Lomitapide

Lomitapide is a prescription medication used to treat high cholesterol in adults with homozygous familial hypercholesterolemia (HoFA), a rare inherited disorder in which the body is unable to remove low-density lipoprotein (LDL) "bad" cholesterol from the blood.

Lomitapide belongs to a group of drugs called microsomal triglyceride transfer protein (MTP) inhibitors, which help lower cholesterol levels.

This medication comes in capsule form and is taken once a day, at least 2 hours after an evening meal, with water.

Common side effects of lomitapide include diarrhea, nausea, and vomiting.  Do not drink grapefruit juice or more than one alcoholic beverage a day while taking lomitapide.

Lomitapide is a prescription medication used with diet and other treatments, in people with a rare inherited disorder in which the body is unable to remove low-density lipoprotein (LDL) "bad" cholesterol from the blood, called homozygous familial hypercholesterolemia (HoFA).

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Lomitapide may be found in some form under the following brand names:

• Juxtapid

Lomitapide can cause serious side effects, including:

• liver problems. See “Drug Precautions”..
• harm to your unborn baby. See “Drug Precautions".
• gastrointestinal symptoms. Diarrhea, nausea/vomiting, and stomach pain/discomfort are very common with lomitapide. Strictly following a low-fat diet may help lower the chance of having these symptoms.
• problems absorbing certain nutrients. Lomitapide 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.
• increased levels of certain blood thinners. Lomitapide can increase the level of the blood thinner, warfarin (Coumadin, Jantoven). If you take warfarin, your doctor should check your blood clotting times frequently, especially after your dose of lomitapide 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 lomitapide your doctor may do blood tests more often to check your liver.

The most common side effects of lomitapide include:

• diarrhea (loose stool)
• nausea
• vomiting
• stomach cramping or pain
• indigestion
• gas

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 lomitapide. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Before starting a new medicine while taking lomitapide, even if you will only be taking it for a short time, ask your doctor or pharmacist if it is safe to take with lomitapide.

Lomitapide may affect the way other medicines work, and other medicines may affect how lomitapide works.

Certain medicines can affect how your liver breaks down other medicines.

Especially tell your doctor if you take:

• a blood thinner called warfarin
• medicines for high cholesterol, including statins such as atorvastatin or simvastatin, and resins such as colesevelam or cholestyramine
• medicines for bacteria, fungus, or viral infection (including HIV and hepatitis C)
• medicines for depression, high blood pressure, or angina
• birth control pills

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

Lomitapide is available only through certified pharmacies that are enrolled in the lomitapide REMS Program.

Your doctor must be enrolled in the program in order for you to be prescribed lomitapide.

There is a registry that collects information about the effects of taking lomitapide over time. Ask your doctor for more information about this registry.

Lomitapide may cause serious side effects including:

Liver problems. Lomitapide can cause liver problems. Your doctor should do blood tests to check your liver before you start lomitapide, if your dose is increased, and while you take lomitapide. If your tests show some liver problems, your doctor may adjust your dose of lomitapide or stop it altogether.

• Tell your doctor if you have had liver problems, including liver problems while taking other medicines.
• Lomitapide may cause nausea, vomiting and stomach pain, especially if you do not eat a low-fat diet.

These side effects can also be symptoms of liver problems. Tell your doctor right away if you have any of these symptoms of liver problems while taking lomitapide:

• nausea, vomiting or stomach pain that gets worse, does not go away, or changes
• fever
• yellowing of your eyes or skin
• you are more tired than usual
• flu-like symptoms

Drinking alcohol may increase your chance of having liver problems or make your liver problems worse.

You should not have more than 1 alcoholic drink each day while taking lomitapide.

Harm to your unborn baby. Lomitapide may cause harm to your unborn baby.

• If you are pregnant, think you may be pregnant, or are planning to become pregnant, do not take lomitapide.
• If you are a female who can get pregnant, you should have a pregnancy test before you start taking lomitapide. Your pregnancy test must be negative for you to get lomitapide.
• Do not have sex while taking lomitapide unless you are using effective birth control.
• Talk with your doctor or nurse to find the best method of birth control for you.
• Birth control pills may not work as well if you have diarrhea or vomiting.
• If you start taking birth control pills while you are taking lomitapide, tell your doctor. Your doctor might need to change your dose of lomitapide.
• If you become pregnant while taking lomitapide, stop taking lomitapide and call your doctor right away.

Do not take lomitapide if you:

• are pregnant, think you may be pregnant, or are planning to become pregnant. See “Drug Precautions” and "Pregnant" sections.
• take medicines that affect how the body breaks down lomitapide (that is, strong or moderate CYP3A4 inhibitors). Check with your doctor and/or pharmacist to see if you are taking any of these medications. These may include certain medications intended to treat bacterial, fungal or viral infections, and medications to treat depression, high blood pressure, or angina.
• drink grapefruit juice
• have moderate or severe liver problems or active liver disease, including people who have unexplained abnormal liver tests.

Grapefruit and grapefruit juice may interact with lomitapide and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Before you take lomitapide, tell your doctor if you:

• have liver problems
• have kidney problems
• have intestine or bowel problems
• drink alcohol
• are breastfeeding or plan to breastfeed. It is not known if lomitapide passes into your breast milk. You and your doctor should decide if you will take lomitapide or breastfeed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Lomitapide may cause harm to your unborn baby.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Lomitapide falls into category X. Category X medicines should never be used by pregnant women.

• If you are pregnant, think you may be pregnant, or are planning to become pregnant, do not take lomitapide.
• If you are a female who can get pregnant, you should have a pregnancy test before you start taking lomitapide. Your pregnancy test must be negative for you to get lomitapide.
• Do not have sex while taking lomitapide unless you are using effective birth control.
• Talk with your doctor or nurse to find the best method of birth control for you.
• Birth control pills may not work as well if you have diarrhea or vomiting.
• If you start taking birth control pills while you are taking lomitapide, tell your doctor. Your doctor might need to change your dose of lomitapide.
• If you become pregnant while taking lomitapide, stop taking lomitapide and call your doctor right away.

It is not known if lomitapide crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using lomitapide.

• Take lomitapide exactly as your doctor tells you to take it.
• Your doctor will tell you how much lomitapide to take and when to take it.
• Your doctor may change your dose of lomitapide if needed.
• Do not change your lomitapide dose yourself.
• Take lomitapide 1 time each day at least 2 hours after your evening meal.
• Take lomitapide with water.
• You should not take lomitapide with food. Taking lomitapide with food may cause stomach problems.
• Take lomitapide capsules whole. Do not open, crush, dissolve, or chew capsules before swallowing. If you cannot swallow lomitapide capsules whole, tell your doctor. You may need a different medicine.
• If you take a medicine that lowers cholesterol by binding bile acids, such as colesevelam or cholestyramine, take it at least 4 hours before or 4 hours after you take lomitapide. Ask your doctor if you are not sure if you take these medicines.
• To help lower the chance of stomach problems, stay on a low-fat diet. Ask your doctor about talking to a dietician to learn what you should eat while taking lomitapide. lomitapide makes it harder for some nutrients to get into your body. Take Vitamin E and fatty acids each day while you take lomitapide. Ask your doctor, nurse, or dietician how to add them to your diet.
• If you take too much lomitapide, call your doctor right away.
• Do not stop lomitapide unless your doctor tells you to stop it.
• If you miss a dose of lomitapide, take your usual dose the next day at the usual time. If you stop taking lomitapide for more than a week, talk to your doctor before restarting treatment.

The recommended starting dosage of lomitapide is 5 mg once daily, and it should be gradually increased based on how well your body tolerates it. Before your dose is increased, your doctor will order blood tests to check your liver. If you have liver problems, kidney disease, or if you are taking certain other medicines, you may need a dose adjustment.

The maintenance dosage of lomitapide is different for everyone, taking into account goal of therapy and response to treatment. The maximum daily lomitapide dose is 60 mg.

If you take too much lomitapide, call your doctor or seek emergency medical attention right away.

• Store lomitapide at room temperature, between 68°F and 77°F (20°C and 25°C).
• Keep lomitapide in a tightly closed container.
• Keep lomitapide capsules dry.
• Safely throw away medicine that is out of date or no longer needed.

Keep lomitapide and all medicines out of the reach of children.

WARNING: RISK OF HEPATOTOXICITY
Lomitapide can cause elevations in transaminases. In the lomitapide clinical trial, 10 (34%) of the 29 patients treated with lomitapide 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.

Lomitapide 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 lomitapide 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 lomitapide if the ALT or AST are ≥3x ULN. Discontinue lomitapide for clinically significant liver toxicity.

Because of the risk of hepatotoxicity, lomitapide is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the lomitapide REMS Program.