JUXTAPID

). 4 Drug-Drug Interactions). 4 Drug-Drug Interactions). • Pregnancy (see Pregnant Women). • Patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency, or glucose-galactose malabsorption. • Patients who are hypersensitive to JUXTAPID, or to any ingredient in the formulation or component of the container.

For a complete listing, see

, Table 4). The long term consequences of hepatic steatosis associated with JUXTAPID treatment are unknown, including risk of progression to steatohepatitis, fibrosis and cirrhosis. Accordingly, baseline assessment of hepatic fibrosis should be carried out using appropriate imaging technology, and subsequently repeated on an intermittent basis.

Baseline and subsequent intermittent assessment using laboratory markers of hepatic inflammation, as well as of fibrosis, should also be instituted to identify the potential development of steatohepatitis, fibrosis and cirrhosis. 1 Pediatrics).

Renal Impairment:

Patients with end-stage renal disease receiving dialysis should not exceed 40 mg JUXTAPID daily. There are no data available to guide dosing in other patients with renal impairment.

Hepatic Impairment:

Patients with mild hepatic impairment (Child-Pugh A) should not exceed 40 mg JUXTAPID daily (see 10 CLINICAL PHARMACOLOGY). JUXTAPID is contraindicated in patients with moderate to severe hepatic impairment (see 2 CONTRAINDICATIONS).

Women of Reproductive Potential:

JUXTAPID is contraindicated during pregnancy (see 2 CONTRAINDICATIONS). Before initiating treatment in women of reproductive potential, the absence of pregnancy should be confirmed, appropriate advice on effective methods of Product Monograph JUXTAPID (Lomitapide) Page 8 of 36 contraception provided, and effective contraception initiated, as appropriate.

Oral contraceptives are weak CYP3A4 inhibitors; dosing with lomitapide should be separated by 12 hours (see

General Concomitant Use of CYP 3A4 Inhibitors CYP 3A4 inhibitors increase the exposure of lomitapide, with strong inhibitors increasing exposure approximately 27-fold. Concomitant use of strong or moderate CYP 3A4 inhibitors with JUXTAPID (lomitapide) is contraindicated (see 2 CONTRAINDICATIONS).

If treatment with strong or moderate CYP 3A4 inhibitors is unavoidable, JUXTAPID should be stopped during the course of treatment. Grapefruit juice must be omitted from the diet during treatment with JUXTAPID. Weak CYP3A4 inhibitors are expected to increase the exposure of lomitapide when taken simultaneously.

When administered with atorvastatin, the dose of JUXTAPID should either be taken 12 hours apart or be decreased by half. 4 Drug-Drug Interactions and 4 DOSAGE AND ADMINISTRATION). Concomitant Use with HMG-CoA Reductase Inhibitors JUXTAPID increases plasma concentrations of statins.

The risk of myopathy, including rhabdomyolysis, is dose related with use of statins. 4 Drug-Drug Interactions, Table 9). Accordingly, 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) (see 2 CONTRAINDICATIONS).

The effect of lomitapide on the systemic exposure of other statins is less than that seen with simvastatin (see 9 DRUG INTERACTIONS, Table 9), and is dependent both on the dose of statin and that of lomitapide administered. Dose adjustment of statin may be required (see 4 DOSAGE AND ADMINISTRATION).

Product Monograph JUXTAPID (Lomitapide) Page 10 of 36 Use with Warfarin Lomitapide increases the plasma concentrations of warfarin (see 9 DRUG INTERACTIONS, Table 9). Patients taking warfarin should undergo more frequent monitoring of the INR, especially after any changes in JUXTAPID dosage (see 4 DOSAGE AND ADMINISTRATION).

• Patients with moderate or severe hepatic impairment, including those with unexplained persistent abnormal liver function tests (see Hepatic Steatosis). • Patients with a known significant, chronic bowel disease, such as inflammatory bowel disease or malabsorption (see