Generic drug: lomitapide
Brand name: Juxtapid
What is Juxtapid (lomitapide), and how does it work?
Juxtapid (lomitapide) is a prescription medicine used along with diet and other lipid-lowering treatments, including low-density lipoprotein (LDL) apheresis where available, in people with homozygous familial hypercholesterolemia (HoFH) to reduce:
- LDL ("bad") cholesterol
- total cholesterol
- a protein that carries "bad" cholesterol in the blood (apolipoprotein B)
- non-high-density lipoprotein cholesterol (non-HDL-C)
It is not known if Juxtapid is safe and effective in people with high cholesterol who do not have HoFH, including those with heterozygous familial hypercholesterolemia (HeFH).
What are the side effects of Juxtapid?
RISK OF HEPATOTOXICITY
Juxtapid can cause elevations in transaminases. In the Juxtapid clinical trial, 10 (34%) of the 29 patients treated with Juxtapid had at least one elevation in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =3x upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR), or alkaline phosphatase.
Juxtapid also increases hepatic fat, with or without concomitant increases in transaminases. The median absolute increase in hepatic fat was 6% after both 26 and 78 weeks of treatment, from 1% at baseline, measured by magnetic resonance spectroscopy. Hepatic steatosis associated with Juxtapid treatment may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis.
Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT and AST regularly as recommended. During treatment, adjust the dose of Juxtapid if the ALT or AST are =3x ULN. Discontinue Juxtapid for clinically significant liver toxicity.
Because of the risk of hepatotoxicity, Juxtapid is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Juxtapid REMS Program. Prescribe Juxtapid only to patients with a clinical or laboratory diagnosis consistent with HoFH. The safety and effectiveness of Juxtapid have not been established in patients with hypercholesterolemia who do not have HoFH.
Juxtapid can cause serious side effects, including:
- problems absorbing certain nutrients. Juxtapid may decrease your ability to absorb fat-soluble nutrients such as Vitamin E and fatty acids. You should take supplements each day that contain fat-soluble vitamins. People with bowel or pancreas problems may have an increased chance of not being able to absorb these nutrients.
- gastrointestinal symptoms. Diarrhea, nausea, vomiting, and stomach pain or discomfort are very common when taking Juxtapid. Strictly following a low-fat diet may help lower the chance of having these symptoms. Stop taking Juxtapid and tell your doctor if you have severe diarrhea, especially if you also have lightheadedness, decreased urine output, or tiredness.
- increased levels of certain blood thinners. Juxtapid can increase the level of the blood thinner, warfarin. If you take warfarin, your doctor should check your blood clotting times frequently, especially after your dose of Juxtapid changes.
- liver problems caused by certain drugs. Certain medicines can cause liver problems, including isotretinoin, acetaminophen, methotrexate, tetracyclines, and tamoxifen. If you take these medicines with Juxtapid your doctor may do blood tests more often to check your liver.
The most common side effects of Juxtapid include:
Tell your doctor if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of Juxtapid. For more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What is the dosage for Juxtapid?
Initiation And Maintenance Of Therapy
Before beginning treatment with Juxtapid:
- Measure transaminases (ALT, AST), alkaline phosphatase, and total bilirubin;
- Obtain a negative pregnancy test in females of reproductive potential prior to initiating treatment with Juxtapid;
- Initiate a low-fat diet supplying <20% of energy from fat.
The recommended starting dosage of Juxtapid is 5 mg once daily, and the dose should be escalated gradually based on acceptable safety and tolerability. Transaminases should be measured prior to any increase in dose.
The maintenance dosage of Juxtapid should be individualized, taking into account patient characteristics such as goal of therapy and response to treatment, to a maximum of 60 mg daily as described in Table 1. Modify dosing for patients taking concomitant weak CYP3A4 inhibitors and for those with renal impairment or baseline hepatic impairment.
Monitor transaminases during treatment with Juxtapid as described in the prescribing information, and reduce or withhold dosing for patients who develop transaminase values =3x the upper limit of normal (ULN).
Table 1: Recommended Regimen for Titrating Dosage
|DOSAGE||DURATION OF ADMINISTRATION BEFORE CONSIDERING INCREASE TO NEXT DOSAGE|
|5 mg daily||At least 2 weeks|
|10 mg daily||At least 4 weeks|
|20 mg daily||At least 4 weeks|
|40 mg daily||At least 4 weeks|
|60 mg daily||Maximum recommended dosage|
- To reduce the risk of developing a fat-soluble nutrient deficiency due to Juxtapid's mechanism of action in the small intestine, patients treated with Juxtapid should take daily supplements that contain 400 international units vitamin E and at least 200 mg linoleic acid, 210 mg alpha-linolenic acid (ALA), 110 mg eicosapentaenoic acid (EPA), and 80 mg docosahexaenoic acid (DHA).
- Juxtapid should be taken once daily with a glass of water, without food, at least 2 hours after the evening meal because administration with food may increase the risk of gastrointestinal adverse reactions. Patients should swallow Juxtapid capsules whole. Capsules should not be opened, crushed, dissolved, or chewed.
Dosing With Cytochrome P450 3A4 Inhibitors
- Juxtapid is contraindicated with concomitant use of moderate and strong cytochrome P450 3A4 (CYP3A4) inhibitors.
- The recommended maximum dosage of Juxtapid is 30 mg daily with concomitant use of weak CYP3A4 inhibitors (such as alprazolam, amiodarone, amlodipine, atorvastatin, bicalutamide, cilostazol, cimetidine, cyclosporine, fluoxetine, fluvoxamine, ginkgo, goldenseal, isoniazid, lapatinib, nilotinib, pazopanib, ranitidine, ranolazine, ticagrelor, zileuton). However, the recommended maximum dosage of Juxtapid is 40 mg daily with concomitant use of oral contraceptives.
- When initiating a weak CYP3A4 inhibitor in a patient already taking Juxtapid 10 mg daily or more, decrease the dose of Juxtapid by half; patients taking Juxtapid 5 mg daily may continue with the same dosage.
- Careful titration of Juxtapid may then be considered according to LDL-C response and safety/tolerability to a maximum recommended dosage of 30 mg daily except when coadministered with oral contraceptives, in which case the maximum recommended lomitapide dosage is 40 mg daily.
Dose Modification Based On Elevated Transaminases
Table 2 summarizes recommendations for dose adjustment and monitoring for patients who develop elevated transaminases during therapy with Juxtapid.
Table 2: Dose Adjustment and Monitoring for Patients with Elevated Transaminases
|ALT OR AST||TREATMENT AND MONITORING RECOMMENDATIONS*|
|≥3 and <5 ULN||
|*Recommendations based on an ULN of approximately 30-40 international units/L.|
- If transaminase 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 Juxtapid and investigate to identify the probable cause.
Dosing In Patients With Renal Impairment
- Patients with end-stage renal disease receiving dialysis should not exceed 40 mg daily. There are no data available to guide dosing in other patients with renal impairment.
Dosing In Patients With Baseline Hepatic Impairment
- Patients with mild hepatic impairment (Child-Pugh A) should not exceed 40 mg daily.
What drugs interact with Juxtapid?
Moderate And Strong CYP3A4 Inhibitors
- A strong CYP3A4 inhibitor has been shown to increase lomitapide exposure approximately 27-fold.
- Concomitant use of strong CYP3A4 inhibitors (such as boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, tipranavir/ritonavir, voriconazole) with lomitapide is contraindicated.
- Concomitant use of moderate CYP3A4 inhibitors (such as amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil) has not been studied, but concomitant use with lomitapide is contraindicated since lomitapide exposure will likely increase significantly in the presence of these inhibitors.
- Patients must avoid grapefruit juice while taking Juxtapid.
Weak CYP3A4 Inhibitors
- Weak CYP3A4 inhibitors (such as alprazolam, amiodarone, amlodipine, atorvastatin, bicalutamide, cilostazol, cimetidine, cyclosporine, fluoxetine, fluvoxamine, ginkgo, goldenseal, isoniazid, lapatinib, nilotinib, pazopanib, ranitidine, ranolazine, ticagrelor, zileuton) can increase lomitapide exposure approximately 2-fold.
- When administered with weak CYP3A4 inhibitors, the dose of Juxtapid should be decreased by half.
- Careful titration of Juxtapid may then be considered based on LDL-C response and safety/tolerability to a maximum recommended dosage of 30 mg daily except when coadministered with oral contraceptives, in which case the maximum recommended lomitapide dosage is 40 mg daily.
- Lomitapide increases plasma concentrations of both R(+)-warfarin and S(-)-warfarin by approximately 30% and increased the INR 22%. Patients taking warfarin should undergo regular monitoring of INR, particularly after any changes in lomitapide dosage. The dose of warfarin should be adjusted as clinically indicated.
Simvastatin And Lovastatin
- The risk of myopathy, including rhabdomyolysis, with simvastatin and lovastatin monotherapy is dose related. Lomitapide approximately doubles the exposure of simvastatin; therefore, the recommended dose of simvastatin should be reduced by 50% when initiating Juxtapid.
- While taking Juxtapid, limit simvastatin dosage to 20 mg daily (or 40 mg daily for patients who have previously tolerated simvastatin 80 mg daily for at least one year without evidence of muscle toxicity).
- Refer to the simvastatin prescribing information for simvastatin dosing recommendations.
- Interaction between lovastatin and lomitapide has not been studied.
- However, the metabolizing enzymes and transporters responsible for the disposition of lovastatin and simvastatin are similar, suggesting that Juxtapid may increase the exposure of lovastatin; therefore, reducing the dose of lovastatin should be considered when initiating Juxtapid.
- Lomitapide is an inhibitor of P-glycoprotein (P-gp). Coadministration of lomitapide with P-gp substrates (such as aliskiren, ambrisentan, colchicine, dabigatran etexilate, digoxin, everolimus, fexofenadine, imatinib, lapatinib, maraviroc, nilotinib, posaconazole, ranolazine, saxagliptin, sirolimus, sitagliptin, talinolol, tolvaptan, topotecan) may increase the absorption of P-gp substrates.
- Dose reduction of the P-gp substrate should be considered when used concomitantly with lomitapide.
Bile Acid Sequestrants
- Juxtapid has not been tested for interaction with bile acid sequestrants.
- Administration of Juxtapid and bile acid sequestrants should be separated by at least 4 hours since bile acid sequestrants can interfere with the absorption of oral medications.
Is Juxtapid safe to use while pregnant or breastfeeding?
- Based on findings from animal studies, Juxtapid use is contraindicated in pregnancy since it may cause fetal harm.
- There are no data on the presence of lomitapide in human or animal milk, effects on the breastfed infant or on milk production.
- Because of the potential for serious adverse reactions, including hepatotoxicity, advise patients that breastfeeding is not recommended during treatment with Juxtapid.
Juxtapid (lomitapide) is a prescription medicine used along with diet and other lipid-lowering treatments, including low-density lipoprotein (LDL) apheresis where available, in people with homozygous familial hypercholesterolemia (HoFH) to reduce LDL ("bad") cholesterol, total cholesterol, a protein that carries "bad" cholesterol in the blood (apolipoprotein B), and non-high-density lipoprotein cholesterol (non-HDL-C). Serious side effects include problems absorbing certain nutrients, gastrointestinal symptoms, and others.
Multimedia: Slideshows, Images & Quizzes
Cholesterol Levels: What's Normal and How to Lower High Cholesterol
What do cholesterol numbers mean? LDL, HDL, good, bad, and triglycerides - Get the facts on cholesterol, blood testing,...
How to Lower Your Cholesterol & Save Your Heart
Need to lower your cholesterol levels? Use these smart diet tips to quickly and easily lower your blood cholesterol levels....
Cholesterol Drugs: What to Expect With Heart Medication
When diet and exercise aren't enough, should you turn to drugs? Learn cholesterol basics, drug classes, and available drugs along...
Cholesterol: High Triglyceride Foods to Avoid
High triglycerides increase the risk of heart disease. Lower triglyceride levels and reduce cholesterol by eating foods that...
High Cholesterol (Hyperlipidemia) Quiz: Test Your Medical IQ
High cholesterol can be a dangerous condition. Take the Cholesterol Quiz to understand what high cholesterol means in terms of...
Picture of Cholesterol
Cholesterol carried in particles of low density (LDL cholesterol) is referred to as the "bad" cholesterol because elevated levels...
Cholesterol & Triglycerides: Mistakes That Can Affect Your Cholesterol
High cholesterol can be trouble. Find out from WebMD's slideshow if you’re doing things that can make it harder to keep your...
Related Disease Conditions
What Are the Normal Cholesterol Levels According to Age?
Cholesterol is a waxy substance found in all the cells of the body. It is a type of fat that is produced by the liver. Cholesterol also comes from animal-derived foods, such as meat and dairy products.
High cholesterol and triglyceride levels increase the risk of cardiovascular disease. Getting your cholesterol and triglyceride levels in an optimal range will help protect your heart and blood vessels. Cholesterol management may include lifestyle interventions (diet and exercise) as well as medications to get your total cholesterol, LDL, HDL, and triglycerides in an optimal range.
Lower Cholesterol Levels with Diet and Medications
High-density lipoprotein (HDL) cholesterol is considered "good" cholesterol because it actually works to keep the LDL or "bad" cholesterol from building up in your arteries. Foods like extra lean meats, skim milk, and vegetable-based "butter-like" substitutes may help decrease LDL levels in the bloodstream.
Is Squid Rich in Cholesterol?
Squid is part of the same family as oysters, scallops and octopus. Squid is often eaten deep fried. This is known as calamari. Unlike many other animal products, squid is low in saturated fat. Doctors usually do not advise saturated fat to people with high cholesterol. When squid is deep fried, total fat and saturated fat increase.
What Is the Normal Range for Cholesterol Levels?
What is the normal range for cholesterol levels? Learn what cholesterol levels are, why cholesterol levels change, how doctors diagnose cholesterol levels, and what you can do to treat high cholesterol levels.
HDL vs. LDL Cholesterol (Good and Bad)
HDL (high-density lipoprotein), or the "good" cholesterol, and LDL (low-density lipoprotein), or the "bad" cholesterol, are lipoproteins that carry cholesterol through the veins and arteries of the body. HDL and LDL combined, is your "total" blood cholesterol. The difference between the two are that high levels of the "good," or HDL cholesterol, may protect against narrowing of the blood vessels in the body, which protects you against heart attack, stroke, and other cardiovascular diseases. But high levels of LDL, or the "bad" cholesterol, may worsen the narrowing of the blood vessels in the body, which puts you at a greater risk of stroke, heart attack, and cardiovascular diseases, some of which are life threatening.Triglycerides are found in body fat and from the fats you eat.
What Reduces Cholesterol Quickly?
High blood cholesterol levels can be managed to a great extent with lifestyle changes. However, not taking medicine isn’t a solution because only lifestyle changes may not be sufficient to treat high cholesterol levels.
What Are the Causes of High Cholesterol?
Your body naturally produces all the LDL (bad) cholesterol it needs. An unhealthy lifestyle – not enough exercise, too many unhealthy foods – makes your body produce more LDL cholesterol than it needs. This is the cause of high LDL cholesterol for most people.
What Are the Normal Cholesterol Levels By Age?
Cholesterol is a waxy substance found in all the cells of the body. It is a type of fat that is produced by the liver. Cholesterol also comes from animal-derived foods, such as meat and dairy products. It is an essential substance needed by the body for various purposes. Too much cholesterol, however, harms the body and increases the risk of various medical conditions, such as high blood pressure and heart diseases.
Treatment & Diagnosis
- High Cholesterol (Hyperlipidemia) FAQs
- Statins - - Doing More Than Lowering Your Cholesterol?
- Cholesterol: Questions To Ask Your Doctor
- Cholesterol: The Truth About Cholesterol
- Cholesterol: HDL cholesterol ratio
- Cholesterol - Mr. D.T.'s Story of Hope
- Cholesterol Guidelines
- Heart Attack Prevention From a Doctor's Perspective
- Can Menopause Cause High Cholesterol?
- What Should Cholesterol Levels Be After Heart Attack?
- What are Cholesterol-Lowering Statins?
- Do Bile Acid Resins Lower Cholesterol?
- Can Fibrate Drugs Lower Cholesterol?
- How Do I Lower My Cholesterol (Triglycerides)
- Does Hypothyroidism Cause High Cholesterol?
- Does Exercise Lower Cholesterol?
- What Foods Lower Cholesterol?
- Does Stress Cause High Cholesterol?
- Cholesterol Treatment
- Cholesterol, The Basics Of Prevention
Prevention & Wellness
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.