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Details

Stereochemistry ACHIRAL
Molecular Formula C39H37F6N3O2.CH4O3S
Molecular Weight 789.826
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOMITAPIDE MESYLATE

SMILES

CS(O)(=O)=O.FC(F)(F)CNC(=O)C4(CCCCN1CCC(CC1)NC(=O)C2=CC=CC=C2C3=CC=C(C=C3)C(F)(F)F)C5=C(C=CC=C5)C6=C4C=CC=C6

InChI

InChIKey=QKVKOFVWUHNEBX-UHFFFAOYSA-N
InChI=1S/C39H37F6N3O2.CH4O3S/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;1-5(2,3)4/h1-6,9-18,28H,7-8,19-25H2,(H,46,50)(H,47,49);1H3,(H,2,3,4)

HIDE SMILES / InChI
Molecular Formula C39H37F6N3O2
Molecular Weight 693.7204
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula CH4O3S
Molecular Weight 96.106
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including http://www.everipedia.com/Lomitapide/

Lomitapide (INN, marketed as Juxtapid in the US and as Lojuxta in the EU) is a drug for the treatment of familial hypercholesterolemia, developed by Aegerion Pharmaceuticals. It has been tested in clinical trials as single treatment and in combinations with atorvastatin, ezetimibe and fenofibrate. The US Food and Drug Administration (FDA) approved lomitapide on 21 December 2012, as an orphan drug to reduce LDL cholesterol, total cholesterol, apolipoprotein B, and non-high-density lipoprotein (non-HDL) cholesterol in patients with homozygous familial hypercholesterolemia (HoFH). On 31 May 2013 the European Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion with a unanimous vote recommending a marketing authorization for lomitapide. On 31 July 2013 the European Commission approved lomitapide as an adjunct to a low-fat diet and other lipid-lowering medicinal products with or without low density lipoprotein (LDL) apheresis in adult patients with HoFH. UXTAPID directly binds and inhibits microsomal triglyceride transfer protein (MTP), which resides in the lumen of the endoplasmic reticulum, thereby preventing the assembly of apo B containing lipoproteins in enterocytes and hepatocytes. This inhibits the synthesis of chylomicrons and VLDL. The inhibition of the synthesis of VLDL leads to reduced levels of plasma LDL-C.

Originator

Approval Year

2012
595
Targets

Targets

Primary TargetPharmacologyConditionPotency
Microsomal triglyceride transfer protein large subunit
4
Target ID: P55157
Gene ID: 4547.0
Gene Symbol: MTTP
Target Organism: Homo sapiens (Human)
Inhibitor
8297
 8.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
Approved
8429
JUXTAPID

Approved Use

Indicated as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available, to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). Limitations of use: the safety and effectiveness of JUXTAPID have not been established in patients with hypercholesterolemia who do not have HoFH. The effect of JUXTAPID on cardiovascular morbidity and mortality has not been determined.

Launch Date

1.35604797E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5.75 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26686567/
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
24.6 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26686567/
60 mg 1 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
30.2 ng/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M3 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
31 ng/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M3 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
28.6 ng/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M3 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
0.986 ng/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: healthy
age:
sex:
food status:
1.03 ng/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: healthy
age:
sex:
food status:
1.13 ng/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: healthy
age:
sex:
food status:
2.52 ng/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M1 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
2.65 ng/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M1 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
2.74 ng/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M1 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
241 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26686567/
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
403 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26686567/
60 mg 1 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
443 ng*h/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M3 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
450 ng*h/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M3 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
460 ng*h/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M3 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
38.3 ng*h/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: healthy
age:
sex:
food status:
40.2 ng*h/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: healthy
age:
sex:
food status:
43.6 ng*h/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: healthy
age:
sex:
food status:
70.4 ng*h/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M1 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
72.9 ng*h/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M1 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
75.2 ng*h/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M1 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
51.5 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26686567/
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
46.5 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26686567/
60 mg 1 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
46 h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M3 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
45.7 h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M3 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
44 h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M3 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
52.4 h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: healthy
age:
sex:
food status:
47.7 h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: healthy
age:
sex:
food status:
48.8 h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: healthy
age:
sex:
food status:
38.7 h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M1 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
37 h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M1 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
39.1 h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT02044419
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
LOMITAPIDE METABOLITE M1 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.2%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/203858s019lbl.pdf
60 mg 1 times / day unknown, oral
dose: 60 mg
route of administration: Oral
experiment type: UNKNOWN
co-administered:
LOMITAPIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
5 mg 1 times / day steady, oral (starting)
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
Disc. AE: Diarrhea, Abdominal pain...
Other AEs: Alanine aminotransferase increase, Aspartate aminotransferase increase...
AEs leading to
discontinuation/dose reduction:
Diarrhea (7%)
Abdominal pain (3%)
Nausea (3%)
Gastroenteritis (3%)
Weight loss (3%)
Headache (3%)
Uncontrolled INR (3%)
Other AEs:
Alanine aminotransferase increase (34%)
Aspartate aminotransferase increase (34%)
Fatty liver (6%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
60 mg 1 times / day steady, oral
Studied dose
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
Disc. AE: Diarrhea, Nausea...
AEs leading to
discontinuation/dose reduction:
Diarrhea (5 patients)
Nausea (3 patients)
Abdominal discomfort (3 patients)
Vomiting (1 patient)
Diarrhea (5 patients)
Vomiting (4 patients)
Nausea (3 patients)
Gastroenteritis (3 patients)
Influenza (2 patients)
Chest pain (2 patients)
Pyrexia (2 patients)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
200 mg single, oral
Highest studied dose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 41
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 41
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 41
100 mg single, oral
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 41, 166
healthy
n = 7
Health Status: healthy
Population Size: 7
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 41, 166
Disc. AE: Headache...
AEs leading to
discontinuation/dose reduction:
Headache (1 patient)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 41, 166
AEs

AEs

AESignificanceDosePopulation
Abdominal pain 3%
Disc. AE
5 mg 1 times / day steady, oral (starting)
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
Gastroenteritis 3%
Disc. AE
5 mg 1 times / day steady, oral (starting)
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
Headache 3%
Disc. AE
5 mg 1 times / day steady, oral (starting)
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
Nausea 3%
Disc. AE
5 mg 1 times / day steady, oral (starting)
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
Uncontrolled INR 3%
Disc. AE
5 mg 1 times / day steady, oral (starting)
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
Weight loss 3%
Disc. AE
5 mg 1 times / day steady, oral (starting)
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
Alanine aminotransferase increase 34%
5 mg 1 times / day steady, oral (starting)
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
Aspartate aminotransferase increase 34%
5 mg 1 times / day steady, oral (starting)
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
Fatty liver 6%
5 mg 1 times / day steady, oral (starting)
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
Diarrhea 7%
Disc. AE
5 mg 1 times / day steady, oral (starting)
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203858s000lbl.pdf
Vomiting 1 patient
Disc. AE
60 mg 1 times / day steady, oral
Studied dose
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
Chest pain 2 patients
Disc. AE
60 mg 1 times / day steady, oral
Studied dose
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
Influenza 2 patients
Disc. AE
60 mg 1 times / day steady, oral
Studied dose
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
Pyrexia 2 patients
Disc. AE
60 mg 1 times / day steady, oral
Studied dose
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
Abdominal discomfort 3 patients
Disc. AE
60 mg 1 times / day steady, oral
Studied dose
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
Gastroenteritis 3 patients
Disc. AE
60 mg 1 times / day steady, oral
Studied dose
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
Nausea 3 patients
Disc. AE
60 mg 1 times / day steady, oral
Studied dose
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
Nausea 3 patients
Disc. AE
60 mg 1 times / day steady, oral
Studied dose
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
Vomiting 4 patients
Disc. AE
60 mg 1 times / day steady, oral
Studied dose
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
Diarrhea 5 patients
Disc. AE
60 mg 1 times / day steady, oral
Studied dose
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
Diarrhea 5 patients
Disc. AE
60 mg 1 times / day steady, oral
Studied dose
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
unhealthy, 30.7 years (range: 18 - 55 years)
n = 29
Health Status: unhealthy
Condition: homozygous familial hypercholesterolemia
Age Group: 30.7 years (range: 18 - 55 years)
Sex: M+F
Population Size: 29
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 168
Headache 1 patient
Disc. AE
100 mg single, oral
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 41, 166
healthy
n = 7
Health Status: healthy
Population Size: 7
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203858Orig1s000MedR.pdf
Page: p. 41, 166
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inducer
781

inhibitor
1587

substrate
1737
inhibitor
1767
inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1461

CYP1A2
1524

CYP2B6
810

CYP2C19
1478

CYP2E1
882

BCRP
699

OATP1B1
788

OATP1B3
706

OCT1
512

OAT1
599

OAT3
642

OCT2
647
CYP1A2
1054

CYP2B6
664

CYP2C8
693

CYP2C19
991

P-gp
1537

CYP2E1
667
CYP1A2
701

CYP2B6
547
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
BCRP
773
 no
CYP1A2
1692
 no
CYP1A2
1692
 no
CYP2B6
1001
 no
CYP2B6
1001
 no
CYP2C19
1553
 no
CYP2C9
1819
 no
CYP2D6
1891
 no
CYP2E1
970
 no
CYP3A4
1925
 no
OAT1
603
 no
OAT3
644
 no
OATP1B1
803
 no
OATP1B3
715
 no
OCT1
543
 no
OCT2
648
 no
P-gp
1650
 yes [IC50 0.62 uM]
CYP3A4
1925
 yes [IC50 8 uM]
weak (co-administration study)
Comment: lomitapide increased simvastatin cmax/auc ~2x
Page: 22.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1737
 major
yes (co-administration study)
Comment: ketoconazole increased lomitapide exposure 27x
Page: 23.0
P-gp
1537
 no
CYP1A2
1054
 weak
CYP2B6
664
 weak
CYP2C19
991
 weak
CYP2C8
693
 weak
CYP2E1
667
 weak
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:72297
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:72297
ChemicalBook
CB62485047
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB62485047
MolPort
MolPort-028-754-209
https://www.molport.com/shop/molecule-link/MolPort-028-754-209
ZINC
ZINC000027990463
http://zinc15.docking.org/substances/ZINC000027990463
PubMed

PubMed

TitleDatePubMed
Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia.
2007 Jan 11
Gateways to clinical trials.
2009 Jun
Lomitapide, a microsomal triglyceride transfer protein inhibitor for the treatment of hypercholesterolemia.
2010 Feb
Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study.
2013 Jan 5
Patents

Patents

CN103690960A
2
EP1725234B9
2
US2007088089
2
US2007093468
2
US2011112097
2
WO2015121877A2
2

Sample Use Guides

In Vivo Use Guide
Initiate treatment at 5 mg once daily. Titrate dose based on acceptable safety/tolerability: increase to 10 mg daily after at least 2 weeks; and then, at a minimum of 4-week intervals, to 20 mg, 40 mg, and up to the maximum recommended dose of 60 mg daily. Take once daily, whole, with water and without food, at least 2 hours after evening meal.
Route of Administration: Oral
In Vitro Use Guide
In in vitro experiments using unilamellar vesicles, lomitapide inhibited rat, hamster, and human MTP with an inhibitory concentration of 50% (IC50) of 5 to 7 nmol/L. In vitro studies demonstrated a reduction in apoB secretion by hepatocytes on treatment with lomitapide
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:26:49 UTC 2023
Edited
by admin
on Fri Dec 15 15:26:49 UTC 2023
Record UNII
X4S83CP54E
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LOMITAPIDE MESYLATE
ORANGE BOOK   USAN  
USAN  
Official Name English
BMS-201038
Code English
BMS-201038-04
Code English
AEGR-733 MESYLATE
Code English
LOMITAPIDE MESILATE
WHO-DD  
Common Name English
LOMITAPIDE MESILATE [JAN]
Common Name English
LOMITAPIDE MESYLATE [ORANGE BOOK]
Common Name English
Lomitapide mesilate [WHO-DD]
Common Name English
N-(2,2,2-TRIFLUOROETHYL)-9-(4-(4-(((4'-(TRIFLUOROMETHYL)BIPHENYL-2-YL)CARBONYL)AMINO)PIPERIDIN-1-YL)BUTYL)-9H-FLUORENE-9-CARBOXAMIDE METHANESULFONATE
Common Name English
9H-FLUORENE-9-CARBOXAMIDE, N-(2,2,2-TRIFLUOROETHYL)-9-(4-(4-(((4'-(TRIFLUOROMETHYL)(1,1'-BIPHENYL)-2-YL)CARBONYL)AMINO)-1-PIPERIDINYL)BUTYL)-, METHANESULPHONATE
Common Name English
AEGR-733 MESILATE
Common Name English
N-(2,2,2-TRIFLUOROETHYL)-9-(4-(4-(((4'-(TRIFLUOROMETHYL)BIPHENYL-2-YL)CARBONYL)AMINO)PIPERIDIN-1-YL)BUTYL)-9H-FLUORENE-9-CARBOXAMIDE METHANESULPHONATE
Common Name English
9H-FLUORENE-9-CARBOXAMIDE, N-(2,2,2-TRIFLUOROETHYL)-9-(4-(4-(((4'-(TRIFLUOROMETHYL)(1,1'-BIPHENYL)-2-YL)CARBONYL)AMINO)-1-PIPERIDINYL)BUTYL)-, METHANESULFONATE
Common Name English
LOMITAPIDE MESYLATE [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29703
Created by admin on Fri Dec 15 15:26:49 UTC 2023 , Edited by admin on Fri Dec 15 15:26:49 UTC 2023
Code System Code Type Description
ChEMBL
CHEMBL354541
Created by admin on Fri Dec 15 15:26:49 UTC 2023 , Edited by admin on Fri Dec 15 15:26:49 UTC 2023
PRIMARY
PUBCHEM
11274333
Created by admin on Fri Dec 15 15:26:49 UTC 2023 , Edited by admin on Fri Dec 15 15:26:49 UTC 2023
PRIMARY
CHEBI
72299
Created by admin on Fri Dec 15 15:26:49 UTC 2023 , Edited by admin on Fri Dec 15 15:26:49 UTC 2023
PRIMARY
DRUG BANK
DBSALT000110
Created by admin on Fri Dec 15 15:26:49 UTC 2023 , Edited by admin on Fri Dec 15 15:26:49 UTC 2023
PRIMARY
SMS_ID
100000143227
Created by admin on Fri Dec 15 15:26:49 UTC 2023 , Edited by admin on Fri Dec 15 15:26:49 UTC 2023
PRIMARY
FDA UNII
X4S83CP54E
Created by admin on Fri Dec 15 15:26:49 UTC 2023 , Edited by admin on Fri Dec 15 15:26:49 UTC 2023
PRIMARY
EVMPD
SUB119583
Created by admin on Fri Dec 15 15:26:49 UTC 2023 , Edited by admin on Fri Dec 15 15:26:49 UTC 2023
PRIMARY
RXCUI
1364478
Created by admin on Fri Dec 15 15:26:49 UTC 2023 , Edited by admin on Fri Dec 15 15:26:49 UTC 2023
PRIMARY RxNorm
NCI_THESAURUS
C83892
Created by admin on Fri Dec 15 15:26:49 UTC 2023 , Edited by admin on Fri Dec 15 15:26:49 UTC 2023
PRIMARY
USAN
TT-135
Created by admin on Fri Dec 15 15:26:49 UTC 2023 , Edited by admin on Fri Dec 15 15:26:49 UTC 2023
PRIMARY
CAS
202914-84-9
Created by admin on Fri Dec 15 15:26:49 UTC 2023 , Edited by admin on Fri Dec 15 15:26:49 UTC 2023
PRIMARY
CHEBI
72297
Created by admin on Fri Dec 15 15:26:49 UTC 2023 , Edited by admin on Fri Dec 15 15:26:49 UTC 2023
PRIMARY
DAILYMED
X4S83CP54E
Created by admin on Fri Dec 15 15:26:49 UTC 2023 , Edited by admin on Fri Dec 15 15:26:49 UTC 2023
PRIMARY
EPA CompTox
DTXSID60174170
Created by admin on Fri Dec 15 15:26:49 UTC 2023 , Edited by admin on Fri Dec 15 15:26:49 UTC 2023
PRIMARY
Related Record Type Details
Structure of LOMITAPIDE
ACTIVE MOIETY
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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