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.
  • Treatment of acute or mixed mania episodes linked to bipolar I illness (as monotherapy or in conjunction with lithium or valproate).
  • Maintenance treatment of bipolar I disorder.
  • Combined with fluoxetine for bipolar I or treatment-resistant depression
• IM, extended-release (Zyprexa Relprevv):
  • Schizophrenia treatment.
• IM, short-acting (Zyprexa Intra Muscular):
  • Treatment of acute agitation is linked to schizophrenia and manic phases of bipolar I disorder.

• 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 might be investigated when clinical conditions permit) (a lower dose of 5-7.5 mg may be considered when clinical factors warrant).
• Additional dosages of up to 10 mg could be taken into account.
• However, there should be a 2-hour interval between the first and second dosages to gauge responsiveness (maximum daily dose: 30 mg).

Special risk patients:

• Patients who are frail, have a history of hypotensive reactions, or who might be more pharmacodynamically sensitive to olanzapine should be prescribed a lower dose of 2.5 mg.
• Only when patients can be thoroughly monitored, such as in emergency rooms, has the IV approach been studied for treating respiratory d
• The World Federation of Societies of Biological Psychiatry (WFSBP) expert consensus panel recommends, with certain exceptions
• Short-acting injection:
• IM:

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

Note:

• • Monotherapy: IV:
  • Initial:
    • 10 mg.
    • If needed, may provide two additional 5 mg doses in 5-min intervals.
  • Max:
    • 20 mg.

Note:

• However, using parenteral olanzapine and benzodiazepines simultaneously is not recommended due to the possibility of significant drowsiness and cardiorespiratory depression. Midazolam has been studied in combination with lower doses of 5 mg in a single dose.

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

• Monotherapy:
  • Initial:
    • Once daily, take 10-15 mg.
    • Increase by 5 milligrammes each day, spaced no less than 24 hours apart.
  • 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:
• 10 mg once daily on days 2-4, and 10 mg on the first day of chemotherapy come next (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:

• Nonpharmacologic therapies and the treatment of underlying disorders are first measures in the prevention and management of delirium.
• Antipsychotics may be utilised as a short-term supplementary treatment if disturbing symptoms (such as agitation or anxiety) are present.
• P/O: Initial:
  • 5–10 mg once daily (2.5 mg once daily in patients older than 60 years old).
  • Once the required clinical response is attained, titrate daily in 5 mg increments up to 20 mg/day as necessary.
  • Watch the QTc and ECG intervals.
  • After symptoms go away, olanzapine therapy should be decreased over a few days.
  • This plan is supported by professional judgement.
  • Safety and efficacy have not been formally assessed.

• Short-acting injection: IM:

  • 5-10 mg.
  • Repeat as necessary every 2-4 hours (maximum daily dose: 30 mg).

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

• P/O: Initial:
  • 2.5 mg once daily.
  • Increase gradually depending on response and tolerability, up to 5–10 mg/day.
• 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 to the typical daily range of 5-12.5 mg as tolerated.
  • See "Note."

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

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

Note (olanzapine/fluoxetine combination [Symbyax]):

• When combining separate components of fluoxetine with olanzapine as opposed to a fixed-dose combination product (Symbyax), the 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:
  • 2.5–5 mg once daily is advised for patients with a propensity for hypotensive responses, hepatic impairment, a combination of characteristics that may slow down the metabolism of olanzapine (e.g., female, elderly, nonsmoker status), or who may be more pharmacodynamically sensitive to olanzapine.
  • Carefully raise the dose as clinically indicated.

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

• P/O: Initial:
  • 5-10 mg daily.
  • Depending on response and tolerance, adjust the dose up to 20 mg per day every one to two weeks.

Olanzapine (Zyprexa) Dose in the treatment of Schizophrenia:

• P/O:

• Initial:
  • 5-10 mg once daily (within 5 to 7 days, increase to 10 mg once daily).
  • After then, adjust by 5 mg per day at 1-week intervals, up to the maximum daily dose that is advised.
• Maintenance:
  • 10–20 mg once each day.
  • For schizophrenia that is resistant to therapy, doses up to 60 mg per day have been used.
  • However, there is little supporting data (APA [Lehman 2004]).

• Special risk patients:

  • Initial:
    • In patients who are elderly, have a history of hypotensive responses, are debilitated, demonstrate a combination of variables that may slow the metabolism of olanzapine, such as nonsmoking female patients, or who may be more pharmacodynamically sensitive to olanzapine, daily, 5 mg once is advised.
    • Carefully increase the dose as clinically necessary.

• Extended-release injection: IM:

Note:

• Tolerance to oral olanzapine should be established before switching to extended-release injectable.
• Max dose:
  • 300 mg every 2 weeks or 405 mg every 4 weeks.
  • Patients established on oral olanzapine 10 mg daily:
    • Initial dose:
      • four dosages of 210 mg every two weeks or two doses of 405 mg every four weeks.
    • Maintenance dose:
      • 150 mg once every two weeks or 300 mg once every four.
  • Patients established on oral olanzapine 15 mg daily:
    • Initial dose:
      • Every two weeks, 300 mg for 4 doses.
    • Maintenance dose:
      • 405 mg every four weeks, or 210 mg every two.
  • Patients established on oral olanzapine 20 mg daily:
    • Initial & maintenance dose:
      • 300 mg every 2 weeks.

• Special risk patients:

  • Initial:
    • In patients who are elderly, have a history of hypotensive responses, are debilitated, demonstrate a combination of variables that may slow the metabolism of olanzapine, such as nonsmoking female patients, or who may be more pharmacodynamically sensitive to olanzapine, 150 mg is advised every 4 weeks.
    • Carefully increase the dose as clinically necessary.

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

• Initial:
  • 2.5-5 mg daily.
  • Gradually increase to the typical dosage range of 2.5–20 mg per day based on response and tolerability.
  • Clinical trials typically employed weekly or biweekly dosage changes after the initial dose of 2.5 to 5 mg, with a daily maximum of 20 mg.

• Discontinuation of therapy:

  • Gradual dose decrease is indicated to prevent withdrawal symptoms (such as sleeplessness, headaches, and GI issues), unless stopping is necessary owing to serious side effects.
  • To enable the detection of prodromal symptoms of disease return in patients with schizophrenia or bipolar disorder when terminating chronic antipsychotic medication, reducing the dose very gradually over months to years with close monitoring is advised.

• Switching antipsychotics:

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

  • A sudden change and cross-titration (gradually stopping the first antipsychotic and gradually increasing the new antipsychotic) (abruptly discontinuing the first antipsychotic & either increasing the new antipsychotic gradually or starting it at a treatment dose).
  • In individuals with schizophrenia who are at a high risk of relapsing, the current medication may be kept at its full dose while the new medicine is raised (ie, overlap).
  • Once the new medicine is at the therapeutic dose, the first medication is gradually reduced and withdrawn over the course of one to two weeks.
  • According to some specialists, cross-titration and overlap strategies are preferable to sudden change based on clinical experience.

Olanzapine (Zyprexa) Dose in Children

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.
    • To reach the goal dose of 10 mg once daily, increase the dose by 2.5 or 5 mg per week.
  • Max dose:
    • 20 mg/day.

• Adolescents:

  • Initial:
    • 2.5-5 mg once daily.
    • To reach the goal dose of 10 mg once daily, increase the dose every week by 2.5 or 5 mg.
  • Max dose:
    • 20 mg/day.
    • The mean modal dose in clinical trials for adolescents receiving flexible dosing (2.5–20 mg/day) 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.
  • To reach the goal dose of 10 mg once daily, increase the dose by 2.5 or 5 mg per week.
• Max dose:
  • 20 mg/day.
• Note:
  • In one trial, dosages as high as 30 mg/day were used to teenagers who had failed to respond to treatment.
  • Some patients, meanwhile, could not handle doses greater than 20 mg/day (Kumra, 2008).
  • Doses more than 20 mg/day have not been thoroughly assessed for safety and effectiveness.
  • In adolescent flexible-dosing (2.5-20 mg/day) clinical trials, the mean dose was 11.1 mg/day, while the mean modal dose was 12.5 mg/day.
  • The two double-blind comparison trials that included both children and adolescents (n=35, age: 8–19 years with seven children; n=13, age: 7–16 years; mean age: 12.8 + 2.4 years) served as the foundation for the dosing recommendations for children.

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

• Children ≥9 years and Adolescents:

• Limited data available:

• P/O:
  • 1.25 to 2.5 mg once daily have been shown in one small trial and numerous case reports to improve BMI and other disease-related symptoms (such as eating habits and anxiety).
• Reported range:
  • 1.25-12.5 mg/day.
  • Higher doses (>2.5 mg once daily) might not, however, be more effective, according to certain theories.

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:
    • 2.5 mg every other day for three days, then 2.5 mg every day for the rest of the week.
    • By the second week, if necessary, increase to 5 mg/day.
    • Then, if tolerated, increase in 5 mg increments per week.
  • Max dose:
    • 20 mg/day
• Patient weight >40 kg:
  • Initial:
    • 2.5 mg every day for three days.
    • The balance of the week, if necessary, should be increased to 5 mg per day, followed by weekly increases of 5 mg as tolerated.
  • Max dose:
    • 20 mg/day
• At a mean final dose of 14.5 mg/day after 8 weeks of therapy, an open-label research involving 10 juvenile patients (7–13 years old) found statistically significant decreases in tic severity [Yale Global Tic Severity Scale (YGTSS)] from baseline.
• An open-label experiment with 12 children and adolescents (7–14 years old) found a significant reduction (30%) in the overall severity of tics 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 mental health environment; dosage based on a retrospective study of 50 paediatric patients treated with IM olanzapine (children; n=15; mean age: 11 years).
  • Teenagers (n=35; average age: 15 years)] & assessed the 163 given dosages.
  • A 90.2% response rate was seen in the results.

Olanzapine (Zyprexa) Pregnancy Risk Factor: C

• Studies on animal reproduction have revealed negative outcomes.
• When a baby is born, olanzapine can be found in the cord blood because it crosses the placenta.
• Antipsychotic usage in the third trimester is linked to extrapyramidal syndromes (EPS), which are aberrant muscle movements, and withdrawal symptoms in newborns.
• Agitation, feeding issues, and hypotonia can all affect a newborn.
• These side effects may subside on their own or may necessitate hospitalisation.
• Individualized care during pregnancy is advised by ACOG.
• The mental healthcare professional, obstetrician, and primary care provider should all contribute their clinical knowledge to the treatment with psychiatric medication during pregnancy.
• There are very few safety studies on the use of atypical antipsychotics during pregnancy. Regular use is not advised.
• Continued therapy may be more advantageous than stopping treatment if a woman unintentionally takes an atypical antipsychotic while pregnant.
• 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%.
• Using a milk content of 0.033 mg/mL to calculate the RID of olanzapine, an estimated daily infant dosage via breastmilk of 4.95 mg/kg/day was obtained.
• Following maternal dose of olanzapine 266, mcg/kg/day, this milk concentration was attained.
• 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.
• Even though the manufacturer does not advise it, olanzapine is approved for nursing. However, breastfeeding mothers might need to take antipsychotic medication.

Olanzapine (Zyprexa) Dose in Kidney Disease:

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

Olanzapine (Zyprexa) Dose in Liver Disease:

• Except when taken in conjunction with fluoxetine (as distinct components), the first olanzapine dose should be kept at 2.5–5 mg per day, according to the manufacturer's instructions.
• 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):

• The labelling from the manufacturer does not list any contraindications.

Canadian labeling

• Hypersensitivity to olanzapine and/or any formulation ingredient

Warnings and precautions

• Modified cardiac conduction

  • The QT interval may be prolonged and cardiac conduction altered.
  • 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 have been reported, have the potential to be lethal and serious.
  • Myocarditis, nephritis, or pneumonitis, as well as a cutaneous reaction (rash, exfoliative dermatitis), fever, eosinophilia, and lymphadenopathy are possible side effects.
  • Stop taking olanzapine if DRESS is thought to be present.

• Neuroleptic malignant Syndrome (NMS).

  • NMS can be utilised in addition to the utilisation.
  • Keep an eye out for changes in mood, fever, muscle rigidity, 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.
  • Keep an eye on your waist measurement and BMI.
  • The risk of weight gain can be higher with this antipsychotic than with other antipsychotics.

• Cardiovascular disease

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

• Dementia[US Boxed Warning]

  • If given antipsychotics, patients with dementia-related psychosis in their old are more likely to pass away.
  • 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. 
  • The use of olanzapine to treat psychosis brought on by dementia is not authorised.

• Hepatic impairment

  • Patients with hepatic impairment or disease should be cautious.
  • Could raise transaminases, especially 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

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:
  • Is able to be given IV or IM (off-label route).
  • Subcutaneous injections should not be given.
  • When administering intramuscularly, inject slowly and deeply.
  • For an IV route that is not on the label, administer quickly.
  • If vertigo and sleepiness are noticed, the patient should stay in a reclined position until an examination shows bradycardia and postural hypotension are not an issue.
• Extended-release injection:
  • Only for IM gluteal injection.
  • Don't give intravenously or subcutaneously.
  • Aspirate to make sure no blood is seen after a needle is inserted into a muscle.
  • Never rub the injection site.
  • Use the diluent, syringes, and needles included in the first aid package.
  • If there is blood aspiration, get a new kit.
• Tablet:
  • May be given without consideration to food.
• Orally-disintegrating:
  • Peel back the foil blister to remove (do not push the tablet through the foil).
  • As soon as the tablet is removed, put it in your mouth.
  • The tablet can be eaten with or without fluids because it dissolves quickly in saliva.
  • Applied with or without food or 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.
• Moreover, it has a somewhat antagonistic effect on 5-HT-3 and muscarinic M1-5 receptors.
• Olanzapine's precise mode of action in schizophrenia and bipolar illness is uncertain, although it is thought that the medicine antagonises dopamine and serotonin type 2 to produce its desired effects.

The onset of action:

• • For the treatment of aggression, agitation, and insomnia during a week or two.
  • 3–6 weeks for mania and positive psychotic symptoms to be under control.
• Adequate trial:
  • Usually six weeks at the highest doses tolerable

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 metabolised by cytochrome P450-mediated oxidation and direct glucuronidation (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:

• Peak plasma concentrations achieved by an oral dosage are 5 times lower than those produced by IM treatment.
• 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: