Lomitapide

JUXTAPID is indicated as an adjunct to a low-fat diet and exercise and other low density lipoprotein cholesterol (LDL-C) therapies to reduce LDL-C in adults and pediatric patients aged 2 years and older with homozygous familial hypercholesterolemia (HoFH). JUXTAPID is a microsomal triglyceride transfer protein inhibitor indicated as an adjunct to a low-fat diet and exercise and other low-density lipoprotein cholesterol (LDL-C) therapies, to reduce LDL-C in adult and pediatric patients aged 2 years and older with HoFH.

JUXTAPID directly binds and inhibits microsomal triglyceride transfer protein (MTP), which resides in the lumen of the endoplasmic reticulum, thereby preventing the assembly of apo B-containing lipoproteins in enterocytes and hepatocytes. This inhibits the synthesis of chylomicrons and VLDL. The inhibition of the synthesis of VLDL leads to reduced levels of plasma LDL-C.

Before treatment, measure ALT, AST, alkaline phosphatase, and total bilirubin, obtain a negative pregnancy test in females of reproductive potential, initiate a low-fat diet supplying <20% of energy from fat or less than 30 grams of fat, whichever is less. The recommended initiation dosage is: 2 mg for patients aged 2 to 15 years. 5 mg for patients aged 16 years and older. Follow the titration schedule presented in Table 1 according to the patient's age. Select the dosage based on the recommended target LDL-C, safety, and tolerability. For pediatric patients, if a patient crosses over into the next age category, escalate the dose of JUXTAPID up to the maximum recommended dose applicable for the new age group. Measure transaminases prior to any dosage increase. If transaminases are abnormal, reduce or withhold dosing of JUXTAPID and monitor as recommended.

JUXTAPID is contraindicated in the following conditions: Pregnancy. Concomitant administration of JUXTAPID with moderate or strong CYP3A4 inhibitors, as this can increase JUXTAPID exposure. Patients with moderate or severe hepatic impairment (based on Child-Pugh category B or C) and patients with active liver disease, including unexplained persistent elevations of serum transaminases. Pregnancy. Concomitant use with strong or moderate CYP3A4 inhibitors. Moderate or severe hepatic impairment or active liver disease including unexplained persistent abnormal liver function tests.

Boxed warning (risk of hepatotoxicity juxtapid): can cause elevations in transaminases. In the adult clinical trial, 10 (34%) of the 29 patients treated with JUXTAPID had at least one elevation in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 times the upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR), or alkaline phosphatase. Embryo-Fetal Toxicity: 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 adult and 72% of pediatric patients and could affect absorption of concomitant oral medications.

The following important adverse reactions have been observed and are discussed in detail in other sections of the label: Risk of hepatotoxicity Reduced absorption of fat-soluble vitamins, and serum fatty acids Gastrointestinal adverse reactions Most common adverse reactions in adult patients (incidence ≥10%) are diarrhea, nausea, dyspepsia, vomiting, and abdominal pain. Most common adverse reactions in pediatric patients aged 5 to 17 years old (incidence ≥15%) are abdominal pain, alanine aminotransferase increased, aspartate aminotransferase increased, diarrhea, and vomiting.

CYP3A4 inhibitors increase exposure to lomitapide. 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. Follow the titration recommendations provided in the Full PI. Warfarin: Lomitapide increases plasma concentrations of 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. P-glycoprotein (P-gp) Substrates: Consider dose reduction of P-gp substrate because of possible increased absorption with JUXTAPID. Bile Acid Sequestrants: Separate JUXTAPID dosing by at least 4 hours.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (between 59°F and 86°F). Brief exposure to temperatures up to 40°C (104°F) may be tolerated provided the mean kinetic temperature does not exceed 25°C (77°F), however, such exposure should be minimized. Keep container tightly closed and protect from moisture.