OLANZAPINE

Olanzapine is also used to treat bipolar disorder (manic depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods).
Olanzapine is used to treat a variety of psychiatric conditions such as bipolar disorder and schizophrenia, as well as agitation that is related to psychiatric conditions.

CAS Number: 132539-06-1
EC Number: 200-835-2
IUPAC Name: 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine
Chemical Formula: C₁₇H₂₀N₄S
Molecular Weight: 312.44 g/mol

SYNONYMS:
Zyprexa, Zyprexa Zydis, Olanzapinum, 2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine, LNP-101, Eli-Lilly Olanzapine, Olzapin, Zyprexa, Zyprexa Zydis, Olanzapinum, 2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine, LNP-101, Eli-Lilly Olanzapine, Olzapin, LY170053, CP-265,522, Olanzapin, Thienobenzodiazepine derivative, OLA, Olanzapine base

Olanzapine is in a class of medications called atypical antipsychotics.
Olanzapine works by changing the activity of certain natural substances in the brain.
Olanzapine treats schizophrenia and bipolar disorder.

Olanzapine works by balancing the levels of dopamine and serotonin in your brain, substances that help regulate mood, behaviors, and thoughts.
Olanzapine is an atypical antipsychotic that may be used to treat adults and adolescents aged 13 and older with schizophrenia or bipolar I disorder.

Olanzapine is a second-generation (atypical) antipsychotic medication.
The FDA has approved Olanzapine for schizophrenia if the patient is over the age of 13 and bipolar disorder, including mixed or manic episodes.
Olanzapine is also approved for use with fluoxetine, a selective serotonin reuptake inhibitor (SSRI), in patients with episodes of depression associated with bipolar disorder type 1 and treatment-resistant depression.

Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder.
Olanzapine is taken by mouth or by injection into a muscle.

Although its mechanism of action is not entirely clear, Olanzapine is known to block dopamine and serotonin receptors.
Olanzapine was patented in 1991 and approved for medical use in the United States in 1996.
Olanzapine is available as a generic medication.

In 2023, Olanzapine was the 167th most commonly prescribed medication in the United States, with more than 3 million prescriptions.
Olanzapine is on the World Health Organization's List of Essential Medicines.

USES and APPLICATIONS of OLANZAPINE:
Olanzapine may be prescribed for other uses; ask your doctor or pharmacist for more information.
Olanzapine is an antipsychotic medication that can treat several mental health conditions like schizophrenia and bipolar disorder.
Olanzapine balances the levels of dopamine and serotonin in your brain.

These substances help regulate your mood, behaviors and thoughts.
Olanzapine is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions) in adults and teenagers 13 years of age and older.

Olanzapine is also used to treat bipolar disorder (manic depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods) in adults and teenagers 13 years of age and older.
Olanzapine belongs to a group of medications called antipsychotics.

Antipsychotic medications can be used to treat several kinds of mental health conditions.
Olanzapine may be used for other purposes; ask your health care provider or pharmacist if you have questions.
For bipolar I disorder, Olanzapine may be used: alone for manic or mixed episodes, or in combination with lithium or valproate with fluoxetine for depressive episodes in people aged 10 and older.

For treatment-resistant depression, olanzapine is used in combination with fluoxetine (Symbyax).
Olanzapine is available as oral tablets, orally disintegrating tablets, or an injection that is given into a muscle (intramuscular [IM]).
The olanzapine IM preparation is only for acute agitation associated with schizophrenia and bipolar I mania in adults.

Olanzapine may work by blocking certain receptors in the brain, notably dopamine and serotonin, although the exact way it works in schizophrenia and bipolar I disorder is unknown.
Olanzapine was FDA approved on September 30, 1996, under the brand name Zyprexa.

Generic olanzapine is available.
Olanzapine is used to treat a variety of psychiatric conditions such as bipolar disorder and schizophrenia, as well as agitation that is related to psychiatric conditions.

Olanzapine is also sometimes used off-label for treatment of chemotherapy-induced nausea and vomiting and as an appetite stimulant.
For schizophrenia, Olanzapine can be used for both new-onset disease and long-term maintenance.

-Bipolar disorder
Olanzapine is recommended by the National Institute for Health and Care Excellence as a first-line therapy for the treatment of acute mania in bipolar disorder.

Other recommended first-line treatments are aripiprazole, haloperidol, quetiapine, and risperidone.
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.

The Network for Mood and Anxiety Treatments recommends olanzapine as a first-line maintenance treatment for bipolar disorder and the combination of olanzapine with fluoxetine as a second-line treatment for bipolar depression.

A review on the efficacy of olanzapine as maintenance therapy in people with bipolar disorder was published in 2006.
A 2014 meta-analysis concluded that olanzapine with fluoxetine was the most effective among nine treatments for bipolar depression included in the analysis.

MEDICAL USES of OLANZAPINE:
Olanzapine is approved by the FDA for the following indications:

*schizophrenia:
**acute treatment of manic or mixed episodes associated with bipolar I disorder and maintenance treatment of bipolar I disorder.
**adjunct to lithium or valproate in the treatment of manic or mixed episodes associated with bipolar I disorder.
**combination olanzapine/fluoxetine (Symbyax) for the treatment of depressive episodes of bipolar I disorder and for treatment-resistant 

*depression.
**combination olanzapine/samidorphan (Lybalvi) for the treatment of schizophrenia and bipolar I disorder.
Lybalvi suppresses the metabolic side effect of olanzapine.

More precisely, olanzapine produces weight gain of about 9 kg (20 pounds) in the short-term, which typically increases to around 23–45 kg (50–100 pounds) following long-term use.
In contrast, Lybalvi only triggers roughly 5 kg (11 pounds) before subsiding.

In the United Kingdom and Australia, Olanzapine is approved for schizophrenia, moderate to severe manic episodes, alone, or in combination with lithium or valproate and the short-term treatment of acute manic episodes associated with bipolar I disorder.
Olanzapine is also used off-label for the treatment of chemotherapy-induced nausea and vomiting.

SCHIZOPHRENIA
The first-line psychiatric treatment for schizophrenia is antipsychotic medication.
Olanzapine appears to be effective in reducing symptoms of schizophrenia, treating acute exacerbations, and treating early-onset schizophrenia.

HOW SHOULD OLANZAPINE BE USED?
Olanzapine comes as a tablet and an orally disintegrating tablet (tablet that dissolves quickly in the mouth) to take by mouth.
Olanzapine is usually taken once a day with or without food.

Take olanzapine at around the same time every day.
Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.

Take olanzapine exactly as directed.
Do not take more or less of it or take it more often than prescribed by your doctor.

Do not try to push the orally disintegrating tablet through the foil.
Instead, use dry hands to peel back the foil packaging.

Immediately take out the tablet and place it in your mouth.
The tablet will quickly dissolve and can be swallowed with or without liquid.

Your doctor may start you on a low dose of olanzapine and gradually increase your dose.
Olanzapine may help control your symptoms, but it will not cure your condition.

It may take several weeks or longer before you feel the full benefit of olanzapine.
Continue to take olanzapine even if you feel well.

Do not stop taking olanzapine without talking to your doctor.
Your doctor will probably want to decrease your dose gradually.

WHAT IS OLANZAPINE FOR?
Olanzapine belongs to a class of medications known as atypical (second-generation) antipsychotics.
Olanzapine is used to treat and prevent return of symptoms in Schizophrenia and other mental health related conditions such as:
*Hearing, seeing or sensing things that are not real
*Having mistaken beliefs
*Uncontrolled anger
*Being overly suspicious
*Olanzapine can be used to treat symptoms in bipolar disorder such as:
*Very high mood
*Irritability*
*Increased activity and energy
*Depression/low mood
*Olanzapine may be used for other conditions.

PHARMACOLOGY of OLANZAPINE:
Pharmacodynamics
Olanzapine was first discovered while searching for a chemical analog of clozapine that would not require hematological monitoring.
Investigation on a series of thiophene isosteres on 1 of the phenyl rings in clozapine, a thienobenzodiazepine analog (olanzapine) was discovered.

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 nonbenzamides aripiprazole, brexpiprazole, blonanserin, cariprazine, melperone, and perospirone.

KEY POINTS ABOUT OLANZAPINE:
Olanzapine is used to treat some types of mental illness such as bipolar disorder and schizophrenia.
Olanzapine is also called Zyprexa or Zypine.

Find out how to take Olanzapine safely and possible side effects.
Olanzapine is used to treat schizophrenia and bipolar disorderand associated agitation.

Olanzapine doesn't cure these conditions, but is used to help ease the symptoms and help you on your recovery path.
Olanzapine can help improve symptoms such mania with bipolar disorder, the experience of hearing voices (hallucinations), ideas that distress you and don't seem to be based in reality (delusions), and difficulty in thinking clearly (thought disorder).

Olanzapine belongs to a group of medicines called antipsychotics.
Read more about antipsychotic medicines and how they work.

Olanzapine is a thienobenzodiazepine derivative and an atypical or second-generation antipsychotic agent.
Olanzapine's chemical structure contains a thieno[2,3-b][1,5]benzodiazepine core, and has a methyl group attached to the piperazine ring.

The second-generation antipsychotics were introduced in the 90s and quickly gained traction due to their impressive efficacy, reduced risk for extrapyramidal side effects and reduced susceptibility to drug-drug interactions.

Olanzapine was discovered by scientists  and approved to be marketed in the US in 1996.
Olanzapine is a second generation antipsychotic.

Olanzapine is used to treat and prevent return of symptoms in Schizophrenia and other mental health related conditions.
Learn how to use Olanzapine, its common side effects, special precautions to watch out for, and more.

CHEMISTRY of OLANZAPINE:
Olanzapine is unusual in having four well-characterised crystalline polymorphs and many hydrated forms.

CHEMICAL SYNTHESIS of OLANZAPINE:
The preparation of olanzapine was first disclosed in a series of patents from Eli Lilly & Co. in the 1990s.
In the final two steps, 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile was reduced with stannous chloride in ethanol to give the substituted thienobenzodiazepine ring system, and this was treated with methylpiperazine in a mixture of dimethyl sulfoxide and toluene as solvent to produce the drug

PHARMACOKINETICS of OLANZAPINE:
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.
Clearance of olanzapine appears to vary by sex; women have roughly 25% lower clearance than men.

Clearance of olanzapine also varies by race; in self-identified African Americans or Blacks, olanzapine's clearance was 26% higher.
A difference in the clearance is not apparent between individuals identifying as Caucasian, Chinese, or Japanese.
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 patients are taking their medicine may prompt its use.

SOCIETY AND CULTURE of OLANZAPINE:
Legal status
Olanzapine is approved by the US FDA for:
Treatment—in combination with fluoxetine—of depressive episodes associated with bipolar disorder.

Long-term treatment of bipolar I disorder.
Long-term treatment—in combination with fluoxetine—of resistant depression.

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
Treatment of the manifestations of psychotic disorders.

Short-term treatment of acute manic episodes associated with bipolar I disorder.
Short-term treatment of schizophrenia instead of the management of the manifestations of psychotic disorders.

Maintaining treatment response in schizophrenic patients who had been stable for about eight weeks and were then followed for a period of up to eight months.

PHYSICAL and CHEMICAL PROPERTIES of OLANZAPINE:
CAS Number: 132539-06-1
EC Number: 200-835-2
Molecular Formula: C17H20N4S
Molar Mass: 312.44 g/mol
Appearance: Yellow crystalline solid
Physical State: Solid
Melting Point: Approximately 195°C
Boiling Point: Predicted to be around 476°C
Density: Approximately 1.32 g/cm³ (predicted)
Flash Point: Approximately 2°C
Solubility: Practically insoluble in water; 15 mg/mL in DMSO

Chemical Name: 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine
SMILES Notation: CN1CCN(CC1)C/2=N/c4ccccc4Nc3sc(C)cc23
InChIKey: KVWDHTXUZHCGIO-UHFFFAOYSA-N
Polymorphism: Can exist in multiple polymorphic forms, which may affect its stability and bioavailability
Hydrogen Bond Acceptors: 4
Hydrogen Bond Donors: 1
Rotatable Bonds: 1
Topological Polar Surface Area (TPSA): 59.11 Ų
LogP (XLogP): 2.79
Lipinski's Rule of Five Compliance: 0 violations

pKa: Approximately 7.78 (predicted)
BCS Classification: Class II (low solubility, high permeability)
Storage Temperature: 2–8°C
Pharmacokinetic Characteristics:
Bioavailability: Approximately 60–65%
Protein Binding: About 93%
Metabolism: Primarily in the liver via direct glucuronidation and CYP1A2-mediated oxidation
Elimination Half-Life: Approximately 33 hours; extended to about 51.8 hours in the elderly
Excretion: Urine: 57% (7% as unchanged drug); Feces: 30%

FIRST AID MEASURES of OLANZAPINE:
-Description of first-aid measures
*General advice:
Show this material safety data sheet to the doctor in attendance.
*If inhaled:
After inhalation: 
Fresh air.
*In case of skin contact: 
Take off immediately all contaminated clothing. 
Rinse skin with
water/ shower.
*In case of eye contact:
After eye contact: 
Rinse out with plenty of water. 
Call in ophthalmologist. 
Remove contact lenses.
*If swallowed:
After swallowing: 
Immediately make victim drink water (two glasses at most). 
Consult a physician.
-Indication of any immediate medical attention and special treatment needed.
No data available

ACCIDENTAL RELEASE MEASURES of OLANZAPINE:
-Environmental precautions:
Do not let product enter drains.
-Methods and materials for containment and cleaning up:
Cover drains. 
Collect, bind, and pump off spills. 
Observe possible material restrictions. 
Take up dry. 
Dispose of properly. 
Clean up affected area.

FIRE FIGHTING MEASURES of OLANZAPINE:
-Extinguishing media:
*Suitable extinguishing media:
Carbon dioxide (CO2) 
Foam 
Dry powder
*Unsuitable extinguishing media:
For this substance/mixture no limitations of extinguishing agents are given.
-Further information:
Prevent fire extinguishing water from contaminating surface water or the ground water system.

EXPOSURE CONTROLS/PERSONAL PROTECTION of OLANZAPINE:
-Control parameters:
--Ingredients with workplace control parameters:
-Exposure controls:
--Personal protective equipment:
*Eye/face protection:
Use equipment for eye protection. 
Safety glasses
*Body Protection:
protective clothing
*Respiratory protection:
Recommended Filter type: Filter A 
-Control of environmental exposure:
Do not let product enter drains.

HANDLING and STORAGE of OLANZAPINE:
-Conditions for safe storage, including any incompatibilities:
*Storage conditions:
Tightly closed. 
Dry.

STABILITY and REACTIVITY of OLANZAPINE:
-Chemical stability:
The product is chemically stable under standard ambient conditions (room temperature).
-Possibility of hazardous reactions:
No data available