OLANZAPINE TARTRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H20N4S.C4H6O6
Molecular Weight	462.519
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.CN1CCN(CC1)C2=NC3=CC=CC=C3NC4=C2C=C(C)S4

InChI

InChIKey=NFEUHAIRXOEOTJ-LREBCSMRSA-N

InChI=1S/C17H20N4S.C4H6O6/c1-12-11-13-16(21-9-7-20(2)8-10-21)18-14-5-3-4-6-15(14)19-17(13)22-12;5-1(3(7)8)2(6)4(9)10/h3-6,11,19H,7-10H2,1-2H3;1-2,5-6H,(H,7,8)(H,9,10)/t;1-,2-/m.1/s1

HIDE SMILES / InChI

Molecular Formula	C4H6O6
Molecular Weight	150.0868
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C17H20N4S
Molecular Weight	312.432
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020592s067,021086s043,021253s056lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.priory.com/focus3.htm

Olanzapine is a novel antipsychotic agent marketed by Lilly & Co. It has a pleotrophic pharmacology and affects dopaminergic, serotonergic, muscarinic and adrenergic activities. Olanzapine is used to treat the symptoms of psychotic conditions such as schizophrenia and bipolar disorder (manic depression) in adults and children who are at least 13 years old. Olanzapine is sometimes used together with other antipsychotic medications or antidepressants. The mechanism of action of olanzapine, as with other drugs having efficacy in schizophrenia, is unknown. However, it has been proposed that this drug’s efficacy in schizophrenia is mediated through a combination of dopamine and serotonin type 2 (5HT2) antagonism. The mechanism of action of olanzapine in the treatment of acute manic or mixed episodes associated with bipolar I disorder is unknown. Olanzapine treatment led to rapid phosphorylation of kinases from all three pathways in PC12 cells. Phosphorylation of Akt was blocked with selective inhibitors (wortmannin and LY294002), which implicates phosphoinositide 3-kinase (PI3K) in the signaling cascade. Short-term mitogenic effects of olanzapine were abolished with a selective inhibitor of Akt, but not by inhibition of the ERK pathway. Olanzapine is metabolized by the cytochrome P450 system; principally by isozyme 1A2 and to a lesser extent by 2D6. By these mechanisms more than 40% of the oral dose, on average, is removed by the hepatic first-pass effect. Drugs or agents that increase the activity of CYP1A2, notably tobacco smoke, may significantly increase hepatic first-pass clearance of Olanzapine; conversely, drugs which inhibit 1A2 activity (examples: Ciprofloxacin, Fluvoxamine) may reduce Olanzapine clearance. The most common side effects appear to be somnolence and weight gain. About 11% of patients gain weight -especially if on a high starting dose and if they were underweight pre-treatment. Sexual dysfunction is a problem for many patients, although sexual dysfunction in schizophrneia does not appear to be primarily attributable to drugs.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15358979	Antagonist 2778
Serotonin 2a (5-HT2a) receptor 231 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15358979	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 298 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020592s067,021086s043,021253s056lbl.pdf	Primary		Approved 8429	ZYPREXA Approved Use Olanzapine orally disintegrating tablets, USP are atypical antipsychotic indicated: As oral formulation for the: Treatment of schizophrenia. (1.1) Adults: Efficacy was established in three clinical trials in patients with schizophrenia: two 6-week trials and one maintenance trial. (14.1) Adolescents (ages 13 to 17): Efficacy was established in one 6-week trial in patients with schizophrenia (14.1). The increased potential (in adolescents compared with adults) for weight gain and dyslipidemia may lead clinicians to consider prescribing other drugs first in adolescents. (1.1) Acute treatment of manic or mixed episodes associated with bipolar I disorder and maintenance treatment of bipolar I disorder. (1.2) Adults: Efficacy was established in three clinical trials in patients with manic or mixed episodes of bipolar I disorder: two 3- to 4-week trials and one maintenance trial. (14.2) Adolescents (ages 13 to 17): Efficacy was established in one 3-week trial in patients with manic or mixed episodes associated with bipolar I disorder (14.2). The increased potential (in adolescents compared with adults) for weight gain and dyslipidemia may lead clinicians to consider prescribing other drugs first in adolescents. (1.2) Medication therapy for pediatric patients with schizophrenia or bipolar I disorder should be undertaken only after a thorough diagnostic evaluation and with careful consideration of the potential risks. (1.3) Adjunct to valproate or lithium in the treatment of manic or mixed episodes associated with bipolar I disorder. (1.2) Efficacy was established in two 6-week clinical trials in adults (14.2). Maintenance efficacy has not been systematically evaluated. As O lanzapine Orally Disintegrating Tablets, USP and Fluoxetine in Combination for the: Treatment of depressive episodes associated with bipolar I disorder. (1.5) Efficacy was established with Symbyax* (olanzapine and fluoxetine in combination); refer to the product label for Symbyax*. 1.1 Schizophrenia Olanzapine orally disintegrating tablets, USP are indicated for the treatment of schizophrenia. Efficacy was established in three clinical trials in adult patients with schizophrenia: two 6-week trials and one maintenance trial. In adolescent patients with schizophrenia (ages 13 to 17), efficacy was established in one 6-week trial [see Clinical Studies (14.1) Launch Date 1996
Bipolar I disorder 17 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020592s067,021086s043,021253s056lbl.pdf	Primary		Approved 8429	ZYPREXA Approved Use Olanzapine orally disintegrating tablets, USP are atypical antipsychotic indicated: As oral formulation for the: Treatment of schizophrenia. (1.1) Adults: Efficacy was established in three clinical trials in patients with schizophrenia: two 6-week trials and one maintenance trial. (14.1) Adolescents (ages 13 to 17): Efficacy was established in one 6-week trial in patients with schizophrenia (14.1). The increased potential (in adolescents compared with adults) for weight gain and dyslipidemia may lead clinicians to consider prescribing other drugs first in adolescents. (1.1) Acute treatment of manic or mixed episodes associated with bipolar I disorder and maintenance treatment of bipolar I disorder. (1.2) Adults: Efficacy was established in three clinical trials in patients with manic or mixed episodes of bipolar I disorder: two 3- to 4-week trials and one maintenance trial. (14.2) Adolescents (ages 13 to 17): Efficacy was established in one 3-week trial in patients with manic or mixed episodes associated with bipolar I disorder (14.2). The increased potential (in adolescents compared with adults) for weight gain and dyslipidemia may lead clinicians to consider prescribing other drugs first in adolescents. (1.2) Medication therapy for pediatric patients with schizophrenia or bipolar I disorder should be undertaken only after a thorough diagnostic evaluation and with careful consideration of the potential risks. (1.3) Adjunct to valproate or lithium in the treatment of manic or mixed episodes associated with bipolar I disorder. (1.2) Efficacy was established in two 6-week clinical trials in adults (14.2). Maintenance efficacy has not been systematically evaluated. As O lanzapine Orally Disintegrating Tablets, USP and Fluoxetine in Combination for the: Treatment of depressive episodes associated with bipolar I disorder. (1.5) Efficacy was established with Symbyax* (olanzapine and fluoxetine in combination); refer to the product label for Symbyax*. 1.1 Schizophrenia Olanzapine orally disintegrating tablets, USP are indicated for the treatment of schizophrenia. Efficacy was established in three clinical trials in adult patients with schizophrenia: two 6-week trials and one maintenance trial. In adolescent patients with schizophrenia (ages 13 to 17), efficacy was established in one 6-week trial [see Clinical Studies (14.1) Launch Date 1996

C_max

Value	Dose	Co-administered	Analyte	Population
17.3 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/12895191	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		OLANZAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
712 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/12895191	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		OLANZAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
28.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/12895191	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		OLANZAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/33564555	unhealthy, 20 years n = 1 Health Status: unhealthy Condition: paranoid schizophrenia Age Group: 20 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/33564555	Disc. AE: Rhabdomyolysis... AEs leading to discontinuation/dose reduction: Rhabdomyolysis (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/33564555
5 mg 1 times / day steady, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21086lbl.pdf	unhealthy, 83 years (range: 61-97 years) n = 65 Health Status: unhealthy Condition: psychiatric symptoms Age Group: 83 years (range: 61-97 years) Sex: M+F Population Size: 65 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21086lbl.pdf	Disc. AE: Accidental injury, Somnolence... AEs leading to discontinuation/dose reduction: Accidental injury (1%) Somnolence (3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21086lbl.pdf
300 mg 1 times / day multiple, oral Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf	unhealthy, adult n = 67 Health Status: unhealthy Age Group: adult Population Size: 67 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf	Other AEs: Drowsiness, Slurred speech... Other AEs: Drowsiness Slurred speech Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf
40 mg 1 times / day multiple, oral Highest studied dose Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf	unhealthy, adult n = 200 Health Status: unhealthy Condition: schizophrenia \|schizoaffective disorder Age Group: adult Sex: M+F Population Size: 200 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf	Other AEs: Dizziness... Other AEs: Dizziness (6.6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf
2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf
5 mg 1 times / day steady, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf	Disc. AE: Weight gain... AEs leading to discontinuation/dose reduction: Weight gain (0.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf
5 mg 1 times / day steady, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf	unhealthy, old Health Status: unhealthy Condition: DEMENTIA-RELATED PSYCHOSIS Age Group: old Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf	Other AEs: Adverse event... Other AEs: Adverse event (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf

AEs

AE	Significance	Dose	Population
Rhabdomyolysis	1 patient Disc. AE	10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/33564555	unhealthy, 20 years n = 1 Health Status: unhealthy Condition: paranoid schizophrenia Age Group: 20 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/33564555
Accidental injury	1% Disc. AE	5 mg 1 times / day steady, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21086lbl.pdf	unhealthy, 83 years (range: 61-97 years) n = 65 Health Status: unhealthy Condition: psychiatric symptoms Age Group: 83 years (range: 61-97 years) Sex: M+F Population Size: 65 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21086lbl.pdf
Somnolence	3% Disc. AE	5 mg 1 times / day steady, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21086lbl.pdf	unhealthy, 83 years (range: 61-97 years) n = 65 Health Status: unhealthy Condition: psychiatric symptoms Age Group: 83 years (range: 61-97 years) Sex: M+F Population Size: 65 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21086lbl.pdf
Drowsiness		300 mg 1 times / day multiple, oral Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf	unhealthy, adult n = 67 Health Status: unhealthy Age Group: adult Population Size: 67 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf
Slurred speech		300 mg 1 times / day multiple, oral Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf	unhealthy, adult n = 67 Health Status: unhealthy Age Group: adult Population Size: 67 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf
Dizziness	6.6%	40 mg 1 times / day multiple, oral Highest studied dose Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf	unhealthy, adult n = 200 Health Status: unhealthy Condition: schizophrenia \|schizoaffective disorder Age Group: adult Sex: M+F Population Size: 200 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf
Weight gain	0.2% Disc. AE	5 mg 1 times / day steady, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf
Adverse event	grade 5	5 mg 1 times / day steady, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf	unhealthy, old Health Status: unhealthy Condition: DEMENTIA-RELATED PSYCHOSIS Age Group: old Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020592s074,021086s048,021253s061lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 substrate 1737	inhibitor 1767 substrate 1037	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 BSEP 402	CYP1A2 1054 FMO 35 P-gp 1537 BCRP 561 UGT2B10 127 UGT1A4 347 CYP2C19 991 CYP2E1 667	FATP2 5

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020592_Original_Approval_Pkg%20.pdf Page: 310.0	moderate [Ki 36 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020592_Original_Approval_Pkg%20.pdf Page: 310.0	moderate [Ki 491 uM]	no (co-administration study) Comment: olanzapine has no effect on diazepam or N-desmethyldiazepam Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020592_Original_Approval_Pkg%20.pdf Page: 310.0
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020592_Original_Approval_Pkg%20.pdf Page: 310.0	moderate [Ki 715 uM]	no (co-administration study) Comment: olanzapine has no effect on warfarin Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020592_Original_Approval_Pkg%20.pdf Page: 310.0
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020592_Original_Approval_Pkg%20.pdf Page: 310.0	moderate [Ki 89 uM]	no (co-administration study) Comment: olanzapine has no effect on imiprazine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020592_Original_Approval_Pkg%20.pdf Page: 310.0
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020592_Original_Approval_Pkg%20.pdf Page: 310.0	moderate [Ki 920 uM]	no (co-administration study) Comment: olanzapine has no effect on diazepam or N-desmethyldiazepam Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020592_Original_Approval_Pkg%20.pdf Page: 310.0
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22961681/	weak [IC50 54.57 uM]
OCTN2 71	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/31437515/	yes [IC50 1.06 uM]
FATP2 5	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/31437515/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020639ap_Seroquel_phrmrP1.pdf Page: 66.0	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020639ap_Seroquel_phrmrP1.pdf Page: 66.0	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020639ap_Seroquel_phrmrP1.pdf Page: 66.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020592_Original_Approval_Pkg%20.pdf Page: 308.0	weak	weak (co-administration study) Comment: in vivo; imiprazine increases olanzapine exposure by 19% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020592_Original_Approval_Pkg%20.pdf Page: 308.0
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18834354/	yes [Ki >1000 uM]
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020639ap_Seroquel_phrmrP1.pdf Page: 66.0	yes
FMO 35	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020592_Original_Approval_Pkg%20.pdf Page: 308.0	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21843066/	yes
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12404680/	yes
UGT2B10 127	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21750471/	yes
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022173s036lbl.pdf Page: 19, 20	yes	yes (co-administration study) Comment: carbamazepine increases olanzapine clearance by 50%; fluoxetine increased olanzapine Cmax and AUC; omeprazole and rifampin may increase olanzapine clearance Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022173s036lbl.pdf Page: 19, 20

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/12873512/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7735	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7735
ChemicalBook	CB04188690	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB04188690
ChemicalBook	CB34188691	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB34188691
ChemicalBook	CB52743465	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB52743465
ChemicalBook	CB64188692	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB64188692
ChemicalBook	CB6755515	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6755515
MolPort	MolPort-002-885-845	https://www.molport.com/shop/molecule-link/MolPort-002-885-845
Selleck Chemicals	Olanzapine(Zyprexa)	http://www.selleckchem.com/products/Olanzapine(Zyprexa).html
ZINC	ZINC000052957434	http://zinc15.docking.org/substances/ZINC000052957434
eMolecules	902226	https://www.emolecules.com/cgi-bin/more?vid=902226

PubMed

Title	Date	PubMed
Olanzapine optimal dose: results of an open-label multicenter study in schizophrenic patients. Olanzapine Late-Phase II Study Group.	2000 Aug	10997865
Olanzapine-induced urinary incontinence: treatment with ephedrine.	2000 Aug	10982206
Remission of tardive dyskinesia after changing from flupenthixol to olanzapine.	2000 Aug	10954879
Acute confusional states during treatment with risperidone.	2000 Jun	10861920
[A case of mania following olanzapine administration].	2000 Mar-Apr	10974943
Possible neuroleptic malignant syndrome associated with olanzapine.	2000 May	10852098
Serotonin and dopamine antagonism in obsessive-compulsive disorder: effect of atypical antipsychotic drugs.	2000 Nov	11147933
Neuroleptic malignant syndrome associated with olanzapine therapy: a case report.	2000 Nov	11074330
The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia.	2000 Sep	11048906
A naturalistic comparison of clozapine, risperidone, and olanzapine in the treatment of bipolar disorder.	2000 Sep	11030483
Olanzapine and obsessive-compulsive symptoms.	2000 Sep	10974610
Superior efficacy of olanzapine over haloperidol: analysis of patients with schizophrenia from a multicenter international trial.	2001	11232753
Weight change and atypical antipsychotic treatment in patients with schizophrenia.	2001	11232752
Cardiac safety parameters of olanzapine: comparison with other atypical and typical antipsychotics.	2001	11232751
Effective resolution with olanzapine of acute presentation of behavioral agitation and positive psychotic symptoms in schizophrenia.	2001	11232746
Rapid tranquilization with olanzapine in acute psychosis: a case series.	2001	11232745
Antipsychotic medications and the elderly: effects on cognition and implications for use.	2001	11232738
Atypical antipsychotics: new directions and new challenges in the treatment of schizophrenia.	2001	11160792
One further case of pancytopenia induced by olanzapine in a Parkinson's disease patient.	2001	11150845
Treatment of psychogenic polydipsia: comparison of risperidone and olanzapine, and the effects of an adjunctive angiotensin-II receptor blocking drug (irbesartan).	2001 Feb	11270459
Long-term olanzapine treatment: weight change and weight-related health factors in schizophrenia.	2001 Feb	11247108
Priapism associated with polypharmacy.	2001 Feb	11247100
Tolerability and effectiveness of atypical antipsychotics in male geriatric inpatients.	2001 Feb	11241729
Supersensitivity psychosis in patients with schizophrenia after sudden olanzapine withdrawal.	2001 Feb	11221497
A case report of olanzapine-induced hypersensitivity syndrome.	2001 Feb	11217818
Effects of newer atypical antipsychotics on autonomic neurocardiac function: a comparison between amisulpride, olanzapine, sertindole, and clozapine.	2001 Feb	11199953
Olanzapine plasma concentrations and clinical response: acute phase results of the North American Olanzapine Trial.	2001 Feb	11199942
The economic consequences of a drug-drug interaction.	2001 Feb	11199940
Repeated episodes of hypothermia in a subject treated with haloperidol, levomepromazine, olanzapine, and thioridazine.	2001 Feb	11199936
Rehospitalization rates of chronically ill schizophrenic patients discharged on a regimen of risperidone, olanzapine, or conventional antipsychotics.	2001 Feb	11156809
The effects of olanzapine in reducing the emergence of psychosis among nursing home patients with Alzheimer's disease.	2001 Jan	11235926
Short-term effects of olanzapine in Huntington disease.	2001 Jan	11234911
Bodyweight gain with atypical antipsychotics. A comparative review.	2001 Jan	11219487
Treatment of bipolar depression with twice-weekly fluoxetine: management of antidepressant-induced mania.	2001 Jan	11197585
Olanzapine-induced leukopenia with human leukocyte antigen profiling.	2001 Jan	11195261
A novel augmentation strategy for treating resistant major depression.	2001 Jan	11136647
Olanzapine: concordant response in monozygotic twins with schizophrenia.	2001 Jan	11136224
Allelic variation in the 5-HT2C receptor (HT2RC) and the increase in slow wave sleep produced by olanzapine.	2001 Jan 1	11205431
Consistency of atypical antipsychotic superiority to placebo in recent clinical trials.	2001 Jan 1	11163781
Dopamine transporter density in young patients with schizophrenia assessed with [123]FP-CIT SPECT.	2001 Jan 15	11163545
A sensitive high-performance liquid chromatographic method using electrochemical detection for the analysis of olanzapine and desmethylolanzapine in plasma of schizophrenic patients using a new solid-phase extraction procedure.	2001 Jan 5	11204214
Olanzapine-lnduced hyperglycemic nonketonic coma.	2001 Mar	11261526
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	11238736
Atypical antipsychotics and hyperglycaemia.	2001 Mar	11236071
Dose-dependent olanzapine-associated leukopenia: three case reports.	2001 Mar	11236070
Low blood glucose and olanzapine.	2001 Mar	11230004
Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis.	2001 Mar	11229973
Electrooxidation potential as a tool in the early screening for new safer clozapine-like analogues.	2001 Mar 1	11262087
Quantitative determination of olanzapine in rat brain tissue by high-performance liquid chromatography with electrochemical detection.	2001 Mar 5	11254198
Separation of olanzapine, carbamazepine and their main metabolites by capillary electrophoresis with pseudo-stationary phases.	2001 Mar 5	11254196

Patents

Sample Use Guides

In Vivo Use Guide

Schizophrenia: Adults: Oral olanzapine should be administered on a once-a-day schedule without regard to meals, generally beginning with 5 to 10 mg initially, with a target dose of 10 mg/day within several days. Further dosage adjustments, if indicated, should generally occur at intervals of not less than 1 week, since steady state for olanzapine would not be achieved for approximately 1 week in the typical patient. Adolescents: Oral olanzapine should be administered on a once-a-day schedule without regard to meals with a recommended starting dose of 2.5 or 5 mg, with a target dose of 10 mg/day. Efficacy in adolescents with schizophrenia was demonstrated based on a flexible dose range of 2.5 to 20 mg/day in clinical trials, with a mean modal dose of 12.5 mg/day (mean dose of 11.1 mg/day). Bipolar I Disorder (Manic or Mixed Episodes): Adults: Oral olanzapine should be administered on a once-a-day schedule without regard to meals, generally beginning with 10 or 15 mg. Dosage adjustments, if indicated, should generally occur at intervals of not less than 24 hours, reflecting the procedures in the placebo-controlled trials. Adolescents: Oral olanzapine should be administered on a once-a-day schedule without regard to meals with a recommended starting dose of 2.5 or 5 mg, with a target dose of 10 mg/day. Efficacy in adolescents with bipolar I disorder (manic or mixed episodes) was demonstrated based on a flexible dose range of 2.5 to 20 mg/day in clinical trials, with a mean modal dose of 10.7 mg/day (mean dose of 8.9 mg/day). IntraMuscular: Agitation Associated with Schizophrenia and Bipolar I Mania: The efficacy of intramuscular olanzapine for injection in controlling agitation in these disorders was demonstrated in a dose range of 2.5 mg to 10 mg.

Route of Administration: Other

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:04:42 GMT 2023` Edited by `admin` on `Sat Dec 16 08:04:42 GMT 2023`
Record UNII	0KNI3MFH5F
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

OLANZAPINE TARTRATE

Common Name

English

10H-THIENO(2,3-B)(1,5)BENZODIAZEPINE, 2-METHYL-4-(4-METHYL-1-PIPERAZINYL)-, (2R,3R)-2,3-DIHYDROXYBUTANEDIOATE (1:1)

Systematic Name

English

Code System Code Type Description

PUBCHEM

135565848