Olanzapine (Zyprexa) is a second-generation antipsychotic drug that is used in the treatment of schizophrenia, bipolar depression, agitation, and other psychotic episodes.

Olanzapine (Zyprexa) Uses:

• P/O:
  • Manifestations of schizophrenia treatment.
  • Associated with bipolar I disorder (as monotherapy or in combination with lithium or valproate), treatment of acute or mixed mania episodes.
  • Maintenance treatment of bipolar I disorder.
  • In combination with fluoxetine for treatment-resistant or bipolar I depression
• IM, extended-release (Zyprexa Relprevv):
  • Schizophrenia treatment.
• IM, short-acting (Zyprexa Intra Muscular):
  • Associated with schizophrenia and bipolar I mania, treatment of acute agitation.

• Off Label Use of Olanzapine in Adults:

  • Chemotherapy-associated acute & delayed nausea or vomiting, prevention (adults)
  • Chemotherapy-associated breakthrough nausea or vomiting (adults)
  • Delirium
  • Delirium & agitation, intensive care unit (treatment) (alternative agent)
  • Delusional infestation (also called delusional parasitosis)
  • Psychosis/agitation associated with dementia
  • Posttraumatic stress disorder
  • Tourette syndrome

Olanzapine (Zyprexa) Dose in Adults

Olanzapine (Zyprexa) Dose in the treatment of Acute Agitation (associated with bipolar disorder or schizophrenia):

 

Initial dose:

• 10 mg (a lower dose of 5-7.5 mg may be considered when clinical factors warrant).
• Additional doses (up to 10 mg) may be considered.
• however, 2 hours after the initial dose and 4 hours after the second dose should be allowed between doses to evaluate response (max total dose: 30 mg/day)

Special risk patients:

• In patients who are debilitated, consider a lower dose of 2.5 mg, who have a predisposition to hypotensive reactions, or who may be more pharmacodynamically sensitive to olanzapine.Short-acting injection: IM:

• Short-acting injection: IV (off-label route):

Note:

• For respiratory depression, the IV route has only been studied in emergency departments, where patients can be closely monitored.
• The World Federation of Societies of Biological Psychiatry (WFSBP) expert consensus panel recommends against the use of intravenous medications in the management of agitation except in cases where there is no alternative.
  • Monotherapy: IV:
  • Initial:
    • 10 mg.
    • If needed, may provide two additional 5 mg doses in 5-min intervals.
  • Max:
    • 20 mg.

Note:

• Lower doses of 5 mg as a single dose have been studied concomitantly with midazolam, however, due to the potential for excessive sedation and cardiorespiratory depression, concomitant use of parenteral olanzapine & benzodiazepines is not recommended.

Olanzapine (Zyprexa) Dose in the treatment of Bipolar I (acute mixed or manic episodes): Oral:

• Monotherapy:
  • Initial:
    • 10-15 mg once daily.
    • Daily, increase by 5 mg at intervals of not less than 24 hours.
  • Maintenance:
    • 5-20 mg daily.
  • Recommended max dose:
    • 20 mg/day.
• Combination therapy (with lithium or valproate):
  • Initial:
    • 10 mg once daily.
  • Dosing range:
    • 5-20 mg daily

Olanzapine (Zyprexa) Dose in the Chemotherapy-associated acute and delayed nausea or vomiting, prevention (off-label):

• P/O:
• Followed by 10 mg once daily days 2-4, 10 mg on the day of chemotherapy (day 1) (in combination with dexamethasone and palonosetron on day 1 only).

Olanzapine (Zyprexa) Dose in the Chemotherapy-associated breakthrough nausea or vomiting (off-label):

• P/O:
• For 3 days, 10 mg once daily (Navari 2013).

Olanzapine (Zyprexa) Dose in the treatment of Delirium (off-label):

• P/O: For up to 5 days, 5 mg once daily.

Olanzapine (Zyprexa) Dose as an alternative agent in the treatment of Delirium and/or agitation, intensive care unit (off-label):

Note:

• To prevent and manage delirium, Nonpharmacologic interventions and treatment of underlying conditions are initial steps.
• If distressing symptoms (eg, agitation, anxiety) are present, antipsychotics may be used as a short-term adjunctive treatment.
• P/O: Initial:
  • Daily, 5-10 mg once (2.5 mg once daily in patients >60 years of age).
  • As needed, titrate daily in 5 mg increments up to 20 mg/day until the desired clinical response is achieved.
  • Monitor ECG & QTc interval.
  • Olanzapine therapy should be tapered over several days after symptoms resolve.
  • This strategy is based on expert opinion.
  • Efficacy and safety have not been formally evaluated.

• Short-acting injection: IM:

  • 5-10 mg.
  • As needed, may repeat every 2-4 hours (max total dose: 30 mg/day).

Olanzapine (Zyprexa) Dose in the treatment of Delusional infestation (also called delusional parasitosis) (off-label):

• P/O: Initial:
  • 2.5 mg once daily.
  • Up to 5-10 mg/day, increase gradually based on response & tolerability.
• Max:
  • 20 mg/day.

Olanzapine (Zyprexa) Dose in the treatment of Depression:

• Depression associated with bipolar disorder (in combination with fluoxetine):

  • P/O: Initial:
    • 5 mg in the evening.
    • Adjust as tolerated to the usual range of 5-12.5 mg daily.
  • See "Note."

• Treatment-resistant depression (in combination with fluoxetine):

  • P/O: Initial:
    • 5 mg in the evening.
    • Adjust as tolerated to a range of 5-20 mg daily.
  • See "Note."

Note (olanzapine/fluoxetine combination [Symbyax]):

• Rather than a fixed-dose combination product (Symbyax), when using individual components of fluoxetine with olanzapine, approximate dosage correspondence is as follows:
  • Olanzapine 2.5 mg + fluoxetine 20 mg = Symbyax 3/25
  • Olanzapine 5 mg + fluoxetine 20 mg = Symbyax 6/25
  • Olanzapine 12.5 mg + fluoxetine 20 mg = Symbyax 12/25
  • Olanzapine 5 mg + fluoxetine 50 mg = Symbyax 6/50
  • Olanzapine 12.5 mg + fluoxetine 50 mg = Symbyax 12/50

• Special risk patients:

  • Initial:
  • In patients who have a predisposition to hypotensive reactions, 2.5-5 mg once daily is recommended, who have a hepatic impairment, who exhibit a combination of factors that may result in slower metabolism of olanzapine (eg, female, elderly, nonsmoking status), or who may be more pharmacodynamically sensitive to olanzapine.
  • As clinically indicated, increase the dose with caution.

Olanzapine (Zyprexa) Dose in the treatment of Posttraumatic stress disorder (off-label):

• P/O: Initial:
  • 5-10 mg daily.
  • Adjust dose based on response & tolerability every 1-2 weeks, up to 20 mg daily.

Olanzapine (Zyprexa) Dose in the treatment of Schizophrenia:

• P/O:

• Initial:
  • Daily, 5-10 mg once (within 5 to 7 days, increase to 10 mg once daily).
  • thereafter, adjust by 5 mg daily at 1-week intervals, up to a recommended max of 20 mg/day.
• Maintenance:
  • 10-20 mg once daily.
  • Doses up to 60 mg daily have been used in treatment-resistant schizophrenia.
  • However, supporting evidence is limited (APA [Lehman 2004]).

• Special risk patients:

  • Initial:
    • Daily, 5 mg once is recommended in patients who are debilitated, who have a predisposition to hypotensive reactions, who exhibit a combination of factors that may result in slower metabolism of olanzapine (eg, nonsmoking female patients ≥65 years), or who may be more pharmacodynamically sensitive to olanzapine.
    • Increase dose cautiously as clinically indicated.

• Extended-release injection: IM:

Note:

• Prior to changing to extended-release injection, establish tolerance to oral olanzapine.
• Max dose:
  • 300 mg every 2 weeks or 405 mg every 4 weeks.
  • Patients established on oral olanzapine 10 mg daily:
    • Initial dose:
      • 210 mg every 2 weeks for 4 doses or 405 mg every 4 weeks for 2 doses.
    • Maintenance dose:
      • 150 mg every 2 weeks or 300 mg every 4 weeks.
  • Patients established on oral olanzapine 15 mg daily:
    • Initial dose:
      • For 4 doses, 300 mg every 2 weeks.
    • Maintenance dose:
      • 210 mg every 2 weeks or 405 mg every 4 weeks.
  • Patients established on oral olanzapine 20 mg daily:
    • Initial & maintenance dose:
      • 300 mg every 2 weeks.

• Special risk patients:

  • Initial:
    • Every 4 weeks, 150 mg is recommended in patients who are debilitated, who have a predisposition to hypotensive reactions, who exhibit a combination of factors that may result in slower metabolism of olanzapine (eg, nonsmoking female patients ≥65 years), or who may be more pharmacodynamically sensitive to olanzapine.
    • Increase dose cautiously as clinically indicated.

Olanzapine (Zyprexa) Dose in the treatment of Tourette syndrome (off-label):

• Initial:
  • 2.5-5 mg daily.
  • Based on response and tolerability, increase gradually to a usual dosage range of 2.5-20 mg daily.
  • After initial dosage, increments of 2.5 to 5 mg weekly or biweekly were commonly used for dosage adjustments in clinical trials up to a max dosage of 20 mg/day.

• Discontinuation of therapy:

  • To avoid withdrawal symptoms (ie, insomnia, headache, GI symptoms), gradual dose reduction is advised unless discontinuation is due to significant adverse effects.
  • In patients with schizophrenia or bipolar disorder when discontinuing chronic antipsychotic therapy, decreasing the dose very gradually over months to years with close monitoring is suggested to allow for the detection of prodromal symptoms of disease recurrence.

• Switching antipsychotics:

• Limited data available; optimal universal strategy is unknown. Strategies include:

  • Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic) & abrupt change (abruptly discontinuing the first antipsychotic & either increasing the new antipsychotic gradually or starting it at a treatment dose).
  • The current medication may be maintained at full dose as the new medication is increased in patients with schizophrenia at a high risk of relapse (ie, overlap).
  • the first medication is gradually decreased and discontinued over 1-2 weeks once the new medication is at the therapeutic dose.
  • Some experts generally prefer cross-titration and overlap approaches rather than abrupt change based upon clinical experience.

Olanzapine (Zyprexa) Dose in Childrens

Olanzapine (Zyprexa) Dose in the treatment of Bipolar I disorder (acute manic or mixed episodes):

P/O:

• Children 4 to <6 years:

• Limited data available:

  • Initial:
    • 1.25 mg once daily.
  • Increase at weekly intervals according to response and tolerability to target dose:
    • 10 mg/day.
  • Dosing based on an open-label trial in 15 children mean age: 5 ± 0.8 years; mean weight:
    • 20.8 kg.
  • Mean required dose:
    • 6.3 ± 2.3 mg/day that showed significant improvement in manic symptoms.

• Children 6-12 years:

• Limited data available:

  • Initial:
    • 2.5 mg once daily.
    • Increase dose in 2.5 or 5 mg increments at weekly intervals to target dose of 10 mg once daily.
  • Max dose:
    • 20 mg/day.

• Adolescents:

  • Initial:
    • 2.5-5 mg once daily.
    • At weekly intervals, increase the dose in 2.5 or 5 mg increments to target dose of 10 mg once daily.
  • Max dose:
    • 20 mg/day.
    • In adolescent flexible-dosing (2.5-20 mg/day) clinical trials, the mean modal dose was 10.7 mg/day (mean dose: 8.9 mg/day).

Olanzapine (Zyprexa) Dose in the treatment of Schizophrenia:

• Children ≥8 years (Limited data available) and Adolescents:

  • P/O:
• Initial:
  • 2.5-5 mg once daily.
  • Increase dose in 2.5 or 5 mg increments at weekly intervals to target dose of 10 mg once daily.
• Max dose:
  • 20 mg/day.
• Note:
  • In one study of adolescents who were treatment-refractory, doses up to 30 mg/day were used.
  • However, some patients did not tolerate doses > 20 mg/day (Kumra, 2008).
  • Safety and efficacy of doses >20 mg/day have not been fully evaluated.
  • The mean modal dose was 12.5 mg/day in adolescent flexible-dosing (2.5-20 mg/day) clinical trials (mean dose: 11.1 mg/day).
  • Dosing in children is based on two double-blind comparison studies which included both children & adolescents [n=35, age: 8-19 years with seven children; n=13, age: 7-16 years (mean age: 12.8 + 2.4 years)].

Olanzapine (Zyprexa) Dose in the treatment of Anorexia nervosa:

• Children ≥9 years and Adolescents:

• Limited data available:

• P/O:
  • In one small trial and several case reports to improve BMI and other disease-related symptoms (eg, eating attitudes, anxiety), 1.25-2.5 mg once daily has been shown.
  • Another case series used initial doses of 2.5 mg once daily & final doses of 5 mg to 10 mg once daily.
• Reported range:
  • 1.25-12.5 mg/day.
  • However, it has been suggested that higher doses (>2.5 mg once daily) may not be associated with greater efficacy.

Olanzapine (Zyprexa) Dose in the treatment of Tourette syndrome, tic disorder:

• Children ≥7 years and Adolescents:

• Limited data available:

• P/O:

• Patient weight ≤40 kg:
  • Initial:
    • For 3 days, 2.5 mg every other day, increase to 2.5 mg every day for the remainder of the week.
    • If needed, increase to 5 mg/day by second week.
    • Then increase in 5 mg increments at weekly intervals as tolerated.
  • Max dose:
    • 20 mg/day
• Patient weight >40 kg:
  • Initial:
    • For 3 days, 2.5 mg every day.
    • If needed increase to 5 mg every day for the remainder of the week, then increase in 5 mg increments at weekly intervals as tolerated.
  • Max dose:
    • 20 mg/day
• An open-label study of 10 pediatric patients (7-13 years of age) reported significant reductions in tic severity [Yale Global Tic Severity Scale (YGTSS)] from baseline at a mean final dose of 14.5 mg/day after 8 weeks of treatment.
• In total tic severity, an open-label trial of 12 children & adolescents (7-14 years of age) reported a significant reduction (30%) (YGTSS) at a final mean dose of 11.3 mg/day (range: 2.5-20 mg/day).

Olanzapine (Zyprexa) Dose in the treatment of Acute Agitation associated with bipolar disorder or schizophrenia:

Limited data available:

IM (short-acting):

• Children:
  • 5 mg.
• Adolescents:
  • 10 mg.
  • Use in an inpatient psychiatric setting, dosing based on a retrospective report of IM olanzapine which included 50 pediatric patients [children (n=15; mean age: 11 years).
  • Adolescents (n=35; mean age: 15 years)] & evaluated 163 doses administered.
  • Results showed a 90.2% response rate.

Olanzapine (Zyprexa) Pregnancy Risk Factor: C

• Negative events were seen in animal reproduction studies.
• Olanzapine crosses into the placenta and can be detected in cord blood during birth.
• Antipsychotic use during the third trimester is associated with abnormal muscle movements (extrapyramidal syndromes [EPS]) and withdrawal symptoms in infants after delivery.
• The newborn can experience agitation, feeding disorder and hypotonia.
• These effects can be self-limiting, or may require hospitalization.
• ACOG recommends that treatment during pregnancy is individualized.
• Treatment with psychiatric medication during pregnancy should include the clinical expertise of the mental healthcare clinician, obstetrician and primary care provider.
• Safety data regarding atypical antipsychotics during pregnancy is very limited. Routine use is not recommended.
• If a woman is accidentally exposed to an antipsychotic atypical while pregnant, continued therapy may be more beneficial than switching to the agent. Consider risk: benefits
• Olanzapine can be used to treat a woman who is pregnant or for treatment that is already in progress.
• Olanzapine can cause hyperprolactinemia in both males as well as females. This may lead to decreased reproductive function.

Use of Olanzapine while breastfeeding

• Breast milk contains Olanzapine.
• When compared to a maternal dose of 286 mg/kg/day, the relative infant dose (RID), of olanzapine was 1.7%.
• When the RID of the medication is less than 10%, breastfeeding is acceptable.
• Some sources state that breastfeeding should be considered only if the RID for psychotropic drugs is less than 5%.
• Calculating the RID of olanzapine using a milk content of 0.033 mg/mL yielded an estimated daily infant dose via breastmilk of 4.95 mg/kg/day.
• This milk concentration was achieved after maternal administration of olanzapine 266, mcg/kg/day.
• The paper also included breast milk concentrations for additional mother-infant couples.
• The average max milk concentration was found 5.2 hours after the maternal dosage. The RID was 1.02%. Data were taken from six women (range 0.93% to 1.12%).
• The study included women who received oral olanzapine from 5-20 mg/day (mean: 7.75 mg/day), took the medication for 19-395 consecutive days prior to sampling. Infants were between 0.1 and 4.3 months old.
• Olanzapine was detected in the serum of a nursing infant.
• CYP metabolism, which matures with age, may explain why concentrations were higher at 4 months and then decreased as time passed.
• Maternal symptoms vary, but the average maternal dose was between 5-15 mg/day.
• Breastfeeding infants have never experienced adverse events in most cases.
• The most frequent adverse events that were reported to the manufacturer included insomnia, irritability and somnolence.
• For the first month, infants who have been exposed to second-generation antipsychotics via breast milk should be closely monitored for signs such as lethargy, insomnia, appetite changes, and irritability.
• Olanzapine is recommended for breastfeeding, even though it is not recommended by the manufacturer. However, antipsychotic medication may be required in breastfeeding women.

Olanzapine (Zyprexa) Dose in Kidney Disease:

• No dosage adjustment is necessary.
• Not removed by dialysis.

Olanzapine (Zyprexa) Dose in Liver Disease:

• In the manufacturer’s labeling, there are no dosage adjustments provided except when used in combination with fluoxetine (as separate components) the initial olanzapine dose should be limited to 2.5-5 mg daily.
• Use cautiously (cases of hepatitis and liver injury have been reported with olanzapine use).

Common Side Effects of Oral Olanzapine (Zyprexa):

• Cardiovascular:

  • Orthostatic Hypotension

• Central Nervous System:

  • Drowsiness
  • Extrapyramidal Reaction
  • Akathisia
  • Parkinsonian-Like Syndrome
  • Dizziness
  • Headache
  • Fatigue
  • Insomnia

• Endocrine & Metabolic:

  • Increased Serum Prolactin
  • Weight Gain

• Gastrointestinal:

  • Increased Appetite
  • Xerostomia
  • Dyspepsia
  • Constipation

• Hepatic:

  • Increased Serum AST
  • Decreased Serum Bilirubin
  • Increased Serum ALT

• Neuromuscular & Skeletal:

  • Weakness

• Miscellaneous:

  • Accidental Injury

Less Common Side Effects Of Olanzapine (Zyprexa):

• Cardiovascular:

  • Chest Pain
  • Peripheral Edema
  • Tachycardia
  • Hypertension

• Central Nervous System:

  • Personality Disorder
  • Abnormal Gait
  • Hypertonia
  • Restlessness
  • Falling
  • Articulation Impairment

• Endocrine & Metabolic:

  • Increased Gamma-Glutamyl Transferase
  • Increased Uric Acid
  • Menstrual Disease
  • Breast Changes

• Gastrointestinal:

  • Abdominal Pain
  • Vomiting
  • Diarrhea

• Genitourinary:

  • Urinary Incontinence
  • Sexual Disorder
  • Urinary Tract Infection

• Hematologic & Oncologic:

  • Bruise

• Hepatic:

  • Increased Liver Enzymes
  • Increased Serum Alkaline Phosphatase

• Neuromuscular & Skeletal:

  • Tremor
  • Limb Pain
  • Arthralgia
  • Back Pain
  • Muscle Rigidity
  • Dyskinesia

• Ophthalmic:

  • Amblyopia

• Respiratory:

  • Rhinitis
  • Cough
  • Nasopharyngitis
  • Pharyngitis
  • Epistaxis
  • Respiratory Tract Infection
  • Sinusitis

• Miscellaneous:

  • Fever

Rare Side effects of Olanzapine (Zyprexa) Injection:

• Cardiovascular:

  • Hypertension
  • Hypotension
  • Prolonged Q-T Interval On ECG
  • Orthostatic Hypotension

• Central Nervous System:

  • Headache
  • Sedation
  • Drowsiness
  • Akathisia
  • Dizziness
  • Fatigue
  • Extrapyramidal Reaction
  • Abnormality In Thinking
  • Auditory Hallucination
  • Parkinsonian-Like Syndrome
  • Restlessness
  • Pain
  • Abnormal Dreams
  • Procedural Pain
  • Sleep Disorder
  • Dysarthria

• Dermatologic:

  • Acne Vulgaris

• Endocrine & Metabolic:

  • Weight Gain

• Gastrointestinal:

  • Diarrhea
  • Vomiting
  • Xerostomia
  • Increased Appetite
  • Nausea
  • Tooth Infection
  • Toothache
  • Abdominal Pain
  • Flatulence

• Genitourinary:

  • Vaginal Discharge

• Hepatic:

  • Increased Liver Enzymes

• Infection:

  • Viral Infection

• Local:

  • Pain At Injection Site
  • Abscess At Injection Site

• Neuromuscular & Skeletal:

  • Arthralgia
  • Back Pain
  • Muscle Spasm
  • Stiffness
  • Tremor

• Otic:

  • Otalgia

• Respiratory:

  • Cough
  • Nasal Congestion
  • Nasopharyngitis
  • Upper Respiratory Tract Infection
  • Pharyngolaryngeal Pain
  • Sneezing

• Miscellaneous:

  • Fever

Contraindications to Olanzapine (Zyprexa):

• There are no contraindications in the manufacturer's labeling.

Canadian labeling

 

• Hypersensitivity to olanzapine and any component of the formulation

Warnings and precautions

• Modified cardiac conduction

  • May alter the cardiac conduction and extend the QT interval.
  • Life-threatening arrhythmias can be caused by therapeutic doses antipsychotics.
  • Concomitant medication or conditions that cause hypokalemia, bradycardia, and hypomagnesemia may increase the risk.
  • Patients with conduction abnormalities should be cautious.

• Anticholinergic effects

  • Possible anticholinergic side effects: constipation, xerostomia and blurred vision.
  • Patients with reduced gastrointestinal motility, paralytic and ileus, urinary retentions, BPH, xerostomia, and visual problems (including narrow angle glaucoma) should be cautious.
  • Comparatively to other neuroleptics olanzapine is a mild cholinergic antagonist.

• Blood dyscrasias

  • Antipsychotic use has been linked to Leukopenia and Neutropenia in clinical trials and post-marketing reports.
  • Periodic blood count assessments should be done if there are any risk factors, such as low WBC (preexisting) or history of drug-induced neutro-/leukoemia.
  • Stop treatment at the first sign of blood dyscrasias, or if your absolute neutrophil count is 1,000/mm3.

• Effects on the cerebrovascular system:

  • In placebo-controlled studies of olanzapine's unapproved use in dementia-related psychosis patients aged over 60, there was an increase in cerebrovascular effects, including stroke, in some elderly patients.

• Depression in the CNS:

  • CNS depression can lead to mental and physical impairments.
  • It is important to warn patients about tasks that require mental alertness, such as driving or operating machinery.
  • Comparable to other antipsychotics it may be moderately to very sedating.
  • It has been shown that dose-related effects can be observed.

• Dyslipidemia

  • It has been shown that dose-related increases in cholesterol and triglycerides are possible.
  • Patients with abnormally high lipid profiles should be cautious.
  • Dyslipidemia is a higher risk than other antipsychotics.

• Esophageal dysmotility/aspiration

  • Antipsychotic use has been linked to esophageal dysmotility and aspiration.
  • Age increases the risk of developing a health condition.
  • Patients at high risk for aspiration pneumonia (ie Alzheimer's disease) should be treated with caution, especially patients over 75 years.

• Extrapyramidal symptoms

  • Extrapyramidal symptoms (EPS) may occur, including pseudo parkinsonism and acute dystonic reactions.
  • These reactions are generally less common than those caused by conventional antipsychotics. Frequency reports are comparable to placebo.
  • Higher doses of antipsychotics and use by younger patients may increase the risk of dystonia.
  • There are several factors that increase the vulnerability to tardive dyskinesia, including older age, female gender, postmenopausal status and Parkinson disease symptoms.
  • If you have tardive dyskinesia symptoms, discontinue therapy.

• Falls

  • Increased risk of falls from somnolence and orthostatic hypotension, as well as motor or sensory instability.
  • Patients with chronic diseases or taking medications that can increase fall risk should have their fall risk assessed at baseline and periodically throughout treatment.

• Hyperglycemia

  • Hyperglycemia has been linked to the use of antipsychotics.
  • Hyperglycemia can be severe in some cases and may lead to hyperosmolar or even death.
  • Olanzapine could be more associated with hyperglycemia that other antipsychotics atypicals.
  • Patients with diabetes and other disorders of glucose regulation should be cautious.
  • Watch out for a worsening glucose control.
  • Patients at high risk for diabetes (eg obesity or family history), should have a baseline fasting glucose (FBS) and periodic glucose regulation assessments.
  • Hyperglycemia can be dangerous when taken with antipsychotics.

• Hyperprolactinemia

  • It can cause an increase in serum prolactin level due to increased doses.
  • It is not known if hyperprolactinemia can be a clinical sign in breast cancer patients or other prolactin dependent tumours.
  • Prolactin levels were increased in clinical manifestations such as breast-, sexual- and menstrual-related events.

• Multiorgan hypersensitivity reactions (drug response with eosinophilia or systemic symptoms [DRESS]).

  • Multiple-organ hypersensitivity reactions (DRESS), which can be fatal and potentially serious, have been reported.
  • You may experience a cutaneous reaction (rash, exfoliative dermatitis), fever, eosinophilia and lymphadenopathy (eg, liver disease, nephritis or pneumonitis), myocarditis, pericarditis and pericarditis).
  • If DRESS is suspected, discontinue olanzapine.

• Neuroleptic malignant Syndrome (NMS).

  • NMS may be used in conjunction with the use.
  • Monitor for changes in mental status, fever, rigidity of the muscles, and autonomic instability.

• Orthostatic hypotension

  • Orthostatic hypotension may occur.
  • Patients at high risk for this effect and those who cannot tolerate temporary hypotension (cerebrovascular disease or cardiovascular disease), should be cautious.

• Suicidal thoughts:

  • Psychotic illness and bipolar disorder can lead to suicide attempts.
  • Use caution in high-risk patients when initiating therapy
  • Prescriptions for the smallest amount should be written in accordance with good patient care.

• Temperature regulation

  • It is possible to have impaired core body temperature regulation.
  • Be careful with heat exposure, strenuous exercise, heat, dehydration, or concomitant anticholinergic medication.

• Weight loss

  • Significant weight gain (>7%) has been seen with antipsychotic therapy.
  • Product-specific incidences vary.
  • Dose-related changes were observed with olanzapine.
  • Monitor your waist circumference and BMI.
  • When compared to other antipsychotics, the risk of weight gain can be high.

• Cardiovascular disease

  • Patients with severe heart disease, hemodynamic instability or hypercholesterolemia should be cautious.

• Dementia[US Boxed Warning]

  • Patients with dementia-related psychosis in their elderly are at greater risk of dying if they receive antipsychotics.
  • The majority of deaths were either from cardiovascular disease (eg heart failure, sudden death, etc.) or infectious diseases (eg pneumonia).
  • Patients with Parkinson's disease or Lewy body dementia should be cautious. There is a greater risk of adverse reactions, increased sensitivity for extrapyramidal effects and the possibility of irreversible cognitive decline or death.
  • Olanzapine has not been approved for the treatment of dementia-related psychosis.

• Hepatic impairment

  • Patients with hepatic impairment or disease should be cautious.
  • May increase transaminases, primarily ALT.

• Parkinson disease

  • Patients with Parkinson's disease should be treated with caution
  • Motor disturbances can be aggravated by antipsychotics.

• Renal impairment

  • Patients with kidney disease should be cautious.

• Seizures

  • Patients at high risk of seizures should be treated with caution, especially those who have had seizures in the past, are brain damaged, suffered from head trauma or have been drinking, and/or are receiving concurrent treatment with medication that could lower their seizure threshold.
  • Due to an increase in predisposing factors, elderly patients could be at greater risk for seizures.

Olanzapine: Drug Interaction

Risk Factor C (Monitor therapy)
Abiraterone Acetate	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors).
Acetylcholinesterase Inhibitors	May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors.
Acetylcholinesterase Inhibitors (Central)	May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients.
Alcohol (Ethyl)	CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl).
Alizapride	May enhance the CNS depressant effect of CNS Depressants.
Amifampridine	Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine.
Amphetamines	Antipsychotic Agents may diminish the stimulatory effect of Amphetamines.
Anticholinergic Agents	May enhance the adverse/toxic effect of other Anticholinergic Agents.
Antidiabetic Agents	Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Antihepaciviral Combination Products	May decrease the serum concentration of OLANZapine.
Blood Pressure Lowering Agents	May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).
Botulinum Toxin-Containing Products	May enhance the anticholinergic effect of Anticholinergic Agents.
Brexanolone	CNS Depressants may enhance the CNS depressant effect of Brexanolone.
Brimonidine (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Broccoli	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
BuPROPion	May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabis	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
CarBAMazepine	May decrease the serum concentration of OLANZapine.
Chloral Betaine	May enhance the adverse/toxic effect of Anticholinergic Agents.
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of CNS Depressants.
Clarithromycin	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Clarithromycin. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
CloZAPine	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
CNS Depressants	May enhance the adverse/toxic effect of other CNS Depressants.
CYP1A2 Inducers (Moderate)	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
CYP1A2 Inhibitors (Moderate)	May decrease the metabolism of CYP1A2 Substrates (High risk with Inhibitors).
Cyproterone	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
Deferasirox	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors).
Deutetrabenazine	May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased.
Dimethindene (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Doxylamine	May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended.
Dronabinol	May enhance the CNS depressant effect of CNS Depressants.
Droperidol	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Droperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Esketamine	May enhance the CNS depressant effect of CNS Depressants.
Flupentixol	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Flupentixol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
FluvoxaMINE	May increase the serum concentration of OLANZapine.
Gastrointestinal Agents (Prokinetic)	Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).
Glucagon	Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased.
Guanethidine	Antipsychotic Agents may diminish the therapeutic effect of Guanethidine.
Haloperidol	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
HydrOXYzine	May enhance the CNS depressant effect of CNS Depressants.
Itopride	Anticholinergic Agents may diminish the therapeutic effect of Itopride.
Kava Kava	May enhance the adverse/toxic effect of CNS Depressants.
LamoTRIgine	May enhance the sedative effect of OLANZapine.
Lithium	May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine.
Magnesium Sulfate	May enhance the CNS depressant effect of CNS Depressants.
Methylphenidate	Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents.
MetyroSINE	CNS Depressants may enhance the sedative effect of MetyroSINE.
MetyroSINE	May enhance the adverse/toxic effect of Antipsychotic Agents.
Mianserin	May enhance the anticholinergic effect of Anticholinergic Agents.
Minocycline	May enhance the CNS depressant effect of CNS Depressants.
Mirabegron	Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron.
Mirtazapine	CNS Depressants may enhance the CNS depressant effect of Mirtazapine.
Nabilone	May enhance the CNS depressant effect of CNS Depressants.
Nitroglycerin	Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption.
Obeticholic Acid	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors).
Ondansetron	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Peginterferon Alfa-2b	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors).
Pentamidine (Systemic	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Antidepressants (Moderate Risk)	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Antipsychotics (Moderate Risk)	May enhance the QTc-prolonging effect of OLANZapine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Amisulpride; CloZAPine; Droperidol; Flupentixol; OLANZapine; Pimozide.
QT-prolonging Class IC Antiarrhythmics (Moderate Risk)	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Kinase Inhibitors (Moderate Risk)	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Miscellaneous Agents (Moderate Risk	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Domperidone.
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk)	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Quinolone Antibiotics (Moderate Risk)	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Quinagolide	Antipsychotic Agents may diminish the therapeutic effect of Quinagolide.
Ramosetron	Anticholinergic Agents may enhance the constipating effect of Ramosetron.
RifAMPin	May decrease the serum concentration of OLANZapine.
Ritonavir	May decrease the serum concentration of OLANZapine.
Rufinamide	May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.
Saquinavir	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Saquinavir. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Selective Serotonin Reuptake Inhibitors	CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced.
Serotonin Modulators	May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline.
Teriflunomide	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
Tetrabenazine	May enhance the adverse/toxic effect of Antipsychotic Agents.
Tetrahydrocannabinol	May enhance the CNS depressant effect of CNS Depressants.
Tetrahydrocannabinol and Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Thiazide and Thiazide-Like Diuretics	Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics.
Tobacco (Smoked)	May diminish the therapeutic effect of OLANZapine. Tobacco (Smoked) may decrease the serum concentration of OLANZapine.
Topiramate	Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate.
Trimeprazine	May enhance the CNS depressant effect of CNS Depressants.
Valproate Products	May decrease the serum concentration of OLANZapine.
Voriconazole	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Risk Factor D (Consider therapy modification)
Anti-Parkinson Agents (Dopamine Agonist	Antipsychotic Agents (Second Generation [Atypical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider using an alternative antipsychotic agent when possible in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine or quetiapine, which may convey the lowest interaction risk.
Blonanserin	CNS Depressants may enhance the CNS depressant effect of Blonanserin.
Buprenorphine	CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants.
Chlormethiazole	May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.
Domperidone	QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
HYDROcodone	CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Iohexol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.
Iomeprol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.
Iopamidol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.
Mequitazine	Antipsychotic Agents may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to one of these agents when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged.
Methotrimeprazine	CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established.
Opioid Agonists	CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
OxyCODONE	CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Perampanel	May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination.
Pramlintide	May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract.
QT-prolonging Agents (Highest Risk)	May enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Secretin	Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin.
Sodium Oxybate	May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated.
Suvorexant	CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended.
Tapentadol	May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Zolpidem	CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol.
Risk Factor X (Avoid combination)
Aclidinium	May enhance the anticholinergic effect of Anticholinergic Agents.
Amisulpride	Antipsychotic Agents may enhance the adverse/toxic effect of Amisulpride. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Amisulpride	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk).
Azelastine (Nasal	CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
Benzodiazepines	OLANZapine may enhance the adverse/toxic effect of Benzodiazepines. Management: Avoid concomitant use of parenteral benzodiazepines and IM olanzapine due to risks of additive adverse events (e.g., cardiorespiratory depression). Olanzapine prescribing information provides no specific recommendations regarding oral administration.
Bromopride	May enhance the adverse/toxic effect of Antipsychotic Agents.
Bromperidol	May enhance the CNS depressant effect of CNS Depressants.
Cimetropium	Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium.
Eluxadoline	Anticholinergic Agents may enhance the constipating effect of Eluxadoline.
Glycopyrrolate (Oral Inhalation	Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation).
Glycopyrronium (Topical)	May enhance the anticholinergic effect of Anticholinergic Agents.
Ipratropium (Oral Inhalation	May enhance the anticholinergic effect of Anticholinergic Agents.
Levosulpiride	Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride.
Metoclopramide	May enhance the adverse/toxic effect of Antipsychotic Agents.
Orphenadrine	CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxatomide	May enhance the anticholinergic effect of Anticholinergic Agents.
Oxomemazine	May enhance the CNS depressant effect of CNS Depressants.
Paraldehyde	CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
Pimozide	May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk).
Piribedil	Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended.
Potassium Chloride	Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride.
Potassium Citrate	Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate.
Revefenacin	Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin.
Sulpiride	Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride.
Thalidomide	CNS Depressants may enhance the CNS depressant effect of Thalidomide.
Tiotropium	Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium.
Umeclidinium	May enhance the anticholinergic effect of Anticholinergic Agents.

Monitoring Parameters:

• Mental state
• Vital signs (as indicated by a doctor).
• Blood pressure (baseline); repeat 3 months after antipsychotic initiation. Then, yearly.
• Height, weight, BMI, waist circumference, and height (baseline) - Repeat at 4, 8 and 12 weeks after starting or changing therapy. Then quarterly.
• Switch to another antipsychotic if you want to gain >=5% of your initial weight.
• CBC (as indicated by a physician; patients with low WBC, or a history of drug-induced neutropenia/neutropenia should be monitored frequently for the first few months.
• Annually, and as indicated by a physician, electrolytes and liver function.
• Obesity, diabetes, dyslipidemia and hypertension (baseline; repeated annually).
• Fasting plasma glucose/HbA (baseline); repeat this 3 months after you start an antipsychotic and then every year.
• Fasting lipid panel (baseline); repeat 3 months after antipsychotics are started; if LDL levels are normal, repeat every 2-5 years or more if clinically necessary.
• Changes in menstruation, fertility, and development of galactorrhea (at each visit for 12 weeks after antipsychotics are initiated, or until the dose becomes stable, then annually).
• Abnormal involuntary movement or parkinsonian signs (baseline); repeat weekly until dose stabilization is achieved for at least two weeks after introduction, and 2 weeks following any significant dose increases.
• Tardive dyskinesia (every 12 Months; high-risk patients, every 6 Months).
• Ocular examination: Annually for patients over 40 years old; once every two years for younger patients
• Extended-release IM injection
  • Each dose is followed by sedation/delirium lasting for 3 hours

How to administer Olanzapine (Zyprexa)?

• Short-acting injection:
  • May be administered IM or IV (off-label route).
  • Do not administer injection subcutaneously.
  • For IM administration, inject slowly, deep into the muscle.
  • Administer by rapid IV push for off-label IV route.
  • If dizziness & drowsiness are noted, patient should remain recumbent until examination indicates postural hypotension & bradycardia are not a problem.
• Extended-release injection:
  • For IM gluteal injection only.
  • Do not administer IV or subcutaneously.
  • Aspirate to verify that no blood appears after needle insertion into muscle.
  • Do not massage the injection site.
  • Use diluent, syringes & needles provided in convenience kit.
  • Obtain a new kit if the aspiration of blood occurs.
• Tablet:
  • May be administered without regard to meals.
• Orally-disintegrating:
  • Remove from foil blister by peeling back (do not push the tablet through the foil).
  • Place the tablet in the mouth immediately upon removal.
  • The tablet dissolves rapidly in saliva and may be swallowed with or without liquid.
  • May be administered with or without food/meals.

Mechanism of action of Olanzapine (Zyprexa):

• Olanzapine, a second-generation thienobenzodiazepine-antimotic, acts as a powerful antagonist of serotonin 5HT-2A and 5HT-2C, dopamine 1-4, histamine h-1 and alpha -1 adrenergic receptors.
• It also moderately antagonistically affects 5-HT-3 and the muscarinic M1-5 receptors.
• While the exact mechanism of action of olanzapine in schizophrenia and bipolar disorder is unknown, it is believed that the drug acts by antagonizing dopamine and serotonin type 2, which is what is responsible for its efficacy.

The onset of action:

• • Within 1-2 weeks for control of aggression, agitation, insomnia.
  • 3-6 weeks for control of mania and positive psychotic symptoms.
• Adequate trial:
  • Typically 6 weeks at max tolerated doses

Absorption:

• P/O:
• Well absorbed.
• Not affected by food.
• Tablets and orally disintegrating tablets are bioequivalent
• Short-acting injection:
• Rapidly absorbed.

Protein binding, plasma:

• 93% bound to albumin & alpha -glycoprotein

Metabolism:

• Highly metabolized via direct glucuronidation and cytochrome P450 mediated oxidation (CYP1A2, CYP2D6).
• 40% removed via first-pass metabolism

Half-life elimination:

• Oral and IM (short-acting):
• Children:
• (10-18 years; n=8):
  • 37.2 ± 5.1 hours.
• Adults:
  • 30 hours [21-54 hours (5th to 95th percentile)].
  • Approximately 1.5 times greater in elderly
• Extended-release injection:
  • ~30 days

Time to peak, plasma:

• Max plasma concentrations after IM administration are 5 times higher than max plasma concentrations produced by an oral dose.
• Extended-release injection:
  • ~7 day
• Short-acting injection:
  • 15-45 mins
• P/O:
  • Children (10-18 years; n=8):
    • 4.7 ± 3.7 hours.
  • Adults:
    • ~6 hours

Excretion:

• Urine (57%, 7% as unchanged drug).
• Feces (30%)

Clearance:

• P/O:
• Children (10 to 18 years; n=8):
  • Apparent:
    • 9.6 ± 2.4 L/hour.
• Adults:
  • Apparent:
    • 25 L/hour [12 to 47 L/hour (5th to 95th percentile)].
    • 40% increase in olanzapine clearance in smokers.
    • 30% decrease in females

International Brand Names of Olanzapine:

• ZyPREXA
• ZyPREXA Relprevv
• ZyPREXA Zydis
• Abbott-OLANZapine ODT
• ACCEL-OLANZapine
• ACT OLANZapine ODT
• ACT OLANZapine
• APO-OLANZapine
• APO-OLANZapine ODT
• Auro-Olanzapine ODT
• JAMP OLANZapine FC
• JAMP OLANZapine ODT
• Mar-OLANZapine ODT
• Mar-OLANZapine
• MINTOLANZapine ODT
• MYLAN-OLANZapine ODT
• MYLAN-OLANZapine
• PHLOLANZapine ODT
• PHL-OLANZapine
• PMS-OLANZapine
• PMS-OLANZapine ODT
• RAN-OLANZapine
• RAN-OLANZapine ODT
• RIVA-OLANZapine
• RIVA-OLANZapine ODT
• SANDOZ OLANZapine
• SANDOZ OLANZapine ODT
• TEVA-OLANZapine
• TEVA-OLANZapine OD
• TEVA-OLANZapine ODT
• VAN-OLANZapine
• ZyPREXA
• ZyPREXA Zydis
• Aedon
• Arenbil
• Benexafrina OD
• Benzopain
• Dozic
• Egolanza
• Exzapine
• Lanzek
• Lanzek Zydis
• Lanzine
• Lanzine ODT
• Lapozan
• Lopez
• Marathon
• Meflax
• Midax
• Nodoff
• Nykob
• Okpine
• Olan
• Olandoz
• Olankline
• Olanpin
• Olanza
• Olanza OD
• Olanza ODT
• Olanzamed
• Olanzapro
• Olanzax
• Olapin-10
• Olapine
• Olazax
• Olazax Disperzi
• Oleanz
• Olmed
• Onzapin
• Onzapin OD
• Onzapin ODT
• Ozapex
• Ozin
• Placet
• Prexal
• Remital
• Rolyprexa
• Schisolazine
• Tolanz
• Tolaz MD
• Torolan
• Xytrex
• Zalasta
• Zanprex
• Zapilux
• Zapine
• Zappa
• Zelta
• Zeprex
• Zolafren
• Zozapin
• Zypadhera
• ZypAdhera
• Zypeace OD
• Zypine
• Zypine ODT
• Zyprexa
• Zyprexa Velotab
• Zyprexa Zydis
• Zyrepin

Olanzapine Brand Names in Pakistan:

Olanzapine Tablets 5 Mg in Pakistan
Absolute	Xenon Pharmaceuticals (Pvt) Ltd.
Amprexa	Amarant Pharmaceuticals (Pvt)
Amprexa	Shrooq Pharmaceuticals
Avenia	Paramount Pharmaceuticals
Aziva	Noa Hemis Pharmaceuticals
Cirinzapine	Cirin Pharmaceuticals (Pvt) Ltd.
Furmium	Indus Pharma (Pvt) Ltd.
Lepinza	Organic Pharmaceuticals.
Linzap	Hiranis Pharmaceuticals Pvt Ltd
Mirapine	Miracle Pharmaceuticals(Pvt) Ltd
Nirvanol	Standpharm Pakistan (Pvt) Ltd.
Nozapin	Novins International
O-Zip	Glitz Pharma
Olan	Medizan Labs (Pvt) Ltd
Olan-Z	Lowitt Pharmaceuticals (Pvt) Ltd
Olanpia	Aries Pharmaceuticals (Pvt) Ltd
Olansaf	Saaaf Pharmaceuticals
Olanz	Gray`S Pharmaceuticals
Olanzi	Opal Laboratories (Pvt) Ltd.
Olanzia	Werrick Pharmaceuticals
Olanzil	Candid Pharmaceuticals
Olanzin	Rasco Pharma
Olanzip	Ferroza International Pharmaceuticals (Pvt) Ltd.
Olaz	Tg Pharma
Oleanz	Genome Pharmaceuticals (Pvt) Ltd
Olepra	Genetics Pharmaceuticals
Olifass	Fassgen Pharmaceuticals
Olimag	Caraway Pharmaceuticals
Olpresa	Maark Pharma
Olzar	Bryon Pharmaceuticals (Pvt) Ltd.
Onza	Shaheen Pharmaceuticals
Opine	Medicaids Pakistan (Pvt) Ltd.
Ozapine	Medicraft Pharmaceuticals (Pvt) Ltd.
Phrenno	Saydon Pharmaceutical Industries (Pvt) Ltd.
Pinaz	Bio Labs (Pvt) Ltd.
Pinsure	Medisure Laboratories Pakistan (Pvt.) Ltd.
Supzine	Maple Pharmaceuticals (Pvt) Ltd
Swazapin	Swan Pharmaceuticals(Pvt) Ltd
Unexapine	Tg Pharma
Zanzia	English Pharmaceuticals Industries
Zapin	Glitz Pharma
Zapsel	Hansel Pharmacueutical Pvt (Ltd)
Zestine	Pulse Pharmaceuticals
Zopera	Linear Pharma
Zydis	Eli Lilly Pakistan (Pvt) Ltd.
Zypirex	Everest Pharmaceuticals
Zyprexa	Eli Lilly Pakistan (Pvt) Ltd.

 

Olanzapine Tablets 10 Mg in Pakistan
Absolute	Xenon Pharmaceuticals (Pvt) Ltd.
Amprexa	Amarant Pharmaceuticals (Pvt)
Amprexa	Shrooq Pharmaceuticals
Avenia	Paramount Pharmaceuticals
Aziva	Noa Hemis Pharmaceuticals
Cirinzapine	Cirin Pharmaceuticals (Pvt) Ltd.
Furmium	Indus Pharma (Pvt) Ltd.
Lapin	Wise Pharmaceuticals (Pvt) Ltd
Lepinza	Organic Pharmaceuticals.
Linzap	Hiranis Pharmaceuticals Pvt Ltd
Mirapine	Miracle Pharmaceuticals(Pvt) Ltd
Nirvanol	Standpharm Pakistan (Pvt) Ltd.
Nozapin	Novins International
Olan	Medizan Labs (Pvt) Ltd
Olan-Z	Lowitt Pharmaceuticals (Pvt) Ltd
Olanpia	Aries Pharmaceuticals (Pvt) Ltd
Olansaf	Saaaf Pharmaceuticals
Olanz	Gray`S Pharmaceuticals
Olanzi	Opal Laboratories (Pvt) Ltd.
Olanzia	Werrick Pharmaceuticals
Olanzin	Rasco Pharma
Olanzip	Ferroza International Pharmaceuticals (Pvt) Ltd.
Olaz	Tg Pharma
Oleanz	Genome Pharmaceuticals (Pvt) Ltd
Olepra	Genetics Pharmaceuticals
Olifass	Fassgen Pharmaceuticals
Olimag	Caraway Pharmaceuticals
Olinzib	Bloom Pharmaceuticals (Pvt) Ltd.
Olpresa	Maark Pharma
Olzar	Bryon Pharmaceuticals (Pvt) Ltd.
Onza	Shaheen Pharmaceuticals
Ozapine	Medicraft Pharmaceuticals (Pvt) Ltd.
Ozip	Global Pharmaceuticals
Phrenno	Saydon Pharmaceutical Industries (Pvt) Ltd.
Pinaz	Bio Labs (Pvt) Ltd.
Supzine	Maple Pharmaceuticals (Pvt) Ltd
Swazapin	Swan Pharmaceuticals(Pvt) Ltd
Unexapine	Tg Pharma
Zanzia	English Pharmaceuticals Industries
Zapin	Glitz Pharma
Zapsel	Hansel Pharmacueutical Pvt (Ltd)
Zestine	Pulse Pharmaceuticals
Zopera	Linear Pharma
Zydis	Eli Lilly Pakistan (Pvt) Ltd.
Zyprexa	Eli Lilly Pakistan (Pvt) Ltd.
Zyripine	Zain Pharmaceutical

 

Olanzapine Tablets 7.5 Mg in Pakistan
Nilcosyn	Indus Pharma (Pvt) Ltd.
Olanzia	Werrick Pharmaceuticals
Olzar	Bryon Pharmaceuticals (Pvt) Ltd.
Pinsure	Medisure Laboratories Pakistan (Pvt.) Ltd.
Zapsel	Hansel Pharmacueutical Pvt (Ltd)
Zyprexa	Eli Lilly Pakistan (Pvt) Ltd.

 

Olanzapine Capsules 5 Mg in Pakistan
Olanziscot	Scotmann Pharmaceuticals
Prelap	Aptcure Private Limited

 

Olanzapine Capsules 10 Mg in Pakistan
Olanziscot	Scotmann Pharmaceuticals
Prelap	Aptcure Private Limited

 

Olanzapine Capsules 12 Mg in Pakistan
Olanco	Genome Pharmaceuticals (Pvt) Ltd