Usual Adult Dose for Hyperlipidemia

Initial dose: 5 mg orally once a day
Maintenance dose: 5 to 60 mg orally once a day (should be individualized, taking into account the goal of therapy and the response to treatment)
Maximum dose: 60 mg orally once a day

Comments:

• Dose should be escalated gradually based on response, safety, and tolerability. The dose may be escalated using the following incremental schedule: 5 mg orally once a day for a minimum of 2 weeks, then 10 mg, 20 mg, 40 mg, 60 mg orally once a day after a minimum of 4 weekly intervals between each dose increase.
• Lomitapide should be taken with a full glass of water on an empty stomach at least 2 hours after the evening meal.

Usual Adult Dose for Homozygous Familial Hypercholesterolemia

Initial dose: 5 mg orally once a day
Maintenance dose: 5 to 60 mg orally once a day (should be individualized, taking into account the goal of therapy and the response to treatment)
Maximum dose: 60 mg orally once a day

Comments:

• Dose should be escalated gradually based on response, safety, and tolerability. The dose may be escalated using the following incremental schedule: 5 mg orally once a day for a minimum of 2 weeks, then 10 mg, 20 mg, 40 mg, 60 mg orally once a day after a minimum of 4 weekly intervals between each dose increase.
• Lomitapide should be taken with a full glass of water on an empty stomach at least 2 hours after the evening meal.

Renal Dose Adjustments

Mild, moderate, and severe renal impairment, including end-stage renal disease not yet receiving dialysis: Data not available (It is possible that patients with renal impairment who are not yet receiving dialysis may experience increases in lomitapide exposure exceeding 50%)

End-stage renal disease receiving dialysis: Maximum dose should not exceed 40 mg daily since lomitapide exposure in these patients increased approximately 50%.

Liver Dose Adjustments

Mild hepatic dysfunction (Child-Pugh A): Maximum dose not exceeding 40 mg orally once a day
Moderate to severe hepatic dysfunction or active liver disease including unexplained persistent abnormal liver function tests: Contraindicated

If hepatic dysfunction (ALT or AST elevations) develops during treatment:
3 x upper limit of normal (ULN) or more but less than 5 x ULN:

• Repeat test within one week to confirm elevation.
• If confirmed, reduce dose, repeat tests weekly, and obtain additional hepatic related tests (e.g., alkaline phosphatase, total bilirubin, and INR).
• If signs of hepatic dysfunction and/or levels do not fall below 3 x ULN within 4 weeks, withhold dose and refer patient to hepatologist for further investigation.
• Once elevation falls below 3 x ULN consider restarting at reduced dose and monitor hepatic function more frequently.

• Withhold dose and obtain additional hepatic related tests (e.g., alkaline phosphatase, total bilirubin, and INR).
• If signs of hepatic dysfunction and/or levels do not fall below 3 x ULN within 4 weeks, withhold dose and refer patient to hepatologist for further investigation.
• Once elevation falls below 3 x ULN consider restarting at reduced dose and monitor hepatic function more frequently.

Dose Adjustments

Transaminases should be measured prior to any increase in dose.

Weak CYP450 3A4 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) increase the exposure of lomitapide approximately 2-fold. Therefore, lomitapide dosage should not exceed 30 mg daily when it is used concomitantly with these inhibitors.

Patients should follow a low-fat diet supplying less than 20% of energy from fat and the dosage of lomitapide should be increased gradually to reduce the risk of gastrointestinal adverse events.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for lomitapide. This includes elements to assure safe use and an implementation system. For additional information: www.fda.gov/REMS

BOXED WARNINGS:

• HEPATOTOXICITY: Elevations in transaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]), some greater than or equal to 3 times upper limit of normal (ULN); induction of hepatic steatohepatitis, which can progress to cirrhosis over several years.

• PEDIATRIC PATIENTS: Safety and efficacy have not been established in patients younger than 18 years.

Dialysis

Maximum dose should not exceed 40 mg daily since lomitapide exposure in these patients increased approximately 50%.

Other Comments

Before initiating therapy with lomitapide:

• Measure transaminases (ALT, AST), alkaline phosphatase, and total bilirubin.
• Obtain a negative pregnancy test in females of reproductive potential.
• Initiate a low-fat diet supplying less than 20% of energy from fat.

• Lomitapide should be taken with a glass of water on an empty stomach at least 2 hours after the evening meal. Food may increase gastrointestinal adverse reactions.

• Treatment should be initiated by a clinician experienced in the management of lipid disorders.
• Initiate a low fat diet supplying less than 20% of energy from fat prior to initiating lomitapide treatment.
• Patients treated with lomitapide should take daily supplements that contain 400 IU vitamin E, at least 200 mg linoleic acid, 110 mg eicosapentaenoic acid, 210 mg alpha linolenic acid, and 80 mg docosahexaenoic acid per day.

• Grapefruit juice should be eliminated from the diet while being treated with lomitapide.
• Alcohol consumption is not recommended during treatment.
• Lomitapide may have a minor effect on the ability to drive or operate machinery.

Frequently asked questions

• What is the mechanism of action for Juxtapid (lomitapide)?
• Is Juxtapid FDA-approved as a high cholesterol treatment?