost bi-weekly. Patients should adhere to diets with less than 20% in fat calories. 
  • Lomitapide might lead to gastrointestinal side effects such as diarrhea, raised liver fats, and increased hepatic enzymes.  Efficacy and safety in patients who lack homozygous familial hypercholesterolemia remain unproven.
  • Apheresis is also a frequently used treatment in patients suffering from the HoFH who have limited or no response to medications.
  • However, elevated HDL levels have links with lower cardiovascular risk, and it is unclear if therapies that raise the levels of HDL cholesterol would reduce cardiovascular events or death risks.

The above management activities are best accomplished by an interprofessional healthcare team that includes clinicians, specialists, mid-level practitioners, nurses, and pharmacists, all working collaboratively and sharing their findings with the other team members to drive optimal patient outcomes with the fewest adverse events. [Level 5]

Article Details

Article Author

Rehab Rayan

Article Editor:

Saurabh Sharma


4/29/2022 6:33:11 AM

PubMed Link:




Jacobson TA,Maki KC,Orringer CE,Jones PH,Kris-Etherton P,Sikand G,La Forge R,Daniels SR,Wilson DP,Morris PB,Wild RA,Grundy SM,Daviglus M,Ferdinand KC,Vijayaraghavan K,Deedwania PC,Aberg JA,Liao KP,McKenney JM,Ross JL,Braun LT,Ito MK,Bays HE,Brown WV,Underberg JA, National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2. Journal of clinical lipidology. 2015 Nov-Dec;     [PubMed PMID: 26699442]


Jacobson TA,Ito MK,Maki KC,Orringer CE,Bays HE,Jones PH,McKenney JM,Grundy SM,Gill EA,Wild RA,Wilson DP,Brown WV, National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 - executive summary. Journal of clinical lipidology. 2014 Sep-Oct;     [PubMed PMID: 25234560]


Jellinger PS, Impact of new lipid management guidelines on the treatment of extreme and very high-risk patients: AACE/ACE and AHA/ACC guidelines. Journal of diabetes. 2020 Feb;     [PubMed PMID: 31777166]


Jellinger PS,Handelsman Y,Rosenblit PD,Bloomgarden ZT,Fonseca VA,Garber AJ,Grunberger G,Guerin CK,Bell DSH,Mechanick JI,Pessah-Pollack R,Wyne K,Smith D,Brinton EA,Fazio S,Davidson M,Zangeneh F,Bush MA, AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE - EXECUTIVE SUMMARY{sub}Complete Appendix to Guidelines available at http://journals.aace.com{/sub}. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2017 Apr 2;     [PubMed PMID: 28156151]


Lloyd-Jones DM,Morris PB,Ballantyne CM,Birtcher KK,Daly DD Jr,DePalma SM,Minissian MB,Orringer CE,Smith SC Jr, 2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. Journal of the American College of Cardiology. 2017 Oct 3;     [PubMed PMID: 28886926]


Grundy SM,Stone NJ,Bailey AL,Beam C,Birtcher KK,Blumenthal RS,Braun LT,de Ferranti S,Faiella-Tommasino J,Forman DE,Goldberg R,Heidenreich PA,Hlatky MA,Jones DW,Lloyd-Jones D,Lopez-Pajares N,Ndumele CE,Orringer CE,Peralta CA,Saseen JJ,Smith SC Jr,Sperling L,Virani SS,Yeboah J, 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2019 Jun 25;     [PubMed PMID: 30423393]


Samaha FF,McKenney J,Bloedon LT,Sasiela WJ,Rader DJ, Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia. Nature clinical practice. Cardiovascular medicine. 2008 Aug;     [PubMed PMID: 18506154]


Andrus B,Lacaille D, 2013 ACC/AHA guideline on the assessment of cardiovascular risk. Journal of the American College of Cardiology. 2014 Jul 1;     [PubMed PMID: 24768878]


Ajufo E,Rader DJ, New Therapeutic Approaches for Familial Hypercholesterolemia. Annual review of medicine. 2018 Jan 29;     [PubMed PMID: 29414257]


Khoury E,Brisson D,Roy N,Tremblay G,Gaudet D, Review of the long-term safety of lomitapide: a microsomal triglycerides transfer protein inhibitor for treating homozygous familial hypercholesterolemia. Expert opinion on drug safety. 2019 May;     [PubMed PMID: 30945578]


Crismaru I,Pantea Stoian A,Bratu OG,Gaman MA,Stanescu AMA,Bacalbasa N,Diaconu CC, Low-density lipoprotein cholesterol lowering treatment: the current approach. Lipids in health and disease. 2020 May 6;     [PubMed PMID: 32375792]


Lipid-lowering drugs. The Medical letter on drugs and therapeutics. 2019 Feb 11;     [PubMed PMID: 30845106]


Cuchel M,Bloedon LT,Szapary PO,Kolansky DM,Wolfe ML,Sarkis A,Millar JS,Ikewaki K,Siegelman ES,Gregg RE,Rader DJ, Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. The New England journal of medicine. 2007 Jan 11;     [PubMed PMID: 17215532]


Cuchel M,Meagher EA,du Toit Theron H,Blom DJ,Marais AD,Hegele RA,Averna MR,Sirtori CR,Shah PK,Gaudet D,Stefanutti C,Vigna GB,Du Plessis AM,Propert KJ,Sasiela WJ,Bloedon LT,Rader DJ, 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 (London, England). 2013 Jan 5;     [PubMed PMID: 23122768]


Cupido AJ,Reeskamp LF,Kastelein JJP, Novel lipid modifying drugs to lower LDL cholesterol. Current opinion in lipidology. 2017 Aug;     [PubMed PMID: 28445176]