Microsomal triglyceride transfer protein (MTP) inhibitor.
Lomitapide mesylate 5mg, 10mg, 20mg; caps.
As an adjunct to low-fat diet and other lipid-lowering treatments, including LDL apheresis where available, to reduce LDL-C, total cholesterol, apo B, and non-HDL-C in patients with homozygous familial hypercholesterolemia (HoFH). Not for patients with hypercholesterolemia who do not have HoFH. Effect on cardiovascular morbidity, mortality has not been determined.
Juxtapid directly binds and inhibits 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.
The safety and efficacy of Juxtapid were evaluated in a single-arm, open-label, 78-week trial involving 29 adults with HoFH. Patients were instructed to adhere to a low-fat diet and to take dietary supplements. Juxtapid was initiated at 5mg daily and gradually escalated to doses of 10mg, 20mg, 40mg, up to 60mg, based on tolerability and acceptable liver enzymes levels.When added to the existing lipid-lowering therapy of the HoFH patients in the study, Juxtapid significantly reduced LDL-C from a baseline average of 336mg/dL to 190mg/dL (40% mean reduction) at Week 26 in the intent-to-treat population with last observation carried forward for the patients who discontinued prematurely. LDL-C was reduced by an average of 50% for the 23 patients who completed the study through Week 26. After Week 26, during the safety phase, adjustments to concomitant lipid-lowering treatments were allowed. Average reductions in LDL-C were sustained during chronic therapy.
Before starting: measure ALT, AST, alkaline phosphatase, total bilirubin; obtain (–) pregnancy test, initiate low-fat diet supplying <20% of energy from fat. Swallow whole, take 2hrs after PM meal. Initially 5mg once daily. Titrate dose based on safety and tolerability: increase to 10mg daily after at least 2 weeks; and then at a minimum of 4-week intervals, to 20mg, 40mg, and up to max 60mg daily. Supplement with daily Vit.E, linoleic acid, ALA, EPA, and DHA. ESRD on dialysis or baseline mild hepatic impairment: max 40mg daily. Concomitant weak CYP3A4 inhibitors (eg, alprazolam, amiodarone, amlodipine, atorvastatin, bicalutamide, cilostazol, cimetidine, cyclosporine, fluoxetine, fluvoxamine, ginkgo, goldenseal, isoniazid, lapatinib, nilotinib, oral contraceptives, pazopanib, ranitidine, ranolazine, tipranavir/ritonavir, ticagrelor, zileuton): max 30mg daily. Dose adjustments for elevated transaminases: see full labeling.
<18yrs: not studied.
Pregnancy (Cat.X). Concomitant moderate (eg, amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil) or strong (eg, boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) CYP3A4 inhibitors. Moderate to severe hepatic impairment, active liver disease, unexplained persistent elevations of serum transaminases.
Elevations in transaminases and increases in hepatic fat may occur; measure ALT, AST, alkaline phosphatase, total bilirubin before initiating therapy and then ALT, AST regularly and before any dose increase. Adjust dose if ALT or AST are ≥3xULN; discontinue if clinically significant liver toxicity. Adhere to low-fat diet to reduce risk of GI effects. Galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption: avoid. Chronic bowel or pancreatic diseases that predispose to malabsorption. Renal impairment. Females: use effective contraception. Nursing mothers: do not use.
See Contraindications and Adults. Potentiated by CYP3A4 inhibitors (omit grapefruit juice). Reduce dose of simvastatin by 50%, consider reducing lovastatin dose. Potentiates warfarin; monitor INR. Consider dose reduction of P-gp substrates. Max one alcoholic drink/day. Caution with other hepatotoxic drugs. Separate bile acid sequestrants by at least 4hrs.
GI upset, abdominal pain; hepatotoxicity (including steatohepatitis, hepatic failure) possible, reduced absorption of fat soluble vitamins.
Juxtapid REMS Program: only certified providers and pharmacies may prescribe and distribute.