Medication Guide App

Zyprexa Side Effects

Generic Name: olanzapine

Note: This page contains side effects data for the generic drug olanzapine. It is possible that some of the dosage forms included below may not apply to the brand name Zyprexa.

It is possible that some side effects of Zyprexa may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

For the Consumer

Applies to olanzapine: oral tablet, oral tablet disintegrating

As well as its needed effects, olanzapine (the active ingredient contained in Zyprexa) may cause unwanted side effects that require medical attention.

If any of the following side effects occur while taking olanzapine, check with your doctor immediately:

More common
  • Bloating or swelling of the face, arms, hands, lower legs, or feet
  • blurred vision
  • change in vision
  • change in walking and balance
  • clumsiness or unsteadiness
  • difficulty with speaking
  • difficulty with swallowing
  • drooling
  • impaired vision
  • inability to sit still
  • loss of balance control
  • mask-like face
  • muscle trembling, jerking, or stiffness
  • need to keep moving
  • rapid weight gain
  • restlessness
  • shuffling walk
  • slowed movements
  • slurred speech
  • stiffness of the arms and legs
  • tic-like (jerky) movements of the head, face, mouth, and neck
  • tingling of the hands or feet
  • trembling or shaking of the fingers, hands, feet, legs, or arms
  • twisting movements of the body
  • uncontrolled movements, especially of the face, neck, and back
  • unusual weight gain or loss
Less common
  • Bladder pain
  • bloody or cloudy urine
  • bruising
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • chest pain
  • difficult or labored breathing
  • difficult, burning, or painful urination
  • dizziness
  • excessive muscle tone
  • frequent urge to urinate
  • headache
  • inability to move the eyes
  • increased blinking or spasms of the eyelid
  • itching of the vagina or genital area
  • lack of coordination
  • large, flat, blue, or purplish patches in the skin
  • loss of bladder control
  • loss of memory
  • lower back or side pain
  • muscle tension or tightness
  • nervousness
  • pain during sexual intercourse
  • pounding in the ears
  • problems with memory
  • rhythmic movement of the muscles
  • shortness of breath
  • slow, fast, pounding, or irregular heartbeat or pulse
  • speaking is less clear than usual
  • sticking out the tongue
  • thick, white vaginal discharge with no odor or with a mild odor
  • tightness in the chest
  • twitching
  • uncontrolled twisting movements of the neck, trunk, arms, or legs
  • unusual or incomplete body or facial movements
  • weakness of the arms and legs

Some olanzapine side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

More common
  • Acid or sour stomach
  • back pain
  • belching
  • change in personality
  • difficulty having a bowel movement (stool)
  • discouragement
  • feeling sad or empty
  • fever
  • heartburn
  • increased appetite
  • increased cough
  • indigestion
  • lack of appetite
  • lack or loss of strength
  • loss of interest or pleasure
  • runny nose
  • sleeplessness
  • sneezing
  • stomach discomfort, upset, or pain
  • stuffy nose
  • thirst
  • trouble with concentrating
  • unable to sleep
  • watering of the mouth
Less common
  • Blemishes on the skin
  • body aches or pain
  • chills
  • cold sweats
  • congestion
  • cough
  • dry skin
  • dryness or soreness of the throat
  • false or unusual sense of well-being
  • heavy menstrual bleeding (periods)
  • hoarseness
  • joint pain
  • lack of feeling or emotion
  • leg cramps
  • pain in the arms or legs
  • pimples
  • sweating
  • tender, swollen glands in the neck
  • uncaring feelings
  • voice change
  • vomiting

For Healthcare Professionals

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

Nervous system

Somnolence may occur more frequently at higher dosages.

Placebo-controlled clinical trials involving patients receiving olanzapine (the active ingredient contained in Zyprexa) with either valproate or lithium for the treatment of bipolar mania reported a discontinuation rate of 3% due to somnolence.

At least one case of olanzapine-associated neuroleptic malignant syndrome has been reported. Fever, altered consciousness, autonomic dysfunction and muscle rigidity are the hallmarks of the neuroleptic malignant syndrome. The neuroleptic malignant syndrome is associated with a case mortality rate of about 20%. Immediate discontinuation of neuroleptic therapy, consideration of dantrolene therapy, as well as intensive monitoring and supportive care are indicated if the syndrome occurs.

A 52 year old male on long-term lithium therapy for the treatment of bipolar l disorder reported sleep-related eating disorder (SRED) occurring within days of initiating treatment with olanzapine 10 mg per day for an acute manic phase. The incidents of SRED disappeared rapidly and definitively after olanzapine therapy was discontinued.

Lower (worse) baseline scores predicted greater cognitive improvement. Change In cognitive performance was weakly related to change in symptom scores.[Ref]

Nervous system side effects have frequently included somnolence, tremor, insomnia, dizziness, speech disorder, abnormal gait, amnesia, paresthesia, apathy, confusion, tremor, akathisia, hypertonia, articulation impairment, incoordination, abnormal dreams, emotional lability, agitation, nervousness, and hostility. Akinesia, alcohol misuse, antisocial reaction, ataxia, CNS stimulation, cogwheel rigidity, delirium, dementia, depersonalization, dysarthria, facial paralysis, hypesthesia, hypokinesia, hypotonia, incoordination, stimulant misuse, stupor, stuttering, tardive dyskinesia, vertigo, and withdrawal syndrome have also been reported. Circumoral paresthesia, coma, encephalopathy, neuralgia, neuropathy, nystagmus, paralysis, subarachnoid hemorrhage, tobacco misuse, and sleep related eating disorder have been reported rarely. Seizures (including a case of fatal status epilepticus) have been reported in 0.9% of treated patients during premarketing clinical trials. Rare cases of neuroleptic malignant syndrome and somnambulism have been reported. A case of Parkinsonism has also been reported.

Olanzapine has been associated with improvement on cognitive test performance in patients in the early stages of schizophrenia.[Ref]


Cardiovascular side effects have frequently included postural hypotension, tachycardia, and hypertension. Atrial fibrillation, bradycardia, cerebrovascular accident, congestive heart failure, heart arrest, hemorrhage, migraine, pallor, palpitation, vasodilatation, and ventricular extrasystoles have also been reported. Arteritis, heart failure, venous thromboembolism, and pulmonary embolus have been reported rarely.

An increased risk of mortality, possibly due to heart failure or sudden death, has been reported with the use of atypical antipsychotic agents, including olanzapine (the active ingredient contained in Zyprexa) in the treatment of behavioral disorders in the elderly patient with dementia.[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. Similar results (i.e., increased risk of mortality with atypical antipsychotics) were reported in another meta-analysis involving elderly dementia patients that consisted of 15 randomized, placebo-controlled trials (n=3353) of 10 to 12 weeks in duration. Olanzapine is not approved by the FDA for use in the treatment of behavioral disorders in elderly patients with dementia.

Cerebrovascular adverse events (e.g., stroke, transient ischemic attack) which included fatalities have been reported in trials of olanzapine on elderly patients with dementia-related psychosis. There was a significantly higher incidence of cerebrovascular adverse events in patients treated with olanzapine when compared to patients treated with placebo. However, the association between the use of atypical antipsychotics (i.e., risperidone, olanzapine) and the risk of cerebrovascular events appears to be somewhat controversial. The results of a case-control study found no increased risk of cerebrovascular events in elderly patients treated with atypical antipsychotics.

The results of a large retrospective cohort study appear to indicate that atypical antipsychotic agents (i.e., risperidone, olanzapine, clozapine, quetiapine) increase the risk of venous thromboembolism in elderly patients; however, these events seem to be rare.

A 24 year old, nonsmoking healthy female participating in a pharmacokinetic study developed hypotension and bradycardia within approximately 1 to 2 hours following a single 5 mg oral dose. Serum samples revealed a shorter Tmax of 3 hours and a higher Cmax of 13 ng/mL compared to the average Tmax and Cmax of 5 hours and 7.3 ng/mL, respectively.[Ref]


Metabolic side effects have frequently included weight gain. Binge eating and increases in food craving have been associated with olanzapine (the active ingredient contained in Zyprexa) Acidosis, cyanosis, increased alkaline phosphatase, bilirubinemia, dehydration, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, hyperlipidemia, hyperuricemia, hypoglycemia, hypokalemia, and hyponatremia have also been reported. Gout, hyperkalemia, hypernatremia, hypoproteinemia, ketosis, and water intoxication have been reported rarely. A large scale clinical trial at clinically relevant doses has reported significant reductions in glucose tolerance during treatment with olanzapine.[Ref]

The results of the large scale clinical trial noted that treatment related changes in glucose tolerance were largely explained by changes in insulin sensitivity.

In one study, mean weight gain during olanzapine treatment trended toward a plateau after the initial 39 weeks with no further significant gain for up to three years. A higher baseline body mass index was predictive of a lower long-term weight gain. However, dose was not a significant predictor of greater long-term weight change.

Because olanzapine may stimulate appetite and increase weight gain, olanzapine meets the Beers criteria as a medication that is potentially inappropriate for use in older adults.

Clinical placebo-controlled trials involving patients receiving olanzapine with either valproate or lithium for the treatment of bipolar mania reported a discontinuation rate of 1% due to weight gain.

Based on a case report, it has been suggested that olanzapine's hypertriglyceridemic effects may be unrelated to its propensity to cause weight gain.[Ref]


Gastrointestinal side effects have frequently included dry mouth, increased appetite, thirst, constipation, dyspepsia, increased salivation, vomiting, and flatulence. Dysphagia, esophagitis, fecal impaction, fecal incontinence, gastritis, gastroenteritis, gingivitis, melena, mouth ulceration, nausea and vomiting, oral moniliasis, periodontal abscess, rectal hemorrhage, stomatitis, tongue edema, taste perversion, and tooth caries have also been reported. Aphthous stomatitis, enteritis, eructation, esophageal ulcer, glossitis, ileus, intestinal obstruction, and tongue discoloration have been reported rarely. Isolated cases of olanzapine-induced acute pancreatitis have been reported during postmarketing use.[Ref]

Nausea and dry mouth have been reported to be dose related.

A 65 year old man developed fecal incontinence following initiation of treatment with olanzapine 2.5 mg daily. This effect continued until the patient's next scheduled exam, at approximately 20 days after initiation of therapy, at which point olanzapine was discontinued. Fecal incontinence resolved within approximately 24 hours. No organic cause for fecal incontinence was determined, rectal exam was negative, sigmoidoscopy results were normal, and lab tests were all within normal limits.[Ref]


Hepatic side effects have rarely included hepatitis, liver fatty deposit, and cholestatic or mixed liver injury. Transient and moderate, asymptomatic elevations in liver function tests have been reported.[Ref]

Placebo-controlled clinical trials reported a 2% discontinuation rate due to increases in SGPT with olanzapine compared to 0% for placebo.

A 78 year old woman diagnosed with acute depression with psychotic features developed fever, malaise, arthralgia, upper abdominal pain, anorexia, and nausea approximately 13 days after initiating therapy with olanzapine 10 mg per day. Concomitant medications included calcium, vitamin D, multivitamin, and occasional acetaminophen. The patient had no history of liver disease, intravenous drug use, alcohol use, or blood transfusions. Physical examination revealed dry mucous membranes and a palpable, firm, tender liver. Lab results revealed a slight increase in leukocyte count and an increase in aspartate aminotransferase, alanine aminotransferase, total bilirubin, and alkaline phosphatase levels. All serologic tests were negative. Symptoms resolved and liver function test decreased with 4 days, and patient was completely recovered with all lab tests within normal limits within 4 weeks of onset.[Ref]


Respiratory side effects have frequently included rhinitis, increased cough, pharyngitis, and dyspnea. Apnea, asthma, epistaxis, hemoptysis, hyperventilation, hypoxia, laryngitis, and voice alterations have also been reported. Atelectasis, hiccup, hypoventilation, lung edema, and stridor have been reported rarely. Postmarketing reports have included pneumonia and lower respiratory tract infection which may be fatal.[Ref]

An increased risk of mortality, possibly due to an infection, such as pneumonia, has been reported with the use of atypical antipsychotic agents, including olanzapine, in the treatment of behavioral disorders in the elderly patient with dementia.

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]


A study of U.S. military veterans with schizophrenia has reported that patients on olanzapine (the active ingredient contained in Zyprexa) had 1.27 times as many cases of diabetes when compared to patients taking decades old drugs for psychosis including haloperidol, thioridazine, and others.

Over an eight year period that ended in 2002, 288 cases of olanzapine-associated diabetes have been reported, 75 of which resulted in severe illness and 23 in death. One group of investigators suggests that olanzapine may precipitate or unmask diabetes in susceptible patients. One study on olanzapine-associated diabetes concluded that the number of reports, temporal relationship to the start of olanzapine therapy, relatively young age, and improvement on drug withdrawal suggests that olanzapine may precipitate or unmask diabetes in susceptible patients.

Additional studies have confirmed that patients receiving atypical antipsychotics (i.e., clozapine, risperidone, olanzapine, quetiapine, ziprasidone) are at an increased risk of developing hyperglycemia and/or diabetes mellitus.

Hyperprolactinemia in some patients may cause sexual dysfunction, menstrual irregularities, and osteoporosis. In addition, as many as one-third of human breast cancers may be prolactin-dependent in vitro.[Ref]

Endocrine side effects have included hyperprolactinemia, hyperglycemia, and diabetes mellitus. Diabetic ketoacidosis (may be fatal) and goiter have been reported rarely.[Ref]


Hematologic side effects have rarely included anemia, leukocytosis, leukopenia, lymphadenopathy, thrombocytopenia, normocytic anemia, neutropenia, leukopenia, agranulocytosis, eosinophilia, agranulocytosis, and thrombocythemia.[Ref]


Ocular side effects have frequently included amblyopia, abnormal vision, and conjunctivitis. Abnormality of accommodation, blepharitis, cataract, diplopia, dry eyes, eye hemorrhage, eye inflammation, eye pain, ocular muscle abnormality have also been reported. Glaucoma, corneal lesion, keratoconjunctivitis, macular hypopigmentation, miosis, mydriasis, esotropia, and pigment deposits in the lens have been reported rarely. One possible case of olanzapine-induced oculogyric crisis and another case of bilateral eyelid edema have also been reported. At least one case of blepharoclonus has also been associated with olanzapine (the active ingredient contained in Zyprexa) [Ref]


Other side effects have frequently included asthenia, accidental injury, back pain, fever, chest pain, dental pain, peripheral edema, edema, and flu syndrome. Enlarged abdomen, chills, face edema, intentional injury, malaise, moniliasis, neck pain, neck rigidity, pelvic pain, photosensitivity reaction, ear pain, tinnitus, and deafness have also been reported. Chills and fever, hangover effect, and sudden death have been reported rarely. In addition, rare cases of withdrawal syndrome following discontinuation of olanzapine (the active ingredient contained in Zyprexa) have been reported. One possible case of increased serum creatine kinase, without neuromalignant syndrome, has been reported.[Ref]

In one reported case of withdrawal, symptoms included shaking, body aches, nausea, headache, reduced sleep, piloerection, blurred vision, fearfulness, nightmares, depression, restlessness in the arms and legs, and unformed auditory hallucinations.

Placebo-controlled clinical trials involving patients receiving olanzapine with either valproate or lithium for the treatment of bipolar mania reported a discontinuation rate of 1% due to peripheral edema.

A 34 year old white female with a history of bipolar disorder was diagnosed with bilateral 2-plus pitting edema in the ankles and dorsum of the feet approximately 10 days after initiating therapy with olanzapine 10 mg daily. Concomitant therapy included long-term routine use of bupropion and diazepam. All lab tests and clinical findings were found to be within normal limits. Olanzapine was discontinued and the edema resolved. Approximately 2 weeks after discontinuation, olanzapine 10 mg daily was resumed upon patients request, and again within approximately 10 days the bilateral edema recurred. Olanzapine was discontinued immediately, and the edema resolved within approximately 10 days.[Ref]


In one reported case of hypersensitivity syndrome, the patient presented with a severe, generalized pruritic skin eruption, fever, eosinophilia, and toxic hepatitis 60 days after ingestion of olanzapine (the active ingredient contained in Zyprexa) [Ref]

Hypersensitivity side effects have rarely included hypersensitivity syndrome.[Ref]


Genitourinary side effects have included urinary incontinence, and urinary tract infection in 2% of patients. Dysmenorrhea and vaginitis have been reported in 2% of female patients. Amenorrhea, decreased menstruation, lactation, increased menstruation, menorrhagia, metrorrhagia, premenstrual syndrome, enlarged uterine fibroids, and vaginal hemorrhage have also been reported in female patients. Impotence and abnormal ejaculation have been reported in male patients. Breast pain, cystitis, dysuria, glycosuria, gynecomastia, hematuria, polyuria, pyuria, urinary retention, urinary urgency, urination impairment, albuminuria, mastitis, and oliguria have also been reported. Priapism, which required treatment in some cases, has been reported occasionally.[Ref]

A 35 year old male with no prior history of mental illness nor history of psychotropic medication use developed priapism within approximately 14 hours after a single dose of olanzapine 10 mg for the treatment of schizoaffective disorder. The patient reported the condition to his clinician approximately 48 hours later. Several treatment options were tried before eventual detumescence of the penis occurred. The patient was reported to have permanent impotence as a result of his prolonged priapism.

A 27 year old female receiving valproate (6 month duration) for bipolar disorder reported painful swelling of the clitoris of 3 day duration following approximately 4 weeks of treatment with olanzapine 5 mg daily for mania. The patient was positive for intermittent, 2 to 3 times a month for 2 years, alcohol and cannabis use. The patient had no history of clitoral priapism or clitoral related pathology, routine physical and laboratory investigations were normal. Clitoral swelling resolved within approximately 2 days of discontinuation of olanzapine therapy.[Ref]


Musculoskeletal side effects have included extremity pain (other than joint pain) and joint pain in 5% of patients. Joint stiffness and twitching have been reported frequently. Arthritis, arthrosis, leg cramps, and myasthenia have also been reported. Bone pain, bursitis, myopathy, osteoporosis, rheumatoid arthritis, and rhabdomyolysis have been reported rarely.[Ref]


A 26-year-old male receiving treatment with olanzapine (the active ingredient contained in Zyprexa) 20 mg daily for approximately 2 years developed progressively increasing slate gray pigmentation of the dorsal aspect of both hands over a period of 4 months. Past medical history was insignificant, and negative for previous dermatologic disorders. All serum blood levels were within normal limits. Drug-induced acral melanosis was determined based on lab and clinical findings, with olanzapine as the offending agent due to temporal association.

Eruptive xanthomas was diagnosed via biopsy in a 31 year old male, 21 year old male, and a 50 year old Filipino female following approximately 4 to 8 weeks of treatment with olanzapine. Personal history was negative for diabetes mellitus or glucose intolerance in all cases; however, one case was positive for familial history of diabetes mellitus. Upon clinical evaluation, all patients were found to be positive for severe hyperglycemia and hypertriglyceridemia. Following initiation of appropriate treatment for diabetes mellitus and hypertriglyceridemia, the 31 year old male was found to be compliant with treatment, experienced normalization of serum glucose and triglycerides, and resolution of xanthomas despite continuation of olanzapine therapy; the 21 year old male was found to be noncompliant with treatment, continued to experience hypertriglyceridemia, and continued to exhibit persistent eruptive xanthomas; the 50 year old female was unavailable for follow-up.[Ref]

Dermatologic side effects have frequently included ecchymosis, sweating, acne, and dry skin. Alopecia, contact dermatitis, eczema, maculopapular rash, pruritus, seborrhea, skin discoloration, skin ulcer, urticaria, and vesiculobullous rash have also been reported. Hirsutism, papular rash, and eruptive xanthomas have been reported rarely. One case of hyperpigmentation has been reported.[Ref]


Psychiatric side effects have frequently included depression, euphoria, delusions, manic reaction, and schizophrenic reaction. Obsessive-compulsive symptoms and suicide attempt have also been reported.[Ref]


In general, clinical placebo-controlled trials have reported no difference in the incidence of discontinuation due to side effects in patients receiving olanzapine (the active ingredient contained in Zyprexa) versus placebo for the treatment of schizophrenia or monotherapy for bipolar mania. However, clinical studies involving valproate or lithium monotherapy for treatment of bipolar mania reported a 2% discontinuation rate due to side effects as compared to 11% when olanzapine was added.[Ref]


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