Homozygous Familial Hypercholesterolemia

JUXTAPID is 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).

Limitations of Use

• The safety and effectiveness of JUXTAPID have not been established in patients with hypercholesterolemia who do not have HoFH.
• The effect of JUXTAPID on cardiovascular morbidity and mortality has not been determined.

Initiation and Maintenance of Therapy

Before beginning treatment with JUXTAPID:

• Measure transaminases (ALT, AST), alkaline phosphatase, and total bilirubin [see WARNINGS AND PRECAUTIONS];
• Obtain a negative pregnancy test in females of reproductive potential [see WARNINGS AND PRECAUTIONS]; and,
• Initiate a low-fat diet supplying < 20% of energy from fat [see WARNINGS AND PRECAUTIONS].

The recommended starting dosage of JUXTAPID is 5 mg once daily, and the dose should be escalated gradually based on acceptable safety and tolerability. Transaminases should be measured prior to any increase in dose [see WARNINGS AND PRECAUTIONS]. The maintenance dosage of JUXTAPID should be individualized, taking into account patient characteristics such as goal of therapy and response to treatment, to a maximum of 60 mg daily as described in Table 1. Modify dosing for patients taking concomitant CYP3A4 inhibitors, renal impairment, or baseline hepatic impairment. Dose adjustments are also required for patients who develop transaminase values ≥ 3x the upper limit of normal (ULN) during treatment with JUXTAPID.

Table 1: Recommended Regimen for Titrating Dosage

To reduce the risk of developing a fat-soluble nutrient deficiency due to JUXTAPID's mechanism of action in the small intestine, patients treated with JUXTAPID should take daily supplements that contain 400 international units vitamin E and at least 200 mg linoleic acid, 210 mg alpha-linolenic acid (ALA), 110 mg eicosapentaenoic acid (EPA), and 80 mg docosahexaenoic acid (DHA) [see WARNINGS AND PRECAUTIONS].

Administration

JUXTAPID should be taken once daily with a glass of water, without food, at least 2 hours after the evening meal because administration with food may increase the risk of gastrointestinal adverse reactions [see WARNINGS AND PRECAUTIONS]. Patients should swallow JUXTAPID capsules whole. Capsules should not be opened, crushed, dissolved, or chewed.

Dosing with Cytochrome P450 3A4 Inhibitors

JUXTAPID is contraindicated with concomitant use of moderate and strong cytochrome P450 3A4 (CYP3A4) inhibitors [see CONTRAINDICATIONS and DRUG INTERACTIONS].

The recommended maximum dosage of JUXTAPID is 30 mg daily with concomitant use of weak CYP3A4 inhibitors (such as alprazolam, amiodarone, amlodipine, atorvastatin, bicalutamide, cilostazol, cimetidine, cyclosporine, fluoxetine, fluvoxamine, ginkgo, goldenseal, isoniazid, lapatinib, nilotinib, oral contraceptives, pazopanib, ranitidine, ranolazine, tipranavir/ritonavir, ticagrelor, zileuton) [see DRUG INTERACTIONS].

Dose Modification Based on Elevated Transaminases

Table 2 summarizes recommendations for dose adjustment and monitoring for patients who develop elevated transaminases during therapy with JUXTAPID [see WARNINGS AND PRECAUTIONS].

Table 2: Dose Adjustment and Monitoring for Patients with Elevated Transaminases

If transaminase elevations are accompanied by clinical symptoms of liver injury (such as nausea, vomiting, abdominal pain, fever, jaundice, lethargy, flu-like symptoms), increases in bilirubin ≥ 2x ULN, or active liver disease, discontinue treatment with JUXTAPID and investigate to identify the probable cause [see WARNINGS AND PRECAUTIONS].

Dosing in Patients with Renal Impairment

Patients with end-stage renal disease receiving dialysis should not exceed 40 mg daily. There are no data available to guide dosing in other patients with renal impairment [see Use In Specific Populations].

Dosing in Patients with Baseline Hepatic Impairment

Patients with mild hepatic impairment (Child-Pugh A) should not exceed 40 mg daily [see Use In Specific Populations].

Dosage Forms And Strengths

5 mg: Orange/orange hard gelatin capsule printed with black ink “A733” and “5 mg”
10 mg: Orange/white hard gelatin capsule printed with black ink “A733” and “10 mg”
20 mg: White/white hard gelatin capsule printed with black ink “A733” and “20 mg”

Storage And Handling

5 mg capsules

Orange/orange hard gelatin capsule printed with black ink “A733” and “5 mg”

Bottles of 28 NDC 76431-105-01

10 mg capsules

Orange/white hard gelatin capsule printed with black ink “A733” and “10 mg”

Bottles of 28 NDC 76431-110-01

20 mg capsules

White/white hard gelatin capsule printed with black ink “A733” and “20 mg”

Bottles of 28 NDC 76431-120-01

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (between 59°F and 86°F). Brief exposure to temperatures up to 40°C (104°F) may be tolerated provided the mean kinetic temperature does not exceed 25°C (77°F); however, such exposure should be minimized. Keep container tightly closed and protect from moisture.

Aegerion Pharmaceuticals, Inc., 101 Main Street, Suite 1850, Cambridge, MA 02142. Tel: 617-500-7867. Fax: 617-945-7968. Revised: December 2012

Last reviewed on RxList: 1/7/2013
This monograph has been modified to include the generic and brand name in many instances.