Lomitapide Mesylate (1 brand name, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- JUXTAPID
Boxed Warning
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. In the pediatric clinical trial (5 to 17 years of age), 6 (14%) of the 43 patients experienced elevations in ALT and/or AST ≥ 3 times ULN. No concomitant clinically meaningful elevations in total bilirubin or alkaline phosphatase were observed [see Warnings and Precautions (5.1)]. JUXTAPID also increases hepatic fat, with or without concomitant increases in transaminases. The median absolute increase in hepatic fat in adult patients was 6% after both 26 and 78 weeks of treatment, from 1% at baseline, measured by magnetic resonance spectroscopy (MRS). The median absolute increase in hepatic fat in pediatric patients aged 5 to 17 years was 4% after 24 weeks and 104 weeks of treatment, from 3% at baseline, measured by nuclear magnetic resonance (NMR). Hepatic steatosis associated with JUXTAPID treatment may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis [see Warnings and Precautions (5.1)]. 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 JUXTAPID if the ALT or AST are ≥3 times ULN. Discontinue JUXTAPID for clinically significant liver toxicity [see Dosage and Administration (2.7) and Warnings and Precautions (5.1)]. Because of the risk of hepatotoxicity, JUXTAPID is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the JUXTAPID REMS Program [see Warnings and Precautions (5.2)]. Prescribe JUXTAPID only to patients with a clinical or laboratory diagnosis
Indications and Usage
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).
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)]. 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 [see Warnings and Precautions (5.1) and Use in Specific Populations (8.7)].
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)]
Mechanism of Action
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.
Overdosage
There is no specific treatment in the event of overdose of JUXTAPID. 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.