Interaction between weak CYP3A4 inhibitors and lomitapide has not been studied. Based on cross-studies comparisons, the lomitapide exposure approximately doubles in the presence of oral contraceptives, which are weak CYP3A4 inhibitors. Do not exceed 30 mg daily of JUXTAPID when used concomitantly with weak CYP3A4 inhibitors. [See Dosage and Administration (2.3) and Drug Interactions (7.2)].

Effect of Lomitapide on other Drugs

Table 6 summarizes the effects of lomitapide on the AUC and Cmax of coadministered drugs.

Table 6: Effect of Lomitapide on the Systemic Exposure of Coadministered Drugs  a 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). Refer to the simvastatin prescribing information for additional dosing recommendations.
b Patients taking warfarin should undergo regular monitoring of the INR, especially after any changes in lomitapide dosage. QD = once daily; INR = international normalized ratio; ↑ = increase; ↓ = decrease
COADMINISTERED DRUG DOSING OF
COADMINISTERED
DRUG DOSING OF
LOMITAPIDE CHANGE OF COADMINISTERED DRUG
EXPOSURE WITH / WITHOUT
LOMITAPIDE
    AUC Cmax
Dosage adjustment necessary when coadministered with lomitapide
Simvastatina 40 mg single dose

20 mg single dose
 60 mg QD × 7 days

10 mg QD x 7 days
 Simvastatin
Simvastatin acid

Simvastatin
Simvastatin acid ↑ 99%
↑ 71%

↑ 62%
↑ 39%   ↑ 102%
↑ 57%

↑ 65%
↑ 35%
Warfarinb 10 mg single dose 60 mg QD x 12 days R(+) warfarin
S(-) warfarin
INR ↑ 28%
↑ 30%

↑ 7% ↑ 14%
↑ 15%

↑ 22%
No dosing adjustments required for the following:
Atorvastatin 20 mg single dose
20 mg single dose 60 mg QD × 7 days
10 mg QD × 7 days Atorvastatin acid
Atorvastatin acid ↑ 52%
↑ 11% ↑ 63%
↑ 19%
Rosuvastatin 20 mg single dose
20 mg single dose 60 mg QD × 7 days
10 mg QD × 7 days Rosuvastatin
Rosuvastatin ↑ 32%
↑ 2% ↑ 4%
↑ 6%
Fenofibrate, micronized 145 mg single dose 10 mg QD × 7 days Fenofibric acid ↓ 10% ↓ 29%
Ezetimibe 10 mg single dose 10 mg QD × 7 days Total
ezetimibe ↑ 6% ↑ 3%
Extended release niacin 1000 mg single dose 10 mg QD × 7 days Nicotinic acid
Nicotinuric acid ↑ 10%
↓ 21% ↑ 11%
↓ 15%
Ethinyl estradiol 0.035 mg QD x 28 days 50 mg QD x 8 days Ethinyl estradiol ↓ 8% ↓ 8%
Norgestimate 0.25 mg QD x 28 days 50 mg QD x 8 days 17-Deacetyl norgestimate ↑ 6% ↑ 2%
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13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityIn a 2-year dietary carcinogenicity study in mice, lomitapide was administered at doses of 0.3, 1.5, 7.5, 15, or 45 mg/kg/day. There were statistically significant increases in the incidences of liver adenomas and carcinomas in males at doses ≥1.5 mg/kg/day (≥2-times the MRHD at 60 mg based on AUC) and in females at ≥7.5 mg/kg/day (≥10-times the human exposure at 60 mg based on AUC). Incidences of small intestinal carcinomas in males and combined adenomas and carcinomas