Lomitapide Mesylate

1 INDICATIONS AND USAGE JUXTAPID is a microsomal triglyceride transfer protein inhibitor indicated 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) ( 1 ). Limitations of Use 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) ( 1 ). The effect of JUXTAPID on cardiovascular morbidity and mortality has not been determined ( 1 ).

6 ADVERSE REACTIONS The following important adverse reactions have been observed and are discussed in detail in other sections of the label: Risk of hepatotoxicity [see Warnings and Precautions (5.1) ] Reduced absorption of fat-soluble vitamins, and serum fatty acids [see Warnings and Precautions (5.4) ] Gastrointestinal adverse reactions [see Warnings and Precautions (5.5) ] Most common adverse reactions (incidence ≥28%) are diarrhea, nausea, vomiting, dyspepsia, and abdominal pain ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Amryt Pharmaceuticals DAC at 1-855-303-2347 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to JUXTAPID during pregnancy. For additional information visit www.JUXTAPID.com or call the Global Lomitapide Pregnancy Exposure Registry (PER) at 1-877-902-4099. Healthcare professionals are encouraged to call the PER at 1-877-902-4099 to enroll patients who become pregnant during JUXTAPID treatment.

WARNING: 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) ≥3× upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR), or alkaline phosphatase [see Warnings and Precautions (5.1) ]. 5 WARNINGS AND PRECAUTIONS 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 ( 5.3 , 8.1 , 8.3 ). Gastrointestinal adverse reactions occur in 93% of patients and could affect absorption of concomitant oral medications ( 5.5 ). 5.1 Risk of Hepatotoxicity JUXTAPID can cause elevations in transaminases and hepatic steatosis, as described below [see Warnings and Precautions (5.2) ] . To what extent JUXTAPID-associated hepatic steatosis promotes the elevations in transaminases is unknown. 4 CONTRAINDICATIONS JUXTAPID is contraindicated in the following conditions: Pregnancy [see Warnings and Precautions (5.3) and Use in Specific Populations (8.1) ] . Concomitant administration of JUXTAPID with moderate or strong CYP3A4 inhibitors, as this can increase JUXTAPID exposure [see Warnings and Precautions (5.6) , Drug Interactions (7.1) , and Clinical Pharmacology (12.3) ].