Olanzapine side effects and how to avoid them

Olanzapine side effects include orthostatic hypotension, weight gain, and hyperglycemia. Here's how to avoid them.

By Keith Gardner, R.Ph. | Jul. 12, 2021

Olanzapine, also known by Eli Lilly and Company’s brand name Zyprexa, is a prescription medication that works in the brain to treat the symptoms of schizophrenia. Olanzapine is among a more recently discovered group of antipsychotics classified as “atypical” or “second-generation” antipsychotics. The exact mechanism of action of olanzapine is unknown, although it is thought it reduces or eliminates symptoms of psychosis primarily by its effects on brain chemicals, or neurotransmitters, such as dopamine and serotonin.

Olanzapine is approved by the U.S. Food and Drug Administration (FDA) for use in people 13 years or older for the treatment of schizophrenia, manic or mixed episodes of bipolar disorder, and long-term treatment of bipolar disorder. In combination with fluoxetine, an antidepressant, it is approved for use in treatment-resistant depression (depressive episodes that do not get better after trying at least two other antidepressants).

Olanzapine is available in several different dosage forms including oral tablet, orally disintegrating tablet (brand name Zyprexa Zydis), immediate-release intramuscular (IM) injection, and extended-release injection (brand name Zyprexa Relprevv).

As with any medication, it is important to be aware of side effects and other drug interactions. The following drug information highlights potential olanzapine side effects and how to avoid them.

Common side effects of olanzapine

The most common side effects of olanzapine seen in controlled clinical studies include:

Orthostatic hypotension (temporary lowering of blood pressure, usually related to suddenly standing to an upright position)
Constipation
Weight gain
Hyperglycemia (high blood sugar, or glucose, levels)
Dizziness
Personality disorder
Restlessness
Lack of energy
Fever
Dry mouth
Indigestion
Increased appetite
Drowsiness
Tremor
Back pain
Speech disorder
Increased salivation
Amnesia
Tingling or pricking sensation in hands and feet
Thirst
Depression
Impaired or dim vision
Parkinsonism (tremor, mask-like facial expression, drooling, rigidity, or stiff gait)
Extrapyramidal events (movement disorders such as restlessness, spastic contractions of muscles, or jerky movements of the face and body)

These are not all the possible side effects of olanzapine. For more information regarding side effects talk to your healthcare professional.

Orthostatic hypotension

Orthostatic hypotension is the temporary low blood pressure usually related to suddenly standing from a seated or lying position. Symptoms associated with orthostatic hypotension include dizziness, irregular heartbeat, or fainting. Orthostatic hypotension is most likely to occur during the initiation of olanzapine therapy or when it is given in combination with other medicines that may heighten the orthostatic effect of olanzapine, such as Valium (diazepam) or alcohol.

To help prevent orthostatic hypotension, you should stand upright or otherwise change positions slowly and lie down if you feel dizzy or faint. You should contact your healthcare professional if you experience signs and symptoms associated with orthostatic hypotension.

Weight gain

Weight gain is a common adverse effect for all atypical antipsychotics, including olanzapine.

In an analysis of all clinical studies where olanzapine was compared to a placebo, adult patients taking olanzapine gained an average of 5.7 pounds compared to an average weight loss of 0.6 pounds in placebo-treated patients. In long-term studies lasting at least 48 weeks, the average weight gain for adult patients on olanzapine was 12.3 pounds.

In clinical studies for adolescent patients older than 13 years of age, the increase in weight was even greater than in adults. In long-term studies lasting at least 24 weeks, the average weight gain was 24.6 pounds.

When starting olanzapine, you should check your weight regularly and contact your doctor if you see a rapid weight increase. Consider meeting with a dietician for help with a diet plan, if necessary.

Hyperglycemia (high blood sugar)

Compared to other atypical antipsychotics, olanzapine is more likely to result in an increase in blood sugar, or glucose, levels. Average increases of up to 15 mg/dL were reported in clinical trials. These increases in blood glucose levels were even higher in patients with unstable blood glucose levels when entering the clinical study. In an analysis of patients who completed up to 12 months of therapy, the rate of increase in blood glucose levels slowed after approximately six months.

Before starting olanzapine, you should discuss the potential risk of high blood glucose levels and the associated adverse events with your healthcare professional. Blood glucose levels should be frequently monitored for signs of worsening control. If you have diabetes, consult your healthcare professional about how often to check your blood glucose while taking olanzapine.

Serious side effects of olanzapine

Olanzapine has an FDA-mandated “boxed warning,” also called a black box warning, regarding its use in older adults with dementia-related psychosis having an increased risk of death primarily due to cardiovascular events or infections. Zyprexa Relprevv (olanzapine injection) has a boxed warning regarding delirium and sedation following injection.

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Antipsychotics, including olanzapine, may cause the following rare, but serious side effects:

Increased risk of death in older people who are confused, have memory loss, or have lost touch with reality (dementia-related psychosis). The use of olanzapine is contraindicated, i.e., not approved for these patients.
Severe hyperglycemia (high blood sugar) in patients who may or may not already have diabetes; high blood sugar may lead to a buildup of acid in the blood due to excess ketones (ketoacidosis), coma, or death.
High fat (cholesterol and triglycerides) levels in the blood may occur, especially in teenagers. Healthcare professionals should perform blood tests to check cholesterol and triglyceride levels before prescribing olanzapine and routinely during treatment.
Neuroleptic malignant syndrome (NMS), a rare reaction that affects the nervous system and causes symptoms like a high fever and muscle stiffness.
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome has been reported with olanzapine use. DRESS is a hypersensitivity reaction that can have a broad range of symptoms, including fever, rash, facial swelling, enlarged lymph nodes, and kidney or liver injury.
Tardive dyskinesia has been associated with antipsychotic drugs, including olanzapine. Symptoms are repetitive body movements that can not be controlled and usually affect the face and tongue.
Difficulty with control of body temperature. Symptoms include sweating too much or not at all, dry mouth, feeling very hot, feeling thirsty, and inhibited urination.

How long do olanzapine side effects last?

Most side effects tend to go away as the body adjusts to the medicine. Once you begin olanzapine therapy you should be monitored by your healthcare professional for progression of potential long-term side effects such as weight gain, high blood sugar, tardive dyskinesia, or high cholesterol and triglyceride levels in the blood.

Olanzapine contraindications and warnings

Abuse potential

Olanzapine is not considered an addictive medicine nor does it have habit-forming potential, but you should not abruptly discontinue it as withdrawal symptoms may occur. Withdrawal symptoms of olanzapine may include the return of psychotic symptoms, agitation, anxiety, diarrhea, trouble sleeping, muscle pain, nausea, sweating, and restlessness.

Overdose

In clinical studies of olanzapine, overdosage was identified in 67 patients. In the patient taking the largest identified amount (300 mg), the only symptoms reported were sleepiness and slurred speech. In the overdose patients who were clinically evaluated, vital signs were usually within normal limits. In the general population, symptoms of overdose include drowsiness, agitation, aggression, slurred speech, confusion, increased heart rate, jerky or uncontrolled muscle movements, trouble breathing, or fainting. There is no specific antidote for an overdose of olanzapine and any overdose event should be immediately reported to a healthcare professional.

Restrictions

The safety and effectiveness of olanzapine in children younger than 13 years old have not been established and its use is not recommended.

Older adults with dementia-related psychosis treated with antipsychotic medications, including olanzapine, are at an increased risk of death. Olanzapine is not approved for use in patients with dementia-related psychosis.

Women who are pregnant or planning to become pregnant should discuss the risks and benefits of olanzapine treatment with their healthcare professionals. Antipsychotic use, including olanzapine, has caused abnormal muscle movements and withdrawal symptoms in newborns following delivery. It is not recommended that breastfeeding women taking olanzapine since olanzapine passes into breast milk and may adversely affect the infant.

Olanzapine interactions

The following are potential drug interactions that may occur when taking olanzapine with other medications. This is not an exhaustive list and you should always talk to your healthcare professional for medical advice regarding drug and food interactions before taking olanzapine.

Alcohol, Valium (diazepam), and antihypertensive agents, including ACE inhibitors (Prinivil, Zestril), calcium channel blockers (Norvasc, Procardia), and diuretics (hydrochlorothiazide), increase the possibility of experiencing orthostatic hypotension.
Luvox (fluvoxamine), Prilosec (omeprazole), and Rimactane (rifampin) may affect the amount of time olanzapine stays active in the body and may necessitate a dosage adjustment.
Anticholinergic drugs given with olanzapine can increase the risk for severe gastrointestinal (GI) adverse reactions. Common anticholinergic drugs include:
- OTC drugs: Chlor-Trimeton, Tavist, Dramamine, Benadryl, Unisom, Bonine, Phenergan
- Rx drugs: Amitriptyline, doxepin, imipramine, Paxil (paroxetine), Ditropan (oxybutynin), Detrol (tolterodine), dicyclomine, hyoscyamine, Transderm Scop (scopolamine)

How to avoid olanzapine side effects

1. Talk to your healthcare professional about your health history

Before starting olanzapine, tell your healthcare professional if you’ve ever had:

Heart disease or problems
Seizures
Diabetes or hyperglycemia (high blood sugar levels)
High cholesterol or triglyceride levels in your blood
Liver problems
Low or high blood pressure
Strokes or “mini-strokes” (also called transient ischemic attacks or TIAs)
Alzheimer’s disease
Narrow-angle glaucoma
Enlarged prostate in men
Bowel obstruction
Phenylketonuria (Zyprexa Zydis contains phenylalanine)
Breast cancer
Thoughts of suicide or hurting yourself
You are pregnant or plan to become pregnant
Breastfeeding or plan to breastfeed
If you exercise a lot or are in hot places often

2. Beware of drowsiness

Because dizziness or drowsiness may occur, avoid driving or hazardous activity until you know how olanzapine will affect you. Also, avoid drinking alcohol.

3. Monitor blood sugar, cholesterol, and triglyceride levels

You may need to frequently test your blood sugar levels and cholesterol and triglyceride levels. Olanzapine is more likely than other atypical antipsychotics to raise blood sugar levels. It’s also associated with weight gain and increased fat levels in the blood, especially in teenagers.

4. Stay cool and hydrated

Some antipsychotics impair the body’s ability to regulate temperature. Avoid becoming overheated or dehydrated and drink plenty of fluids, particularly in hot weather or while exercising.

5. Take olanzapine as directed

Follow the directions on your prescription label and read all medication guides or instruction sheets.
Your healthcare professional may occasionally change your dose; use the olanzapine exactly as directed.
Olanzapine can be taken with or without food.
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, skip the missed dose and take your next dose at the regular time (i.e., don’t take two at the same time).
Do not stop using olanzapine abruptly. You should discuss with your healthcare professional how to gradually taper your dose to prevent withdrawal symptoms.