Juxtapid

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Juxtapid

Classes

Microsomal Triglyceride Transfer Protein (MTP) Inhibitors

Administration

Hazardous Drugs Classification
NIOSH 2016 List: Group 3
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown. Eye/face and respiratory protection may be needed during preparation and administration.

Oral Administration

Lomitapide should be administered without food at least 2 hours after the evening meal; administration with food may increase the risk of gastrointestinal adverse reactions.

Oral Solid Formulations

Instruct patients to take lomitapide with a glass of water.
The capsules should not be opened, crushed, dissolved, or chewed.

Adverse Reactions
Severe

diarrhea / Early / 14.0-14.0
elevated hepatic enzymes / Delayed / 14.0-14.0
vomiting / Early / 10.0-10.0
abdominal pain / Early / 7.0-7.0
hepatotoxicity / Delayed / Incidence not known

Moderate

steatosis / Delayed / 78.0-78.0
chest pain (unspecified) / Early / 24.0-24.0
constipation / Delayed / 21.0-21.0
angina / Early / 10.0-10.0
palpitations / Early / 10.0-10.0

Mild

nausea / Early / 65.0-65.0
dyspepsia / Early / 38.0-38.0
weight loss / Delayed / 24.0-24.0
flatulence / Early / 21.0-21.0
influenza / Delayed / 21.0-21.0
pharyngitis / Delayed / 17.0-17.0
fatigue / Early / 17.0-17.0
back pain / Delayed / 14.0-14.0
tenesmus / Delayed / 10.0-10.0
gastroesophageal reflux / Delayed / 10.0-10.0
fever / Early / 10.0-10.0
nasal congestion / Early / 10.0-10.0
headache / Early / 10.0-10.0
dizziness / Early / 10.0-10.0
hypovitaminosis / Delayed / Incidence not known
myalgia / Early / Incidence not known
alopecia / Delayed / Incidence not known

Boxed Warning
Ethanol ingestion, hepatic disease, hepatotoxicity, requires an experienced clinician

Because of the risk of hepatotoxicity, lomitapide is available only through a Risk Evaluation and Mitigation Strategy (REMS) program called the JUXTAPID REMS Program, and requires an experienced clinician to carefully monitor the patient in accordance with the REMS program recommendations. Lomitapide may cause elevations in serum transaminases. Lomitapide also increases hepatic fat, with or without concomitant increases in transaminases. The resultant increase in hepatic fat may cause steatohepatitis, which may cause progressive liver disease that may lead to cirrhosis over several years. Despite the serious potential for hepatotoxicity, hepatic failure has not been reported. Measure liver function tests (LFTs) such as ALT, AST, alkaline phosphatase, and total bilirubin prior to initiation of lomitapide therapy. Lomitapide is contraindicated in patients with moderate or severe hepatic impairment (based on Child-Pugh category B or C) or active hepatic disease, including unexplained persistent elevations of serum transaminases. If the baseline liver-related tests are abnormal, initiation of lomitapide may be considered after an appropriate work-up and the baseline abnormalities are explained or resolved. During the first year, measure LFTs prior to each increase in dose or monthly, whichever occurs first. After the first year, do these tests at least every 3 months and before any increase in dose. If elevations of transaminases are observed, adjust the lomitapide dose. At any time during treatment, if elevations are persistent or clinically significant, discontinue lomitapide. If transaminase elevations are accompanied by clinical symptoms of liver injury or active liver disease (such as nausea, vomiting, abdominal pain, fever, jaundice, lethargy, flu-like symptoms) or increases in bilirubin to 2 times the upper limit of normal (ULN) or greater, or if the patient has active liver disease, discontinue treatment with lomitapide and identify the probable cause. Ethanol ingestion may increase levels of hepatic fat and induce or exacerbate liver injury. It is recommended that patients taking lomitapide should not consume more than one alcoholic drink per day. Caution should be exercised if the drug is used along with other medications with a known potential for liver toxicity. The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.

Common Brand Names

Juxtapid

Dea Class

Rx

Description

Microsomal triglyceride transfer protein inhibitor
Used to lower LDL, total, and non-HDL cholesterol and apo-B concentrations in patients with homozygous familial hypercholesterolemia
Boxed warning for hepatotoxicity; prescribers, pharmacies, and patients must enroll in the Juxtapid REMS program

Dosage And Indications
For the treatment of homozygous familial hypercholesterolemia (HoFH) as an adjunct to low-fat diet and other lipid-lowering treatments.
NOTE: Lomitapide is indicated as an adjunct to low-fat diet and other lipid-lowering treatments, including low-density lipoprotein 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).
Oral dosage Adults

5 mg PO once daily, initially. May increase dose to 10 mg PO once daily after at least 2 weeks, then 20 mg PO once daily after at least 4 weeks, then 40 mg PO once daily after at least 4 weeks, then 60 mg PO once daily after at least 4 weeks. Measure transaminases prior to initiation of therapy and before any dose increase. Max: 60 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Dosing Considerations
Hepatic Impairment

Child-Pugh A (mild hepatic impairment): Do not exceed 40 mg/day PO.
Child-Pugh B or C (moderate or severe hepatic impairment): Use is contraindicated.

Renal Impairment

CrCl more than 80 mL/min: No dosage adjustment is needed.
CrCl 80 mL/min or less: Data to guide dosage adjustment recommendations in patients with mild, moderate, or severe renal impairment, including those with end-stage renal disease not yet receiving dialysis, are not available. It is possible that patients with renal impairment who are not yet receiving dialysis may experience a 50% or greater increase in lomitapide exposure.
 
Intermittent hemodialysis
Do not exceed 40 mg/day PO lomitapide in patients with end-stage renal disease receiving hemodialysis. Lomitapide exposure increased approximately 50% in these patients compared with healthy volunteers.

Drug Interactions

Acetaminophen: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Aspirin: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Caffeine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Chlorpheniramine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Codeine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Dextromethorphan: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Diphenhydramine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Hydrocodone: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Ibuprofen: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Oxycodone: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Phenylephrine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Acetaminophen; Pseudoephedrine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Adagrasib: (Contraindicated) Concomitant use of adagrasib and lomitapide is contraindicated; if treatment with adagrasib is unavoidable, lomitapide should be stopped during treatment. Adagrasib is a strong CYP3A inhibitor and lomitapide is a CYP3A substrate. Coadministration with another strong CYP3A inhibitor increased lomitapide exposure approximately 27-fold.
Afatinib: (Moderate) If the concomitant use of lomitapide and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of lomitapide. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate and lomitapide is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
Aliskiren: (Moderate) Concomitant use of lomitapide and aliskiren may result in increased serum concentrations of aliskiren. According to the manufacturer of lomitapide, dose reduction of aliskiren should be considered during concurrent use. Lomitapide is an inhibitor of P-glycoprotein (P-gp) and aliskiren is a P-gp substrate.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of lomitapide and aliskiren may result in increased serum concentrations of aliskiren. According to the manufacturer of lomitapide, dose reduction of aliskiren should be considered during concurrent use. Lomitapide is an inhibitor of P-glycoprotein (P-gp) and aliskiren is a P-gp substrate.
Alprazolam: (Major) Concomitant use of lomitapide and alprazolam may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Alprazolam is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Amiodarone: (Major) Concomitant use of lomitapide and amiodarone may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Amiodarone is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as amiodarone. The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Amlodipine: (Major) Concomitant use of lomitapide and amlodipine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Amlodipine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Amlodipine; Atorvastatin: (Major) Concomitant use of lomitapide and amlodipine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Amlodipine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. (Major) Concomitant use of lomitapide and atorvastatin may result in increased lomitapide concentrations. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Atorvastatin is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Amlodipine; Benazepril: (Major) Concomitant use of lomitapide and amlodipine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Amlodipine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Amlodipine; Celecoxib: (Major) Concomitant use of lomitapide and amlodipine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Amlodipine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Amlodipine; Olmesartan: (Major) Concomitant use of lomitapide and amlodipine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Amlodipine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Amlodipine; Valsartan: (Major) Concomitant use of lomitapide and amlodipine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Amlodipine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Major) Concomitant use of lomitapide and amlodipine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Amlodipine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Concomitant use of clarithromycin and lomitapide is contraindicated. If treatment with clarithromycin is unavoidable, lomitapide should be stopped during the course of treatment. Markedly increased transaminases have been reported with coadministration. Clarithromycin is a strong CYP3A4 inhibitor and lomitapide is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor increased lomitapide exposure approximately 27-fold.
Aprepitant, Fosaprepitant: (Contraindicated) Concomitant use of multi-day regimens of aprepitant with lomitapide is contraindicated; if treatment with multi-day aprepitant is unavoidable, lomitapide should be stopped during treatment. Do not exceed a lomitapide dose of 30 mg if using with a single dose of aprepitant 125 mg or 40 mg. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor. A strong inhibitor increased the exposure of lomitapide by 27-fold; therefore, the exposure to lomitapide will likely increase significantly in the presence of moderate inhibitors as well. When administered as a single oral or single intravenous dose, the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate.
Asciminib: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with asciminib is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Asciminib is a weak CYP3A inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A inhibitors.
Atazanavir: (Contraindicated) Concomitant use of atazanavir and lomitapide is contraindicated. If treatment with atazanavir is unavoidable, lomitapide should be stopped during the course of treatment. Atazanavir is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use.
Atazanavir; Cobicistat: (Contraindicated) Concomitant use of atazanavir and lomitapide is contraindicated. If treatment with atazanavir is unavoidable, lomitapide should be stopped during the course of treatment. Atazanavir is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use. (Contraindicated) Concomitant use of cobicistat and lomitapide is contraindicated due to the potential of markedly increased lomitapide concentrations and the associated elevation of serum transaminases. Cobicistat is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence another strong CYP3A4 inhibitor.
Atorvastatin: (Major) Concomitant use of lomitapide and atorvastatin may result in increased lomitapide concentrations. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Atorvastatin is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Atorvastatin; Ezetimibe: (Major) Concomitant use of lomitapide and atorvastatin may result in increased lomitapide concentrations. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Atorvastatin is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Avacopan: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with avacopan is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Avacopan is a weak CYP3A inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A inhibitors.
Belumosudil: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with belumosudil is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Belumosudil is a weak CYP3A inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A inhibitors.
Benzhydrocodone; Acetaminophen: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Berotralstat: (Contraindicated) Concomitant use of berotralstat and lomitapide is contraindicated due to increased lomitapide exposure. If treatment with berotralstat is unavoidable, lomitapide should be stopped during the course of treatment. Lomitapide is a CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use based on the 27-fold increase in exposure observed with coadministration of a strong CYP3A4 inhibitor.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving lomitapide. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving lomitapide. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; lomitapide inhibits P-gp.
Bicalutamide: (Major) Concomitant use of lomitapide and bicalutamide may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Bicalutamide is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Bile acid sequestrants: (Moderate) Separate administration of lomitapide and bile acid sequestrants by at least 4 hours. Although this interaction has not been studied, bile acid sequestrants can interfere with the absorption of oral medications.
Butalbital; Acetaminophen: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Butalbital; Acetaminophen; Caffeine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Ceritinib: (Contraindicated) Concomitant use of ceritinib and lomitapide is contraindicated; if treatment with ceritinib is unavoidable, lomitapide should be stopped during treatment. Ceritinib is a strong CYP3A4 inhibitor and lomitapide is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor increased lomitapide exposure approximately 27-fold.
Cilostazol: (Major) Concomitant use of lomitapide and cilostazol may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Cilostazol is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Cimetidine: (Major) Concomitant use of lomitapide and cimetidine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Cimetidine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Ciprofloxacin: (Contraindicated) Concomitant use of ciprofloxacin and lomitapide is contraindicated. If treatment with ciprofloxacin is unavoidable, lomitapide should be stopped during the course of treatment. Ciprofloxacin is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use.
Clarithromycin: (Contraindicated) Concomitant use of clarithromycin and lomitapide is contraindicated. If treatment with clarithromycin is unavoidable, lomitapide should be stopped during the course of treatment. Markedly increased transaminases have been reported with coadministration. Clarithromycin is a strong CYP3A4 inhibitor and lomitapide is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor increased lomitapide exposure approximately 27-fold.
Cobicistat: (Contraindicated) Concomitant use of cobicistat and lomitapide is contraindicated due to the potential of markedly increased lomitapide concentrations and the associated elevation of serum transaminases. Cobicistat is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence another strong CYP3A4 inhibitor.
Colchicine: (Major) Avoid concomitant use of colchicine and lomitapide due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and lomitapide is a P-gp inhibitor.
Conivaptan: (Contraindicated) Concomitant use of conivaptan and lomitapide is contraindicated due to increased lomitapide exposure. If treatment with conivaptan is unavoidable, lomitapide should be stopped. Lomitapide is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor. Although concomitant use of moderate CYP3A inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use based on the 27-fold increase in exposure observed with coadministration of a strong CYP3A inhibitor.
Crizotinib: (Contraindicated) Concomitant use of crizotinib and lomitapide is contraindicated due to increased lomitapide exposure. If treatment with crizotinib is unavoidable, lomitapide should be stopped during the course of treatment. Lomitapide is a CYP3A4 substrate and crizotinib is a moderate CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use based on the 27-fold increase in exposure observed with coadministration of a strong CYP3A4 inhibitor.
Cyclosporine: (Major) Concomitant use of lomitapide and cyclosporine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Cyclosporine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Dabigatran: (Moderate) Concomitant use of lomitapide and dabigatran may result in increased serum concentrations of dabigatran. According to the manufacturer of lomitapide, dose reduction of dabigatran should be considered during concurrent use. Lomitapide is an inhibitor of P-glycoprotein (P-gp) and dabigatran is a P-gp substrate.
Dabrafenib: (Major) The concomitant use of dabrafenib and lomitapide may lead to decreased lomitapide concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of lomitapide efficacy. Dabrafenib is a moderate CYP3A4 inducer and lomitapide is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Darunavir: (Contraindicated) Concomitant use of darunavir and lomitapide is contraindicated due to the potential for markedly increased lomitapide concentrations and the associated elevation of serum transaminases. Darunavir is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence another strong CYP3A4 inhibitor.
Darunavir; Cobicistat: (Contraindicated) Concomitant use of cobicistat and lomitapide is contraindicated due to the potential of markedly increased lomitapide concentrations and the associated elevation of serum transaminases. Cobicistat is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence another strong CYP3A4 inhibitor. (Contraindicated) Concomitant use of darunavir and lomitapide is contraindicated due to the potential for markedly increased lomitapide concentrations and the associated elevation of serum transaminases. Darunavir is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence another strong CYP3A4 inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Concomitant use of cobicistat and lomitapide is contraindicated due to the potential of markedly increased lomitapide concentrations and the associated elevation of serum transaminases. Cobicistat is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence another strong CYP3A4 inhibitor. (Contraindicated) Concomitant use of darunavir and lomitapide is contraindicated due to the potential for markedly increased lomitapide concentrations and the associated elevation of serum transaminases. Darunavir is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence another strong CYP3A4 inhibitor.
Desogestrel; Ethinyl Estradiol: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Dienogest; Estradiol valerate: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Digoxin: (Moderate) Concomitant use of lomitapide and digoxin may result in increased serum concentrations of digoxin. According to the manufacturer of lomitapide, dose reduction of digoxin should be considered during concurrent use. Lomitapide is an inhibitor of P-glycoprotein (P-gp) and digoxin is a P-gp substrate.
Diltiazem: (Contraindicated) Concomitant use of diltiazem and lomitapide is contraindicated. If treatment with diltiazem is unavoidable, lomitapide should be stopped during the course of treatment. Diltiazem is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use.
Drospirenone: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Drospirenone; Estetrol: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Drospirenone; Estradiol: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Drospirenone; Ethinyl Estradiol: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Duvelisib: (Contraindicated) Concomitant use of duvelisib and lomitapide is contraindicated due to increased lomitapide exposure. If treatment with duvelisib is unavoidable, lomitapide should be stopped during the course of treatment. Lomitapide is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use based on the 27-fold increase in exposure observed with coadministration of a strong CYP3A4 inhibitor.
Elagolix; Estradiol; Norethindrone acetate: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Elbasvir; Grazoprevir: (Moderate) Administering lomitapide with elbasvir; grazoprevir may result in elevated lomitapide plasma concentrations. Lomitapide is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Concomitant use of cobicistat and lomitapide is contraindicated due to the potential of markedly increased lomitapide concentrations and the associated elevation of serum transaminases. Cobicistat is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence another strong CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concomitant use of cobicistat and lomitapide is contraindicated due to the potential of markedly increased lomitapide concentrations and the associated elevation of serum transaminases. Cobicistat is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence another strong CYP3A4 inhibitor.
Encorafenib: (Moderate) Coadministration of encorafenib with lomitapide may result in increased toxicity or decreased efficacy of lomitapide. Lomitapide is a sensitive CYP3A4 substrate. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established.
Ertugliflozin; Sitagliptin: (Moderate) Concomitant use of lomitapide and sitagliptin may result in increased serum concentrations of sitagliptin. According to the manufacturer of lomitapide, dose reduction of sitagliptin should be considered during concurrent use. Lomitapide is an inhibitor of P-glycoprotein (P-gp) and sitagliptin is a P-gp substrate.
Erythromycin: (Contraindicated) Concomitant use of erythromycin and lomitapide is contraindicated. If treatment with erythromycin is unavoidable, lomitapide should be stopped during the course of treatment. Erythromycin is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use.
Estradiol; Levonorgestrel: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Estradiol; Norethindrone: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Estradiol; Norgestimate: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Ethanol: (Major) Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury. Patients taking lomitapide should not consume more than one alcohol-containing drink per day. (Moderate) Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury. Patients taking lomitapide should not consume more than one alcohol-containing drink per day.
Ethinyl Estradiol; Norelgestromin: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Ethinyl Estradiol; Norgestrel: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Etonogestrel; Ethinyl Estradiol: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Everolimus: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with everolimus is necessary; concomitant use may significantly increase the serum concentration of lomitapide. Also, monitor everolimus whole blood trough concentrations and watch for everolimus-related adverse reactions. Everolimus is a weak CYP3A4 inhibitor and a P-glycoprotein (P-gp) substrate; lomitapide is a sensitive CYP3A4 substrate and a P-gp inhibitor. The exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
Ezetimibe; Simvastatin: (Major) Reduce the simvastatin dose by 50% when starting lomitapide due to an increased risk for myopathy, including rhabdomyolysis. In patients taking lomitapide, do not exceed a simvastatin dose of 20 mg/day in general, or 40 mg/day in patients who have previously tolerated simvastatin 80 mg/day for at least 1 year without evidence of muscle toxicity. For patients chronically receiving simvastatin 80 mg/day who need to be started on lomitapide, consider switching to an alternative statin with less potential for interaction. Carefully weigh the benefits of combined use of lomitapide and simvastatin against the potential risks. Lomitapide increases the simvastatin exposure by approximately 2-fold.
Fedratinib: (Contraindicated) Concomitant use of fedratinib and lomitapide is contraindicated due to increased lomitapide exposure. If treatment with fedratinib is unavoidable, lomitapide should be stopped during the course of treatment. Lomitapide is a CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use based on the 27-fold increase in exposure observed with coadministration of a strong CYP3A4 inhibitor.
Fluconazole: (Contraindicated) Concomitant use of fluconazole and lomitapide is contraindicated. If treatment with fluconazole is unavoidable, lomitapide should be stopped during the course of treatment. Fluconazole is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use.
Fluoxetine: (Major) Concomitant use of lomitapide and fluoxetine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Fluoxetine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Fluvoxamine: (Contraindicated) Concomitant use of lomitapide, a CYP3A4 substrate, and moderate inhibitors of CYP3A4, such as fluvoxamine, is contraindicated due to the potential for lomitapide toxicity.
Fosamprenavir: (Contraindicated) Concomitant use of fosamprenavir and lomitapide is contraindicated due to increased lomitapide exposure. If treatment with fosamprenavir is unavoidable, lomitapide should be stopped during the course of treatment. Lomitapide is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Although concomitant use of moderate CYP3A inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use based on the 27-fold increase in exposure observed with coadministration of a strong CYP3A inhibitor.
Fostamatinib: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with fostamatinib is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Fostamatinib is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Ginkgo, Ginkgo biloba: (Major) Concomitant use of lomitapide and ginkgo, ginkgo biloba may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Ginkgo, ginkgo biloba is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Grapefruit juice: (Contraindicated) Grapefruit juice must be omitted from the diet during lomitapide therapy. Grapefruit juice inhibits the enterocyte CYP3A4 isoenzyme and may decrease lomitapide metabolism.
Imatinib: (Contraindicated) Concomitant use of imatinib, STI-571 and lomitapide is contraindicated. If treatment with imatinib is unavoidable, lomitapide should be stopped during the course of treatment. Imatinib is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use.
Indinavir: (Contraindicated) Concomitant use of indinavir and lomitapide is contraindicated. If treatment with indinavir is unavoidable, lomitapide should be stopped during the course of treatment. Indinavir is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
Isavuconazonium: (Contraindicated) Concomitant use of isavuconazonium and lomitapide is contraindicated. If treatment with isavuconazonium is unavoidable, lomitapide should be stopped during the course of treatment. Isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use.
Isoniazid, INH: (Major) Concomitant use of lomitapide and isoniazid, INH may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Isoniazid, INH is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Concomitant use of lomitapide and isoniazid, INH may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Isoniazid, INH is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Isoniazid, INH; Rifampin: (Major) Concomitant use of lomitapide and isoniazid, INH may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Isoniazid, INH is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Isotretinoin: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as isotretinoin. The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Istradefylline: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with istradefylline 40 mg daily is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Istradefylline administered as 40 mg daily is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. There was no effect on drug exposure when istradefylline 20 mg daily was coadministered with a sensitive CYP3A4 substrate.
Itraconazole: (Contraindicated) Lomitapide is contraindicated for use during and for 2 weeks after itraconazole therapy. Itraconazole is a strong CYP3A4 inhibitor; exposure to lomitapide was increased 27-fold in the presence of another strong CYP3A4 inhibitor.
Ivosidenib: (Moderate) Monitor for loss of efficacy of lomitapide during coadministration of ivosidenib; a lomitapide dose adjustment may be necessary. Lomitapide is a sensitive substrate of CYP3A4; ivosidenib induces CYP3A4 and may lead to decreased lomitapide concentrations.
Ketoconazole: (Contraindicated) Concomitant use of ketoconazole and lomitapide is contraindicated. If treatment with ketoconazole is unavoidable, lomitapide should be stopped during the course of treatment. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) Concomitant use of clarithromycin and lomitapide is contraindicated. If treatment with clarithromycin is unavoidable, lomitapide should be stopped during the course of treatment. Markedly increased transaminases have been reported with coadministration. Clarithromycin is a strong CYP3A4 inhibitor and lomitapide is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor increased lomitapide exposure approximately 27-fold.
Lapatinib: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with lapatinib is necessary; also monitor for an increase in lapatinib-related adverse reactions. Concomitant use may significantly increase the serum concentration of lomitapide. Lapatinib is a P-glycoprotein (P-gp) substrate and a weak CYP3A4 inhibitor. Lomitapide is a P-gp inhibitor and a CYP3A4 substrate. The exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. Increased plasma concentrations of lapatinib are likely when administered with P-gp inhibitors.
Larotrectinib: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with larotrectinib is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Larotrectinib is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Lefamulin: (Major) Concomitant use of oral lefamulin and lomitapide is contraindicated due to increased lomitapide exposure. If treatment with oral lefamulin is unavoidable, lomitapide should be stopped during the course of treatment. Lomitapide is a CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use based on the 27-fold increase in exposure observed with coadministration of a strong CYP3A4 inhibitor.
Lenacapavir: (Contraindicated) Concomitant use of lenacapavir and lomitapide is contraindicated due to increased lomitapide exposure. If treatment with lenacapavir is unavoidable, lomitapide should be stopped during the course of treatment. Lomitapide is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor. Although concomitant use of moderate CYP3A inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use based on the 27-fold increase in exposure observed with coadministration of a strong CYP3A inhibitor.
Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of lomitapide; monitor for potential reduction in efficacy. Lomitapide is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure

and therapeutic efficacy of lomitapide; monitor for potential reduction in efficacy. Lomitapide is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Letermovir: (Contraindicated) Concurrent use of lomitapide and letermovir is contraindicated due to the potential for increased lomitapide exposure and adverse events. If treatment with letermovir is unavoidable, lomitapide should be stopped during letermovir treatment. Coadministration may increase lomitapide concentration and risk for adverse events. Lomitapide is a sensitive substrate of CYP3A4. Letermovir is a moderate CYP3A4 inhibitor.
Leuprolide; Norethindrone: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Levamlodipine: (Major) Concomitant use of lomitapide and amlodipine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Amlodipine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Levoketoconazole: (Contraindicated) Concomitant use of ketoconazole and lomitapide is contraindicated. If treatment with ketoconazole is unavoidable, lomitapide should be stopped during the course of treatment. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
Levonorgestrel: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Levonorgestrel; Ethinyl Estradiol: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Lonafarnib: (Contraindicated) Concomitant use of lonafarnib and lomitapide is contraindicated; if treatment with lonafarnib is unavoidable, lomitapide should be stopped during treatment. Lomitapide is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lomitapide exposure by approximately 27-fold.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with lomitapide. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and lomitapide is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with lomitapide. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and lomitapide is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Contraindicated) Concomitant use of ritonavir and lomitapide is contraindicated. If treatment with ritonavir is unavoidable, lomitapide should be stopped during the course of treatment. Ritonavir is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
Lovastatin: (Major) The risk of developing myopathy, including rhabdomyolysis may be increased if lovastatin is administered concomitantly with lomitapide. Consider reducing the dose of lovastatin when initiating lomitapide. Although the interaction between lovastatin and lomitapide has not been studied, coadministration of lomitapide and simvastatin approximately doubles the exposure to simvastatin. Because the metabolizing enzymes and transporters responsible for the disposition of lovastatin and simvastatin are similar, increased exposure to lovastatin should also be expected.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of lomitapide by decreasing its systemic exposure. If used together, monitor patients closely for loss of lomitapide efficacy; a lomitapide dosage adjustment may be required to obtain the desired therapeutic effect. Lomitapide is a substrate of CYP3A4; lumacaftor; ivacaftor is a strong CYP3A inducer.
Maraviroc: (Moderate) Concomitant use of lomitapide and maraviroc may result in increased serum concentrations of maraviroc. According to the manufacturer of lomitapide, dose reduction of maraviroc should be considered during concurrent use. Lomitapide is an inhibitor of P-glycoprotein (P-gp) and maraviroc is a P-gp substrate.
Maribavir: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with maribavir is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Maribavir is a weak CYP3A inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A inhibitors.
Metformin; Sitagliptin: (Moderate) Concomitant use of lomitapide and sitagliptin may result in increased serum concentrations of sitagliptin. According to the manufacturer of lomitapide, dose reduction of sitagliptin should be considered during concurrent use. Lomitapide is an inhibitor of P-glycoprotein (P-gp) and sitagliptin is a P-gp substrate.
Methotrexate: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as methotrexate. The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Mipomersen: (Major) Mipomersen has not been studied in combination with other LDL-lowering agents that can also increase hepatic fat, such as lomitapide. Therefore, the combined use of mipomersen and lomitapide is not recommended.
Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions and consider dose reduction of naldemedine if coadministered with lomitapide. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a P-gp substrate; lomitapide is a moderate P-gp inhibitor.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and lomitapide. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and lomitapide is a P-gp inhibitor.
Nefazodone: (Contraindicated) Concomitant use of nefazodone and lomitapide is contraindicated. If treatment with nefazodone is unavoidable, lomitapide should be stopped during the course of treatment. Nefazodone is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
Nelfinavir: (Contraindicated) Concomitant use of nelfinavir and lomitapide is contraindicated. If treatment with nelfinavir is unavoidable, lomitapide should be stopped during the course of treatment. Nelfinavir is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
Niacin; Simvastatin: (Major) Reduce the simvastatin dose by 50% when starting lomitapide due to an increased risk for myopathy, including rhabdomyolysis. In patients taking lomitapide, do not exceed a simvastatin dose of 20 mg/day in general, or 40 mg/day in patients who have previously tolerated simvastatin 80 mg/day for at least 1 year without evidence of muscle toxicity. For patients chronically receiving simvastatin 80 mg/day who need to be started on lomitapide, consider switching to an alternative statin with less potential for interaction. Carefully weigh the benefits of combined use of lomitapide and simvastatin against the potential risks. Lomitapide increases the simvastatin exposure by approximately 2-fold.
Nilotinib: (Contraindicated) Concomitant use of nilotinib and lomitapide is contraindicated due to increased lomitapide exposure. If treatment with nilotinib is unavoidable, lomitapide should be stopped during the course of treatment. Lomitapide is a CYP3A4 substrate and nilotinib is a moderate CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use based on the 27-fold increase in exposure observed with coadministration of a strong CYP3A4 inhibitor.
Nirmatrelvir; Ritonavir: (Contraindicated) Concomitant use of ritonavir and lomitapide is contraindicated. If treatment with ritonavir is unavoidable, lomitapide should be stopped during the course of treatment. Ritonavir is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. (Contraindicated) Concomitant use of ritonavir-boosted nirmatrelvir and lomitapide is contraindicated due to the potential for hepatotoxicity and gastrointestinal adverse reactions. Consider temporary discontinuation of lomitapide during treatment with ritonavir-boosted nirmatrelvir and for at least 2 to 3 days after treatment completion; if not feasible, consider alternative COVID-19 therapy. Coadministration may increase lomitapide exposure resulting in increased toxicity. Lomitapide is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Norethindrone: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Norethindrone; Ethinyl Estradiol: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Norgestimate; Ethinyl Estradiol: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Norgestrel: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Olanzapine; Fluoxetine: (Major) Concomitant use of lomitapide and fluoxetine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Fluoxetine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Major) Concomitant use of lomitapide and amlodipine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Amlodipine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Oral Contraceptives: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Osilodrostat: (Major) Decrease the dose of lomitapide by one-half (not to exceed 30 mg/day PO) if coadministration with osilodrostat is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Osilodrostat is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Pacritinib: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with pacritinib is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Pacritinib is a weak CYP3A inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A inhibitors.
Palbociclib: (Major) Concomitant use of lomitapide and palbociclib may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Palbociclib is a weak, time-dependent CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Pazopanib: (Major) Concomitant use of lomitapide and pazopanib may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Pazopanib is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Perindopril; Amlodipine: (Major) Concomitant use of lomitapide and amlodipine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Amlodipine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Pirtobrutinib: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with pirtobrutinib is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Pirtobrutinib is a weak CYP3A inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A inhibitors.
Posaconazole: (Contraindicated) Concomitant use of posaconazole and lomitapide is contraindicated. If treatment with posaconazole is unavoidable, lomitapide should be stopped during the course of treatment. Posaconazole is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
Pralsetinib: (Major) Avoid concomitant use of lomitapide with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and lomitapide is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and lomitapide due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and lomitapide is a P-gp inhibitor.
Ranitidine: (Major) Concomitant use of lomitapide and ranitidine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Ranitidine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Ranolazine: (Major) Concomitant use of lomitapide and ranolazine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Ranolazine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, concomitant use may result in increased serum concentrations of ranolazine. According to the manufacturer of lomitapide, dose reduction of ranolazine should be considered during concurrent use. Lomitapide is an inhibitor of P-glycoprotein (P-gp) and ranolazine is a P-gp substrate.
Relugolix: (Major) Avoid concomitant use of relugolix and oral lomitapide. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer lomitapide at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and lomitapide is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral lomitapide. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer lomitapide at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and lomitapide is a P-gp inhibitor. (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Ribociclib: (Contraindicated) Concomitant use of ribociclib and lomitapide is contraindicated; if treatment with ribociclib is unavoidable, lomitapide should be stopped during treatment. Ribociclib is a strong CYP3A4 inhibitor and lomitapide is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor increased lomitapide exposure approximately 27-fold.
Ribociclib; Letrozole: (Contraindicated) Concomitant use of ribociclib and lomitapide is contraindicated; if treatment with ribociclib is unavoidable, lomitapide should be stopped during treatment. Ribociclib is a strong CYP3A4 inhibitor and lomitapide is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor increased lomitapide exposure approximately 27-fold.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with lomitapide is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and lomitapide is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with lomitapide; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and lomitapide is a P-gp inhibitor.
Ritlecitinib: (Contraindicated) Concomitant use of ritlecitinib and lomitapide is contraindicated due to increased lomitapide exposure. If treatment with ritlecitinib is unavoidable, lomitapide should be stopped during the course of treatment. Lomitapide is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor. Although concomitant use of moderate CYP3A inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use based on the 27-fold increase in exposure observed with coadministration of a strong CYP3A inhibitor.
Ritonavir: (Contraindicated) Concomitant use of ritonavir and lomitapide is contraindicated. If treatment with ritonavir is unavoidable, lomitapide should be stopped during the course of treatment. Ritonavir is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
Rucaparib: (Major) The lomitapide dose should not exceed 30 mg per day PO during concurrent use with rucaparib. Lomitapide is a sensitive substrate of CYP3A4 and rucaparib is a weak CYP3A4 inhibitor. The exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Saquinavir: (Contraindicated) Concomitant use of saquinavir and lomitapide is contraindicated. If treatment with saquinavir is unavoidable, lomitapide should be stopped during the course of treatment. Saquianvir is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
Segesterone Acetate; Ethinyl Estradiol: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur.
Selpercatinib: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with selpercatinib is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Selpercatinib is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Simvastatin: (Major) Reduce the simvastatin dose by 50% when starting lomitapide due to an increased risk for myopathy, including rhabdomyolysis. In patients taking lomitapide, do not exceed a simvastatin dose of 20 mg/day in general, or 40 mg/day in patients who have previously tolerated simvastatin 80 mg/day for at least 1 year without evidence of muscle toxicity. For patients chronically receiving simvastatin 80 mg/day who need to be started on lomitapide, consider switching to an alternative statin with less potential for interaction. Carefully weigh the benefits of combined use of lomitapide and simvastatin against the potential risks. Lomitapide increases the simvastatin exposure by approximately 2-fold.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of lomitapide. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and lomitapide is a P-gp inhibitor.
Sitagliptin: (Moderate) Concomitant use of lomitapide and sitagliptin may result in increased serum concentrations of sitagliptin. According to the manufacturer of lomitapide, dose reduction of sitagliptin should be considered during concurrent use. Lomitapide is an inhibitor of P-glycoprotein (P-gp) and sitagliptin is a P-gp substrate.
Spironolactone: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with spironolactone is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Spironolactone is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Spironolactone; Hydrochlorothiazide, HCTZ: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with spironolactone is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Spironolactone is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Stiripentol: (Moderate) Consider a dose adjustment of lomitapide when coadministered with stiripentol. Coadministration may alter plasma concentrations of lomitapide resulting in an increased risk of adverse reactions and/or decreased efficacy. Lomitapide is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with lomitapide is necessary. Talazoparib is a P-gp substrate and lomitapide is a P-gp inhibitor.
Telmisartan; Amlodipine: (Major) Concomitant use of lomitapide and amlodipine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Amlodipine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Temsirolimus: (Moderate) Monitor for an increase in temsirolimus-related adverse reactions if coadministration with lomitapide is necessary. Temsirolimus is a P-glycoprotein (P-gp) substrate and lomitapide is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of temsirolimus.
Tetracyclines: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as tetracyclines. The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Ticagrelor: (Major) Concomitant use of lomitapide and ticagrelor may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Ticagrelor is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Tipranavir: (Contraindicated) Concomitant use of tipranavir boosted with ritonavir and lomitapide is contraindicated. If treatment with tipranavir boosted with ritonavir is unavoidable, lomitapide should be stopped during the course of treatment. Tipranavir boosted with ritonavir is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
Topotecan: (Major) Avoid coadministration of lomitapide with oral topotecan due to increased topotecan exposure; lomitapide may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and lomitapide is a P-gp inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Tramadol; Acetaminophen: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as acetaminophen (> 4 g/day PO for >= 3 days/week). The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Trandolapril; Verapamil: (Contraindicated) Concomitant use of verapamil and lomitapide is contraindicated. If treatment with verapamil is unavoidable, lomitapide should be stopped during the course of treatment. Verapamil is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use.
Trofinetide: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with trofinetide is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Trofinetide is a weak CYP3A inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A inhibitors.
Tucatinib: (Contraindicated) Concomitant use of tucatinib and lomitapide is contraindicated; if treatment with tucatinib is unavoidable, lomitapide should be stopped during treatment. Tucatinib is a strong CYP3A4 inhibitor and lomitapide is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor increased lomitapide exposure approximately 27-fold.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with lomitapide. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the P-gp drug transporter; lomitapide is a P-gp inhibitor.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with lomitapide due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of lomitapide. Venetoclax is a P-glycoprotein (P-gp) substrate; lomitapide is a P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Verapamil: (Contraindicated) Concomitant use of verapamil and lomitapide is contraindicated. If treatment with verapamil is unavoidable, lomitapide should be stopped during the course of treatment. Verapamil is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use.
Viloxazine: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with viloxazine is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Viloxazine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Vonoprazan; Amoxicillin: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with vonoprazan is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Vonoprazan is a weak CYP3A inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A inhibitors.
Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) Concomitant use of clarithromycin and lomitapide is contraindicated. If treatment with clarithromycin is unavoidable, lomitapide should be stopped during the course of treatment. Markedly increased transaminases have been reported with coadministration. Clarithromycin is a strong CYP3A4 inhibitor and lomitapide is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor increased lomitapide exposure approximately 27-fold. (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with vonoprazan is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Vonoprazan is a weak CYP3A inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A inhibitors.
Voriconazole: (Contraindicated) Concomitant use of voriconazole and lomitapide is contraindicated. If treatment with voriconazole is unavoidable, lomitapide should be stopped during the course of treatment. Voriconazole is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
Voxelotor: (Contraindicated) Concomitant use of voxelotor and lomitapide is contraindicated due to increased lomitapide exposure. If treatment with voxelotor is unavoidable, lomitapide should be stopped during the course of treatment. Lomitapide is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. Although concomitant use of moderate CYP3A inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use based on the 27-fold increase in exposure observed with coadministration of a strong CYP3A inhibitor.
Warfarin: (Major) Coadministration of warfarin and lomitapide results in increased serum concentrations of warfarin. Monitor the INR regularly, especially after dose adjustments of lomitapide and adjust the warfarin dose as clinically indicated during concurrent use. Lomitapide increases the plasma concentrations of both R-warfarin and S-warfarin by approximately 30% and the INR by 22%. In the lomitapide clinical trials, difficulty controlling INR led to early discontinuation in 1 of 5 patients receiving concomitant warfarin therapy.

How Supplied

Juxtapid Oral Cap: 5mg, 10mg, 20mg, 30mg, 40mg, 60mg

Maximum Dosage
Adults

60 mg/day PO.

Geriatric

60 mg/day PO.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism Of Action

Lomitapide directly binds and inhibits microsomal triglyceride transfer protein (MTP) in the lumen of the endoplasmic reticulum. This prevents the assembly of apo B-containing lipoproteins in enterocytes and hepatocytes, thereby inhibiting the synthesis of chylomicrons and VLDL. Inhibition of VLDL synthesis leads to reduced levels of plasma LDL-C.

Pharmacokinetics

Lomitapide is administered orally. The drug is 99.8% plasma-protein bound. Lomitapide undergoes extensive metabolism by the liver. Lomitapide is metabolized to its major metabolites, M1 and M3, via cytochrome P450 (CYP) 3A4; also, CYP 1A2, 2B6, 2C8, and 2C19 may metabolize lomitapide to a small extent to M1. M1 is the moiety that retains the piperidine ring, whereas M3 retains the rest of the lomitapide molecule in vitro. M1 and M3 do not inhibit activity of microsomal triglyceride transfer protein in vitro. Up to 60% of a dose is excreted in the urine with M1 as the major urinary metabolite. Approximately 35% is excreted in the feces with the major component as lomitapide. The mean terminal half-life of lomitapide is 39.7 hours.

Oral Route

The pharmacokinetics of lomitapide are approximately dose-proportional for single oral doses from 10—100 mg. After oral administration of a 60 mg dose of lomitapide, peak plasma concentrations are reached in about 6 hours in healthy volunteers. The absolute bioavailability is approximately 7%.

Pregnancy And Lactation
Pregnancy

Lomitapide is contraindicated for use during pregnancy because the drug may cause fetal harm. Females of reproductive potential should have a negative pregnancy test before starting lomitapide and should use effective contraception during therapy. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Healthcare professionals are encouraged to call the registry to enroll patients who become pregnant during lomitapide therapy. Available human data are insufficient to draw conclusions about any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, lomitapide was teratogenic in rats and ferrets at lomitapide exposures estimated to be less than human therapeutic exposure when administered during organogenesis. There was no evidence of teratogenicity in rabbits at 3 times the maximum recommended human dose (MRHD) of 60 mg based on body surface area. Embryo-fetal lethality was observed in rabbits at 6 times the MRHD. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to lomitapide; information about the registry can be obtained at www.JUXTAPID.com or by calling 1-877-902-4099.

There are no data on the presence of lomitapide in human milk, effects on the breastfed infant, or on milk production. Due to the potential for serious adverse effects, such as hepatotoxicity and tumorigenicity, breastfeeding is not recommended during lomitapide therapy. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.