Olanzapine

Name: Olanzapine

What Is Zyprexa (Olanzapine)?

Zyprexa is the brand name of olanzapine, a prescription drug used to treat schizophrenia and bipolar disorder. It's also used to treat depression when used with other medications.

Zyprexa is part of a class of drugs known as atypical antipsychotics, which work to help restore the balance of dopamine, a natural substances in your brain known as a neurotransmitter. By taking this drug you may be able to decrease hallucinations, reduce feelings of agitation, and think more clearly and positively.

This medication is also used for preventing chemotherapy-induced nausea and vomiting. Unless directed by your doctor, never use Zyprexa for off-label use.

Manufactured by Eli Lilly, Zyprexa was approved by the Food and Drug Administration (FDA) for the treatment of psychotic disorders in 1996.

In 2009, the FDA approved Zyprexa Relprevv extended-release injectable suspension to treat adults with schizophrenia. The intramuscular injection, which comes in 210 milligram (mg), 300 mg, and 405 mg, can sustain the delivery of the drug for up to four weeks.

Teva Pharmaceuticals USA, Dr. Reddy's Labs, and other companies manufacture olanzapine tablets and the disintegrating tablet is made by Dr. Reddy's, Apotex Par Pharmaceutical Companies, and other companies. Eli Lilly and Co. make the extended-release injection, Zyprexa Relprevv.

Zyprexa Warnings

Zyprexa may help control your symptoms, but it is not a cure. It takes several weeks or longer before you will feel the full effects of the drug. Never stop taking Zyprexa without first speaking with your doctor, even if you don't feel well.

Adults with dementia who use Zyprexa may face a slightly increased risk of serious side effects like stroke, heart failure, fast/irregular heartbeat, and pneumonia. The drug is not approved to treat dementia-related behavioral problems.

Because of risk for severe sedation (including coma) and delirium after each injection, patients must be observed for at least three hours in a registered facility with ready access to emergency response services.

Taking this drug may cause you to develop hyperglycemia, an increase in your blood sugar, even if you don't have diabetes. If you suffer from schizophrenia, you already have a great chance of diabetes and this drug only increases that risk.

If you notice that you are urinating frequently, have extreme thirst, blurred vision, or weakness, let your doctor know right away because these could be signs of high blood sugar, which can lead to serious health problems.

Zyprexa might also cause you to have a fast or slow heartbeat, dizziness, and lightheadedness. You might also faint if you get up too fast when lying down. This is more likely to occur when you begin the medication. In addition, Zyprexa may lead to increased fat levels in your blood.

Using Zyprexa has been known to make cooling down after exposure to extreme heat or vigorous exercise more difficult.

Anyone who has the inherited condition, phenylketonuria, which requires a special diet to prevent mental retardation, should be aware that the disintegrating tablets have aspartame, which forms phenylalanine.

While this medication is approved to treat teenagers, it is only one part of a total program that should include counseling and educational support. Teenagers who take this drug are more likely to gain weight than adults as well as to develop increased levels of fat in their blood and liver problems. They might also suffer from side effects ranging from breast discharge and breast enlargement to sleepiness.

Tell you doctor if you have ever had a stroke or mini-stroke or heart attack, or if you have heart disease, an irregular heartbeat, seizures, breast cancer, or any condition that may make it hard for you to swallow.

Be sure to discuss high and low blood pressure, low white blood cell counts, and high levels of fat in your blood.

Other conditions that could keep you from using Zyprexa include:

  • Liver or prostate disease
  • Paralytic ileus, whereby food can't move through your intestine
  • Glaucoma
  • High blood sugar
  • Stomach or bowel problems, including decreased muscle movement
  • Enlarged prostate
  • A history of breast, pancreas, or pituitary cancer or if you are at risk of breast cancer
  • Neuroleptic malignant syndrome (NMS)
  • Aspiration pneumonia
  • A family history of diabetes
  • Severe vomiting or diarrhea
  • Suicidal thoughts/attempts
  • Alzheimer's disease or dementia

Before your doctor prescribes this medication and during your treatment, let him/her know if you are dehydrated. In addition, tell your physician if you've ever had to quit taking a mental illness drug in the past because of severe side effects.

In the event you have surgery, including dental surgery, be sure the person operating knows you are on Zyprexa.

Pregnancy and Zyprexa

You should not take Zyprexa if you are pregnant or planning to become pregnant. In addition, you can't use this drug if you are breastfeeding.

Olanzapine Overview

Olanzapine is a prescription medication used to treat schizophrenia. It is also used to treat bipolar disorder. Olanzapine belongs to a group of drugs called atypical antipsychotics, which work by altering the activity and levels of certain natural chemicals in the brain.

This medication comes in a tablet and an orally disintegrating tablet. Olanzapine is taken once a day, with or without food.

The orally disintegrating tablet is placed on the tongue, and the tablet will disintegrate quickly in your saliva so that you can easily swallow it with or without drinking liquid. Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing.

Olanzapine is also available in a short-acting injection and in a long acting injection and is to be given directly into the muscle. 

Common side effects of olanzapine include lack of energy, dry mouth, increased appetite, somnolence, and tremor (shakes). 

Olanzapine and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant. It is not known if olanzapine will harm your unborn baby.

Olanzapine Usage

  • Take olanzapine exactly as prescribed. Your doctor may need to change (adjust) the dose of olanzapine until it is right for you.
  • If you miss a dose of olanzapine, take the missed dose as soon as you remember. If it is almost time for the next dose, just skip the missed dose and take your next dose at the regular time. Do not take two doses of olanzapine at the same time.
  • To prevent serious side effects, do not stop taking olanzapine suddenly. If you need to stop taking olanzapine, your doctor can tell you how to safely stop taking it.
  • If you take too much olanzapine, call your doctor or poison control center at 1-800-222-1222 right away, or get emergency treatment.
  • Olanzapine can be taken with or without food.
  • Olanzapine is usually taken one time each day.

Orally disintegrating tablets:

  • Be sure that your hands are dry.
  • Keep the tablet in its blister pack until you are ready to take it. Open the package and peel back the foil from the tablet blister. Do not push a tablet through the foil or you may damage the tablet.
  • As soon as you open the blister, remove the tablet and put it into your mouth.
  • The tablet will disintegrate quickly in your saliva so that you can easily swallow it with or without drinking liquid. Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing.

Olanzapine Intramuscular Injection:

  • Is intended for intramuscular use only.
  • Do not administer intravenously or subcutaneously.
  • Inject slowly, deep into the muscle mass.

Call your doctor if you do not think you are getting better or have any concerns about your condition while taking olanzapine.

What should I discuss with my healthcare provider before taking olanzapine?

Olanzapine is not approved for use in psychotic conditions related to dementia. Olanzapine may increase the risk of death in older adults with dementia-related conditions.

You should not take olanzapine if you are allergic to it.

Long-term use of olanzapine can cause a serious movement disorder that may not be reversible. Symptoms include uncontrollable muscle movements of your lips, tongue, eyes, face, arms, or legs. The longer you take olanzapine, the more likely you are to develop this movement disorder. The risk of this side effect is higher in women and older adults.

To make sure olanzapine is safe for you, tell your doctor if you have ever had:

  • liver disease;

  • heart disease, high or low blood pressure;

  • low white blood cell (WBC) counts;

  • high cholesterol or triglycerides;

  • heart failure, heart attack, or stroke;

  • breast cancer;

  • seizures or epilepsy;

  • diabetes;

  • an enlarged prostate or difficulty urinating;

  • bowel problems; or

  • narrow-angle glaucoma.

Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Taking antipsychotic medication during the last 3 months of pregnancy may cause problems in the newborn, such as withdrawal symptoms, breathing problems, feeding problems, fussiness, tremors, and limp or stiff muscles. However, you may have withdrawal symptoms or other problems if you stop taking your medicine during pregnancy. If you become pregnant while taking olanzapine, do not stop taking it without your doctor's advice.

Olanzapine can pass into breast milk and may harm a nursing baby. You should not breast-feed while using olanzapine.

The olanzapine orally disintegrating tablet (Zyprexa Zydis) may contain phenylalanine. Talk to your doctor before using this form of olanzapine if you have phenylketonuria (PKU).

Olanzapine dosing information

Usual Adult Dose for Bipolar Disorder:

Monotherapy:
-Initial dose: 10 or 15 mg orally once a day
-Dose adjustments: If indicated, dose adjustments should occur at intervals of at least 24 hours in 5 mg increments/decrements.
-Maintenance dose: 5 to 20 mg orally once a day
-Maximum dose: 20 mg/day

Adjunctive Treatment with Lithium or Valproate:
-Initial dose: 10 mg orally once a day
-Maintenance dose: 5 to 20 mg orally once a day
-Maximum dose: 20 mg/day

Treatment of Depressive Episodes Associated with Bipolar I Disorder (In Combination with Fluoxetine):
-Initial dose: 5 mg orally once a day (with fluoxetine)
-Dose adjustments: Should be made with the individual components within the dose range of 5 to 12.5 mg as indicated according to efficacy and tolerability.
-Maximum dose: 18 mg/day (with fluoxetine)

Uses:
-Acute treatment of manic or mixed episodes associated with bipolar I disorder and maintenance treatment of bipolar I disorder
-Treatment of manic or mixed episode associated with bipolar disorder as an adjunct to lithium or valproate
-Treatment of depressive episodes associated with bipolar I disorder when used in combination with fluoxetine

Usual Adult Dose for Schizophrenia:

Oral:
-Initial dose: 5 to 10 mg orally once a day
-Target dose: 10 mg orally once a day within the first several days; further dose adjustments, if needed, should occur at intervals of not less than 1 week in 5 mg increments/decrements.
-Maximum dose: 20 mg orally once a day

Oral Formulations Comments:
-Efficacy has been demonstrated in doses of 10 to 15 mg per day; doses above 10 mg per day were not demonstrated as more efficacious.
-Dose increases above 10 mg per day should occur only after a clinical assessment.

Parenteral:
Dosing for Extended-release Injectable Suspension (Based on Corresponding Oral Doses):
If the target oral olanzapine dose is 10 mg/day:
-Initial dose: 210 mg IM every 2 weeks OR 405 mg IM every 4 weeks for the first 8 weeks
-Maintenance dose: 150 mg IM every 2 weeks OR 300 mg IM every 4 weeks

If the target oral olanzapine dose is 15 mg/day:
-Initial dose: 300 mg IM every 2 weeks for the first 8 weeks
-Maintenance dose: 210 mg IM every 2 weeks OR 405 mg IM every 4 weeks

If the target oral olanzapine dose is 20 mg/day:
-Initial dose: 300 mg IM every 2 weeks for the first 8 weeks
-Maintenance dose: 300 mg IM every 2 weeks

Parenteral Formulations Comments:
-Tolerability should be established with oral formulations prior to initiating IM extended-release therapy.
-Efficacy has been demonstrated with doses from 150 to 300 mg IM every 2 weeks and 405 mg IM every 4 weeks.

Use: Treatment of schizophrenia

Usual Adult Dose for Depression:

Treatment of Depressive Episodes Associated with Bipolar I Disorder (In Combination with Fluoxetine):
-Initial dose: 5 mg orally once a day (with fluoxetine)
-Dose adjustments: Should be made with the individual components within the dose range of 5 to 20 mg as indicated according to efficacy and tolerability
-Maximum dose: 18 mg/day (with fluoxetine)

Comments:
-The safety of co-administration of doses above 18 mg has not been evaluated in clinical studies.
-Monotherapy is not indicated for treatment resistant depression.

Use: For the treatment of treatment-resistant depression (major depressive disorder in patients who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode) based on clinical studies

Usual Adult Dose for Agitated State:

Immediate-release Injection:
-Initial dose: 10 mg IM once
-Dose range: 2.5 to 10 mg
-Subsequent doses up to 10 mg may be given every 2 hours for agitation that persists following the initial dose
-Maximum number of doses: 3 doses in 24 hours; additional doses in patients with clinically significant postural hypotension are not recommended

Comments:
-The efficacy of repeated doses in agitated patients has not been systematically evaluated in controlled clinical trials.
-The safety of total daily dose greater than 30 mg (or 10 mg injections given more frequently than 2 hours after the initial dose and 4 hours after the second dose) has not been evaluated in clinical trials; maximal dosing may be associated with significant orthostatic hypotension.
-If ongoing therapy is clinically indicated, oral olanzapine may be initiated in a range of 5 to 20 mg per day as soon as clinically appropriate.

Use: For the treatment of acute agitation associated with schizophrenia and bipolar I mania

Usual Geriatric Dose for Agitated State:

Immediate-release Injection:
-Initial dose: 5 mg IM once
-Subsequent doses may be given for agitation that persists following the initial dose
-Maximum dose: 10 mg IM 2 to 4 hours apart; additional doses in patients with clinically significant postural hypotension are not recommended

Comments:
-The efficacy of repeated doses in agitated patients has not been systematically evaluated in controlled clinical trials.
-The safety of total daily dose greater than 30 mg (or 10 mg injections given more frequently than 2 hours after the initial dose and 4 hours after the second dose) has not been evaluated in clinical trials; maximal dosing may be associated with significant orthostatic hypotension.
-If ongoing therapy is clinically indicated, oral olanzapine may be initiated in a range of 5 to 20 mg per day as soon as clinically appropriate.

Use: For the treatment of acute agitation associated with schizophrenia and bipolar I mania

Usual Pediatric Dose for Schizophrenia:

Oral:
13 to 17 years:
-Initial dose: 2.5 to 5 mg orally once a day
-Target dose: 10 mg orally once a day; further dose adjustments, if needed, should occur at intervals of not less than 1 week in 2.5 to 5 mg increments/decrements.
-Maximum dose: 20 mg orally/day

Comments:
-Efficacy has been demonstrated in the range of 2.5 to 20 mg per day; a mean modal dose of 12.5 mg per day (mean dose 11.1 mg per day) was demonstrated in adolescent schizophrenia efficacy trials.
-Medication therapy for adolescents should be initiated only after a thorough diagnostic evaluation and careful consideration given to the risks associated with treatment; medication treatment should be part of a total treatment program that includes psychological, educational, and social interventions.
-When deciding among the alternative treatments, clinicians should consider the increased potential for weight gain and dyslipidemia in this population compared to adults.

Use: Treatment of schizophrenia

Usual Pediatric Dose for Bipolar Disorder:

Treatment of Depressive Episodes Associated with Bipolar I Disorder (In Combination with Fluoxetine):
10 to 17 years:
-Initial dose: 2.5 mg orally once a day (with fluoxetine)
-Dose adjustments: Should be made with the individual components within the dose range of 5 to 12.5 mg as indicated according to efficacy and tolerability.
-Maximum dose: 12.5 mg/day (with fluoxetine)

Comments:
-Medication therapy for adolescents should be initiated only after a thorough diagnostic evaluation and careful consideration given to the risks associated with treatment; medication treatment should be part of a total treatment program that includes psychological, educational, and social interventions.
-When deciding among the alternative treatments, clinicians should consider the increased potential for weight gain and dyslipidemia in this population compared to adults.

Treatment of Manic or Mixed Episodes Associated with Bipolar I Disorder:
13 to 17 years:
-Initial dose: 2.5 to 5 mg orally once a day
-Target dose: 10 mg orally once a day; dose adjustments, if needed, should occur at intervals of not less than 1 week in 2.5 to 5 mg increments/decrements.
-Maximum dose: 20 mg/day

Comment: Efficacy has been demonstrated in the range of 2.5 to 20 mg per day; a mean modal dose of 10.7 mg per day (mean dose 8.9 mg per day) was demonstrated in adolescent clinical trials.

Uses:
-Acute treatment of manic or mixed episodes associated with bipolar I disorder and maintenance treatment of bipolar I disorder
-Treatment of depressive episodes associated with bipolar I disorder when used in combination with fluoxetine

Usual Pediatric Dose for Depression:

Treatment of Depressive Episodes Associated with Bipolar I Disorder (In Combination with Fluoxetine):
10 to 17 years:
-Initial dose: 2.5 mg orally once a day (with fluoxetine)
-Dose adjustments: Should be made with the individual components within the dose range of 3 to 12 mg as indicated according to efficacy and tolerability
-Maximum dose: 12 mg/day (with fluoxetine)

Comments:
-The safety of co-administration of doses above 12 mg has not been evaluated in clinical studies.
-Monotherapy is not indicated for treatment resistant depression.

Use: For the treatment of treatment-resistant depression (major depressive disorder in patients who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode) based on clinical studies

What other drugs will affect olanzapine?

Taking olanzapine with other drugs that make you sleepy or slow your breathing can cause dangerous or life-threatening side effects. Ask your doctor before taking a sleeping pill, narcotic pain medicine, prescription cough medicine, a muscle relaxer, or medicine for anxiety, depression, or seizures.

Other drugs may interact with olanzapine, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Special Populations Gender

Clearance is approximately 30% lower in women.

Dietary Considerations

Tablets may be taken without regard to meals. Some products may contain phenylalanine.

Drug Interactions

Abiraterone Acetate: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

Acetylcholinesterase Inhibitors: Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. Monitor therapy

Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Amifampridine: May diminish the anticholinergic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Amifampridine. Monitor therapy

Amisulpride: Antipsychotic Agents may enhance the adverse/toxic effect of Amisulpride. Avoid combination

Amphetamines: Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Monitor therapy

Analgesics (Opioid): CNS Depressants may enhance the CNS depressant effect of Analgesics (Opioid). Management: Avoid concomitant use of opioid analgesics 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. Consider therapy modification

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Antihepaciviral Combination Products: May decrease the serum concentration of OLANZapine. Monitor therapy

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. Consider therapy modification

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

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. Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CarBAMazepine: May decrease the serum concentration of OLANZapine. Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Monitor therapy

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. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

CYP1A2 Inducers (Moderate): May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy

CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Monitor therapy

Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy

Deferasirox: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination

FluvoxaMINE: May increase the serum concentration of OLANZapine. Monitor therapy

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination

Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Monitor therapy

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

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. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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. Consider therapy modification

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. Consider therapy modification

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. Consider therapy modification

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

LamoTRIgine: May enhance the sedative effect of OLANZapine. Monitor therapy

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Lithium: May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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. Consider therapy modification

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. 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. Consider therapy modification

Methylphenidate: May enhance the adverse/toxic effect of Antipsychotic Agents. Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Avoid combination

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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. Monitor therapy

Obeticholic Acid: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

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. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Peginterferon Alfa-2b: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy

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. Consider therapy modification

Piribedil: May diminish the therapeutic effect of Antipsychotic Agents. Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Avoid combination

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. Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification

Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Monitor therapy

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

Ritonavir: May decrease the serum concentration of OLANZapine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

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. Consider therapy modification

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. Monitor therapy

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. Monitor therapy

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. Consider therapy modification

Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. Avoid combination

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. Consider therapy modification

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. Consider therapy modification

Teriflunomide: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Valproate Products: May decrease the serum concentration of OLANZapine. Monitor therapy

Vemurafenib: May increase the serum concentration of CYP1A2 Substrates. Management: Consider alternatives to such combinations whenever possible, particularly if the CYP1A2 substrate has a relatively narrow therapeutic index. Consider therapy modification

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. Consider therapy modification

For Healthcare Professionals

Applies to olanzapine: intramuscular powder for injection, intramuscular powder for injection extended release, oral tablet, oral tablet disintegrating

Nervous system

Post-Injection delirium/sedation syndrome, a collection of signs and symptoms consistent with olanzapine overdose has been reported following injections of the extended-release IM suspension. Events occurred in less than 0.1% of injections and in approximately 2% of patients receiving injections for up to 46 months. Onset of events ranged from soon after injection to greater than 3 hours later. The majority of patients were hospitalized and some required supportive care, including intubation. Two deaths have been reported occurring 3 to 4 days after receiving the appropriate dose of the extended-release IM suspension. In these patients, very high olanzapine blood levels were reported after death. A study undertaken to determine the cause of the elevated drug levels in these 2 deaths provides inconclusive results. As reported in a 3-23-2015 drug safety communication issued by the US Food and Drug Administration, a study in animals found much of the drug level increases could have occurred after death, but the possibility that the deaths were caused by a rapid, but delayed entry of the drug in to the bloodstream could not be ruled out.

Akathisia most commonly occurred with oral doses of 15 mg/day; akathisia events included akathisia and hyperkinesia.

Dyskinetic events included buccoglossal syndrome, choreoathetosis, dyskinesia, and tardive dyskinesia.

Dystonic events included dystonia, generalized spasm, neck rigidity, oculogyric crisis, opisthotonos, and torticollis.

Parkinsonism/parkinsonism events most commonly occurred with oral doses of 15 mg/day and included akinesia, cogwheel rigidity, extrapyramidal syndrome, hypertonia, hypokinesia, masked facies, and tremor.

Sedation most commonly occurred in adolescent patients given oral doses at least 2.5 mg/day over 3 weeks; sedation included hypersomnia, lethargy, sedation, and somnolence.

Somnolence and tremor most commonly occurred with oral doses given with lithium or valproate.[Ref]

Oral formulations:
Very common (10% or more): Somnolence (up to 52%), sedation (up to 48%), akathisia/akathisia events (up to 27%), tremor (up to 23%), parkinsonism/parkinsonism events (up to 20%), dizziness (up to 18%), headache (up to 17%), any extrapyramidal event (up to 10%)
Common (1% to 10%): Abnormal gait, amnesia, articulation impairment, dyskinesia/dyskinetic events, dystonia/dystonic events, hypertonia, incoordination, mild/transient anticholinergic effects, paresthesia, speech disorder
Uncommon (0.1% to 1%): Ataxia, cerebrovascular accident, dysarthria, restless legs syndrome, seizures, stupor, tardive dyskinesia
Rare (0.01% to 0.1%): Coma, hangover effect, neuroleptic malignant syndrome
Frequency not reported: Akinesia, choreoathetosis, cogwheel rigidity, dyskinesia, dystonia, extrapyramidal disorder, generalized spasm, hypersomnia, hypokinesia, masked facies, movement disorder, myoclonus, opisthotonos, tardive dyskinesia, twitching
Postmarketing reports: Diabetic coma

Immediate-release IM injection:
Very common (10% or more): Sedation (up to 44.1%)
Common (1% to 10%): Abnormal gait, akathisia/akathisia events, any extrapyramidal events, dizziness, parkinsonism/parkinsonism events, somnolence, speech disorder, tremor
Uncommon (0.1% to 1%): Amnesia, restless legs syndrome, syncope
Frequency not reported: Akinesia, choreoathetosis, cogwheel rigidity, dyskinesia, dyskinetic events, dystonia, dystonic events, extrapyramidal disorder, generalized spasm, hyperkinesia, hypersomnia, hypertonia, hypokinesia, masked facies, movement disorder, myoclonus, opisthotonos, twitching
Postmarketing reports: Diabetic coma, neuroleptic malignant syndrome, seizures

Extended-release IM injection:
Very common (10% or more): Headache/tension headache (up to 18%), sedation/somnolence (up to 13%)
Common (1% to 10%): Akathisia, dizziness, dysarthria, dyskinesia, hypersomnia, mild/transient anticholinergic effects, parkinsonism, tremor
Uncommon (0.1% to 1%): Amnesia, dystonia, seizures, restless legs syndrome, tardive dyskinesia
Rare (0.01% to 0.1%): Neuroleptic malignant syndrome
Frequency not reported: Abnormal gait, ataxia, cerebrovascular adverse reactions, coma, convulsions, dystonia, extrapyramidal symptoms, speech disorder, tardive extrapyramidal syndromes
Postmarketing reports: Diabetic coma[Ref]

Cardiovascular

Oral formulations:
Common (1% to 10%): Chest pain, edema, hypertension, peripheral edema, postural/orthostatic hypotension, tachycardia
Uncommon (0.1% to 1%): Bradycardia, deep vein thrombosis, QT prolongation, vasodilation
Rare (0.01% to 0.1%): Ventricular tachycardia/fibrillation
Postmarketing reports: Cardiac arrest, torsade de pointes, venous thromboembolic events, venous thromboembolism, ventricular arrhythmia

Immediate-release IM injection:
Common (1% to 10%): Bradycardia, hypotension, peripheral edema, postural/orthostatic hypotension, tachycardia
Uncommon (0.1% to 1%): Photosensitivity reaction
Postmarketing reports: Deep vein thrombosis, cardiac arrest, QT prolongation, torsade de pointes, venous thromboembolic events, venous thromboembolism, ventricular arrhythmia

Extended-release IM injection:
Common (1% to 10%): Bradycardia with/without hypotension/syncope, edema, electrocardiogram QT-corrected interval prolonged, hypertension, hypotension, orthostatic hypotension, peripheral edema, tachycardia
Uncommon (0.1% to 1%): Deep vein thrombosis, thromboembolism
Rare (0.01% to 0.1%): Ventricular tachycardia/fibrillation
Postmarketing reports: Cardiac arrest, deep vein thrombosis, torsades de pointes, venous thromboembolic events/venous thromboembolism[Ref]

Collective data gathered from 17 placebo-controlled clinical studies (n=5106) involving the use of atypical antipsychotic agents, including olanzapine, for the treatment of behavioral disorders in the elderly patient with dementia showed a risk of death 1.6 to 1.7 times greater in the drug treated patient than in the placebo treated patient. The average length of duration for the trials was 10 weeks with the cause of death in the majority of cases, though not all, reported as either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Olanzapine is not approved by the FDA for use in the treatment of behavioral disorders in elderly patients with dementia.[Ref]

Metabolic

Oral formulations:
Very common (10% or more): Weight gain/increased weight greater than/equal to 7% of baseline body weight (up to 89.4%), fasting borderline to high triglycerides (up to 59.5%), fasting borderline to high total cholesterol (up to 38.9%), increased appetite (up to 29%), fasting normal to high triglycerides (up to 26.9%), fasting borderline to high glucose (up to 14.3%) thirst (up to 10%)
Common (1% to 10%): Fasting normal to high glucose, fasting normal to high total cholesterol, high uric acid, hyperglycemia, increased alkaline phosphatase, increased triglyceride levels, weight gain greater than/equal to 15% of baseline body weight
Uncommon (0.1% to 1%): Development/exacerbation of diabetes with/without ketoacidosis or coma (sometimes fatal)
Postmarketing reports: Diabetic ketoacidosis, hypertriglyceridemia, random cholesterol levels of 240 mg/dL or higher, random triglyceride levels of 1000 mg/dL or higher

Immediate-release IM injection:
Very common (10% or more): Weight gain/increased weight greater than/equal to 7% of baseline body weight (up to 89.4%), fasting borderline to high triglycerides/hypertriglyceridemia (up to 70.7%), fasting borderline to high total cholesterol/hypercholesterolemia (up to 55.2%), fasting borderline to high glucose/hyperglycemia (up to 26%)
Common (1% to 10%): Increased appetite, weight gain greater than/equal to 15% of baseline body weight
Postmarketing reports: Diabetic ketoacidosis, pre-existing diabetes exacerbation, random cholesterol levels of 240 mg/dL or higher, random triglyceride levels of 1000 mg/dL or higher

Extended-release IM injection:
Very common (10% or more): Weight gain/increased weight greater than/equal to 7% of baseline body weight (up to 64.4%)
Common (1% to 10%): Fasting borderline to high cholesterol/glucose/triglycerides, fasting normal to high cholesterol/triglycerides/glucose, high uric acid, increased alkaline phosphatase, increased appetite, weight gain greater than/equal to 15% of baseline body weight
Uncommon (0.1% to 1%): Development/exacerbation of diabetes with/without ketoacidosis or coma (sometimes fatal)
Frequency not reported: Changes in cholesterol/LDL/triglycerides/sodium
Postmarketing reports: Diabetic ketoacidosis, hyperglycemia, random cholesterol levels of 6.21 mmol/L or higher, random triglyceride levels of 11.29 mmol/L or higher[Ref]

Olanzapine appears to have a greater association than some other atypical antipsychotics for increasing glucose levels. Mean increases of up to 15 mg/dL have been reported. The differences in mean changes in serum glucose were higher in patients with evidence of glucose dysregulation at baseline. In an analysis of patients who completed 9 to 12 months of therapy, the rate on increase in mean blood glucose slowed after approximately 6 months.

Clinically significant alterations in lipids have been observed including serum triglyceride elevations greater than 500 mg/dL. In long-term studies of at least 48-weeks in adults, increased from baseline in mean fasting cholesterol, LDL, triglycerides were 5.6 mg/dL, 2.5 mg/dL, and 18.7 mg/dL, respectively. Mean increases in fasting lipid values (total cholesterol, LDL and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline.

In 13 placebo-controlled monotherapy trials, olanzapine-treated patients gained an average of 2.6 kg compared to an average 0.3 kg weight loss in placebo patients; 22.5% gained at least 7% of their baseline weight, 4.2% at least 15% of their baseline (compared to 3% and 0.3% in placebo). Clinically significant weight gain was observed across all baseline BMIs. With longer term exposure (at least 24 weeks), weight gain of 7%, 15%, or 25% or more were reported in 89.4%, 55.3%, and 29.1%, respectively. Weight gain and increased appetite were reported in 40.6%, 7.1%, and 2.5% of adolescents receiving this drug in short term treatment (approximately 22 days), respectively.[Ref]

Gastrointestinal

Oral formulations:
Very common (10% or more): Dry mouth (up to 32%), constipation (up to 11%), dyspepsia (up to 11%)
Common (1% to 10%): Abdominal pain, diarrhea, dyspepsia, increased salivation, nausea, vomiting
Uncommon (0.1% to 1%): Abdominal distention, tongue edema
Rare (0.01% to 0.1%): Ileus, intestinal obstruction, pancreatitis
Frequency not reported: Buccoglossal syndrome, lower/upper abdominal pain

Immediate-release IM injection:
Common (1% to 10%): Constipation, dry mouth
Uncommon (0.1% to 1%): Abdominal distention, nausea
Frequency not reported: Buccoglossal syndrome
Postmarketing reports: Pancreatitis, vomiting

Extended-release IM injection:
Common (1% to 10%): Abdominal pain/upper abdominal pain, constipation, diarrhea, dry mouth, flatulence, nausea, toothache, tooth infection/abscess, vomiting
Uncommon (0.1% to 1%): Abdominal distention
Rare (0.01% to 0.1%): Pancreatitis[Ref]

Abdominal pain included abdominal pain, lower abdominal pain, and upper abdominal pain.

Nausea and dry mouth have been reported to be dose related. Dry mouth was more commonly reported when given orally with lithium or valproate.[Ref]

Hepatic

Oral formulations:
Very common (10% or more): AST elevated (up to 27.6%), decreased total bilirubin (up to 22.1%), ALT 3-times upper limit of normal (3 x ULN) (up to 12.1%)
Common (1% to 10%): Asymptomatic liver enzyme elevations (ALT, AST), high gamma glutamyltransferase (GGT)
Uncommon (0.1% to 1%): Bilirubinemia/increased total bilirubin
Rare (0.01% to 0.1%): Fatty liver deposit
Frequency not reported: Hepatitis, hepatocellular/cholestatic hepatitis, mixed liver injury
Postmarketing reports: Jaundice

Immediate-release IM injection:
Very common (10% or more): AST elevated (up to 27.6%), decreased total bilirubin (up to 22.1%), ALT 3 x ULN (up to 12.1%)
Postmarketing reports: Cholestatic/mixed liver injury, jaundice, total bilirubin increased

Extended-release IM injection:
Common (1% to 10%): ALT 3 x ULN, High GGT levels, asymptomatic liver enzyme elevations (ALT, AST), increased hepatic enzymes (AST, ALT, GGT), low total bilirubin
Uncommon (0.1% to 1%): ALT elevation greater than 200 international units/L, increased total bilirubin
Rare (0.01% to 0.1%): Hepatocellular/cholestatic hepatitis, mixed liver injury
Frequency not reported: Changes in direct bilirubin/GGT
Postmarketing reports: Jaundice[Ref]

Transient, asymptomatic elevations of hepatic transaminases were commonly seen, especially early in treatment.[Ref]

Respiratory

Oral formulations:
Common (1% to 10%): Dyspnea, increased cough, nasopharyngitis, pharyngitis, respiratory tract infection, rhinitis, sinusitis
Uncommon (0.1% to 1%): Epistaxis, pulmonary embolism
Rare (0.01% to 0.1%): Lung edema
Frequency not reported: Lower respiratory tract infection, pneumonia, upper respiratory tract infection, viral respiratory tract infection, viral upper respiratory tract infection

Immediate-release IM injection:
Common (1% to 10%): Pneumonia
Uncommon (0.1% to 1%): Epistaxis
Postmarketing reports: Pulmonary embolism

Extended-release IM injection:
Common (1% to 10%): Cough, nasal/sinus congestion, nasopharyngitis, pharyngolaryngeal pain, sneezing, upper respiratory tract infection
Uncommon (0.1% to 1%): Epistaxis, pulmonary embolism
Rare (0.01% to 0.1%):
Frequency not reported: Pneumonia[Ref]

Endocrine

Oral formulations:
Very common (10% or more): Prolactin level elevation (up to 47.4%)
Uncommon (0.1% to 1%): Gynecomastia/male breast enlargement

Immediate-release IM injection:
Very common (10% or more): Increased prolactin (up to 47.4%)
Uncommon (0.1% to 1%): Gynecomastia/male breast enlargement

Extended-release IM injection:
Very common (10% or more): Plasma prolactin level elevation (up to 30%)
Uncommon (0.1% to 1%): Gynecomastia/male breast enlargement[Ref]

In clinical studies, changes in prolactin levels were found to be statistically significantly different based on dose, higher doses were associated with higher levels of prolactin. In a study of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of normal (ULN) in approximately 30% of patients who had normal baseline prolactin values. The majority of these elevations were mild, and remained below 2 x ULN.

Approximately 47% of treated adolescent patients had significantly higher prolactin levels compared to adults.[Ref]

Hematologic

Oral formulations:
Common (1% to 10%): Eosinophilia, leukopenia, neutropenia
Uncommon (0.1% to 1%): Thrombocytopenia, thromboembolism

Immediate-release IM injection:
Common (1% to 10%): Eosinophilia, leukopenia, neutropenia
Postmarketing reports: Thrombocytopenia

Extended-release IM injection:
Common (1% to 10%): Eosinophilia, leukopenia, neutropenia
Rare (0.01% to 0.1%): Thrombocytopenia
Frequency not reported: Changes in monocytes/eosinophils, high leukocyte count, treatment-emergent low platelet count[Ref]

Ocular

Oral formulations:
Common (1% to 10%): Amblyopia, abnormal vision
Uncommon (0.1% to 1%): Accommodation abnormality, dry eyes, oculogyration
Rare (0.01% to 0.1%): Mydriasis
Frequency not reported: Oculogyric crisis

Immediate-release IM injection:
Frequency not reported: Oculogyric crisis

Extended-release IM injection:
Uncommon (0.1% to 1%): Oculogyration[Ref]

Other

Oral formulations:
Very common (10% or more): Asthenia (up to 20%), fatigue (up to 14%), accidental injury (up to 12%)
Common (1% to 10%): Fever/pyrexia, extremity pain (other than joint), lethargy, residual events, nonspecific events
Uncommon (0.1% to 1%): Chills
Rare (0.01% to 0.1%): Chills and fever, hypothermia, sudden death/sudden unexplained death
Frequency not reported: Falls, increased body temperature, neonatal drug withdrawal syndrome

Immediate-release IM injection:
Common (1% to 10%): Asthenia, fatigue, pyrexia, residual events
Frequency not reported: Falls, lethargy
Postmarketing reports: Sudden unexplained death

Extended-release IM injection:
Common (1% to 10%): Asthenia, ear pain, fatigue, fever/pyrexia, overdose, pain, procedural pain
Rare (0.01% to 0.1%): Hypothermia
Frequency not reported: Death, falls, increased body temperature, lethargy, neonatal drug withdrawal syndrome, sudden death/sudden unexplained death, weakness[Ref]

Asthenia most frequently occurred in oral doses of 15 mg/day.

Residual events included movement disorder, myoclonus, and twitching.[Ref]

Hypersensitivity

Oral formulations:
Uncommon (0.1% to 1%): Hypersensitivity
Postmarketing reports: Allergic reaction, anaphylactoid reaction, angioedema

Immediate-release IM injection:
Postmarketing reports: Allergic reaction, anaphylactoid reaction, angioedema

Extended-release IM injection:
Uncommon (0.1% to 1%): Hypersensitivity
Postmarketing reports: Allergic reaction, anaphylactoid reaction, angioedema[Ref]

Genitourinary

Oral formulations:
Common (1% to 10%): Dysmenorrhea, erectile dysfunction, glucosuria, urinary incontinence, urinary tract infection, vaginitis
Uncommon (0.1% to 1%): Amenorrhea, breast enlargement/pain, decreased menstruation, galactorrhea, impaired urination, impotence, increased menstruation, menorrhagia, metrorrhagia, polyuria, urinary frequency, urinary hesitation, urinary retention, urinary urgency
Rare (0.01% to 0.1%): Priapism

Immediate-release IM injection:
Common (1% to 10%): Erectile dysfunction, urinary incontinence
Uncommon (0.1% to 1%): Amenorrhea, breast enlargement, galactorrhea
Postmarketing reports: Priapism, urinary hesitation, urinary retention

Extended-release IM injection:
Common (1% to 10%): Erectile dysfunction, vaginal discharge
Uncommon (0.1% to 1%): Amenorrhea, breast enlargement, galactorrhea, urinary hesitation, urinary incontinence, urinary retention
Rare (0.01% to 0.1%): Priapism[Ref]

Musculoskeletal

Oral formulations:
Common (1% to 10%): Arthralgia, back pain, high creatine/creatinine phosphokinase, joint pain, musculoskeletal stiffness
Rare (0.01% to 0.1%): Osteoporosis, rhabdomyolysis
Frequency not reported: Neck rigidity, torticollis

Immediate-release IM injection:
Common (1% to 10%): Arthralgia
Uncommon (0.1% to 1%): Increased creatinine phosphokinase
Rare (0.01% to 0.1%): Elevated creatine kinase levels
Frequency not reported: Neck rigidity, torticollis
Postmarketing reports: Rhabdomyolysis

Extended-release IM injection:
Common (1% to 10%): Arthralgia, back pain, high creatine phosphokinase, muscle spasms, musculoskeletal spasms
Rare (0.01% to 0.1%): Rhabdomyolysis[Ref]

Dermatologic

Oral formulations:
Common (1% to 10%): Acne, dry skin, ecchymosis, rash, sweating/diaphoresis
Uncommon (0.1% to 1%): Alopecia, face edema, photosensitivity reaction
Frequency not reported: Drug reaction with eosinophilia and systemic symptoms (DRESS), erythema, pruritus, urticaria

Immediate-release IM injection:
Postmarketing reports: Alopecia, drug reaction with eosinophilia and systemic symptoms (DRESS), pruritus, rash, sweating/diaphoresis, urticaria

Extended-release IM injection:
Common (1% to 10%): Acne, rash
Uncommon (0.1% to 1%): Alopecia, photosensitivity reaction
Frequency not reported: Diaphoresis/sweating, erythema
Postmarketing reports: Drug reaction with eosinophilia and systemic symptoms (DRESS), pruritus, urticaria[Ref]

Psychiatric

Oral formulations:
Very common (10% or more): Depression (up to 18%), insomnia (up to 12%)
Common (1% to 10%): Apathy, confusion, decreased libido, euphoria, personality disorder, restlessness
Uncommon (0.1% to 1%): Suicide attempt
Rare (0.01% to 0.1%): Discontinuation symptoms
Frequency not reported: Anxiety, visual hallucinations/hallucinations
Postmarketing reports: Discontinuation reaction

Immediate-release IM injection:
Common (1% to 10%): Decreased libido
Frequency not reported: Hallucinations
Postmarketing reports: Anxiety, discontinuation reaction, insomnia

Extended-release IM injection:
Common (1% to 10%): Abnormal dreams, abnormal thinking, auditory hallucinations, decreased libido, restlessness, sleep disorder
Rare (0.01% to 0.1%): Discontinuation reaction/symptoms
Frequency not reported: Aggression, agitation, anxiety, confusion, delirium, hallucinations, insomnia, other cognitive impairment, visual hallucinations[Ref]

For the collection of adverse reactions, the term personality disorder was used to collect data on nonaggressive objectionable behavior.

Depression most commonly occurred with oral doses given with lithium or valproate.[Ref]

Local

Immediate-release IM injection:
Common (1% to 10%): Injection site pain

Extended-release IM injection:
Common (1% to 10%): Anesthesia, bruising, buttock pain, hemorrhage, induration, injection site induration/mass/pain, irritation
Rare (0.01% to 0.1%): Injection site abscess requiring/not requiring surgical intervention
Frequency not reported: Edema-type reaction, erythema-type reaction, nodule-type reaction, non-specific injection-site reaction[Ref]

Immunologic

Extended-release IM injection:
Common (1% to 10%): Viral infection[Ref]

Renal

Oral formulations:
Common (1% to 10%): Glycosuria

Immediate-release IM injection:
Common (1% to 10%): Glycosuria

Extended-release IM injection:
Common (1% to 10%): Glycosuria[Ref]

Some side effects of olanzapine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Usual Adult Dose for Depression

Treatment of Depressive Episodes Associated with Bipolar I Disorder (In Combination with Fluoxetine):
-Initial dose: 5 mg orally once a day (with fluoxetine)
-Dose adjustments: Should be made with the individual components within the dose range of 5 to 20 mg as indicated according to efficacy and tolerability
-Maximum dose: 18 mg/day (with fluoxetine)

Comments:
-The safety of co-administration of doses above 18 mg has not been evaluated in clinical studies.
-Monotherapy is not indicated for treatment resistant depression.

Use: For the treatment of treatment-resistant depression (major depressive disorder in patients who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode) based on clinical studies

Usual Pediatric Dose for Depression

Treatment of Depressive Episodes Associated with Bipolar I Disorder (In Combination with Fluoxetine):
10 to 17 years:
-Initial dose: 2.5 mg orally once a day (with fluoxetine)
-Dose adjustments: Should be made with the individual components within the dose range of 3 to 12 mg as indicated according to efficacy and tolerability
-Maximum dose: 12 mg/day (with fluoxetine)

Comments:
-The safety of co-administration of doses above 12 mg has not been evaluated in clinical studies.
-Monotherapy is not indicated for treatment resistant depression.

Use: For the treatment of treatment-resistant depression (major depressive disorder in patients who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode) based on clinical studies

Renal Dose Adjustments

No adjustment recommended

Liver Dose Adjustments

Data not available

Upsides

  • Used to relieve symptoms of psychosis and agitation associated with schizophrenia and manic or mixed episodes of bipolar I disorder.
  • May also be used in addition to fluoxetine for the treatment of treatment-resistant depression and depression associated with bipolar I disorder.

Bottom Line

Olanzapine is an antipsychotic used in the treatment of schizophrenia and several other disorders. Weight gain associated with olanzapine is common.

Response and Effectiveness

  • Peak blood levels are reached within six hours of taking a single dose of oral olanzapine. Effects are long lasting, so olanzapine should be dosed once a day; however, it may take several weeks of continued dosing before a reduction in symptoms is seen.
  • Concentrations of olanzapine in the blood reach a steady level after approximately one week of regular dosing.

View as a slideshow

(web3)