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Lomitapide and mipomersen are antihyperlipidemic agents indicated for treating homozygous familial hypercholesterolemia (HoFH). Lomitapide is approved by the US Food and Drug Administration (FDA) for use alongside other antilipidemic drugs and a low-fat diet to lower serum lipids, decrease low-density lipoprotein (LDL) cholesterol (LDL-C), total cholesterol, apolipoprotein B (apo-B), and non–high-density lipoprotein cholesterol in patients with HoFH. Patients with HoFH might present with arcus corneae, tendinous xanthomas, xanthelasma, and planar or tuberous xanthomas. Lomitapide could be beneficial for HoFH patients exhibiting insufficient response to PCSK9 inhibitor treatment, those with atherosclerotic cardiovascular disease and a baseline LDL-C of 190 mg/dL or higher, and those who demonstrate insufficient responses to statins, whether used alone or in combination with PCSK9 inhibitors or ezetimibe. Lomitapide rapidly binds to and inhibits microsomal triglyceride transfer protein (MTP) within the endoplasmic reticulum lumen, which impedes the synthesis of lipoproteins containing apo-B in both hepatocytes and enterocytes. This process reduces the production of very low-density lipoprotein and chylomicrons, thereby lowering plasma LDL-C levels. The safety and efficacy of lomitapide have not been established for heterozygous familial hypercholesterolemia. This activity elucidates the indications, mechanism of action, pharmacokinetics, adverse event profile, and other relevant interactions essential for interprofessional healthcare team members in treating patients with HoFH and related conditions. Objectives: Identify appropriate candidates for lomitapide therapy based on clinical indications and contraindications. Screen patients for potential contraindications and risk factors before initiating lomitapide treatment, considering factors such as disease severity, comorbidities, and medication history. Implement appropriate dosing strategies and titration schedules for lomitapide therapy according to patient response and tolerance. Collaborate with other healthcare professionals to ensure comprehensive care for patients with homozygous familial hypercholesterolemia receiving lomitapide therapy. Access free multiple choice questions on this topic.

The considerations for suspected toxicity include the following: Elevate transaminases: In a clinical trial, approximately 34% of patients exhibited elevated levels of ALT or AST that were approximately three times or greater than the upper limit of normal (ULN). No significant clinically relevant elevations in alkaline phosphatase, total bilirubin, or the international normalized ratio (INR) are apparent.[25][12] Elevate liver fats: This can occur with or without related transaminase 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 steatohepatitis and cirrhosis. Before starting therapy, assess AST, ALT, alkaline phosphatase, and total bilirubin and routinely check AST and ALT as required afterward. Modify the lomitapide dosage during treatment if the AST or ALT reaches three times the ULN or more. Stop lomitapide in case of clinically meaningful hepatic toxicity. Due to hepatotoxicity, lomitapide is only available through the REMS program, as mentioned above. Prescribe lomitapide only to patients confirmed clinically or by laboratory results to have HoFH. Lomitapide efficacy and safety remain unconfirmed in patients diagnosed with hypercholesterolemia other than from HoFH.[26] No antidote is available for lomitapide overdose. In severe overdose of lomitapide, provide supportive care. Hemodialysis is unlikely to be effective as lomitapide has high plasma protein binding.

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 familial (genetic) abnormalities in metabolizing fats. The evaluation begins by measuring serum lipid levels, including total cholesterol, triglycerides, HDL-C, quantified LDL-C, and VLDL. Screening exams should occur at ages 9 to 11, then at ages 17 to 21, and ages 2 to 8 (for a significant family history of severe hyperlipidemia, premature coronary artery disease, or other risk factors). Adults should have screening starting at age 20 and then every subsequent 5 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 (AHA/ACC) recommend treatment for all patients in the 4 key risk groups and those with raised lipid profiles and other risk factors to decrease ASCVD risk. Although management relies on particular abnormalities in the lipid profile, 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 MTP inhibitor, which affects the secretion of triglyceride-rich lipoproteins in the intestine and the liver. The dose starts low and is raised step-by-step, almost bi-weekly. Patients should adhere to diets with less than 20% fat calories. Lomitapide might lead to gastrointestinal adverse effects such as diarrhea, hepatic steatosis, and increased hepatic enzymes. Pharmacists should educate patients about adverse effects. Apheresis is also a frequently used treatment in patients suffering from HoFH who have limited or no response to medications.

Lomitapide is a MTP inhibitor, which affects the secretion of triglyceride-rich lipoproteins in the intestine and the liver. The dose starts low and is raised step-by-step, almost bi-weekly. Patients should adhere to diets with less than 20% fat calories. Lomitapide might lead to gastrointestinal adverse effects such as diarrhea, hepatic steatosis, and increased hepatic enzymes. Pharmacists should educate patients about adverse effects. Apheresis is also a frequently used treatment in patients suffering from HoFH who have limited or no response to medications. Patients diagnosed with HoFH should be promptly referred to a lipid specialist for further management.[27] A global retrospective cohort study on HoFH revealed late diagnosis, undertreatment, and increased premature cardiovascular risk. Multi-lipid-lowering therapy is associated with better outcomes and lower LDL cholesterol levels. Global disparities in treatment, LDL cholesterol control, and cardiovascular event-free survival among HoFH patients require a critical re-evaluation of global health policies to reduce inequalities and improve outcomes for patients with HoFH.[28] The aforementioned management activities are most effectively carried out by an interprofessional healthcare team comprising clinicians, specialists, advanced practice practitioners, nursing staff, and pharmacists. They work collaboratively, engage in shared decision-making, and communicate their findings with other team members to ensure optimal patient outcomes while minimizing adverse events.