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

Details

Stereochemistry RACEMIC
Molecular Formula C26H30Cl2F3NO
Molecular Weight 500.4245
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of HALOFANTRINE

SMILES

CCCCN(CCCC)CCC(c1cc2c(cc(cc2Cl)Cl)c3cc(ccc31)C(F)(F)F)O

InChI

InChIKey=FOHHNHSLJDZUGQ-UHFFFAOYSA-N
InChI=1S/C26H30Cl2F3NO/c1-3-5-10-32(11-6-4-2)12-9-25(33)23-16-22-21(14-18(27)15-24(22)28)20-13-17(26(29,30)31)7-8-19(20)23/h7-8,13-16,25,33H,3-6,9-12H2,1-2H3

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created using several sources including: https://www.sri.com/newsroom/press-releases/sri-international-celebrates-50-years-drug-discovery-and-development-contrib; http://www.drugbank.ca/drugs/DB01218

Halofantrine is a blood schizonticidal antimalarial agent with no apparent action on the sporozoite, gametocyte or hepatic stages of the infection. It is used only to treat but not to prevent malaria. Has been marketed by GlaxoSmithKline as HALFAN (halofantrine hydrochloride) in 250 mg tablets indicated for the treatment of adults who can tolerate oral medication and who have mild to moderate malaria (equal to or less than 100,000 parasites/mm3) caused by Plasmodium falciparum or Plasmodium vivax. Among side effects is cardiac arrhythmia. It belongs to the phenanthrene class of compounds that includes quinine and lumefantrine. It was reported that halofantrine binds to hematin in vitro (crystal structure of the complex) and to to plasmpesin, a haemoglobin degrading enzyme unique to the malarial parasites.

Originator

Curator's Comment:: In the 1970s, SRI developed halofantrine for the U.S. Army as a treatment for drug-resistant malaria. It was distributed by the World Health Organization (WHO). It was approved by FDA as an antimalarial in 1992 under the SmithKline Beecham (now GlaxoSmithKline) brand name, Halfan®.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.79 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
HALFAN

Approved Use

Halfan tablets are indicated for the treatment of adults who can tolerate oral medication and who have mild to moderate malaria (equal to or less than 100,000 parasites/mm3) caused by Plasmodium falciparum or Plasmodium vivax.

Launch Date

7.5548158E11
Curative
HALFAN

Approved Use

Halfan tablets are indicated for the treatment of adults who can tolerate oral medication and who have mild to moderate malaria (equal to or less than 100,000 parasites/mm3) caused by Plasmodium falciparum or Plasmodium vivax.

Launch Date

7.1193598E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
114 μg/L
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DESBUTYLHALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
191 μg/L
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DESBUTYLHALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
79 μg/L
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DESBUTYLHALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1218 μg/L
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: HIGH-FAT
185 μg/L
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
345 μg/L
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
546 μg/L
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
3200 ng/mL
500 mg 3 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
HALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
17.33 mg × h/L
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DESBUTYLHALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
24.46 mg × h/L
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DESBUTYLHALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
8.76 mg × h/L
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DESBUTYLHALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
11.3 mg × h/L
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: HIGH-FAT
3.92 mg × h/L
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
7.86 mg × h/L
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
9.36 mg × h/L
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
81 h
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
98 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
72 h
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
8 day
500 mg 3 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
HALOFANTRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
Doses

Doses

DosePopulationAdverse events​
500 mg 3 times / day single, oral
Recommended
Dose: 500 mg, 3 times / day
Route: oral
Route: single
Dose: 500 mg, 3 times / day
Sources: Page: 7
unhealthy, adult
n = 933
Health Status: unhealthy
Condition: malaria
Age Group: adult
Sex: unknown
Population Size: 933
Sources: Page: 7
Disc. AE: Vomiting of medication, Consciousness decreased...
Other AEs: Convulsions, Stomatitis...
AEs leading to
discontinuation/dose reduction:
Vomiting of medication (3 patients)
Consciousness decreased (2 patients)
Other AEs:
Convulsions (3 patients)
Stomatitis (3 patients)
Pulmonary edema (1 patient)
Tetany (1 patient)
Hypertensive crisis (1 patient)
Cerebrovascular accident (1 patient)
Sources: Page: 7
AEs

AEs

AESignificanceDosePopulation
Cerebrovascular accident 1 patient
500 mg 3 times / day single, oral
Recommended
Dose: 500 mg, 3 times / day
Route: oral
Route: single
Dose: 500 mg, 3 times / day
Sources: Page: 7
unhealthy, adult
n = 933
Health Status: unhealthy
Condition: malaria
Age Group: adult
Sex: unknown
Population Size: 933
Sources: Page: 7
Hypertensive crisis 1 patient
500 mg 3 times / day single, oral
Recommended
Dose: 500 mg, 3 times / day
Route: oral
Route: single
Dose: 500 mg, 3 times / day
Sources: Page: 7
unhealthy, adult
n = 933
Health Status: unhealthy
Condition: malaria
Age Group: adult
Sex: unknown
Population Size: 933
Sources: Page: 7
Pulmonary edema 1 patient
500 mg 3 times / day single, oral
Recommended
Dose: 500 mg, 3 times / day
Route: oral
Route: single
Dose: 500 mg, 3 times / day
Sources: Page: 7
unhealthy, adult
n = 933
Health Status: unhealthy
Condition: malaria
Age Group: adult
Sex: unknown
Population Size: 933
Sources: Page: 7
Tetany 1 patient
500 mg 3 times / day single, oral
Recommended
Dose: 500 mg, 3 times / day
Route: oral
Route: single
Dose: 500 mg, 3 times / day
Sources: Page: 7
unhealthy, adult
n = 933
Health Status: unhealthy
Condition: malaria
Age Group: adult
Sex: unknown
Population Size: 933
Sources: Page: 7
Consciousness decreased 2 patients
Disc. AE
500 mg 3 times / day single, oral
Recommended
Dose: 500 mg, 3 times / day
Route: oral
Route: single
Dose: 500 mg, 3 times / day
Sources: Page: 7
unhealthy, adult
n = 933
Health Status: unhealthy
Condition: malaria
Age Group: adult
Sex: unknown
Population Size: 933
Sources: Page: 7
Convulsions 3 patients
500 mg 3 times / day single, oral
Recommended
Dose: 500 mg, 3 times / day
Route: oral
Route: single
Dose: 500 mg, 3 times / day
Sources: Page: 7
unhealthy, adult
n = 933
Health Status: unhealthy
Condition: malaria
Age Group: adult
Sex: unknown
Population Size: 933
Sources: Page: 7
Stomatitis 3 patients
500 mg 3 times / day single, oral
Recommended
Dose: 500 mg, 3 times / day
Route: oral
Route: single
Dose: 500 mg, 3 times / day
Sources: Page: 7
unhealthy, adult
n = 933
Health Status: unhealthy
Condition: malaria
Age Group: adult
Sex: unknown
Population Size: 933
Sources: Page: 7
Vomiting of medication 3 patients
Disc. AE
500 mg 3 times / day single, oral
Recommended
Dose: 500 mg, 3 times / day
Route: oral
Route: single
Dose: 500 mg, 3 times / day
Sources: Page: 7
unhealthy, adult
n = 933
Health Status: unhealthy
Condition: malaria
Age Group: adult
Sex: unknown
Population Size: 933
Sources: Page: 7
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer





Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 1.06 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: grapefruit juice increased halofantrine area under the plasma concentration versus time curve (AUC) and peak plasma concentration by 2.8-fold
minor
minor
minor
minor
minor
minor
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
In vitro cultivation of Cryptosporidium parvum and screening for anticryptosporidial drugs.
1990 Aug

Sample Use Guides

The recommended treatment consists of 2 courses of 1500 mg. One course dosage is 500 mg (2 x 250 mg tablets) given every 6 hours for 3 doses, repeated in 7 days. Halofantrine is administered at least 1 hour before or 2 hours after food.
Route of Administration: Oral
In Vitro Use Guide
Antimalarial activity of halofantrine against 33 strains of P. falciparum isolated from naturally acquired malaria infections in Thailand was determined using a radioisotope microdilution method. 0.2-25 ng/ml of halofantrine was added to test isolates of P. falciparum. Susceptibility response ID50 was 0.63-0.73 ng/ml.
Name Type Language
HALOFANTRINE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
9-PHENANTHRENEMETHANOL, 1,3-DICHLORO-.ALPHA.-(2-(DIBUTYLAMINO)ETHYL)-6-(TRIFLUOROMETHYL)-
Systematic Name English
(+/-)-HALOFANTRINE
Common Name English
HALOFANTRINE [VANDF]
Common Name English
HALOFANTRINE [WHO-DD]
Common Name English
DL-WR-171669
Code English
HALOFANTRINE [MI]
Common Name English
1,3-DICHLORO-.ALPHA.-(2-(DIBUTYLAMINO)ETHYL)-6-(TRIFLUOROMETHYL)-9-PHENANTHRENEMETHANOL
Systematic Name English
HALOFANTRINE [INN]
Common Name English
Classification Tree Code System Code
WHO-ATC P01BX01
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
NCI_THESAURUS C271
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
FDA ORPHAN DRUG 61791
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
NDF-RT N0000175482
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
Code System Code Type Description
WIKIPEDIA
HALOFANTRINE
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY
EPA CompTox
69756-53-2
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY
MESH
C023768
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY
MERCK INDEX
M5900
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY Merck Index
CAS
66051-63-6
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
SUPERSEDED
ECHA (EC/EINECS)
274-104-1
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY
DRUG BANK
DB01218
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY
ChEMBL
CHEMBL1107
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY
CAS
69756-53-2
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY
RXCUI
50749
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY RxNorm
EVMPD
SUB07998MIG
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY
FDA UNII
Q2OS4303HZ
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY
DRUG CENTRAL
1350
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY
PUBCHEM
37393
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY
NCI_THESAURUS
C65838
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY
INN
4749
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY
LACTMED
Halofantrine
Created by admin on Sat Jun 26 13:22:02 UTC 2021 , Edited by admin on Sat Jun 26 13:22:02 UTC 2021
PRIMARY