Identification
- Summary
Lomitapide is a microsomal triglyceride transfer protein inhibitor used to lower cholesterol associated with homozygous familial hypercholesterolemia (HoFH), reducing risk of cardiovascular events such as myocardial infarction and stroke.
- Brand Names
- Juxtapid, Lojuxta
- Generic Name
- Lomitapide
- DrugBank Accession Number
- DB08827
- Background
Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor used in homozygous familial hypercholesterolemia (HoFH) patients. It is marketed under the name Juxtapid (R).
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Lomitapide (DB08827)
- Weight
- Average: 693.7204
Monoisotopic: 693.278996673 - Chemical Formula
- C39H37F6N3O2
- Synonyms
- Lomitapida
- Lomitapide
- Lomitapidum
- External IDs
- AEGR 733
- AEGR-733
- AEGR-773
- BMS 201038
- BMS-201038-01
- BMS-201038-04
Pharmacology
- Indication
Used in homozygous familial hypercholesterolemia (HoFH) patients to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B), and non-high-density lipoprotein cholesterol (non-HDL-C).
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Homozygous familial hypercholesterolemia •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Lomitapide directly inhibits microsomal triglyceride transfer protein (MTP).
- Mechanism of action
Within the lumen of the endoplasmic reticulum, lomitapide inhibits microsomal triglyceride transfer protein (MTP), which prevents the formation of apolipoprotein B, and, thus, the formation of VLDL and chylomicrons as well. Altogether, this leads to a reduction of low-density lipoprotein cholesterol.
Target Actions Organism AMicrosomal triglyceride transfer protein large subunit antagonistHumans - Absorption
In healthy patients, time to maximum lomitapide concentration is about 6 hours with a single dose of 60 mg. Lomitapide has an approximate absolute bioavailability of 7%.
- Volume of distribution
The steady state volume of distribution is about 985-1292 L.
- Protein binding
Plasma protein binding is about 99.8%
- Metabolism
Lomitapide is mainly metabolized by CYP3A4 to it's inactive metabolites, M1 and M3. CYP enzymes that metabolize lomitapide to a minor extent include CYP 1A2,2B6,2C8,2C19.
- Route of elimination
About 52.9-59.5% is eliminated by the urine and 33.4-35.1% is eliminated by the feces.
- Half-life
Lomitapide half-life is about 39.7 hours.
- Clearance
Not Available
- Adverse Effects
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Contra-indicated in pregnancy, and moderate to severe hepatic insufficiency (Child-Pugh category B or C). Severe GI adverse reactions may occur.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Lomitapide can be increased when it is combined with Abametapir. Abatacept The metabolism of Lomitapide can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Lomitapide. Acalabrutinib The metabolism of Lomitapide can be decreased when combined with Acalabrutinib. Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Lomitapide. - Food Interactions
- Avoid grapefruit products.
- Take with food. Food decreases the risk of GI side effects.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Lomitapide mesylate X4S83CP54E 202914-84-9 QKVKOFVWUHNEBX-UHFFFAOYSA-N - International/Other Brands
- Lojuxta
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Juxtapid Capsule 10 mg Oral Amryt Pharmaceuticals DAC 2014-05-06 Not applicable Canada 
Juxtapid Capsule 40 mg/1 Oral Amryt Pharmaceutcials DAC 2013-01-03 2020-09-25 US 
Juxtapid Capsule 10 mg/1 Oral Amryt Pharmaceuticals DAC 2013-01-03 Not applicable US Juxtapid Capsule 5 mg Oral Amryt Pharmaceuticals DAC 2014-05-06 Not applicable Canada Juxtapid Capsule 30 mg/1 Oral Amryt Pharmaceuticals DAC 2013-01-03 Not applicable US
Categories
- ATC Codes
- C10AX12 — Lomitapide
- Drug Categories
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Hepatotoxic Agents
- Heterocyclic Compounds, Fused-Ring
- Hypolipidemic Agents
- Hypolipidemic Agents Indicated for Hyperlipidemia
- Lipid Modifying Agents
- Lipid Modifying Agents, Plain
- Microsomal Triglyceride Transfer Protein Inhibitor
- Microsomal Triglyceride Transfer Protein Inhibitors
- Narrow Therapeutic Index Drugs
- Non-statin Hypolipidemic Agents Indicated for Hyperlipidemia
- P-glycoprotein inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as fluorenes. These are compounds containing a fluorene moiety, which consists of two benzene rings connected through either a cyclopentane, cyclopentene, or cyclopenta-1,3-diene.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Fluorenes
- Sub Class
- Not Available
- Direct Parent
- Fluorenes
- Alternative Parents
- Biphenyls and derivatives / Trifluoromethylbenzenes / Benzamides / Benzoyl derivatives / Aralkylamines / Piperidines / Fatty amides / Amino acids and derivatives / Secondary carboxylic acid amides / Trialkylamines show 7 more
- Substituents
- Alkyl fluoride / Alkyl halide / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzamide / Benzoic acid or derivatives / Benzoyl show 23 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- piperidines, benzamides, fluorenes, (trifluoromethyl)benzenes (CHEBI:72297)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 82KUB0583F
- CAS number
- 182431-12-5
- InChI Key
- MBBCVAKAJPKAKM-UHFFFAOYSA-N
- InChI
- InChI=1S/C39H37F6N3O2/c40-38(41,42)25-46-36(50)37(33-13-5-3-10-30(33)31-11-4-6-14-34(31)37)21-7-8-22-48-23-19-28(20-24-48)47-35(49)32-12-2-1-9-29(32)26-15-17-27(18-16-26)39(43,44)45/h1-6,9-18,28H,7-8,19-25H2,(H,46,50)(H,47,49)
- IUPAC Name
- N-(2,2,2-trifluoroethyl)-9-(4-{4-[4'-(trifluoromethyl)-[1,1'-biphenyl]-2-amido]piperidin-1-yl}butyl)-9H-fluorene-9-carboxamide
- SMILES
- FC(F)(F)CNC(=O)C1(CCCCN2CCC(CC2)NC(=O)C2=C(C=CC=C2)C2=CC=C(C=C2)C(F)(F)F)C2=CC=CC=C2C2=CC=CC=C12
References
- General References
- Cuchel M, Meagher EA, du Toit Theron H, Blom DJ, Marais AD, Hegele RA, Averna MR, Sirtori CR, Shah PK, Gaudet D, Stefanutti C, Vigna GB, Du Plessis AM, Propert KJ, Sasiela WJ, Bloedon LT, Rader DJ: Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet. 2013 Jan 5;381(9860):40-6. doi: 10.1016/S0140-6736(12)61731-0. Epub 2012 Nov 2. [Article]
- Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, Ikewaki K, Siegelman ES, Gregg RE, Rader DJ: Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007 Jan 11;356(2):148-56. [Article]
- FDA Approved Drug Products: Juxtapid (lomitapide) capsules [Link]
- External Links
- KEGG Drug
- D09637
- PubChem Compound
- 9853053
- PubChem Substance
- 175427108
- ChemSpider
- 8028764
- BindingDB
- 50098320
- 1364479
- ChEBI
- 72297
- ChEMBL
- CHEMBL354541
- ZINC
- ZINC000027990463
- PharmGKB
- PA166114922
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Lomitapide
- FDA label
- Download (930 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Homozygous Familial Hypercholesterolaemia (HoFH) 1 3 Completed Treatment Homozygous Familial Hypercholesterolaemia (HoFH) 2 3 Completed Treatment Primary Hypercholesterolemia 1 3 Withdrawn Treatment Homozygous Familial Hypercholesterolaemia (HoFH) 1 2 Completed Treatment High Cholesterol 3
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 10 mg/1 Capsule Oral 10 mg Capsule Oral 20 mg/1 Capsule Oral 20 mg Capsule Oral 30 mg/1 Capsule Oral 40 mg/1 Capsule Oral 5 mg/1 Capsule Oral 5 mg Capsule Oral 60 mg/1 Capsule, coated Oral 10 mg Capsule, coated Oral 20 mg Capsule, coated Oral 5 mg Capsule Oral 30 MG Capsule Oral 40 MG Capsule Oral 60 MG - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5739135 No 1998-04-14 2015-04-14 US US5712279 No 1998-01-27 2016-02-21 US US6492365 No 2002-12-10 2019-12-10 US US8618135 No 2013-12-31 2025-03-07 US US7932268 No 2011-04-26 2027-08-19 US US9265758 No 2016-02-23 2025-03-07 US US9433617 No 2016-09-06 2025-03-07 US US9364470 No 2016-06-14 2025-03-07 US US9861622 No 2018-01-09 2025-03-07 US US10016404 No 2018-07-10 2025-03-07 US US10555938 No 2020-02-11 2025-03-07 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 8.88e-05 mg/mL ALOGPS logP 7.19 ALOGPS logP 7.9 Chemaxon logS -6.9 ALOGPS pKa (Strongest Acidic) 12.27 Chemaxon pKa (Strongest Basic) 9.05 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 61.44 Å2 Chemaxon Rotatable Bond Count 12 Chemaxon Refractivity 181.73 m3·mol-1 Chemaxon Polarizability 68.13 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 244.50499 predictedDeepCCS 1.0 (2019) [M+H]+ 246.40993 predictedDeepCCS 1.0 (2019) [M+Na]+ 252.15036 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Protein heterodimerization activity
- Specific Function
- Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces (PubMed:23475612, PubMed:8939939, PubMed:26224785, PubMed:25108285, PubMed:22236406). Requ...
- Gene Name
- MTTP
- Uniprot ID
- P55157
- Uniprot Name
- Microsomal triglyceride transfer protein large subunit
- Molecular Weight
- 99350.255 Da
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
Drug created at January 03, 2013 20:34 / Updated at January 02, 2024 23:48