U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C21H46NO4P
Molecular Weight 407.568
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MILTEFOSINE

SMILES

CCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C

InChI

InChIKey=PQLXHQMOHUQAKB-UHFFFAOYSA-N
InChI=1S/C21H46NO4P/c1-5-6-7-8-9-10-11-12-13-14-15-16-17-18-20-25-27(23,24)26-21-19-22(2,3)4/h5-21H2,1-4H3

HIDE SMILES / InChI
Molecular Formula C21H46NO4P
Molecular Weight 407.568
Charge 0
Count
Stereochemistry RACEMIC
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.ncbi.nlm.nih.gov/pubmed/?term=18472998; http://www.ncbi.nlm.nih.gov/pubmed/?term=11355955; http://www.ncbi.nlm.nih.gov/pubmed/?term=16730362

Miltefosine is an anti-leishmanial agent. It is an alkyl phospholipids compound, was originally intended for breast cancer and other solid tumors. However, it could not be developed as an oral agent because of dose-limiting gastro-intestinal toxicity, and only a topical formulation is approved for skin metastasis. But Miltefosine showed excellent antileishmanial activity both in vitro and in experimental models. Miltefosine is effective in vitro against both promastigotes and amastigotes of various species of Leishmania and also other kinetoplastidae (Trypanosoma cruzi,T. brucei) and other protozoan parasites (Entamoeba histolytica, Acanthamoeba). Mechanism of action is unknown. It is likely to involve interaction with lipids (phospholipids and sterols), including membrane lipids, inhibition of cytochrome c oxidase (mitochondrial function), and apoptosis-like cell death. Miltefosine is approved for the treatment of Visceral leishmaniasis (due to Leishmania donovani), Cutaneous leishmaniasis (due to Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis) and Mucosal leishmaniasis (due to Leishmania braziliensis).

CNS Activity

CNS Active
3828
Curator's Comment: Some blood-brain barrier penetration by miltefosine in a human, although with low-level CSF accumulation.

Originator

ASTA Medica
5
Curator's Comment: Discovered by German scientists Hansjorg Eibl, (Max Planck Institute for Biophysical Chemistry), and Clemens Unger ( Gottingen, Germany) miltefosine was prioritized for development in TDR, in partnership with ASTA Medica (now Zentaris), in 1996.

Approval Year

2014
450
Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: UNIPROT: B7TYN7 (Cytochrome c oxidase subunit 1)
Antagonist
2760
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Approved
8360
IMPAVIDO

Approved Use

Indicated in adults and adolescents ≥12 years of age weighing ≥ 30 kg for the treatment of visceral leishmaniasis caused by Leishmania donovani; Cutaneous leishmaniasis caused by Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis; Mucosal leishmaniasis caused by Leishmania braziliensis.

Launch Date

1.39518725E12
Curative
Approved
8360
IMPAVIDO

Approved Use

Indicated in adults and adolescents ≥12 years of age weighing ≥ 30 kg for the treatment of visceral leishmaniasis caused by Leishmania donovani; Cutaneous leishmaniasis caused by Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis; Mucosal leishmaniasis caused by Leishmania braziliensis.

Launch Date

1.39518725E12
Curative
Approved
8360
IMPAVIDO

Approved Use

Indicated in adults and adolescents ≥12 years of age weighing ≥ 30 kg for the treatment of visceral leishmaniasis caused by Leishmania donovani; Cutaneous leishmaniasis caused by Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis; Mucosal leishmaniasis caused by Leishmania braziliensis.

Launch Date

1.39518725E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
66.2 μg/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204684s000lbl.pdf
50 mg 2 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MILTEFOSINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
37.3 μg/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204684s000lbl.pdf
50 mg 3 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MILTEFOSINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
636 μg × h/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204684s000lbl.pdf
50 mg 2 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MILTEFOSINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
295 μg × h/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204684s000lbl.pdf
50 mg 3 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MILTEFOSINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.4 day
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204684s000lbl.pdf
50 mg 2 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MILTEFOSINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
6.8 day
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204684s000lbl.pdf
50 mg 3 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MILTEFOSINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204684s000lbl.pdf
50 mg 2 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MILTEFOSINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204684s000lbl.pdf
50 mg 3 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MILTEFOSINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg 1 times / day multiple, oral (mean)
Studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
unhealthy, at least 12 years of age
n = 120
Health Status: unhealthy
Condition: leishmaniasis
Age Group: at least 12 years of age
Population Size: 120
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
Disc. AE: AST increased, ALT increased...
AEs leading to
discontinuation/dose reduction:
AST increased (0.8%)
ALT increased (0.8%)
Vomiting (0.8%)
Anorexia (0.8%)
Blood urea nitrogen increased (0.8%)
Creatinine increased (0.8%)
Oliguria (0.8%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
50 mg 2 times / day multiple, oral
Studied dose
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
unhealthy, at least 12 years of age
n = 299
Health Status: unhealthy
Condition: leishmaniasis
Age Group: at least 12 years of age
Sex: M+F
Population Size: 299
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Disc. AE: Stevens-Johnson syndrome, Rash...
AEs leading to
discontinuation/dose reduction:
Stevens-Johnson syndrome (0.3%)
Rash (0.3%)
Diarrhea (grade 4, 0.3%)
Hyperbilirubinemia (0.3%)
Thrombocytopenia (0.3%)
Arthritis (0.3%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
50 mg 3 times / day multiple, oral
Recommended
Dose: 50 mg, 3 times / day
Route: oral
Route: multiple
Dose: 50 mg, 3 times / day
Sources:
https://www.who.int/selection_medicines/committees/expert/18/applications/Miltefosine_application.pdf
Page: applications/Miltefosine_application.pdf - p.13
unhealthy, median age of 25 years
n = 89
Health Status: unhealthy
Condition: leishmaniasis
Age Group: median age of 25 years
Sex: M+F
Population Size: 89
Sources:
https://www.who.int/selection_medicines/committees/expert/18/applications/Miltefosine_application.pdf
Page: applications/Miltefosine_application.pdf - p.13
Disc. AE: Motion sickness, Headache...
AEs leading to
discontinuation/dose reduction:
Motion sickness (1.1%)
Headache (1.1%)
Sources:
https://www.who.int/selection_medicines/committees/expert/18/applications/Miltefosine_application.pdf
Page: applications/Miltefosine_application.pdf - p.13
50 mg 3 times / day multiple, oral
Recommended
Dose: 50 mg, 3 times / day
Route: oral
Route: multiple
Dose: 50 mg, 3 times / day
Sources:
https://www.who.int/selection_medicines/committees/expert/18/applications/Miltefosine_application.pdf
Page: applications/Miltefosine_application.pdf - p.14
unhealthy, median age of 25 years
n = 89
Health Status: unhealthy
Condition: leishmaniasis
Age Group: median age of 25 years
Sex: M+F
Population Size: 89
Sources:
https://www.who.int/selection_medicines/committees/expert/18/applications/Miltefosine_application.pdf
Page: applications/Miltefosine_application.pdf - p.14
Other AEs: Vomiting, Vomiting...
Other AEs:
Vomiting (grade 3-4, 3%)
Vomiting (grade 4-5, 3%)
Sources:
https://www.who.int/selection_medicines/committees/expert/18/applications/Miltefosine_application.pdf
Page: applications/Miltefosine_application.pdf - p.14
300 mg 1 times / week multiple, oral
MTD
Dose: 300 mg, 1 times / week
Route: oral
Route: multiple
Dose: 300 mg, 1 times / week
Sources:
https://www.karger.com/Article/Abstract/217014
unhealthy, median age of 56 years
n = 15
Health Status: unhealthy
Condition: cancer
Age Group: median age of 56 years
Sex: M+F
Population Size: 15
Sources:
https://www.karger.com/Article/Abstract/217014
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (grade 3, 6.7%)
Vomiting (grade 3, 6.7%)
Diarrhoea (grade 3, 6.7%)
Sources:
https://www.karger.com/Article/Abstract/217014
50 mg 3 times / day multiple, oral (mean)
Recommended
Dose: 50 mg, 3 times / day
Route: oral
Route: multiple
Dose: 50 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/1325463/
unhealthy, median age of 58 years
n = 54
Health Status: unhealthy
Condition: cancer
Age Group: median age of 58 years
Sex: M+F
Population Size: 54
Sources:
https://pubmed.ncbi.nlm.nih.gov/1325463/
DLT: Nausea, Vomiting...
Dose limiting toxicities:
Nausea (grade 1-2)
Vomiting (grade 1-2)
Sources:
https://pubmed.ncbi.nlm.nih.gov/1325463/
AEs

AEs

AESignificanceDosePopulation
ALT increased 0.8%
Disc. AE
100 mg 1 times / day multiple, oral (mean)
Studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
unhealthy, at least 12 years of age
n = 120
Health Status: unhealthy
Condition: leishmaniasis
Age Group: at least 12 years of age
Population Size: 120
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
AST increased 0.8%
Disc. AE
100 mg 1 times / day multiple, oral (mean)
Studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
unhealthy, at least 12 years of age
n = 120
Health Status: unhealthy
Condition: leishmaniasis
Age Group: at least 12 years of age
Population Size: 120
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
Anorexia 0.8%
Disc. AE
100 mg 1 times / day multiple, oral (mean)
Studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
unhealthy, at least 12 years of age
n = 120
Health Status: unhealthy
Condition: leishmaniasis
Age Group: at least 12 years of age
Population Size: 120
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
Blood urea nitrogen increased 0.8%
Disc. AE
100 mg 1 times / day multiple, oral (mean)
Studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
unhealthy, at least 12 years of age
n = 120
Health Status: unhealthy
Condition: leishmaniasis
Age Group: at least 12 years of age
Population Size: 120
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
Creatinine increased 0.8%
Disc. AE
100 mg 1 times / day multiple, oral (mean)
Studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
unhealthy, at least 12 years of age
n = 120
Health Status: unhealthy
Condition: leishmaniasis
Age Group: at least 12 years of age
Population Size: 120
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
Oliguria 0.8%
Disc. AE
100 mg 1 times / day multiple, oral (mean)
Studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
unhealthy, at least 12 years of age
n = 120
Health Status: unhealthy
Condition: leishmaniasis
Age Group: at least 12 years of age
Population Size: 120
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
Vomiting 0.8%
Disc. AE
100 mg 1 times / day multiple, oral (mean)
Studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
unhealthy, at least 12 years of age
n = 120
Health Status: unhealthy
Condition: leishmaniasis
Age Group: at least 12 years of age
Population Size: 120
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Page: nda/2014/204684Orig1s000MedR.pdf - p.159
Arthritis 0.3%
Disc. AE
50 mg 2 times / day multiple, oral
Studied dose
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
unhealthy, at least 12 years of age
n = 299
Health Status: unhealthy
Condition: leishmaniasis
Age Group: at least 12 years of age
Sex: M+F
Population Size: 299
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Hyperbilirubinemia 0.3%
Disc. AE
50 mg 2 times / day multiple, oral
Studied dose
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
unhealthy, at least 12 years of age
n = 299
Health Status: unhealthy
Condition: leishmaniasis
Age Group: at least 12 years of age
Sex: M+F
Population Size: 299
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Rash 0.3%
Disc. AE
50 mg 2 times / day multiple, oral
Studied dose
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
unhealthy, at least 12 years of age
n = 299
Health Status: unhealthy
Condition: leishmaniasis
Age Group: at least 12 years of age
Sex: M+F
Population Size: 299
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Stevens-Johnson syndrome 0.3%
Disc. AE
50 mg 2 times / day multiple, oral
Studied dose
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
unhealthy, at least 12 years of age
n = 299
Health Status: unhealthy
Condition: leishmaniasis
Age Group: at least 12 years of age
Sex: M+F
Population Size: 299
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Thrombocytopenia 0.3%
Disc. AE
50 mg 2 times / day multiple, oral
Studied dose
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
unhealthy, at least 12 years of age
n = 299
Health Status: unhealthy
Condition: leishmaniasis
Age Group: at least 12 years of age
Sex: M+F
Population Size: 299
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Diarrhea grade 4, 0.3%
Disc. AE
50 mg 2 times / day multiple, oral
Studied dose
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
unhealthy, at least 12 years of age
n = 299
Health Status: unhealthy
Condition: leishmaniasis
Age Group: at least 12 years of age
Sex: M+F
Population Size: 299
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204684Orig1s000MedR.pdf
Headache 1.1%
Disc. AE
50 mg 3 times / day multiple, oral
Recommended
Dose: 50 mg, 3 times / day
Route: oral
Route: multiple
Dose: 50 mg, 3 times / day
Sources:
https://www.who.int/selection_medicines/committees/expert/18/applications/Miltefosine_application.pdf
Page: applications/Miltefosine_application.pdf - p.13
unhealthy, median age of 25 years
n = 89
Health Status: unhealthy
Condition: leishmaniasis
Age Group: median age of 25 years
Sex: M+F
Population Size: 89
Sources:
https://www.who.int/selection_medicines/committees/expert/18/applications/Miltefosine_application.pdf
Page: applications/Miltefosine_application.pdf - p.13
Motion sickness 1.1%
Disc. AE
50 mg 3 times / day multiple, oral
Recommended
Dose: 50 mg, 3 times / day
Route: oral
Route: multiple
Dose: 50 mg, 3 times / day
Sources:
https://www.who.int/selection_medicines/committees/expert/18/applications/Miltefosine_application.pdf
Page: applications/Miltefosine_application.pdf - p.13
unhealthy, median age of 25 years
n = 89
Health Status: unhealthy
Condition: leishmaniasis
Age Group: median age of 25 years
Sex: M+F
Population Size: 89
Sources:
https://www.who.int/selection_medicines/committees/expert/18/applications/Miltefosine_application.pdf
Page: applications/Miltefosine_application.pdf - p.13
Vomiting grade 3-4, 3%
50 mg 3 times / day multiple, oral
Recommended
Dose: 50 mg, 3 times / day
Route: oral
Route: multiple
Dose: 50 mg, 3 times / day
Sources:
https://www.who.int/selection_medicines/committees/expert/18/applications/Miltefosine_application.pdf
Page: applications/Miltefosine_application.pdf - p.14
unhealthy, median age of 25 years
n = 89
Health Status: unhealthy
Condition: leishmaniasis
Age Group: median age of 25 years
Sex: M+F
Population Size: 89
Sources:
https://www.who.int/selection_medicines/committees/expert/18/applications/Miltefosine_application.pdf
Page: applications/Miltefosine_application.pdf - p.14
Vomiting grade 4-5, 3%
50 mg 3 times / day multiple, oral
Recommended
Dose: 50 mg, 3 times / day
Route: oral
Route: multiple
Dose: 50 mg, 3 times / day
Sources:
https://www.who.int/selection_medicines/committees/expert/18/applications/Miltefosine_application.pdf
Page: applications/Miltefosine_application.pdf - p.14
unhealthy, median age of 25 years
n = 89
Health Status: unhealthy
Condition: leishmaniasis
Age Group: median age of 25 years
Sex: M+F
Population Size: 89
Sources:
https://www.who.int/selection_medicines/committees/expert/18/applications/Miltefosine_application.pdf
Page: applications/Miltefosine_application.pdf - p.14
Diarrhoea grade 3, 6.7%
300 mg 1 times / week multiple, oral
MTD
Dose: 300 mg, 1 times / week
Route: oral
Route: multiple
Dose: 300 mg, 1 times / week
Sources:
https://www.karger.com/Article/Abstract/217014
unhealthy, median age of 56 years
n = 15
Health Status: unhealthy
Condition: cancer
Age Group: median age of 56 years
Sex: M+F
Population Size: 15
Sources:
https://www.karger.com/Article/Abstract/217014
Nausea grade 3, 6.7%
300 mg 1 times / week multiple, oral
MTD
Dose: 300 mg, 1 times / week
Route: oral
Route: multiple
Dose: 300 mg, 1 times / week
Sources:
https://www.karger.com/Article/Abstract/217014
unhealthy, median age of 56 years
n = 15
Health Status: unhealthy
Condition: cancer
Age Group: median age of 56 years
Sex: M+F
Population Size: 15
Sources:
https://www.karger.com/Article/Abstract/217014
Vomiting grade 3, 6.7%
300 mg 1 times / week multiple, oral
MTD
Dose: 300 mg, 1 times / week
Route: oral
Route: multiple
Dose: 300 mg, 1 times / week
Sources:
https://www.karger.com/Article/Abstract/217014
unhealthy, median age of 56 years
n = 15
Health Status: unhealthy
Condition: cancer
Age Group: median age of 56 years
Sex: M+F
Population Size: 15
Sources:
https://www.karger.com/Article/Abstract/217014
Nausea grade 1-2
DLT
50 mg 3 times / day multiple, oral (mean)
Recommended
Dose: 50 mg, 3 times / day
Route: oral
Route: multiple
Dose: 50 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/1325463/
unhealthy, median age of 58 years
n = 54
Health Status: unhealthy
Condition: cancer
Age Group: median age of 58 years
Sex: M+F
Population Size: 54
Sources:
https://pubmed.ncbi.nlm.nih.gov/1325463/
Vomiting grade 1-2
DLT
50 mg 3 times / day multiple, oral (mean)
Recommended
Dose: 50 mg, 3 times / day
Route: oral
Route: multiple
Dose: 50 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/1325463/
unhealthy, median age of 58 years
n = 54
Health Status: unhealthy
Condition: cancer
Age Group: median age of 58 years
Sex: M+F
Population Size: 54
Sources:
https://pubmed.ncbi.nlm.nih.gov/1325463/
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1709

inhibitor
1579
substrate
1010

inhibitor
1752
substrate
1193

inhibitor
1837
inhibitor
1599

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A1
110

CYP1A2
1509

CYP1B1
19

CYP2A6
704

CYP2B6
799

CYP2C8
901

CYP2C18
10

CYP2C19
1463

CYP2E1
876

CYP3A5
73

CYP3A7
7

CYP4A1
8
CYP1A1
348

CYP1A2
1032

CYP1B1
92

CYP2A6
523

CYP2B6
660

CYP2C8
688

CYP2C18
139

CYP2C19
985

CYP2E1
648

CYP3A5
391

CYP3A7
110

CYP4A1
1

ABCA3
1

P-gp
1527
CYP3A
126
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A1
218
 no
CYP1A2
1673
 no
CYP1B1
68
 no
CYP2A6
736
 no
CYP2B6
985
 no
CYP2C18
13
 no
CYP2C19
1537
 no
CYP2C8
955
 no
CYP2C9
1803
 no
CYP2D6
1875
 no
CYP2E1
964
 no
CYP3A
295
 no
CYP3A4
1909
 no
CYP3A5
130
 no
CYP3A7
22
 no
CYP4A1
25
 no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP1A1
348
 no
CYP1A2
1032
 no
CYP1B1
92
 no
CYP2A6
523
 no
CYP2B6
660
 no
CYP2C18
139
 no
CYP2C19
985
 no
CYP2C8
688
 no
CYP2C9
1010
 no
CYP2D6
1193
 no
CYP2E1
648
 no
CYP3A4
1709
 no
CYP3A5
391
 no
CYP3A7
110
 no
CYP4A1
1
 no
ABCA3
1
 yes
P-gp
1527
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1632
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:75283
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:75283
ChemicalBook
CB6370752
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6370752
MolPort
MolPort-003-665-519
https://www.molport.com/shop/molecule-link/MolPort-003-665-519
Selleck Chemicals
miltefosine-hexadecylphosphocholine
http://www.selleckchem.com/products/miltefosine-hexadecylphosphocholine.html
eMolecules
748094
https://www.emolecules.com/cgi-bin/more?vid=748094
PubMed

PubMed

TitleDatePubMed
Recent strategies for the chemotherapy of visceral leishmaniasis.
1999 Dec
Mononuclear cell recruitment, granuloma assembly, and response to treatment in experimental visceral leishmaniasis: intracellular adhesion molecule 1-dependent and -independent regulation.
2000 Nov
Proinflammatory and cytotoxic effects of hexadecylphosphocholine (miltefosine) against drug-resistant strains of Trypanosoma cruzi.
2002 Nov
Single-dose liposomal amphotericin B in the treatment of visceral leishmaniasis in India: a multicenter study.
2003 Sep 15
Use of Leishmania donovani field isolates expressing the luciferase reporter gene in in vitro drug screening.
2005 Sep
Development of miltefosine as an oral treatment for leishmaniasis.
2006 Dec
In vitro activity of hexadecylphosphocholine (miltefosine) against metronidazole-resistant and -susceptible strains of Trichomonas vaginalis.
2006 Feb
Visceral leishmaniasis (kala-azar)--the Bihar (India) perspective.
2006 Jul
Drug policy for visceral leishmaniasis: a cost-effectiveness analysis.
2007 Feb
Treatment of Bolivian mucosal leishmaniasis with miltefosine.
2007 Feb 1
Synthesis, self-aggregation and biological properties of alkylphosphocholine and alkylphosphohomocholine derivatives of cetyltrimethylammonium bromide, cetylpyridinium bromide, benzalkonium bromide (C16) and benzethonium chloride.
2013 Aug
Effect of alkylphospholipids on Candida albicans biofilm formation and maturation.
2013 Jan
Synthesis and antifungal activities of miltefosine analogs.
2013 Sep 1
Patents

Patents

CN101475585A
1
DE10313272A1
1
US5290769
1
WO1987003480A3
1

Sample Use Guides

In Vivo Use Guide
For adults and adolescents ≥12 years of age weighing 30 to 44 kg - one 50 mg capsule twice daily for 28 consecutive days, 45 kg or greater - one 50 mg capsule three times daily for 28 consecutive days. Administer with food to ameliorate gastrointestinal adverse reactions.
Route of Administration: Oral
In Vitro Use Guide
Miltefosine was tested in vitro against L. donovani promastigotes. The cells death profile was initially slow when concentrations up to 20 mkM were used. Subsequently, a very rapid and dose-dependent death occurred with miltefosine concentrations between 20 and 50 mkM, reaching approximately 100% at around 40 mkM. Approximately 50% death was observed with miltefosine at a concentration of 25 mkM.
Substance Class Chemical
Created
by admin
on Thu Jul 06 22:48:22 UTC 2023
Edited
by admin
on Thu Jul 06 22:48:22 UTC 2023
Record UNII
53EY29W7EC
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MILTEFOSINE
DASH   INN   MART.   MI   WHO-DD  
INN  
Official Name English
IMPAVIDO
Brand Name English
MILTEFOSINE [MI]
Common Name English
miltefosine [INN]
Common Name English
D-18506
Code English
HDPC
Common Name English
Miltefosine [WHO-DD]
Common Name English
MILTEFOSINE [ORANGE BOOK]
Common Name English
MILTEFOSINE [MART.]
Common Name English
NSC-758968
Code English
NSC-605583
Code English
Classification Tree Code System Code
NCI_THESAURUS C2188
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
WHO-ESSENTIAL MEDICINES LIST 6.5.2
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
WHO-VATC QL01XX09
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
FDA ORPHAN DRUG 229406
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
FDA ORPHAN DRUG 540216
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
FDA ORPHAN DRUG 590217
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
NDF-RT N0000190851
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
FDA ORPHAN DRUG 275409
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
EU-Orphan Drug EU/3/05/282
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
WHO-ATC L01XX09
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
FDA ORPHAN DRUG 565016
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
FDA ORPHAN DRUG 565216
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
FDA ORPHAN DRUG 565116
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
FDA ORPHAN DRUG 843921
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
Code System Code Type Description
NSC
605583
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
DAILYMED
53EY29W7EC
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
PUBCHEM
3599
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
NCI_THESAURUS
C1170
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
CAS
58066-85-6
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
INN
6362
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
FDA UNII
53EY29W7EC
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
MERCK INDEX
M7549
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY Merck Index
CHEBI
75283
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
DRUG CENTRAL
1810
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
WIKIPEDIA
Miltefosine
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
MESH
C039128
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
EVMPD
SUB08969MIG
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
SMS_ID
100000091387
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
DRUG BANK
DB09031
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
RXCUI
1494066
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY RxNorm
EPA CompTox
DTXSID7045942
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
ChEMBL
CHEMBL125
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
NSC
758968
Created by admin on Thu Jul 06 22:48:22 UTC 2023 , Edited by admin on Thu Jul 06 22:48:22 UTC 2023
PRIMARY
Related Record Type Details
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
Structure of MILTEFOSINE
EXCRETED UNCHANGED
The urinary excretion of the unchanged drug on Day 23 after repeated oral administration of miltefosine to adult patients was below 0.2% of the daily dose
URINE
Related Record Type Details
Structure of CHOLINE
METABOLITE INACTIVE -> PARENT
PLASMA
Related Record Type Details
Structure of MILTEFOSINE
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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