Olanzapine

Olanzapine, sold under the trade name

Zyprexa among others, is an atypical
antipsychotic primarily used to treat
schizophrenia and bipolar disorder.[7] For
schizophrenia, it can be used for both new
onset disease and long term
maintenance.[7] It is taken by mouth or by
injection into a muscle.[7]
 Olanzapine

Clinical data
Trade names Zyprexa, others[1]
AHFS/Drugs.com Monograph
MedlinePlus a601213
License data EU EMA: by INN
US FDA: Olanzapine
Pregnancy AU: C
category US: C (Risk not ruled
out)

Routes of By mouth, intramuscular

administration
injection
ATC code N05AH03 (WHO )

Legal status
Legal status AU: S4 (Prescription
only)
CA: ℞-only
NZ: Prescription
medicine
UK: POM (Prescription
only)
US: ℞-only

Pharmacokinetic data
Bioavailability 60-65%[2][3][4]
Protein binding 93%[5]
Metabolism Liver (direct
glucuronidation and
CYP1A2 mediated
oxidation)
Elimination half-life 33 hours, 51.8 hours
(elderly)[5]
Excretion Urine (57%; 7% as
unchanged drug), faeces
(30%)[5][6]

Identifiers

IUPAC name
2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine

CAS Number 132539-06-1  

PubChem CID 4585

IUPHAR/BPS 47
DrugBank DB00334  

ChemSpider 10442212  

UNII N7U69T4SZR
KEGG D00454  

ChEBI CHEBI:7735  

ChEMBL ChEMBL715  

CompTox Dashboard DTXSID9023388

(EPA)
ECHA InfoCard 100.125.320

Chemical and physical data

Formula C17H20N4S
Molar mass 312.439 g·mol−1
3D model (JSmol) Interactive image
Melting point 195 °C (383 °F)
Solubility in water Practically insoluble in
 water mg/mL (20 °C)

SMILES
CN1CCN(CC1)C/2=N/c4ccccc4Nc3sc(C)cc\23

InChI
InChI=1S/C17H20N4S/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/h3-6,11,19H,7-10H2,1-2H3 
Key:KVWDHTXUZHCGIO-UHFFFAOYSA-N 

   (what is this?)  (verify)

Common side effects include weight gain,

movement disorders, dizziness, feeling
tired, constipation, and dry mouth.[7] Other
side effects include low blood pressure
with standing, allergic reactions,
neuroleptic malignant syndrome, high
blood sugar, seizures, gynecomastia,
erectile dysfunction, and tardive
dyskinesia.[7] In older people with
dementia, its use increases the risk of
death.[7] Use in the later part of pregnancy
may result in a movement disorder in the
baby for some time after birth.[7] Although
how it works is not entirely clear, it blocks
dopamine and serotonin receptors.[7]

Olanzapine was patented in 1971 and

approved for medical use in the United
States in 1996.[7][8] It is available as a
generic medication.[7] In the United States,
the wholesale cost is less than US$0.25
per dose as of 2018.[9] In 2016, it was
prescribed more than 2 million times in the
United States.[10]

Medical uses
Schizophrenia

The first-line psychiatric treatment for

schizophrenia is antipsychotic medication;
with olanzapine being one such
medication.[11] Olanzapine appears to be
effective in reducing symptoms of
schizophrenia, treating acute
exacerbations, and treating early-onset
schizophrenia.[12][13][14][15] The usefulness
of maintenance therapy, however, is
difficult to determine as more than half of
people in trials quit before the six-week
completion date.[16] Treatment with
olanzapine (like clozapine) may result in
increased weight gain and increased
glucose and cholesterol levels when
compared to most other second-
generation antipsychotic drugs used to
treat schizophrenia.[13][17]

Comparison

National Institute for Health and Care

Excellence, the British Association for
Psychopharmacology, and the World
Federation of Societies for Biological
Psychiatry suggest that there is little
difference in effectiveness between
antipsychotics in prevention of relapse,
and recommend that the specific choice of
antipsychotic be chosen based on a
person's preference and the drug's side
effect profile.[18][19][20] The U.S. Agency for
Healthcare Research and Quality
concludes that olanzapine is not different
from haloperidol in the treatment of
positive symptoms and general
psychopathology, or in overall assessment,
but that it is superior for the treatment of
negative and depressive symptoms.[21] It
has a lower risk of causing movement
disorders than typical antipsychotics.[12]

In a 2013 comparison of 15 antipsychotic

drugs in schizophrenia, olanzapine was
ranked third in efficacy. It was 5% more
effective than risperidone (4th), 24-27%
more effective than haloperidol,
quetiapine, and aripiprazole, and 33% less
effective than clozapine (1st).[12] A 2013
review of first episode schizophrenia
concluded that olanzapine is superior to
haloperidol in providing a lower
discontinuation rate, and in short-term
symptom reduction, response rate,
negative symptoms, depression, cognitive
function, discontinuation due to poor
efficacy, and long-term relapse, but not in
positive symptoms or on the Clinical
Global Impressions score. In contrast,
pooled second generation antipsychotics
showed superiority to first generation
antipsychotics only against the
discontinuation, negative symptoms (with
a much larger effect seen among industry-
compared to government-sponsored
studies), and cognition scores. Olanzapine
caused less extrapyramidal side effects,
less akathisia, but caused significantly
more weight gain, serum cholesterol
increase, and triglyceride increase than
haloperidol.[22] A 2012 review concluded
that among 10 atypical antipsychotics,
only clozapine, olanzapine, and risperidone
were better than first generation
antipsychotics.[23] A 2011 review
concluded that neither first- nor second
generation antipsychotics produce
clinically meaningful changes in Clinical
Global Impression scores but found that
olanzapine and amisulpride produce larger
effects on the PANSS and BPRS batteries
than five other second generation
antipsychotics or pooled first generation
antipsychotics.[24] A 2010 Cochrane
systematic review found that olanzapine
may have a slight advantage in
effectiveness when compared to
aripiprazole, quetiapine, risperidone and
ziprasidone.[17] No differences in
effectiveness was detected when
comparing olanzapine to amisulpride and
clozapine.[17]
A 2014 meta analysis of 9 published trials
having minimum duration 6 months and
median duration 52 weeks concluded that
olanzapine, quetiapine, and risperidone
had better effects on cognitive function
than amisulpride and haloperidol.[25]

Bipolar disorder

Olanzapine is recommended by the

National Institute of Health and Care
Excellence as a first line therapy for the
treatment of acute mania in bipolar
disorder.[26] Other recommended first lines
are haloperidol, quetiapine and
risperidone.[26] It is recommended in
combination with fluoxetine as a first line
therapy for acute bipolar depression; and
as a second line treatment by itself for the
maintenance treatment of bipolar
disorder.[26]

The Network for Mood and Anxiety

Treatments (CANMAT) recommends
olanzapine as a first line maintenance
treatment in bipolar disorder and the
combination of olanzapine with fluoxetine
as second line treatment for bipolar
depression.[27]

A 2014 meta analysis concluded that

olanzapine plus fluoxetine was the most
effective among nine treatments for
bipolar depression included in the
analysis.[28]

Other uses

Evidence does not support the use of

atypical antipsychotics, including
olanzapine, in eating disorders.[29]

Olanzapine has not been rigorously

evaluated in generalized anxiety disorder,
panic disorder, delusional parasitosis, or
post-traumatic stress disorder. Olanzapine
is no less effective than lithium or
valproate and more effective than placebo
in treating bipolar disorder.[30] It has also
been used for Tourette syndrome and
stuttering.[31]

Olanzapine has been studied for the

treatment of hyperactivity, aggressive
behavior, and repetitive behaviors in
autism.[32]

Olanzapine is frequently prescribed off-

label for the treatment of insomnia,
including difficult falling asleep and
staying asleep. The daytime sedation
experienced with olanzapine is generally
comparable to quetiapine and lurasidone,
which is a frequent complaint in clinical
trials. In some cases, the sedation due to
olanzapine impaired the ability of people
to wake up at a consistent time every day.
There does appear to be some evidence of
efficacy for treating insomnia, but long-
term studies (especially for safety) are still
needed.[33]

Specific populations

Pregnancy and lactation

Olanzapine is associated with the highest

placental exposure of any atypical
antipsychotic.[34] Despite this, the available
evidence suggests it is safe during
pregnancy, although the evidence is
insufficiently strong to say anything with a
high degree of confidence.[34] Olanzapine
is associated with weight gain which
according to recent studies may put
olanzapine-treated patients' offspring at a
heightened risk for neural tube defects
(e.g. spina bifida).[35][36] Breastfeeding in
women taking olanzapine is advised
against due to the fact that olanzapine is
secreted in breast milk with one study
finding that the exposure to the infant (in
mg per kg of body weight, that is) is about
1.8% that to the mother.[5]

Elderly
Citing an increased risk of stroke, in 2004
the Committee on the Safety of Medicines
(CSM) in the UK issued a warning that
olanzapine and risperidone, both atypical
antipsychotic medications, should not be
given to elderly patients with dementia. In
the U.S., olanzapine comes with a black
box warning for increased risk of death in
elderly patients. It is not approved for use
in patients with dementia-related
psychosis.[37] However, a BBC
investigation in June 2008 found that this
advice was being widely ignored by British
doctors.[38] Evidence suggested that
elderly are more likely to experience
weight gain on olanzapine compared to
aripiprazole and risperidone.[39]

Adverse effects
The principal side effect of olanzapine is
weight gain, which may be profound in
some cases and/or associated with
derangement in the blood lipid and blood
sugar profiles (see section metabolic
effects). A recent meta-analysis of the
efficacy and tolerance of 15 antipsychotic
drugs (APDs) found that it had the highest
propensity for causing weight gain out of
the 15 APD compared with a SMD of
0.74[12] Extrapyramidal side effects,
although potentially serious, are infrequent
to rare from olanzapine[40] but may include
tremors and muscle rigidity.

Several patient groups are at a heightened

risk of side effects from olanzapine and
antipsychotics in general. Olanzapine may
produce non-trivial high blood sugar in
people with diabetes mellitus. Likewise,
the elderly are at a greater risk of falls and
accidental injury. Young males appear to
be at heightened risk of dystonic
reactions, although these are relatively rare
with olanzapine. Most antipsychotics,
including olanzapine, may disrupt the
body's natural thermoregulatory systems,
thus permitting excursions to dangerous
levels when situations (exposure to heat,
strenuous exercise) occur.[5][6][41][42][43]

Other side effects include galactorrhea,

amenorrhea, gynecomastia, and erectile
dysfunction (impotence).[44]

Paradoxical effects

Olanzapine is used therapeutically to treat

serious mental illness. Occasionally, it can
have the opposite effect and provoke
serious paradoxical reactions in a small
subgroup of people, causing unusual
changes in personality, thoughts, or
behavior; hallucinations and excessive
thoughts about suicide have also been
linked to olanzapine use.[45]

Metabolic effects

The US Food and Drug Administration

requires all atypical antipsychotics to
include a warning about the risk of
developing hyperglycemia and diabetes,
both of which are factors in the metabolic
syndrome. These effects may be related to
the drugs' ability to induce weight gain,
although there are some reports of
metabolic changes in the absence of
weight gain.[46][47] Studies have indicated
that olanzapine carries a greater risk of
causing and exacerbating diabetes than
another commonly prescribed atypical
antipsychotic, risperidone. Of all the
atypical antipsychotics, olanzapine is one
of the most likely to induce weight gain
based on various measures.[48][49][50][51][52]
The effect is dose dependent in
humans[53] and animal models of
olanzapine-induced metabolic side
effects. There are some case reports of
olanzapine-induced diabetic
ketoacidosis.[54] Olanzapine may decrease
insulin sensitivity,[55][56] though one 3-week
study seems to refute this.[57] It may also
increase triglyceride levels.[49]
Despite weight gain, a large multi-center
randomized National Institute of Mental
Health study found that olanzapine was
better at controlling symptoms because
patients were more likely to remain on
olanzapine than the other drugs.[58] One
small, open-label, non-randomized study
suggests that taking olanzapine by orally
dissolving tablets may induce less weight
gain,[59] but this has not been
substantiated in a blinded experimental
setting.

Post-injection
delirium/sedation syndrome
Post-injection delirium/sedation syndrome
(PDSS) is a rare syndrome that is specific
to the long-acting injectable formulation of
olanzapine, olanzapine pamoate.[60] The
incidence of PDSS with olanzapine
pamoate is estimated to be 0.07% of
administrations, and is unique among
other second-generation, long-acting
antipsychotics (e.g. paliperidone
palmitate), which don't appear to carry the
same risk.[60] PDSS is characterized by
symptoms of delirium (e.g. confusion,
difficulty speaking, and uncoordinated
movements) and sedation.[60] While not all
people with PDSS will exhibit both delirium
and sedation, most of them will (83%).[60]
Although less specific to PDSS, a majority
of cases (67%) involved a feeling of
general discomfort.[60] It is thought that
PDSS may occur due to accidental
injection and absorption of olanzapine
pamoate into the bloodstream, where it
can act more rapidly, as opposed to slowly
distributing out from muscle tissue.[60]
Utilizing the proper, intramuscular injection
technique for olanzapine pamoate helps to
decrease the risk of PDSS, though it does
not eliminate the risk entirely.[60] This is
why the FDA advises that people that are
injected with olanzapine pamoate be
watched for 3 hours after administration,
in the event that PDSS occurs.[60]
Animal toxicology

Olanzapine has demonstrated

carcinogenic effects in multiple studies
when exposed chronically to female mice
and rats, but not male mice and rats. The
tumors found were in either the liver or
mammary glands of the animals.[61]

Discontinuation

The British National Formulary

recommends a gradual withdrawal when
discontinuing antipsychotics to avoid
acute withdrawal syndrome or rapid
relapse.[62] Symptoms of withdrawal
commonly include nausea, vomiting, and
loss of appetite.[63] Other symptoms may
include restlessness, increased sweating,
and trouble sleeping.[63] Less commonly
there may be a feeling of the world
spinning, numbness, or muscle pains.[63]
Symptoms generally resolve after a short
period of time.[63]

There is tentative evidence that

discontinuation of antipsychotics can
result in psychosis.[64] It may also result in
reoccurrence of the condition that is being
treated.[65] Rarely tardive dyskinesia can
occur when the medication is stopped.[63]
Overdose
Symptoms of an overdose include
tachycardia, agitation, dysarthria,
decreased consciousness, and coma.
Death has been reported after an acute
overdose of 450 mg, but also survival after
an acute overdose of 2000 mg.[66]
Fatalities generally have occurred with
olanzapine plasma concentrations greater
than 1000 ng/mL post-mortem, with
concentrations up to 5200 ng/mL
recorded (though this might represent
confounding by dead tissue, which may
release olanzapine into the blood upon
death).[67] There is no known specific
antidote for olanzapine overdose, and
even physicians are recommended to call
a certified poison control center for
information on the treatment of such a
case.[66] Olanzapine is considered
moderately toxic in overdose, more toxic
than quetiapine, aripiprazole, and the
SSRIs and less toxic than the MAOIs and
TCAs.[34]

Interactions
Drugs or agents that increase the activity
of the enzyme CYP1A2, notably tobacco
smoke, may significantly increase hepatic
first-pass clearance of olanzapine;
conversely, drugs which inhibit CYP1A2
activity (examples: ciprofloxacin,
fluvoxamine) may reduce olanzapine
clearance.[68] Carbamazepine, a known
enzyme inducer, has decreased the
concentration/dose ration of olanzapine
by 33% compared to olanzapine alone.[67]
Another enzyme inducer, ritonavir, has also
been shown to decrease the body's
exposure to olanzapine, due to its
induction of the enzymes CYP1A2 and
uridine 5'-diphospho-
glucuronosyltransferase
(UGT).[67]Probenecid increases the total
exposure (area under the curve, or AUC)
and maximum plasma concentration
(Cmax) of olanzapine.[67] Although
olanzapine's metabolism includes the
minor metabolic pathway of CYP2D6, the
presence of the CYP2D6 inhibitor
fluoxetine does not have a clinically
significant effect on olanzapine's
clearance.[67]

Pharmacology
Pharmacodynamics
Olanzapine[69]
Site Ki (nM) Action Ref
[70][71]
5-HT1A 2,063–2,720 Antagonist
[69][71]
5-HT1B 509–660 ND
[69][71]
5-HT1D 540–1,582 ND
[69][71]
5-HT1E 2,010–2,408 ND
[71]
5-HT1F 310 ND
[72][73]
5-HT2A 1.32–24.2 Inverse agonist
[74][75]
5-HT2B 11.8–12.0 Inverse agonist
[73][75]
5-HT2C 6.4–29 Inverse agonist
[69]
5-HT3 202 Antagonist
[69]
5-HT5A 1,212 Full Agonist
[69][76]
5-HT6 6.0–42 Antagonist
[69][77]
5-HT7 105–365 Antagonist
[69][70]
α1A 109–115 Antagonist
[69]
α1B 263 Antagonist
[71][77]
α2A 192–470 Antagonist
[70][71]
α2B 82–180 Antagonist
[70][71]
α2C 29–210 Antagonist
[69][71]
β1 >10,000 ND
[69][71]
β2 >10,000 ND
[73][77]
D1 35–118 Antagonist
[78][79]
D2 3.00–106 Antagonist
[71][73]
D2L 31–38 Antagonist
[71][80]
D2S 21–52 Antagonist
[78][79]
D3 7.8–91 Antagonist
[78][81]
D4 1.6–50 Antagonist
[82][83]
D4.2 17–102 Antagonist
[80]
D4.4 21–60 Antagonist
[69][73]
D5 74–90 Antagonist
[69][71]
H1 0.65–4.9 Inverse agonist
[69]
H2 44 Antagonist
[69]
H3 3,713 Antagonist
[69]
H4 >10,000 Antagonist
[84][85]
M1 2.5–73 Antagonist
[76]
M2 48–622 Antagonist
[75][76]
M3 13–126 Antagonist
 [76][84]
M4 10–350 Antagonist
[76][84]
M5 6.0–82 Antagonist
[71]
σ1 >5,000 ND

σ2 ND ND ND
[71]
Opioid >10,000 ND
[69]
nACh >10,000 ND

NMDA [69]
>10,000 ND
(PCP)
[69][81]
SERT ≥3,676 ND
[69]
NET >10,000 ND
[69]
DAT >10,000 ND
[69][71]
VDCC >10,000 ND
[71]
VGSC >5,000 ND
[86]
hERG 6,013 Blocker

Values are Ki (nM). The smaller the value,

the more strongly the drug binds to the site.
All data are for human cloned proteins,
except H3 (guinea pig), σ1 (guinea pig),
opioid (rodent), NMDA/PCP (rat), VDCC,
and VGSC.[69]

Olanzapine has a higher affinity for 5-HT2A

serotonin receptors than D2 dopamine
receptors, which is a common property of
most atypical antipsychotics, aside from
the benzamide antipsychotics such as
amisulpride along with the non-
benzamides aripiprazole, brexpiprazole,
blonanserin, cariprazine, melperone and
perospirone.

Olanzapine had the highest affinity of any

second-generation antipsychotic towards
the P-glycoprotein in one in vitro study.[87]
P-glycoprotein transports a myriad of
drugs across a numerous of different
biological membranes (found in numerous
body systems) including the blood-brain
barrier (a semi-permeable membrane
which filters the contents of blood prior to
it reaching the brain); P-GP inhibition could
mean that less brain exposure to
olanzapine results from this interaction
with the P-glycoprotein.[88] A relatively
large quantity of commonly encountered
foods and medications inhibit P-GP, and it
is fairly common for pharmaceuticals to
be either substrates of P-GP, or to inhibit
its action; both substrates and inhibitors of
P-GP effectively increase the permeability
of the blood brain barrier to P-GP
substrates and subsequently increase the
central activity of the substrate while
reducing the local effects on the GI tract.
The mediation of olanzapine in the central
nervous system by P-GP means that any
other substance or drug which interacts
with P-GP increases the risk for toxic
accumulations of both olanzapine and the
other drug.[89]
Olanzapine is a potent antagonist of the
muscarinic M3 receptor,[90] which may
underlie its diabetogenic side
effects.[91][92] Additionally, olanzapine also
exhibits a relatively low affinity for
serotonin 5-HT1, GABAA, beta-adrenergic
receptors, and benzodiazepine binding
sites.[40][93]

The mode of action of olanzapine's

antipsychotic activity is unknown. It may
involve antagonism of dopamine and
serotonin receptors. Antagonism of
dopamine receptors is associated with
extrapyramidal effects such as tardive
dyskinesia (TD), and with therapeutic
effects. Antagonism of muscarinic
acetylcholine receptors is associated with
anticholinergic side effects such as dry
mouth and constipation, in addition it may
suppress or reduce the emergence of
extrapyramidal effects for the duration of
treatment, however it offers no protection
against the development of tardive
dyskinesia. In common with other second
generation (atypical) antipsychotics,
olanzapine poses a relatively low risk of
extrapyramidal side effects including TD,
due to its higher affinity for the 5HT2A
receptor over the D2 receptor.[94]
Antagonizing H1 histamine receptors
causes sedation and may cause weight
gain, although antagonistic actions at
serotonin 5-HT2C and dopamine D2
receptors have also been associated with
weight gain and appetite stimulation.[95]

Pharmacokinetics

Metabolism

Olanzapine is metabolized by the

cytochrome P450 (CYP) system;
principally by isozyme 1A2 (CYP1A2) and
to a lesser extent by CYP2D6. By these
mechanisms more than 40% of the oral
dose, on average, is removed by the
hepatic first-pass effect.[40] The clearance
of olanzapine appears to vary by sex;
women have approximately 25% lower
clearance than men.[67] The clearance of
olanzapine also varies by race; in self-
identified African-Americans or Black
individuals, olanzapine's clearance was
26% higher.[67] There does not appear to
be a difference in the clearance between
individuals identifying as Caucasian,
Chinese, or Japanese.[67] Routine,
pharmacokinetic monitoring of olanzapine
plasma levels is generally unwarranted,
though unusual circumstances (e.g. the
presence of drug-drug interactions) or a
desire to determine if a patient is taking
their medicine or not may prompt its
use.[67]

Society and culture

Zyprexa (olanzapine) 10 mg tablets (AU)

Regulatory status

Olanzapine is approved in the United

States by the Food and Drug
Administration (FDA) for:
Treatment—in combination with
fluoxetine—of depressive episodes
associated with bipolar disorder
(December 2003).[96]
Long-term treatment of bipolar I
disorder (January 2004).[97][98]
Long-term treatment—in combination
with fluoxetine—of resistant depression
(March 2009).[99]
Oral formulation: acute and
maintenance treatment of schizophrenia
in adults, acute treatment of manic or
mixed episodes associated with bipolar
I disorder (monotherapy and in
combination with lithium or sodium
valproate)
Intramuscular formulation: acute
agitation associated with schizophrenia
and bipolar I mania in adults
Oral formulation combined with
fluoxetine: treatment of acute
depressive episodes associated with
bipolar I disorder in adults, or treatment
of acute, resistant depression in
adults[100]
Treatment of the manifestations of
psychotic disorders (September
1996[101] – March 2000).[102]
Short-term treatment of acute manic
episodes associated with bipolar I
disorder (March 2000).[102]
 Short-term treatment of schizophrenia
instead of the management of the
manifestations of psychotic disorders
(March 2000).[102]
Maintaining treatment response in
schizophrenic patients who had been
stable for approximately eight weeks
and were then followed for a period of
up to eight months (November
2000).[102]

The drug became generic in 2011. Sales of

Zyprexa in 2008 were $2.2 billion in the US,
and $4.7 billion worldwide.[103]

Controversy and litigation

Eli Lilly has faced many lawsuits from
people who claimed they developed
diabetes or other diseases after taking
Zyprexa, as well as by various
governmental entities, insurance
companies, and others. Lilly produced a
large number of documents as part of the
discovery phase of this litigation, which
started in 2004; the documents were ruled
to be confidential by a judge and placed
under seal, and later themselves became
the subject of litigation.[104]

In 2006, Lilly paid $700 million to settle

around 8,000 of these lawsuits,[105] and in
early 2007, Lilly settled around 18,000
suits for $500 million, which brought the
total Lilly had paid to settle suits related to
the drug to $1.2 billion.[106][107]

A December 2006 New York Times article

based on leaked company documents
concluded that the company had engaged
in a deliberate effort to downplay
olanzapine's side effects.[106][108] The
company denied these allegations and
stated that the article had been based on
cherry picked documents.[106][107] The
documents were provided to the Times by
Jim Gottstein, a lawyer who represented
mentally ill patients, who obtained them
from a doctor, David Egilman, who was
serving as an expert consultant on the
case.[104] In 2007 Lilly filed a protection
order to stop the dissemination of some of
the documents, which Judge Jack B.
Weinstein of the Brooklyn Federal District
Court granted, and criticized the New York
Times reporter, Gottstein, and Egilman in
the ruling.[104] The Times of London also
received the documents and reported that
as early as 1998, Lilly considered the risk
of drug-induced obesity to be a "top threat"
to Zyprexa sales.[107] On October 9, 2000,
senior Lilly research physician Robert
Baker noted that an academic advisory
board he belonged to was "quite
impressed by the magnitude of weight
gain on olanzapine and implications for
glucose."[107]

Lilly had threatened Egilman with criminal

contempt charges regarding the
documents he took and provided to
reporters; in September 2007 he agreed to
pay Lilly $100,000 in return for the
company’s agreement to drop the threat of
charges.[109]

In September 2008 Judge Weinstein

issued an order to make public Lilly's
internal documents about the drug in a
different suit brought by insurance
companies, pension funds, and other
payors.[104]

In March 2008 Lilly settled a suit with the

state of Alaska[110] and in October 2008,
Lilly agreed to pay $62 million to 32 states
and the District of Columbia to settle suits
brought under state consumer protection
laws.[109]

In 2009, Eli Lilly pleaded guilty to a US

federal criminal misdemeanor charge of
illegally marketing Zyprexa for off-label
use and agreed to pay $1.4 billion.[111][112]

Trade names
Olanzapine is generic and is available
under many trade names worldwide.[1]
List of trade names for olanzapine[1]
Aedon, Alonzap, Amulsin, Anzap, Anzatric, Anzorin, Apisco, Apo-Olanzapine, Apo-Olanzapine
A
ODT, Apsico, Arenbil, Arkolamyl

B Benexafrina, Bloonis

C Caprilon, Cap-Tiva, Clingozan

D Deprex, Domus, Dopin

E Egolanza, Elynza, Emzypine, Epilanz-10, Exzapine

F Fontanivio, Fordep

I Irropia

J Jolyon-MD

K Kozylex

L Lanopin, Lanzapine, Lanzep, Lapenza, Lapozan, Lazap, Lazapir, Lazapix, Lezapin-MD, Lopez

M Marathon, Meflax, Midax

N Niolib, Nodoff, Norpen Oro, Nykob, Nyzol

O Oferta, Oferta-Sanovel, Olace, Oladay, Oladay-F, Olaffar, Olan, Olanap, Olancell, Olandix,
Olandoz, Olandus, Olankline, Olanpax, Olanstad, Olanza, Olanza Actavis, Olanza Actavis ODT,
Olanzalet,Olanzalux, Olanzamed, Olanzapin 1A Pharma, Olanzapin AbZ, Olanzapin Accord,
Olanzapin Actavis, Olanzapin AL, Olanzapin Apotex, Olanzapin Aristo, Olanzapin axcount,
Olanzapin beta, Olanzapin Bluefish, Olanzapin Cipla, Olanzapin easypharm, Olanzapin Egis,
Olanzapin G.L., Olanzapin Genera, Olanzapin Genericon, Olanzapin Helvepharm, Olanzapin
Hennig, Olanzapin Heumann, Olanzapin HEXAL, Olanzapin Krka, Olanzapin Lilly, Olanzapin
Mylan, Olanzapin Niolib, Olanzapin Orion, Olanzapin PCD, Olanzapin PharmaS, Olanzapin
Ranbaxy, Olanzapin ratiopharm, Olanzapin ReplekFarm, Olanzapin Rth, Olanzapin Sandoz,
Olanzapin Spirig HC, Olanzapin Stada, Olanzapin SUN, Olanzapin Teva, Olanzapin Viketo,
Olanzapin Zentiva, Olanzapina Accord, Olanzapina Actavis, Olanzapina Actavis PTC,
Olanzapina Aldal, Olanzapina Almus, Olanzapina Alter, Olanzapina Angenerico, Olanzapina
Anipaz, Olanzapina Apotex, Olanzapina APS, Olanzapina Arrowblue, Olanzapina Aspen,
Olanzapina Aurobindo, Olanzapina Basi, Olanzapina Bexalabs, Olanzapina Blixie, Olanzapina
Bluefish, Olanzapina Bluepharma, Olanzapina Cantabria, Olanzapina Ceapharma, Olanzapina
Ciclum, Olanzapina Cinfa, Olanzapina Cipla, Olanzapina Combix, Olanzapina Doc Generici,
 Olanzapina Dr. Reddy's, Olanzapina Eulex, Olanzapina Eurogenerici, Olanzapina Fantex,
Olanzapina Farmoz, Olanzapina Flas Pharma Combix, Olanzapina Genedec, Olanzapina
Generis, Olanzapina Germed, Olanzapina Glenmark, Olanzapina Green Avet, Olanzapina
Helm, Olanzapina Kern Pharma, Olanzapina Krka, Olanzapina La Santé, Olanzapina Labesfal,
Olanzapina Leugim, Olanzapina Lilly, Olanzapina LPH, Olanzapina Mabo, Olanzapina
Medana, Olanzapina Medis, Olanzapina Medley, Olanzapina Mylan, Olanzapina Nakozap,
Olanzapina Nolian, Olanzapina Normon, Olanzapina Ozilormar, Olanzapina Parke-Davis,
Olanzapina Pensa, Olanzapina Pensa Pharma, Olanzapina Pharmakern, Olanzapina
Polipharma, Olanzapina Polpharma, Olanzapina Qualigen, Olanzapina Ranbaxy, Olanzapina
Ratio, Olanzapina Ratiopharm, Olanzapina Reconir, Olanzapina Reddy, Olanzapina Rospaw,
Olanzapina Sabacur, Olanzapina Sandoz, Olanzapina Sarb, Olanzapina Stada, Olanzapina
Sun, Olanzapina TAD, Olanzapina Technigen, Olanzapina Terapia, Olanzapina Teva,
Olanzapina Tevagen, Olanzapina tolife, Olanzapina Torrent, Olanzapina Vegal, Olanzapina
Vida, Olanzapina Winthrop, Olanzapina Wynn, Olanzapina Kraz, Olanzapina Zentiva,
Olanzapina Zerpi, Olanzapina Zonapir, Olanzapin-Actavis, Olanzapin-CT, Olanzapine 1A
Pharma, Olanzapine Accord, Olanzapine Actavis, Olanzapine Adamed, Olanzapine Alter,
Olanzapine Alvogen, Olanzapine Apotex, Olanzapine Arrow Génériques, Olanzapine Auro,
Olanzapine Aurobindo, Olanzapine Biogaran, Olanzapine Bluefish, Olanzapine CF, Olanzapine
Clonmel, Olanzapine Cristers, Olanzapine Dexcel, Olanzapine EG, Olanzapine Egis,
Olanzapine Evolugen, Olanzapine Galenicum, Olanzapine Generichealth, Olanzapine
Glenmark, Olanzapine GSK, Olanzapine Isomed, Olanzapine Jacobsen, Olanzapine Jubilant,
Olanzapine Lekam, Olanzapine Lesvi, Olanzapine Medana, Olanzapine Mylan, Olanzapine
Neopharma, Olanzapine Niolib, Olanzapine Nyzol, Olanzapine Odis Mylan, Olanzapine ODT
Generichealth, Olanzapine ODT Sanis Health, Olanzapine ODT Teva, Olanzapine ODT-DRLA,
Olanzapine Orion, Olanzapine Polpharma, Olanzapine Prasco, Olanzapine Ranbaxy,
Olanzapine Ratiopharm, Olanzapine Sandoz, Olanzapine Sanis Health, Olanzapine Sanovel,
Olanzapine Stada, Olanzapine Sun, Olanzapine Synthon, Olanzapine Teva, Olanzapine
Torrent, Olanzapine Zentiva, Olanzapine Zentiva Lab, Olanzapine Zydus, Olanzapine-DRLA,
Olzapine

U
V

Z Zyprexa

Dosage forms

Olanzapine is marketed in a number of

countries, with tablets ranging from 2.5 to
20 milligrams. Zyprexa (and generic
olanzapine) is available as an orally-
disintegrating "wafer" which rapidly
dissolves in saliva. It is also available in 10
milligram vials for intramuscular
injection.[68]

Research
Olanzapine has been studied as an
antiemetic, particularly for the control of
chemotherapy-induced nausea and
vomiting (CINV).[113]

In general, olanzapine appears to be about

as effective as aprepitant for the
prevention of CINV, though there are some
concerns for its use in this population. For
example, concomitant use of
metoclopramide or haloperidol increases
the risk for extrapyramidal symptoms
(EPS). Otherwise, olanzapine appears to
be fairly well tolerated for this indication,
with somnolence being the most common
side effect.[114]
Olanzapine has been considered as part of
an early psychosis approach for
schizophrenia. The Prevention through
Risk Identification, Management, and
Education (PRIME) study, funded by the
National Institute of Mental Health and Eli
Lilly, tested the hypothesis that olanzapine
might prevent the onset of psychosis in
people at very high risk for schizophrenia.
The study examined 60 patients with
prodromal schizophrenia, who were at an
estimated risk of 36–54% of developing
schizophrenia within a year, and treated
half with olanzapine and half with
placebo.[115] In this study, patients
receiving olanzapine did not have a
significantly lower risk of progressing to
psychosis. Olanzapine was effective for
treating the prodromal symptoms, but was
associated with significant weight
gain.[116]

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External links
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related to Olanzapine.

Zyprexa.com - official Zyprexa brand

website from Eli Lilly and Company
Zyprexa package insert
Berenson A (December 17, 2006). "Lilly
Settles With 18,000 Over Zyprexa" . The
New York Times.

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