Lomitapide

What is Lomitapide?

• Lomitapide (Juxtapid) is a microsomal triglyceride transfer protein inhibitor used as a lipid-lowering agent for the treatment of familial hypercholesterolemia.

Lomitapide skeletal

Lomitapid

What are the uses of this medicine?

This medicine is 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)

Limitations of Use:

• It is not known if Juxtapid can decrease problems from high cholesterol, such as heart attack, stroke, death or other health problems.
• 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).
• Juxtapid should not be taken with certain medicines or food. You should not drink grapefruit juice. Ask your doctor or pharmacist to make sure you can take Juxtapid with your other medicines, and tell your doctor about any new medicines you might take even for only a short time.
• It is not known if Juxtapid is safe and effective in people with kidney problems including people with end-stage kidney disease who are not on dialysis.
• It is not known if Juxtapid is safe and effective when used in children under the age of 18.

How does this medicine work?

• Lomitapide (loe mi' ta pide) is a potent, orally available inhibitor of the hepatic microsomal triglyceride transfer protein (MTTP) and is used to treat severe forms of familial hypercholesterolemia.
• MTTP is responsible for transferring triglyceride to apolipoprotein B in the liver which is necessary for the assembly of very low density lipoproteins, the precursors of low density lipoproteins (LDL).
• Inhibition of apolipoprotein B assembly leads to a marked decrease in circulating LDL cholesterol and triglycerides.
• Lomitapide is typically used in combination with statins.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• are pregnant, think you may be pregnant, or are planning to become pregnant.
• take medicines that affect how the body breaks down Juxtapid (that is, strong or moderate CYP3A4 inhibitors).
• drink grapefruit juice
• have moderate or severe liver problems or active liver disease, including people who have unexplained abnormal liver tests.

What drug interactions can this medicine cause?

• Strong and moderate CYP3A4 inhibitors are contraindicated with Juxtapid. Patients must avoid grapefruit juice.
• When administered with weak CYP3A4 inhibitors, the dose of Juxtapid should be decreased by half.
• Lomitapide increases plasma concentrations of both warfarin. Monitor international normalized ratio (INR) regularly, especially with Juxtapid dose adjustment.
• Simvastatin and lovastatin exposure increase with Juxtapid. Limit dose when co-administered with Juxtapid due to myopathy risk.
• Coadministration of lomitapide with P-gp substrates may increase the absorption of P-gp substrates. Dose reduction of the P-gp substrate should be considered when used concomitantly with lomitapide.
• 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 this medicine FDA approved?

• Lomitapide was approved for use in the United States in 2012, but its indications were limited to patients with homozygous familial hypercholesterolemia. Use of lomitapide can be associated with serum aminotransferase elevations and increase in hepatic fat.
• Because of the risk of liver injury, lomitapide is available only as a part of a "Risk Evaluation and Mitigation Strategy" [REMS] that requires regular monitoring of liver tests.

How should this medicine be used?

• Before treatment, measure ALT, AST, alkaline phosphatase, and total bilirubin; obtain a negative pregnancy test in females of reproductive potential; and initiate a low-fat diet supplying <20% of energy from fat.

Recommended dosage:

• Initiate treatment at 5 mg once daily. Titrate dose based on acceptable safety/tolerability, increase to 10 mg daily after at least 2 weeks; and then, at a minimum of 4-week intervals, to 20 mg, 40 mg, and up to the maximum recommended dose of 60 mg daily .
• Due to reduced absorption of fat-soluble vitamins/fatty acids. Take daily vitamin E, linoleic acid, alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) supplements .
• Take once daily, whole, with water and without food, at least 2 hours after evening meal.
• Patients with end-stage renal disease on dialysis or with baseline mild hepatic impairment should not exceed 40 mg daily.

Administration:

• Take Juxtapid exactly as your doctor tells you to take it.
• Your doctor will tell you how much Juxtapid to take and when to take it.
• Your doctor may change your dose of Juxtapid if needed.
• Do not change your Juxtapid dose yourself.
• Take Juxtapid 1 time each day at least 2 hours after your evening meal.
• Take Juxtapid with water.
• You should not take Juxtapid with food. Taking Juxtapid with food may cause stomach problems.
• Take Juxtapid capsules whole. Do not open, crush, dissolve, or chew capsules before swallowing. If you cannot swallow Juxtapid 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 Juxtapid. 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 Juxtapid. Juxtapid makes it harder for some nutrients to get into your body. Take Vitamin E and fatty acids each day while you take Juxtapid. Ask your doctor, nurse, or dietician how to add them to your diet.
• If you take too much Juxtapid, call your doctor right away.
• Do not stop Juxtapid unless your doctor tells you to stop it.
• If you miss a dose of Juxtapid, take your usual dose the next day at the usual time. If you stop taking Juxtapid for more than a week, talk to your doctor before restarting treatment.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Capsules: 5 mg, 10 mg, 20 mg, and 30 mg

This medicine is available in fallowing brand namesː

• Juxtapid

What side effects can this medication cause?

The most common side effects of this medicine include:

• diarrhea
• nausea
• vomiting
• indigestion
• stomach cramping/pain

Juxtapid can cause serious side effects, including:

• Liver problems
• Harm to your unborn baby
• problems absorbing certain nutrients
• gastrointestinal symptoms
• increased levels of certain blood thinners
• liver problems caused by certain drugs

What special precautions should I follow?

• Juxtapid may cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. Discontinue Juxtapid if pregnancy detected.
• Gastrointestinal adverse reactions occur in 93% of patients and could affect absorption of concomitant oral medications.
• Because of the risk of hepatotoxicity associated with Juxtapid therapy, Juxtapid is available through a restricted program under the REMS.
• Patients with rare, hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should avoid Juxtapid as this may result in diarrhea and malabsorption.

What to do in case of emergency/overdose?

• Treatment of overdosage:
• In the event of overdose, the patient should be treated symptomatically and supportive measures instituted as required.
• Liver-related tests should be monitored.
• Hemodialysis is unlikely to be beneficial given that lomitapide is highly protein bound.

Can this medicine be used in pregnancy?

• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Juxtapid during pregnancy.

Can this medicine be used in children?

• Safety and effectiveness have not been established in pediatric patients.

What are the active and inactive ingredients in this medicine?

• Active ingredient: lomitapide mesylate
• Inactive ingredients: pregelatinized starch, sodium starch glycolate, microcrystalline cellulose, lactose monohydrate, silicon dioxide, magnesium stearate
• Capsule shell: The capsule shells of all strengths contain gelatin and titanium dioxide; the 5 mg, 10 mg and 30 mg capsules also contain red iron oxide; and the 30 mg capsules also contain yellow iron oxide. The imprinting ink contains shellac, black iron oxide, and propylene glycol.

Who manufactures and distributes this medicine?

• Juxtapid is a registered trademark and the property of the Amryt Pharma Group All rights reserved.
• Manufactured for:

Amryt Pharmaceuticals DAC, Dublin, Ireland

What should I know about storage and disposal of this medication?

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

Lipid lowering medications

• Bile Acid Resins/Sequestrants

• • Cholestyramine
  • Colesevelam
  • Colestipol

• Fibrates
  • Clofibrate
  • Fenofibrate
  • Gemfibrozil

• Monoclonal Antibodies - Anti-PCSK9
  • Alirocumab
  • Evolocumab

• Niacin (Nicotinic Acid)

• • Omega-3 Fatty Acids,
  • Icosapent Ethyl
  • Omega-3 Acid Ethyl Esters
  • Omega-3 Carboxylic Acids

• Statins
  • Atorvastatin
  • Fluvastatin
  • Lovastatin
  • Pitavastatin
  • Pravastatin
  • Rosuvastatin
  • Simvastatin

• Miscellaneous
  • Ezetimibe
  • Lomitapide
  • Mipomersen

• Dailymed label info on Lomitapide
• FDA Lomitapide