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Details

Stereochemistry ACHIRAL
Molecular Formula C22H28N4O6
Molecular Weight 444.4809
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MITOXANTRONE

SMILES

OCCNCCNC1=CC=C(NCCNCCO)C2=C1C(=O)C3=C(C2=O)C(O)=CC=C3O

InChI

InChIKey=KKZJGLLVHKMTCM-UHFFFAOYSA-N
InChI=1S/C22H28N4O6/c27-11-9-23-5-7-25-13-1-2-14(26-8-6-24-10-12-28)18-17(13)21(31)19-15(29)3-4-16(30)20(19)22(18)32/h1-4,23-30H,5-12H2

HIDE SMILES / InChI
Molecular Formula C22H28N4O6
Molecular Weight 444.4809
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Mitoxantrone (NOVANTRONE) is a synthetic antineoplastic anthracenedione. Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity. Mitoxantrone has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen pre sentation, as well as the secretion of interferon gamma, TNFα, and IL-2. NOVANTRONE is indicated for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (i.e., patients whose neurologic status is significantly abnormal between relapses). NOVANTRONE in combination with corticosteroids is indicated as initial chemotherapy for the treatment of patients with pain related to advanced hormone-refractory prostate cancer. NOVANTRONE in combination with other approved drug(s) is indicated in the initial therapy of acute nonlymphocytic leukemia (ANLL) in adults. This category includes myelogenous, promyelocytic, monocytic, and erythroid acute leukemias.

CNS Activity

CNS Non-penetrant
1018
Curator's Comment: Mitoxantrone does not cross the blood-brain barrier to any appreciable extent.

Originator

Approval Year

1987
114
Targets

Targets

Primary TargetPharmacologyConditionPotency
Ubiquitin carboxyl-terminal hydrolase 11
2
Target ID: P51784
Gene ID: 8237.0
Gene Symbol: USP11
Target Organism: Homo sapiens (Human)
Inhibitor
8146
Inhibitor
8146
Inhibitor
8146
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8307
NOVANTRONE

Approved Use

Mitoxantrone injection USP (concentrate) is indicated for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (i.e., patients whose neurologic status is significantly abnormal between relapses). Mitoxantrone injection USP (concentrate) is not indicated in the treatment of patients with primary progressive multiple sclerosis. The clinical patterns of multiple sclerosis in the studies were characterized as follows: secondary progressive and progressive relapsing disease were characterized by gradual increasing disability with or without superimposed clinical relapses, and worsening relapsing-remitting disease was characterized by clinical relapses resulting in a step-wise worsening of disability. Mitoxantrone injection USP (concentrate) in combination with corticosteroids is indicated as initial chemotherapy for the treatment of patients with pain related to advanced hormone-refractory prostate cancer. Mitoxantrone injection USP (concentrate) in combination with other approved drug(s) is indicated in the initial therapy of acute nonlymphocytic leukemia (ANLL) in adults. This category includes myelogenous, promyelocytic, monocytic, and erythroid acute leukemias.

Launch Date

5.6721598E11
Primary
Approved
8307
NOVANTRONE

Approved Use

NOVANTRONE is indicated for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (i.e., patients whose neurologic status is significantly abnormal between relapses). NOVANTRONE is not indicated in the treatment of patients with primary progressive multiple sclerosis. The clinical patterns of multiple sclerosis in the studies were characterized as follows: secondary progressive and progressive relapsing disease were characterized by gradual increasing disability with or without superimposed clinical relapses, and worsening relapsing-remitting disease was characterized by clinical relapses resulting in a step-wise worsening of disability. NOVANTRONE in combination with corticosteroids is indicated as initial chemotherapy for the treatment of patients with pain related to advanced hormone-refractory prostate cancer. NOVANTRONE in combination with other approved drug(s) is indicated in the initial therapy of acute nonlymphocytic leukemia (ANLL) in adults. This category includes myelogenous, promyelocytic, monocytic, and erythroid acute leukemias.

Launch Date

5.6721598E11
Primary
Approved
8307
NOVANTRONE

Approved Use

NOVANTRONE is indicated for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (i.e., patients whose neurologic status is significantly abnormal between relapses). NOVANTRONE is not indicated in the treatment of patients with primary progressive multiple sclerosis. The clinical patterns of multiple sclerosis in the studies were characterized as follows: secondary progressive and progressive relapsing disease were characterized by gradual increasing disability with or without superimposed clinical relapses, and worsening relapsing-remitting disease was characterized by clinical relapses resulting in a step-wise worsening of disability. NOVANTRONE in combination with corticosteroids is indicated as initial chemotherapy for the treatment of patients with pain related to advanced hormone-refractory prostate cancer. NOVANTRONE in combination with other approved drug(s) is indicated in the initial therapy of acute nonlymphocytic leukemia (ANLL) in adults. This category includes myelogenous, promyelocytic, monocytic, and erythroid acute leukemias.

Launch Date

5.6721598E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
6.429 mg/L
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/8402672
90 mg/m² single, intravenous
dose: 90 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MITOXANTRONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
5.195 mg × h/L
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/8402672
90 mg/m² single, intravenous
dose: 90 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MITOXANTRONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1922 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/8410125
40 mg/m² single, intravenous
dose: 40 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MITOXANTRONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1.26 μg × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/1558794
12 mg/m² 1 times / 3 weeks multiple, intravenous
dose: 12 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
MITOXANTRONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
37.1 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/8410125
40 mg/m² single, intravenous
dose: 40 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MITOXANTRONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
19.83 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/1558794
12 mg/m² 1 times / 3 weeks multiple, intravenous
dose: 12 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
MITOXANTRONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
22%
DRUG LABEL
https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/fcb8ef8a-f770-4416-8fc5-fa01d98c8eee/spl-doc?hl=MITOXANTRONE
MITOXANTRONE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
39 mg/m2 1 times / 4 weeks multiple, intravenous
Highest studied dose
Dose: 39 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 39 mg/m2, 1 times / 4 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/10445421/
unhealthy, adult
n = 11
Health Status: unhealthy
Condition: metastatic breast cancer
Age Group: adult
Sex: F
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/10445421/
DLT: Granulocytopenia...
Other AEs: Thrombocytopenia, Nausea and vomiting...
Dose limiting toxicities:
Granulocytopenia (grade 4, 11 patient)
Other AEs:
Thrombocytopenia (grade 3, 11 patient)
Nausea and vomiting (grade 1-2, 9 patients)
Stomatitis (grade 1-3, 6 patients)
Alopecia (grade 1-3, 5 patients)
Diarrhea (grade 1-2, 3 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/10445421/
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Disc. AE: Urinary tract infection, Leukopenia...
Other AEs: Nausea, Alopecia...
AEs leading to
discontinuation/dose reduction:
Urinary tract infection (32%)
Leukopenia (19%)
Depression (1 patient)
Left ventricular dysfunction (1 patient)
Bone pain (1 patient)
Emesis (1 patient)
Renal failure (1 patient)
Other AEs:
Nausea (76%)
Alopecia (61%)
Menstrual disorder (61%)
Amenorrhea (43%)
Upper respiratory tract infection (53%)
Stomatitis (19%)
Arrhythmia (18%)
Diarrhea (16%)
Urine abnormal (11%)
ECG abnormal (11%)
Constipation (10%)
Back pain (8%)
Sinusitis (6%)
Headache (6%)
Gamma-GT increased (15%)
SGOT increased (8%)
Granulocytopenia (6%)
Anemia (6%)
SGPT increased (5%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
AEs

AEs

AESignificanceDosePopulation
Diarrhea grade 1-2, 3 patients
39 mg/m2 1 times / 4 weeks multiple, intravenous
Highest studied dose
Dose: 39 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 39 mg/m2, 1 times / 4 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/10445421/
unhealthy, adult
n = 11
Health Status: unhealthy
Condition: metastatic breast cancer
Age Group: adult
Sex: F
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/10445421/
Nausea and vomiting grade 1-2, 9 patients
39 mg/m2 1 times / 4 weeks multiple, intravenous
Highest studied dose
Dose: 39 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 39 mg/m2, 1 times / 4 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/10445421/
unhealthy, adult
n = 11
Health Status: unhealthy
Condition: metastatic breast cancer
Age Group: adult
Sex: F
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/10445421/
Alopecia grade 1-3, 5 patients
39 mg/m2 1 times / 4 weeks multiple, intravenous
Highest studied dose
Dose: 39 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 39 mg/m2, 1 times / 4 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/10445421/
unhealthy, adult
n = 11
Health Status: unhealthy
Condition: metastatic breast cancer
Age Group: adult
Sex: F
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/10445421/
Stomatitis grade 1-3, 6 patients
39 mg/m2 1 times / 4 weeks multiple, intravenous
Highest studied dose
Dose: 39 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 39 mg/m2, 1 times / 4 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/10445421/
unhealthy, adult
n = 11
Health Status: unhealthy
Condition: metastatic breast cancer
Age Group: adult
Sex: F
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/10445421/
Thrombocytopenia grade 3, 11 patient
39 mg/m2 1 times / 4 weeks multiple, intravenous
Highest studied dose
Dose: 39 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 39 mg/m2, 1 times / 4 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/10445421/
unhealthy, adult
n = 11
Health Status: unhealthy
Condition: metastatic breast cancer
Age Group: adult
Sex: F
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/10445421/
Granulocytopenia grade 4, 11 patient
DLT
39 mg/m2 1 times / 4 weeks multiple, intravenous
Highest studied dose
Dose: 39 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 39 mg/m2, 1 times / 4 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/10445421/
unhealthy, adult
n = 11
Health Status: unhealthy
Condition: metastatic breast cancer
Age Group: adult
Sex: F
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/10445421/
Bone pain 1 patient
Disc. AE
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Depression 1 patient
Disc. AE
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Emesis 1 patient
Disc. AE
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Left ventricular dysfunction 1 patient
Disc. AE
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Renal failure 1 patient
Disc. AE
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Constipation 10%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
ECG abnormal 11%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Urine abnormal 11%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Gamma-GT increased 15%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Diarrhea 16%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Arrhythmia 18%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Stomatitis 19%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Leukopenia 19%
Disc. AE
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Urinary tract infection 32%
Disc. AE
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Amenorrhea 43%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
SGPT increased 5%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Upper respiratory tract infection 53%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Anemia 6%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Granulocytopenia 6%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Headache 6%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Sinusitis 6%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Alopecia 61%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Menstrual disorder 61%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Nausea 76%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Back pain 8%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
SGOT increased 8%
12 mg/m2 1 times / 3 months multiple, intravenous
Recommended
Dose: 12 mg/m2, 1 times / 3 months
Route: intravenous
Route: multiple
Dose: 12 mg/m2, 1 times / 3 months
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
unhealthy, adult
n = 62
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: M+F
Population Size: 62
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1532
inhibitor
1695
inhibitor
1789

OverviewOther

Other InhibitorOther SubstrateOther Inducer
OCT1
498

CYP1A2
1463

CYP2A6
670

CYP2C19
1410

CYP2E1
846

OATP1B3
691

OATP1B1
770
OATP1B1
389

BCRP
545

MRP1
102

P-gp
1491
BCRP
74
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1620
 no
CYP2A6
702
 no
CYP2C19
1484
 no
CYP2C9
1747
 no
CYP2D6
1826
 no
CYP2E1
929
 no
CYP3A4
1857
 no
OCT1
513
 weak [Ki 85 uM]
CYP2E1
929
 weak
OATP1B1
785
 weak
OATP1B3
700
 yes [IC50 3.39 uM]
BCRP
751
 yes
MRP2
452
 yes
MRP4
235
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
BCRP
545
 yes
MRP1
102
 yes
OATP1B1
389
 yes
P-gp
1491
 yes
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:50729
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:50729
ChemicalBook
CB1246423
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1246423
MolPort
MolPort-003-849-239
https://www.molport.com/shop/molecule-link/MolPort-003-849-239
ZINC
ZINC000003794794
http://zinc15.docking.org/substances/ZINC000003794794
eMolecules
742146
https://www.emolecules.com/cgi-bin/more?vid=742146
PubMed

PubMed

TitleDatePubMed
First-line treatment of metastatic breast cancer with mitoxantrone, vinorelbine, and carboplatin.
1999 Dec
Camptothecin resistance: role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells.
1999 Dec 1
Sinus bradycardia due to mitoxantrone.
2000 Apr
Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2.
2000 Aug
Sinus bradycardia secondary to mitoxantrone.
2000 Jun
Treatment of patients with recurrent and primary refractory acute myelogenous leukemia using mitoxantrone and intermediate-dose cytarabine: a pharmacologically based regimen.
2000 May 1
A systematic overview of chemotherapy effects in acute myeloid leukaemia.
2001
Salvage chemotherapy with mitoxantrone, fludarabine, cytarabine, and cisplatin (MIFAP) in relapsing and refractory lymphoma.
2001
Mitoxantrone and paclitaxel combination chemotherapy in metastatic breast cancer.
2001
5'-deoxy-5-fluorouridine, medroxyprogestrone acetate and mitoxantrone hydrochloride for advanced or recurrent breast cancer.
2001
High remission rate in acute myeloblastic leukemia with only two days of chemotherapy.
2001 Apr
Immunomodulatory drugs for multiple sclerosis: a systematic review of clinical and cost effectiveness.
2001 Apr
Combination chemotherapy with mitoxantrone, methotrexate, and mitomycin (MMM regimen) in malignant pleural mesothelioma: a phase II study.
2001 Apr
HPV16-E6 enhances mitoxantrone sensitivity in a human ovarian cancer line: an isolated instance or a trend?
2001 Apr
The DNA helicase activity of yeast Sgs1p is essential for normal lifespan but not for resistance to topoisomerase inhibitors.
2001 Aug
Resistance to topoisomerase poisons due to loss of DNA mismatch repair.
2001 Aug 15
Docetaxel in prostate cancer.
2001 Feb
Anthracycline adjuvant chemotherapy: how much is enough?
2001 Feb 1
Acute heart failure after allogeneic blood stem cell transplantation due to massive myocardial infiltration by cytotoxic T cells of donor origin.
2001 Jan
Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BCrp/ABCP1), in flavopiridol-resistant human breast cancer cells.
2001 Jan
[Chemotherapy in gastroenterologic neuroendocrine tumors].
2001 Jun
Secondary acute myelogenous leukemia and myelodysplasia without abnormalities of chromosome 11q23 following treatment of acute leukemia with topoisomerase II-based chemotherapy.
2001 Jun
Results of a phase III prospective, randomised trial, comparing mitoxantrone and vinorelbine (MV) in combination with standard FAC/FEC in front-line therapy of metastatic breast cancer.
2001 Jun
Esters of 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinones with melphalan as multifunctional anticancer agents.
2001 Jun 4
Cladribine in combination with mitoxantrone and cyclophosphamide(CMC) in the treatment of heavily pre-treated patients with advanced indolent lymphoid malignancies.
2001 Mar
Optimal timing and dosage of chemotherapy as a combined treatment with androgen withdrawal in the human prostate LNCaP tumour model.
2001 Mar 23
Combined action of PSC 833 (Valspodar), a novel MDR reversing agent, with mitoxantrone, etoposide and cytarabine in poor-prognosis acute myeloid leukemia.
2001 May
Phase II study of docetaxel, estramustine, and low-dose hydrocortisone in men with hormone-refractory prostate cancer: a final report of CALGB 9780. Cancer and Leukemia Group B.
2001 May 1
Patents

Patents

04278689
2
JP2002541200A
12
JP2002541233A
392
JP2004523497A
78
JP2004534728A
75
JP2006516548A
15
JP2007508039A
109
JP2009526755A
434
JP2011510954A
140
JP2011525180A
172
JP4527401B2
30
JP4701159B2
69
JP4758474B2
84
JP4785252B2
2
JP4818917B2
29
JP4851943B2
41
JPH06321927A
2

Sample Use Guides

In Vivo Use Guide
The recommended dosage of NOVANTRONE (Mitoxantrone) is 12 mg/m2 given as a short (approximately 5 to 15 minutes) intravenous infusion every 3 months.
Route of Administration: Intravenous
In Vitro Use Guide
Treatment of B-CLL cells for 48 h with mitoxantrone (0.5 ug/ml) induced a decrease in cell viability as determined by MTT assay.
Substance Class Chemical
Created
by admin
on Fri Dec 16 16:13:35 UTC 2022
Edited
by admin
on Fri Dec 16 16:13:35 UTC 2022
Record UNII
BZ114NVM5P
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MITOXANTRONE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
mitoxantrone [INN]
Common Name English
NSC-279836
Code English
MITOXANTRONE [IARC]
Common Name English
Mitoxantrone [WHO-DD]
Common Name English
MITOXANTRONE [VANDF]
Common Name English
MISOSTOL
Brand Name English
MITOXANTRONE [MI]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 128499
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
NCI_THESAURUS C253
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
FDA ORPHAN DRUG 125199
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
WHO-ATC L01DB07
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
NDF-RT N0000000176
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
NDF-RT N0000175609
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
LIVERTOX NBK547931
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
WHO-VATC QL01DB07
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
FDA ORPHAN DRUG 96696
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
Code System Code Type Description
MESH
D008942
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
INN
4922
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
FDA UNII
BZ114NVM5P
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
DAILYMED
BZ114NVM5P
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
ChEMBL
CHEMBL58
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
WIKIPEDIA
MITOXANTRONE
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
CAS
65271-80-9
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
PUBCHEM
4212
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
EPA CompTox
DTXSID4046947
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
RXCUI
7005
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY RxNorm
CHEBI
50729
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
NSC
279836
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
NCI_THESAURUS
C62050
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
DRUG BANK
DB01204
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
EVMPD
SUB09012MIG
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
IUPHAR
7242
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
LACTMED
Mitoxantrone
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
MERCK INDEX
M7572
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY Merck Index
DRUG CENTRAL
1821
Created by admin on Fri Dec 16 16:13:35 UTC 2022 , Edited by admin on Fri Dec 16 16:13:35 UTC 2022
PRIMARY
Related Record Type Details
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> SUBSTRATE
MULTIDRUG AND TOXIN EXTRUSION PROTEIN 1
TRANSPORTER -> INHIBITOR
MRP-1
TRANSPORTER -> SUBSTRATE
ATP-BINDING CASSETTE SUB-FAMILY B MEMBER 5
TRANSPORTER -> SUBSTRATE
Related Record Type Details
Structure of 1,4-BIS(2-AMINOETHYLAMINO)-5,8-DIHYDROXYANTHRACENE-9,10-DIONE
METABOLITE -> PARENT
Structure of MITOXANTRONE GLUCURONIDE
METABOLITE -> PARENT
Related Record Type Details
Structure of MITOXANTRONE
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