Details
Stereochemistry | ACHIRAL |
Molecular Formula | C18H19ClN4 |
Molecular Weight | 326.823 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1CCN(CC1)C2=NC3=C(NC4=C2C=CC=C4)C=CC(Cl)=C3
InChI
InChIKey=QZUDBNBUXVUHMW-UHFFFAOYSA-N
InChI=1S/C18H19ClN4/c1-22-8-10-23(11-9-22)18-14-4-2-3-5-15(14)20-16-7-6-13(19)12-17(16)21-18/h2-7,12,20H,8-11H2,1H3
DescriptionCurator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/10372606
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/10372606
Clozapine was discovered in 1958 by an anesthetist and now it is used for the treatment of schizophrenia. Although the exact mechanism of its action is unknown, the effect of clozapine on schizophrenia is associated with inhibition of dopamine D2 and serotonin 2A receptors.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL217 |
160.0 nM [Ki] | ||
Target ID: CHEMBL224 |
5.4 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | CLOZARIL Approved UseClozaril is an atypical antipsychotic indicated for: Treatment-resistant schizophrenia. Launch Date1989 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
98 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10606838 |
12.5 mg single, oral dose: 12.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLOZAPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
319 ng/mL |
100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CLOZAPINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1348 nM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10606838 |
12.5 mg single, oral dose: 12.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLOZAPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
18.6 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10606838 |
12.5 mg single, oral dose: 12.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLOZAPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
12 h |
100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CLOZAPINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3% |
100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CLOZAPINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
289 mg 1 times / day multiple, oral (mean) Recommended Dose: 289 mg, 1 times / day Route: oral Route: multiple Dose: 289 mg, 1 times / day Sources: |
unhealthy, 41 n = 22 Health Status: unhealthy Condition: refractory psychotic mania Age Group: 41 Sex: M+F Population Size: 22 Sources: |
Other AEs: Sedation, Salivation... Other AEs: Sedation (14 patients) Sources: Salivation (6 patients) Constipation (6 patients) Nausea and vomiting (5 patients) Dizziness (4 patients) Fever (4 patients) |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Disc. AE: Orthostatic hypotension, Sedation... Other AEs: Sedation, Hypersalivation... AEs leading to discontinuation/dose reduction: Orthostatic hypotension (13 patients) Other AEs:Sedation (1 patient) Dysphagia (1 patient) Fever (2 patients) Tachycardia (2 patients) Myocarditis (1 patient) Leukopenia (3 patients) Parkinsonism (1 patient) Myocardial infarction (3 patients) Ataxia (1 patient) Cardiomyopathy (1 patient) Sedation (28 patients) Sources: Hypersalivation (25 patients) Constipation (16 patients) Weight gain (8 patients) Leukopenia (4 patients) Tachycardia (3 patients) Leukopenia (2 patients) Seizure (2 patients) Dysphagia (1 patient) Fever (1 patient) Fatigue (1 patient) |
450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Other AEs: Dry mouth, Urinary hesitancy... Other AEs: Dry mouth (20%) Sources: Urinary hesitancy (10%) Constipation (60%) Nausea (60%) Dyspepsia (70%) Headache (40%) Somnolence (100%) Lethargy (90%) Myoclonus (30%) Stuttering (20%) Sialorrhea (80%) Sweating (50%) Urinary frequency (40%) Dysphagia (20%) Orthostatic hypotension (10%) Dizziness (60%) Increased appetite (50%) |
900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Other AEs: Drowsiness, Tachycardia... Other AEs: Drowsiness (21%) Sources: Tachycardia (17%) Constipation (16%) Dizziness (14%) Hypotension (13%) Hyperthermia (13%) Salivation (13%) Hypertension (12%) Headache (10%) Nausea and vomiting (10%) Dry mouth (5%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Sedation | 14 patients | 289 mg 1 times / day multiple, oral (mean) Recommended Dose: 289 mg, 1 times / day Route: oral Route: multiple Dose: 289 mg, 1 times / day Sources: |
unhealthy, 41 n = 22 Health Status: unhealthy Condition: refractory psychotic mania Age Group: 41 Sex: M+F Population Size: 22 Sources: |
Dizziness | 4 patients | 289 mg 1 times / day multiple, oral (mean) Recommended Dose: 289 mg, 1 times / day Route: oral Route: multiple Dose: 289 mg, 1 times / day Sources: |
unhealthy, 41 n = 22 Health Status: unhealthy Condition: refractory psychotic mania Age Group: 41 Sex: M+F Population Size: 22 Sources: |
Fever | 4 patients | 289 mg 1 times / day multiple, oral (mean) Recommended Dose: 289 mg, 1 times / day Route: oral Route: multiple Dose: 289 mg, 1 times / day Sources: |
unhealthy, 41 n = 22 Health Status: unhealthy Condition: refractory psychotic mania Age Group: 41 Sex: M+F Population Size: 22 Sources: |
Nausea and vomiting | 5 patients | 289 mg 1 times / day multiple, oral (mean) Recommended Dose: 289 mg, 1 times / day Route: oral Route: multiple Dose: 289 mg, 1 times / day Sources: |
unhealthy, 41 n = 22 Health Status: unhealthy Condition: refractory psychotic mania Age Group: 41 Sex: M+F Population Size: 22 Sources: |
Constipation | 6 patients | 289 mg 1 times / day multiple, oral (mean) Recommended Dose: 289 mg, 1 times / day Route: oral Route: multiple Dose: 289 mg, 1 times / day Sources: |
unhealthy, 41 n = 22 Health Status: unhealthy Condition: refractory psychotic mania Age Group: 41 Sex: M+F Population Size: 22 Sources: |
Salivation | 6 patients | 289 mg 1 times / day multiple, oral (mean) Recommended Dose: 289 mg, 1 times / day Route: oral Route: multiple Dose: 289 mg, 1 times / day Sources: |
unhealthy, 41 n = 22 Health Status: unhealthy Condition: refractory psychotic mania Age Group: 41 Sex: M+F Population Size: 22 Sources: |
Dysphagia | 1 patient | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Fatigue | 1 patient | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Fever | 1 patient | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Ataxia | 1 patient Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Cardiomyopathy | 1 patient Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Dysphagia | 1 patient Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Myocarditis | 1 patient Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Parkinsonism | 1 patient Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Sedation | 1 patient Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Orthostatic hypotension | 13 patients Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Constipation | 16 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Leukopenia | 2 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Seizure | 2 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Fever | 2 patients Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Tachycardia | 2 patients Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Hypersalivation | 25 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Sedation | 28 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Tachycardia | 3 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Leukopenia | 3 patients Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Myocardial infarction | 3 patients Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Leukopenia | 4 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Weight gain | 8 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Orthostatic hypotension | 10% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Urinary hesitancy | 10% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Somnolence | 100% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Dry mouth | 20% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Dysphagia | 20% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Stuttering | 20% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Myoclonus | 30% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Headache | 40% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Urinary frequency | 40% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Increased appetite | 50% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Sweating | 50% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Constipation | 60% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Dizziness | 60% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Nausea | 60% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Dyspepsia | 70% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Sialorrhea | 80% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Lethargy | 90% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Headache | 10% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Nausea and vomiting | 10% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Hypertension | 12% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Hyperthermia | 13% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Hypotension | 13% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Salivation | 13% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Dizziness | 14% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Constipation | 16% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Tachycardia | 17% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Drowsiness | 21% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Dry mouth | 5% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
yes [IC50 42 uM] | ||||
yes [Ki 19 uM] | ||||
yes [Ki 31 uM] | ||||
yes [Ki 69 uM] | ||||
yes [Ki 99 uM] | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | yes (co-administration study) Comment: co-administration with fluvoxamin lead to 3x increase in clozapine Cmin |
|||
minor | ||||
minor | ||||
minor | ||||
minor | weak (co-administration study) Comment: co-administration studies indicate modest (<2x) increase in clozapine exposure when co-administered with CYP3A4 inhibitors |
|||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | yes (pharmacogenomic study) Comment: UGT1A1*28 and UGT1A4*3 alleles contribute significantly to inter-individual variability in CLZ and dmCLZ metabolism Sources: https://pubmed.ncbi.nlm.nih.gov/22565219/ |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
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PubMed
Title | Date | PubMed |
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[Individual conditions of pharmacogenic confusion conditions. Comparison of amitriptyline and clozapine]. | 1976 |
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A retrospective study of clozapine and urinary incontinence in Chinese in-patients. | 1999 Aug |
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The emergence of social phobia during clozapine treatment and its response to fluoxetine augmentation. | 1999 Dec |
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Clozapine pretreatment modifies haloperidol-elicited forebrain Fos induction: a regionally-specific double dissociation. | 1999 Jun |
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Pulmonary embolus possibly associated with clozapine treatment. | 1999 May |
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[The concept of supersensitivity psychosis. The particular case of clozapine]. | 1999 Nov-Dec |
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Transient syncope and ECG changes associated with the concurrent administration of clozapine and diazepam. | 1999 Sep |
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Association of venous thromboembolism and clozapine. | 2000 Apr 1 |
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An unexpected and serious complication of treatment with the atypical antipsychotic drug clozapine. | 2000 Jul |
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Induction of metabolism-dependent and -independent neutrophil apoptosis by clozapine. | 2000 Jul |
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Cloning of rat histamine H(3) receptor reveals distinct species pharmacological profiles. | 2000 Jun |
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Anticholinergic differences among patients receiving standard clinical doses of olanzapine or clozapine. | 2000 Jun |
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Hyperglycemia, hyperlipemia, and periodic paralysis: a case report of new side effects of clozapine. | 2000 Nov |
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Effects of antipsychotic drugs on cholecystokinin and preprotachykinin (substance P) mRNA expression in the rat hippocampal formation. | 2000 Sep |
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Myotoxicity and neurotoxicity during clozapine treatment. | 2000 Sep-Oct |
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Effects of systemic injections of dopaminergic agents on the habituation of rats submitted to an open field test. | 2001 |
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Evidence for an association between polymorphism in the serotonin-2A receptor variant (102T/C) and increment of N100 amplitude in schizophrenics treated with clozapine. | 2001 |
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New onset diabetes and atypical antipsychotics. | 2001 Feb |
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Increased dopamine d(2) receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapine. | 2001 Feb |
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Clozapine-associated reduction in arrest rates of psychotic patients with criminal histories. | 2001 Feb |
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Clozapine therapy for a patient with a history of Hodgkin's disease. | 2001 Jan |
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Fatty acid derivatives of clozapine: prolonged antidopaminergic activity of docosahexaenoylclozapine in the rat. | 2001 Jan |
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Electroconvulsive therapy in rehabilitation: the Hong Kong experience. | 2001 Mar |
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5-HT(2A) and D(2) receptor blockade increases cortical DA release via 5-HT(1A) receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine release. | 2001 Mar |
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Atypical antipsychotics and hyperglycaemia. | 2001 Mar |
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Clozapine and pulmonary embolus. | 2001 Mar |
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Pharmacological characterization of locomotor sensitization induced by chronic phencyclidine administration. | 2001 Mar |
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Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. | 2001 Mar |
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Double activity imaging reveals distinct cellular targets of haloperidol, clozapine and dopamine D(3) receptor selective RGH-1756. | 2001 Mar |
Sample Use Guides
Start with 12.5 mg once daily or twice daily, then increase the total daily dosage in increments of 25 mg to 50 mg per day (if well-tolerated) in order to reach 300 mg to 450 mg per day, in divided doses, by the end of 2 weeks.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25477781
The effects of antipsychotic medication on the energy metabolism of OLN-93 cells were analyzed by adding a vehicle (0.01% HCl, same dissolving solution used to solubilize the antipsychotics), 1 or 10 ug/ml of clozapine to the cell culture for 6 or 24 h.
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
357411
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NCI_THESAURUS |
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LIVERTOX |
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NDF-RT |
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WHO-VATC |
QN05AH02
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WHO-ATC |
N05AH02
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CLOZARIL
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PRIMARY | APPROVED APRIL 2009 | ||
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m3676
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100000092795
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CLOZAPINE
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135398737
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