Indicated for:

Homozygous Familial Hypercholesterolemia:

• As an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available, to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH).

The safety and effectiveness of JUXTAPID have not been established in patients with hypercholesterolemia who do not have HoFH, including those with heterozygous familial hypercholesterolemia (HeFH). Prescribe JUXTAPID only to patients with a clinical or laboratory diagnosis consistent with HoFH. 

The effect of JUXTAPID on cardiovascular morbidity and mortality has not been determined.

Because of the risk of hepatotoxicity, JUXTAPID is available only through a restricted program called the JUXTAPID REMS PROGRAM.

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

During treatment, adjust the dose of JUXTAPID if the ALT or AST are ≥3x ULN. Discontinue JUXTAPID for clinically significant liver toxicity.

Measure liver-related tests (ALT and AST, at a minimum) at least every 3 months and before any increase in dose.

JUXTAPID can cause elevations in transaminases.

If transaminases are abnormal, reduce or withhold dosing of JUXTAPID and monitor as recommended  Discontinue JUXTAPID for persistent or clinically significant elevations.

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 identify the probable cause.

JUXTAPID increases hepatic fat (hepatic steatosis) with or without concomitant increases in transaminases. Hepatic steatosis associated with JUXTAPID treatment may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis.

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.

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.

Patients with mild hepatic impairment (Child-Pugh A) should not exceed 40 mg daily.

Patients treated with JUXTAPID should take daily supplements that contain 400 international units vitamin E and at least 200 mg linoleic acid, 210 mg ALA, 110 mg EPA, and 80 mg DHA. Patients with chronic bowel or pancreatic diseases that predispose to malabsorption may be at increased risk for deficiencies in these nutrients with use of JUXTAPID.

There have been postmarketing reports of severe diarrhea with the use of JUXTAPID, including patients being hospitalized because of diarrhea-related complications such as volume depletion.

JUXTAPID is contraindicated:

• In pregnancy
• Concomitant use with strong or moderate cytochrome P450 3A4 (CYP3A4) inhibitors
• Moderate or severe hepatic impairment or active liver disease (based on Child-Pugh category B or C) and patients with active liver disease, including unexplained persistent elevations of serum transaminases

JUXTAPID has not been studied concomitantly with other LDL-lowering agents that can also increase hepatic fat. Therefore, the combined use of such agents is not recommended.

Grapefruit juice must be omitted from the diet while being treated with JUXTAPID. 

Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury. It is recommended that patients taking JUXTAPID should not consume more than one alcoholic drink per day.

The risk of myopathy, including rhabdomyolysis, with simvastatin and lovastatin monotherapy is dose related.

JUXTAPID is contraindicated with concomitant use of moderate and strong cytochrome P450 3A4 (CYP3A4) inhibitors.

Caution should be exercised when JUXTAPID is used with other medications known to have potential for hepatotoxicity, such as isotretinoin, amiodarone, acetaminophen (>4 g/day for ≥3 days/week), methotrexate, tetracyclines, and tamoxifen.

Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury. It is recommended that patients taking JUXTAPID should not consume more than one alcoholic drink per day.

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 co-administered with oral contraceptives, in which case the maximum recommended lomitapide dosage is 40 mg daily.

Weak CYP3A4 inhibitors can increase the exposure of lomitapide approximately 2-fold; therefore, when JUXTAPID is administered with weak CYP3A4 inhibitors, the dose of JUXTAPID should be decreased by half.

Lomitapide approximately doubles the exposure to simvastatin; therefore, it is recommended to reduce the dose of simvastatin 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).

JUXTAPID increases the plasma concentrations of warfarin. Increases in the dose of JUXTAPID may lead to supratherapeutic anticoagulation, and decreases in the dose of JUXTAPID may lead to subtherapeutic anticoagulation. Difficulty controlling INR contributed to early discontinuation from the HoFH clinical trial for one of five patients taking concomitant warfarin. Patients taking warfarin should undergo regular monitoring of the INR, especially after any changes in JUXTAPID dosage.

Lomitapide is an inhibitor of P-glycoprotein (P-gp). Co-administration 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.

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.

JUXTAPID is contraindicated during pregnancy because JUXTAPID may cause fetal harm when administered to a pregnant woman.

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.

GoToSource

• Dosage greater than 40 mg daily in patients with end-stage renal disease on dialysis or with baseline mild hepatic impairment. GoToSource

• Dosage greater than 60 mg daily. GoToSource

• Dosage greater than 30 mg daily when used with weak CYP3A4 inhibitors. GoToSource

• Use in patients under the age of 18. GoToSource

• Hypercholesterolemia in patients who do not have HoFH. GoToSource

• Prevention of acute coronary syndromes. GoToSource

Elevation in transaminases and increased hepatic fat including hepatic steatosis (fatty liver disease), gastrointestinal disturbances and steatorrhea (excess fat in stools). GoToSource

Increased incidence of tumors of the liver and small bowel. GoToSource

Nasopharyngitis, constipation, gastroenteritis and angina pectoris. GoToSource

No major injury lawsuits reported.