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Zyprexa Side Effects Center

Medical Editor: Melissa Conrad Stöppler, MD

Zyprexa (olanzapine) is an atypical antipsychotic medication used to treat schizophrenia and manic episodes of bipolar disorder. Zyprexa available in generic form known as olanzapine, and may be taken orally or by injection. Side effects of Zyprexa include akathisia (an inability to sit still), constipation, dizziness, and drowsiness.

Drugs that may reduce levels of Zyprexa include carbamazepine (Tegretol, Carbatrol, Equetro), omeprazole (Prilosec), and rifampin (Rifadin, Rifamate, Rifater). There are no adequate studies of olanzapine in pregnant women, and pregnant women should only take Zyprexa if the benefits justify the unknown risks. It is recommended that Zyprexa not be used by nursing mothers since it is excreted in breast milk.

Our Zyprexa Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Zyprexa in Detail - Patient Information: Side Effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using olanzapine and call your doctor at once if you have any of these serious side effects:

  • very stiff (rigid) muscles, high fever, tremors, sweating, confusion, fast or uneven heartbeats, slow heart rate, feeling like you might pass out;
  • twitching or uncontrollable movements of your eyes, lips, tongue, face, arms, or legs;
  • trouble speaking or swallowing;
  • dry mouth, thirst, feeling very hot (with or without sweating), urinating less than usual or not at all;
  • high blood sugar (increased thirst, loss of appetite, fruity breath odor, increased urination, drowsiness, dry skin, nausea, and vomiting);
  • sudden numbness or weakness, confusion, or problems with vision, speech, or balance;
  • fever, chills, body aches, flu symptoms, sores in your mouth and throat;
  • swelling in your hands or feet;
  • changes in personality, unusual thoughts or behavior, hallucinations, or thoughts about hurting yourself; or
  • upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

  • weight gain (more likely in teenagers), increased appetite;
  • headache, dizziness, drowsiness, feeling tired or restless;
  • memory problems;
  • stomach pain, constipation, loss of bladder control;
  • back pain, pain in your arms or legs;
  • numbness or tingly feeling;
  • breast swelling or discharge (in women or men); or
  • missed menstrual periods.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Zyprexa (Olanzapine) »

What is Patient Information Overview?

A concise overview of the drug for the patient or caregiver from First DataBank.

Zyprexa Overview - Patient Information: Side Effects

SIDE EFFECTS: Drowsiness, dizziness, lightheadedness, stomach upset, dry mouth, constipation, increased appetite, or weight gain may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: difficulty swallowing, shaking (tremor), signs of infection (such as fever, persistent sore throat), slow heartbeat, fainting, mental/mood changes (such as confusion, restlessness), numbness/tingling of arms/legs, yellowing eyes/skin, trouble urinating.

This drug may infrequently make your blood sugar level rise, which can cause or worsen diabetes. Tell your doctor immediately if you develop symptoms of high blood sugar, such as increased thirst and urination. If you already have diabetes, be sure to check your blood sugars regularly. Your doctor may need to adjust your diabetes medication, exercise program, or diet.

This drug may also cause significant weight gain and a rise in your blood cholesterol (or triglyceride) levels, especially in teenagers. These effects, along with diabetes, may increase your risk for developing heart disease. Discuss the risks and benefits of treatment with your doctor. (See also Notes section.)

Olanzapine may rarely cause a condition known as tardive dyskinesia. In some cases, this condition may be permanent. Tell your doctor immediately if you develop any unusual/uncontrolled movements (especially of the face, lips, mouth, tongue, arms or legs).

This medication may increase a certain natural substance (prolactin) made by your body. For females, this increase in prolactin may result in unwanted breast milk, missed/stopped periods, or difficulty becoming pregnant. For males, it may result in decreased sexual ability, inability to produce sperm, or enlarged breasts. If you develop any of these symptoms, tell your doctor immediately.

Get medical help right away if you have any very serious side effects, including: seizures.

This medication may rarely cause a very serious condition called neuroleptic malignant syndrome (NMS). Get medical help right away if you have any of the following symptoms: fever, muscle stiffness/pain/tenderness/weakness, severe tiredness, severe confusion, sweating, fast/irregular heartbeat, dark urine, change in the amount of urine.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the entire patient information overview for Zyprexa (Olanzapine)»

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Zyprexa FDA Prescribing Information: Side Effects
(Adverse Reactions)

SIDE EFFECTS

When using ZYPREXA and fluoxetine in combination, also refer to the Adverse Reactions section of the package insert for Symbyax.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect or predict the rates observed in practice.

Clinical Trials in Adults

The information below for olanzapine is derived from a clinical trial database for olanzapine consisting of 8661 adult patients with approximately 4165 patient-years of exposure to oral olanzapine and 722 patients with exposure to intramuscular olanzapine for injection. This database includes: (1) 2500 patients who participated in multiple-dose oral olanzapine premarketing trials in schizophrenia and Alzheimer's disease representing approximately 1122 patient-years of exposure as of February 14, 1995; (2) 182 patients who participated in oral olanzapine premarketing bipolar I disorder (manic or mixed episodes) trials representing approximately 66 patient-years of exposure; (3) 191 patients who participated in an oral olanzapine trial of patients having various psychiatric symptoms in association with Alzheimer's disease representing approximately 29 patient-years of exposure; (4) 5788 patients from 88 additional oral olanzapine clinical trials as of December 31, 2001; and (5) 722 patients who participated in intramuscular olanzapine for injection premarketing trials in agitated patients with schizophrenia, bipolar I disorder (manic or mixed episodes), or dementia. In addition, information from the premarketing 6-week clinical study database for olanzapine in combination with lithium or valproate, consisting of 224 patients who participated in bipolar I disorder (manic or mixed episodes) trials with approximately 22 patient-years of exposure, is included below.

The conditions and duration of treatment with olanzapine varied greatly and included (in overlapping categories) open-label and double-blind phases of studies, inpatients and outpatients, fixed-dose and dose-titration studies, and short-term or longer-term exposure. Adverse reactions were assessed by collecting adverse reactions, results of physical examinations, vital signs, weights, laboratory analytes, ECGs, chest x-rays, and results of ophthalmologic examinations.

Certain portions of the discussion below relating to objective or numeric safety parameters, namely, dose-dependent adverse reactions, vital sign changes, weight gain, laboratory changes, and ECG changes are derived from studies in patients with schizophrenia and have not been duplicated for bipolar I disorder (manic or mixed episodes) or agitation. However, this information is also generally applicable to bipolar I disorder (manic or mixed episodes) and agitation.

Adverse reactions during exposure were obtained by spontaneous report and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping similar types of reactions into a smaller number of standardized reaction categories. In the tables and tabulations that follow, MedDRA and COSTART Dictionary terminology has been used to classify reported adverse reactions.

The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed. A reaction was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. The reported reactions do not include those reaction terms that were so general as to be uninformative. Reactions listed elsewhere in labeling may not be repeated below. It is important to emphasize that, although the reactions occurred during treatment with olanzapine, they were not necessarily caused by it. The entire label should be read to gain a complete understanding of the safety profile of olanzapine.

The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the adverse reactions incidence in the population studied.

Incidence of Adverse Reactions in Short-Term, Placebo-Controlled and Combination Trials

The following findings are based on premarketing trials of (1) oral olanzapine for schizophrenia, bipolar I disorder (manic or mixed episodes), a subsequent trial of patients having various psychiatric symptoms in association with Alzheimer's disease, and premarketing combination trials, and (2) intramuscular olanzapine for injection in agitated patients with schizophrenia or bipolar I mania.

Adverse Reactions Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlled Trials

Schizophrenia - Overall, there was no difference in the incidence of discontinuation due to adverse reactions (5% for oral olanzapine vs 6% for placebo). However, discontinuations due to increases in ALT were considered to be drug related (2% for oral olanzapine vs 0% for placebo).

Bipolar I Disorder (Manic or Mixed Episodes) Monotherapy - Overall, there was no difference in the incidence of discontinuation due to adverse reactions (2% for oral olanzapine vs 2% for placebo).

Agitation - Overall, there was no difference in the incidence of discontinuation due to adverse reactions (0.4% for intramuscular olanzapine for injection vs 0% for placebo).

Adverse Reactions Associated with Discontinuation of Treatment in Short-Term Combination Trials

Bipolar I Disorder (Manic or Mixed Episodes), Olanzapine as Adjunct to Lithium or Valproate - In a study of patients who were already tolerating either lithium or valproate as monotherapy, discontinuation rates due to adverse reactions were 11% for the combination of oral olanzapine with lithium or valproate compared to 2% for patients who remained on lithium or valproate monotherapy. Discontinuations with the combination of oral olanzapine and lithium or valproate that occurred in more than 1 patient were: somnolence (3%), weight gain (1%), and peripheral edema (1%).

Commonly Observed Adverse Reactions in Short-Term, Placebo-Controlled Trials

The most commonly observed adverse reactions associated with the use of oral olanzapine (incidence of 5% or greater) and not observed at an equivalent incidence among placebo-treated patients (olanzapine incidence at least twice that for placebo) were:

Table 9: Common Treatment-Emergent Adverse Reactions Associated with the Use of Oral Olanzapine in 6-Week Trials - SCHIZOPHRENIA

Adverse Reaction Percentage of Patients Reporting Event
Olanzapine
(N=248)
Placebo
(N=118)
Postural hypotension 5 2
Constipation 9 3
Weight gain 6 1
Dizziness 11 4
Personality disordera 8 4
Akathisia 5 1
aPersonality disorder is the COSTART term for designating nonaggressive objectionable behavior.

Table 10: Common Treatment-Emergent Adverse Reactions Associated with the Use of Oral Olanzapine in 3-Week and 4-Week Trials - Bipolar I Disorder (Manic or Mixed Episodes)

Adverse Reaction Percentage of Patients Reporting Event
Olanzapine
(N=125)
Placebo
(N=129)
Asthenia 15 6
Dry mouth 22 7
Constipation 11 5
Dyspepsia 11 5
Increased appetite 6 3
Somnolence 35 13
Dizziness 18 6
Tremor 6 3

Olanzapine Intramuscular - There was 1 adverse reaction (somnolence) observed at an incidence of 5% or greater among intramuscular olanzapine for injection-treated patients and not observed at an equivalent incidence among placebo-treated patients (olanzapine incidence at least twice that for placebo) during the placebo-controlled premarketing studies. The incidence of somnolence during the 24 hour IM treatment period in clinical trials in agitated patients with schizophrenia or bipolar I mania was 6% for intramuscular olanzapine for injection and 3% for placebo.

Adverse Reactions Occurring at an Incidence of 2% or More among Oral Olanzapine-Treated Patients in Short-Term, Placebo-Controlled Trials

Table 11 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred in 2% or more of patients treated with oral olanzapine (doses ≥ 2.5 mg/day) and with incidence greater than placebo who participated in the acute phase of placebo-controlled trials.

Table 11: Treatment-Emergent Adverse Reactions: Incidence in Short-Term, Placebo-Controlled Clinical Trials with Oral Olanzapine

Body System/Adverse Reaction Percentage of Patients Reporting Event
Olanzapine
(N=532)
Placebo
(N=294)
Body as a Whole
Accidental injury 12 8
Asthenia 10 9
Fever 6 2
Back pain 5 2
Chest pain 3 1
Cardiovascular System
Postural hypotension 3 1
Tachycardia 3 1
Hypertension 2 1
Digestive System
Dry mouth 9 5
Constipation 9 4
Dyspepsia 7 5
Vomiting 4 3
Increased appetite 3 2
Hemic and Lymphatic System
Ecchymosis 5 3
Metabolic and Nutritional Disorders
Weight gain 5 3
Peripheral edema 3 1
Musculoskeletal System
Extremity pain (other than joint) 5 3
Joint pain 5 3
Nervous System
Somnolence 29 13
Insomnia 12 11
Dizziness 11 4
Abnormal gait 6 1
Tremor 4 3
Akathisia 3 2
Hypertonia 3 2
Articulation impairment 2 1
Respiratory System
Rhinitis 7 6
Cough increased 6 3
Pharyngitis 4 3
Special Senses
Amblyopia 3 2
Urogenital System
Urinary incontinence 2 1
Urinary tract infection 2 1

Commonly Observed Adverse Reactions in Short-Term Trials of Oral Olanzapine as Adjunct to Lithium or Valproate

In the bipolar I disorder (manic or mixed episodes) adjunct placebo-controlled trials, the most commonly observed adverse reactions associated with the combination of olanzapine and lithium or valproate (incidence of ≥ 5% and at least twice placebo) were:

Table 12: Common Treatment-Emergent Adverse Reactions Associated with the Use of Oral Olanzapine in 6-Week Adjunct to Lithium or Valproate Trials - Bipolar I Disorder (Manic or Mixed Episodes)

Adverse Reaction Percentage of Patients Reporting Event
Olanzapine with lithium or valproate
(N=229)
Placebo with lithium or valproate
(N=115)
Dry mouth 32 9
Weight gain 26 7
Increased appetite 24 8
Dizziness 14 7
Back pain 8 4
Constipation 8 4
Speech disorder 7 1
Increased salivation 6 2
Amnesia 5 2
Paresthesia 5 2

Adverse Reactions Occurring at an Incidence of 2% or More among Oral Olanzapine-Treated Patients in Short-Term Trials of Olanzapine as Adjunct to Lithium or Valproate

Table 13 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred in 2% or more of patients treated with the combination of olanzapine (doses ≥ 5 mg/day) and lithium or valproate and with incidence greater than lithium or valproate alone who participated in the acute phase of placebo-controlled combination trials.

Table 13: Treatment-Emergent Adverse Reactions: Incidence in Short-Term, Placebo-Controlled Clinical Trials of Oral Olanzapine as Adjunct to Lithium or Valproate

Body System/Adverse Reaction Percentage of Patients Reporting Event
Olanzapine with lithium or valproate
(N=229)
Placebo with lithium or valproate
(N=115)
Body as a Whole
Asthenia 18 13
Back pain 8 4
Accidental injury 4 2
Chest pain 3 2
Cardiovascular System
Hypertension 2 1
Digestive System
Dry mouth 32 9
Increased appetite 24 8
Thirst 10 6
Constipation 8 4
Increased salivation 6 2
Metabolic and Nutritional Disorders
Weight gain 26 7
Peripheral edema 6 4
Edema 2 1
Nervous System
Somnolence 52 27
Tremor 23 13
Depression 18 17
Dizziness 14 7
Speech disorder 7 1
Amnesia 5 2
Paresthesia 5 2
Apathy 4 3
Confusion 4 1
Euphoria 3 2
Incoordination 2 0
Respiratory System
Pharyngitis 4 1
Dyspnea 3 1
Skin and Appendages
Sweating 3 1
Acne 2 0
Dry skin 2 0
Special Senses
Amblyopia 9 5
Abnormal vision 2 0
Urogenital System
Dysmenorrheaa 2 0
Vaginitisa 2 0
aDenominator used was for females only (olanzapine, N=128; placebo, N=51).

For specific information about the adverse reactions observed with lithium or valproate, refer to the Adverse Reactions section of the package inserts for these other products.

Adverse Reactions Occurring at an Incidence of 1% or More among Intramuscular Olanzapine for Injection-Treated Patients in Short-Term, Placebo-Controlled Trials

Table 14 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred in 1% or more of patients treated with intramuscular olanzapine for injection (dose range of 2.5-10 mg/injection) and with incidence greater than placebo who participated in the short-term, placebo-controlled trials in agitated patients with schizophrenia or bipolar I mania.

Table 14: Treatment-Emergent Adverse Reactions: Incidence in Short-Term (24 Hour), Placebo-Controlled Clinical Trials with Intramuscular Olanzapine for Injection in Agitated Patients with Schizophrenia or Bipolar I Mania

Body System/Adverse Reaction Percentage of Patients Reporting Event
Olanzapine
(N=415)
Placebo
(N=150)
Body as a Whole
Asthenia 2 1
Cardiovascular System
Hypotension 2 0
Postural hypotension 1 0
Nervous System
Somnolence 6 3
Dizziness 4 2
Tremor 1 0

Additional Findings Observed in Clinical Trials

Dose Dependency of Adverse Reactions in Short-Term, Placebo-Controlled Trials

Extrapyramidal Symptoms: The following table enumerates the percentage of patients with treatment-emergent extrapyramidal symptoms as assessed by categorical analyses of formal rating scales during acute therapy in a controlled clinical trial comparing oral olanzapine at 3 fixed doses with placebo in the treatment of schizophrenia in a 6-week trial.

Table 15: Treatment-Emergent Extrapyramidal Symptoms Assessed by Rating Scales Incidence in a Fixed Dosage Range, Placebo-Controlled Clinical Trial of Oral Olanzapine in Schizophrenia - Acute Phase

  Percentage of Patients Reporting Event
Placebo Olanzapine 5 ± 2.5 mg/day Olanzapine 10 ± 2.5 mg/day Olanzapine 15 ± 2.5 mg/day
Parkinsonisma 15 14 12 14
Akathisiab 23 16 19 27
aPercentage of patients with a Simpson-Angus Scale total score > 3.
bPercentage of patients with a Barnes Akathisia Scale global score ≥ 2.

The following table enumerates the percentage of patients with treatment-emergent extrapyramidal symptoms as assessed by spontaneously reported adverse reactions during acute therapy in the same controlled clinical trial comparing olanzapine at 3 fixed doses with placebo in the treatment of schizophrenia in a 6-week trial.

Table 16: Treatment-Emergent Extrapyramidal Symptoms Assessed by Adverse Reactions Incidence in a Fixed Dosage Range, Placebo-Controlled Clinical Trial of Oral Olanzapine in Schizophrenia - Acute Phase

  Percentage of Patients Reporting Event
Placebo (N=68) Olanzapine 5 ± 2.5 mg/day (N=65) Olanzapine 10 ± 2.5 mg/day (N=64) Olanzapine 15 ± 2.5 mg/day (N=69)
Dystonic eventsa 1 3 2 3
Parkinsonism eventsb 10 8 14 20
Akathisia eventsc 1 5 11 10
Dyskinetic eventsd 4 0 2 1
Residual eventse 1 2 5 1
Any extrapyramidal event 16 15 25 32
aPatients with the following COSTART terms were counted in this category: dystonia, generalized spasm, neck rigidity, oculogyric crisis, opisthotonos, torticollis.
bPatients with the following COSTART terms were counted in this category: akinesia, cogwheel rigidity, extrapyramidal syndrome, hypertonia, hypokinesia, masked facies, tremor.
cPatients with the following COSTART terms were counted in this category: akathisia, hyperkinesia.
dPatients with the following COSTART terms were counted in this category: buccoglossal syndrome, choreoathetosis, dyskinesia, tardive dyskinesia.
ePatients with the following COSTART terms were counted in this category: movement disorder, myoclonus, twitching.

The following table enumerates the percentage of adolescent patients with treatment-emergent extrapyramidal symptoms as assessed by spontaneously reported adverse reactions during acute therapy (dose range: 2.5 to 20 mg/day).

Table 17: Treatment-Emergent Extrapyramidal Symptoms Assessed by Adverse Reactions Incidence in Placebo-Controlled Clinical Trials of Oral Olanzapine in Schizophrenia and Bipolar I Disorder - Adolescents

Categoriesa Percentage of Patients Reporting Event
Placebo
(N=89)
Olanzapine
(N=179)
Dystonic events 0 1
Parkinsonism events 2 1
Akathisia events 4 6
Dyskinetic events 0 1
Nonspecific events 0 4
Any extrapyramidal event 6 10
aCategories are based on Standard MedDRA Queries (SMQ) for extrapyramidal symptoms as defined in MedDRA version 12.0.

The following table enumerates the percentage of patients with treatment-emergent extrapyramidal symptoms as assessed by categorical analyses of formal rating scales during controlled clinical trials comparing fixed doses of intramuscular olanzapine for injection with placebo in agitation. Patients in each dose group could receive up to 3 injections during the trials [see Clinical Studies]. Patient assessments were conducted during the 24 hours following the initial dose of intramuscular olanzapine for injection.

Table 18: Treatment-Emergent Extrapyramidal Symptoms Assessed by Rating Scales Incidence in a Fixed Dose, Placebo-Controlled Clinical Trial of Intramuscular Olanzapine for Injection in Agitated Patients with Schizophrenia

  Percentage of Patients Reporting Event
Placebo Olanzapine IM 2.5 mg Olanzapine IM 5 mg Olanzapine IM 7.5 mg Olanzapine IM 10 mg
Parkinsonisma 0 0 0 0 3
Akathisiab 0 0 5 0 0
aPercentage of patients with a Simpson-Angus Scale total score > 3.
bPercentage of patients with a Barnes Akathisia Scale global score ≥ 2.

The following table enumerates the percentage of patients with treatment-emergent extrapyramidal symptoms as assessed by spontaneously reported adverse reactions in the same controlled clinical trial comparing fixed doses of intramuscular olanzapine for injection with placebo in agitated patients with schizophrenia.

Table 19: Treatment-Emergent Extrapyramidal Symptoms Assessed by Adverse Reactions Incidence in a Fixed Dose, Placebo-Controlled Clinical Trial of Intramuscular Olanzapine for Injectionin Agitated Patients with Schizophrenia

  Percentage of Patients Reporting Event
Placebo
(N=45)
Olanzapine IM 2.5 mg
(N=48)
Olanzapine IM 5 mg
(N=45)
Olanzapine IM 7.5 mg
(N=46)
Olanzapine IM 10 mg
(N=46)
Dystonic eventsa 0 0 0 0 0
Parkinsonism eventsb 0 4 2 0 0
Akathisia eventsc 0 2 0 0 0
Dyskinetic eventsd 0 0 0 0 0
Residual eventse 0 0 0 0 0
Any extrapyramidal events 0 4 2 0 0
aPatients with the following COSTART terms were counted in this category: dystonia, generalized spasm, neck rigidity, oculogyric crisis, opisthotonos, torticollis.
bPatients with the following COSTART terms were counted in this category: akinesia, cogwheel rigidity, extrapyramidal syndrome, hypertonia, hypokinesia, masked facies, tremor.
cPatients with the following COSTART terms were counted in this category: akathisia, hyperkinesia.
dPatients with the following COSTART terms were counted in this category: buccoglossal syndrome, choreoathetosis, dyskinesia, tardive dyskinesia.
ePatients with the following COSTART terms were counted in this category: movement disorder, myoclonus, twitching.

Dystonia, Class Effect: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, the frequency and severity are greater with high potency and at higher doses of first generation antipsychotic drugs. In general, an elevated risk of acute dystonia may be observed in males and younger age groups receiving antipsychotics; however, events of dystonia have been reported infrequently ( < 1%) with olanzapine use.

Other Adverse Reactions: The following table addresses dose relatedness for other adverse reactions using data from a schizophrenia trial involving fixed dosage ranges of oral olanzapine. It enumerates the percentage of patients with treatment-emergent adverse reactions for the 3 fixed-dose range groups and placebo. The data were analyzed using the Cochran-Armitage test, excluding the placebo group, and the table includes only those adverse reactions for which there was a trend.

Table 20: Percentage of Patients from a Schizophrenia Trial with Treatment-Emergent Adverse Reactionsfor the 3 Dose Range Groups and Placebo

Adverse Reaction Percentage of Patients Reporting Event
Placebo
(N=68)
Olanzapine 5 ± 2.5 mg/day
(N=65)
Olanzapine 10 ± 2.5 mg/day
(N=64)
Olanzapine15 ± 2.5 mg/day
(N=69)
Asthenia 15 8 9 20
Dry mouth 4 3 5 13
Nausea 9 0 2 9
Somnolence 16 20 30 39
Tremor 3 0 5 7

Differences among Fixed-Dose Groups Observed in Other Olanzapine Clinical Trials

In a single 8-week randomized, double-blind, fixed-dose study comparing 10 (N=199), 20 (N=200) and 40 (N=200) mg/day of oral olanzapine in patients with schizophrenia or schizoaffective disorder, differences among 3 dose groups were observed for the following safety outcomes: weight gain, prolactin elevation, fatigue and dizziness. Mean baseline to endpoint increase in weight (10 mg/day: 1.9 kg; 20 mg/day: 2.3 kg; 40 mg/day: 3 kg) was observed with significant differences between 10 vs 40 mg/day. Incidence of treatment-emergent prolactin elevation > 24.2 ng/mL (female) or > 18.77 ng/mL (male) at any time during the trial (10 mg/day: 31.2%; 20 mg/day: 42.7%; 40 mg/day: 61.1%) with significant differences between 10 vs 40 mg/day and 20 vs 40 mg/day; fatigue (10 mg/day: 1.5%; 20 mg/day: 2.1%; 40 mg/day: 6.6%) with significant differences between 10 vs 40 and 20 vs 40 mg/day; and dizziness (10 mg/day: 2.6%; 20 mg/day: 1.6%; 40 mg/day: 6.6%) with significant differences between 20 vs 40 mg, was observed.

Other Adverse Reactions Observed During the Clinical Trial Evaluation of Oral Olanzapine

Following is a list of treatment-emergent adverse reactions reported by patients treated with oral olanzapine (at multiple doses ≥ 1 mg/day) in clinical trials. This listing is not intended to include reactions (1) already listed in previous tables or elsewhere in labeling, (2) for which a drug cause was remote, (3) which were so general as to be uninformative, (4) which were not considered to have significant clinical implications, or (5) which occurred at a rate equal to or less than placebo. Reactions are classified by body system using the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients.

Body as a Whole - Infrequent: chills, face edema, photosensitivity reaction, suicide attempt1; Rare: chills and fever, hangover effect, sudden death1.

Cardiovascular System - Infrequent: cerebrovascular accident, vasodilatation.

Digestive System - Infrequent: nausea and vomiting, tongue edema; Rare: ileus, intestinal obstruction, liver fatty deposit.

Hemic and Lymphatic System - Infrequent: leukopenia, thrombocytopenia.

Metabolic and Nutritional Disorders - Infrequent: alkaline phosphatase increased, bilirubinemia, hypoproteinemia.

Musculoskeletal System - Rare: osteoporosis.

Nervous System - Infrequent: ataxia, dysarthria, libido decreased, stupor; Rare: coma.

Respiratory System - Infrequent: epistaxis; Rare: lung edema.

Skin and Appendages - Infrequent: alopecia.

Special Senses - Infrequent: abnormality of accommodation, dry eyes; Rare: mydriasis.

Urogenital System - Infrequent: amenorrhea2, breast pain, decreased menstruation, impotence2, increased menstruation2, menorrhagia2, metrorrhagia2, polyuria2, urinary frequency, urinary retention, urinary urgency, urination impaired.

1 These terms represent serious adverse events but do not meet the definition for adverse drug reactions. They are included here because of their seriousness. 2Adjusted for gender.

Other Adverse Reactions Observed During the Clinical Trial Evaluation of Intramuscular Olanzapine for Injection

Following is a list of treatment-emergent adverse reactions reported by patients treated with intramuscular olanzapine for injection (at 1 or more doses ≥ 2.5 mg/injection) in clinical trials. This listing is not intended to include reactions (1) already listed in previous tables or elsewhere in labeling, (2) for which a drug cause was remote, (3) which were so general as to be uninformative, (4) which were not considered to have significant clinical implications, or (5) for which occurred at a rate equal to or less than placebo. Reactions are classified by body system using the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients.

Body as a Whole - Frequent: injection site pain.

Cardiovascular System - Infrequent: syncope.

Digestive System - Infrequent: nausea.

Metabolic and Nutritional Disorders - Infrequent: creatine phosphokinase increased.

Clinical Trials in Adolescent Patients (age 13 to 17 years)

Commonly Observed Adverse Reactions in Oral Olanzapine Short-Term, Placebo-Controlled Trials

Adverse reactions in adolescent patients treated with oral olanzapine (doses ≥ 2.5 mg) reported with an incidence of 5% or more and reported at least twice as frequently as placebo-treated patients are listed in Table 21.

Table 21: Treatment-Emergent Adverse Reactions of ≥ 5% Incidence among Adolescents (13-17 Years Old) with Schizophrenia or Bipolar I Disorder (Manic or Mixed Episodes)

Adverse Reactions Percentage of Patients Reporting Event
6 Week Trial % Schizophrenia Patients 3 Week Trial % Bipolar Patients
Olanzapine
(N=72)
Placebo
(N=35)
Olanzapine
(N=107)
Placebo
(N=54)
Sedationa 39 9 48 9
Weight increased 31 9 29 4
Headache 17 6 17 17
Increased appetite 17 9 29 4
Dizziness 8 3 7 2
Abdominal painb 6 3 6 7
Pain in extremity 6 3 5 0
Fatigue 3 3 14 6
Dry mouth 4 0 7 0
aPatients with the following MedDRA terms were counted in this category: hypersomnia, lethargy, sedation, somnolence.
bPatients with the following MedDRA terms were counted in this category: abdominal pain, abdominal pain lower, abdominal pain upper.

Adverse Reactions Occurring at an Incidence of 2% or More among Oral Olanzapine-Treated Patients in Short-Term (3-6 weeks), Placebo-Controlled Trials

Adverse reactions in adolescent patients treated with oral olanzapine (doses ≥ 2.5 mg) reported with an incidence of 2% or more and greater than placebo are listed in Table 22.

Table 22: Treatment-Emergent Adverse Reactions of ≥ 2% Incidence among Adolescents (13-17 Years Old) (Combined Incidence from Short-Term, Placebo-Controlled Clinical Trials of Schizophrenia or Bipolar I Disorder [Manic or Mixed Episodes])

Adverse Reaction Percentage of Patients Reporting Event
Olanzapine
(N=179)
Placebo
(N=89)
Sedationa 44 9
Weight increased 30 6
Increased appetite 24 6
Headache 17 12
Fatigue 9 4
Dizziness 7 2
Dry mouth 6 0
Pain in extremity 5 1
Constipation 4 0
Nasopharyngitis 4 2
Diarrhea 3 0
Restlessness 3 2
Liver enzymes increasedb 8 1
Dyspepsia 3 1
Epistaxis 3 0
Respiratory tract infectionc 3 2
Sinusitis 3 0
Arthralgia 2 0
Musculoskeletal stiffness 2 0
aPatients with the following MedDRA terms were counted in this category: hypersomnia, lethargy, sedation, somnolence.
bThe terms alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic enzyme were combined under liver enzymes.
cPatients with the following MedDRA terms were counted in this category: lower respiratory tract infection, respiratory tract infection, respiratory tract infection viral, upper respiratory tract infection, viral upper respiratory tract infection.

Vital Signs and Laboratory Studies

Vital Sign Changes

Oral olanzapine was associated with orthostatic hypotension and tachycardia in clinical trials. Intramuscular olanzapine for injection was associated with bradycardia, hypotension, and tachycardia in clinical trials [see WARNINGS AND PRECAUTIONS].

Laboratory Changes

Olanzapine Monotherapy in Adults: An assessment of the premarketing experience for olanzapine revealed an association with asymptomatic increases in ALT, AST, and GGT. Within the original premarketing database of about 2400 adult patients with baseline ALT ≤ 90 IU/L, the incidence of ALT elevations to > 200 IU/L was 2% (50/2381). None of these patients experienced jaundice or other symptoms attributable to liver impairment and most had transient changes that tended to normalize while olanzapine treatment was continued.

In placebo-controlled olanzapine monotherapy studies in adults, clinically significant ALT elevations (change from < 3 times the upper limit of normal [ULN] at baseline to ≥ 3 times ULN) were observed in 5% (77/1426) of patients exposed to olanzapine compared to 1% (10/1187) of patients exposed to placebo. ALT elevations ≥ 5 times ULN were observed in 2% (29/1438) of olanzapine-treated patients, compared to 0.3% (4/1196) of placebo-treated patients. ALT values returned to normal, or were decreasing, at last follow-up in the majority of patients who either continued treatment with olanzapine or discontinued olanzapine. No patient with elevated ALT values experienced jaundice, liver failure, or met the criteria for Hy's Rule.

Rare postmarketing reports of hepatitis have been received. Very rare cases of cholestatic or mixed liver injury have also been reported in the postmarketing period.

Caution should be exercised in patients with signs and symptoms of hepatic impairment, in patients with preexisting conditions associated with limited hepatic functional reserve, and in patients who are being treated with potentially hepatotoxic drugs.

Olanzapine administration was also associated with increases in serum prolactin [see WARNINGS AND PRECAUTIONS], with an asymptomatic elevation of the eosinophil count in 0.3% of patients, and with an increase in CPK.

Olanzapine Monotherapy in Adolescents: In placebo-controlled clinical trials of adolescent patients with schizophrenia or bipolar I disorder (manic or mixed episodes), greater frequencies for the following treatment-emergent findings, at anytime, were observed in laboratory analytes compared to placebo: elevated ALT ( ≥ 3X ULN in patients with ALT at baseline < 3X ULN), (12% vs 2%); elevated AST (28% vs 4%); low total bilirubin (22% vs 7%); elevated GGT (10% vs 1%); and elevated prolactin (47% vs 7%).

In placebo-controlled olanzapine monotherapy studies in adolescents, clinically significant ALT elevations (change from < 3 times ULN at baseline to ≥ 3 times ULN) were observed in 12% (22/192) of patients exposed to olanzapine compared to 2% (2/109) of patients exposed to placebo. ALT elevations ≥ 5 times ULN were observed in 4% (8/192) of olanzapine-treated patients, compared to 1% (1/109) of placebo-treated patients. ALT values returned to normal, or were decreasing, at last follow-up in the majority of patients who either continued treatment with olanzapine or discontinued olanzapine. No adolescent patient with elevated ALT values experienced jaundice, liver failure, or met the criteria for Hy's Rule.

ECG Changes

In pooled studies of adults as well as pooled studies of adolescents, there were no significant differences between olanzapine and placebo in the proportions of patients experiencing potentially important changes in ECG parameters, including QT, QTc (Fridericia corrected), and PR intervals. Olanzapine use was associated with a mean increase in heart rate compared to placebo (adults: +2.4 beats per minute vs no change with placebo; adolescents: +6.3 beats per minute vs -5.1 beats per minute with placebo). This increase in heart rate may be related to olanzapine's potential for inducing orthostatic changes [see WARNINGS AND PRECAUTIONS].

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ZYPREXA. Because these reactions are reported voluntarily from a population of uncertain size, it is difficult to reliably estimate their frequency or evaluate a causal relationship to drug exposure.

Adverse reactions reported since market introduction that were temporally (but not necessarily causally) related to ZYPREXA therapy include the following: allergic reaction (e.g., anaphylactoid reaction, angioedema, pruritus or urticaria), diabetic coma, diabetic ketoacidosis, discontinuation reaction (diaphoresis, nausea or vomiting), jaundice, neutropenia, pancreatitis, priapism, rash, rhabdomyolysis, and venous thromboembolic events (including pulmonary embolism and deep venous thrombosis). Random cholesterol levels of ≥ 240 mg/dL and random triglyceride levels of ≥ 1000 mg/dL have been reported.

Read the entire FDA prescribing information for Zyprexa (Olanzapine) »

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