AUDIENCE: Psychiatry, Dermatology, Patient
ISSUE: FDA is warning that the antipsychotic medicine olanzapine can cause a rare but serious skin reaction that can progress to affect other parts of the body. FDA is adding a new warning to the drug labels for all olanzapine-containing products that describes this severe condition known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).
A search of the FDA Adverse Event Reporting System (FAERS) database identified 23 cases of DRESS reported with olanzapine worldwide since 1996, when the first olanzapine-containing product was approved. FAERS includes only reports submitted to FDA, so there are likely to be additional cases about which FDA is unaware. One patient taking olanzapine experienced DRESS and died; however, this patient was taking multiple medicines that could also have contributed to death (see the Data Summary section at http://www.fda.gov/Drugs/DrugSafety/ucm499441.htm for more information).
DRESS may start as a rash that can spread to all parts of the body. It can include fever and swollen lymph nodes and a swollen face. It causes a higher-than-normal number of infection-fighting white blood cells called eosinophils that can cause inflammation, or swelling. DRESS can result in injury to organs including the liver, kidneys, lungs, heart, or pancreas, and can lead to death. DRESS is a potentially fatal drug reaction with a mortality rate of up to 10%.
BACKGROUND: Olanzapine is an antipsychotic medicine used to treat mental health disorders schizophrenia and bipolar disorder. It can decrease hallucinations, in which people hear or see things that do not exist, and other psychotic symptoms such as disorganized thinking. Olanzapine is available under the brand names Zyprexa, Zyprexa Zydis, Zyprexa Relprevv, and Symbyax, and also as generics.
RECOMMENDATIONS: Patients taking olanzapine-containing products who develop a fever with a rash and swollen lymph glands, or swelling in the face, should seek medical care right away. The combined symptoms together are commonly seen in DRESS. Talk with your health care professional about any questions or concerns. Do not stop taking olanzapine or change your dose without first talking with your health care professional. Sudden stopping of the medicine can be harmful without your health care professional's direct supervision.
Health care professionals should immediately stop treatment with olanzapine if DRESS is suspected. There is currently no specific treatment for DRESS. The important ways to manage DRESS are early recognition of the syndrome, discontinuation of the offending agent as soon as possible, and supportive care. Treatment with systemic corticosteroids should be considered in cases with extensive organ involvement. When prescribing the medicine, explain the signs and symptoms of severe skin reactions to your patients and tell them when to seek immediate medical care.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
For people being treated with olanzapine extended-release (long-acting) injection:
When you receive olanzapine extended-release injection, the medication is usually released slowly into your blood over a period of time. However, when you receive olanzapine extended-release injection, there is a small chance that olanzapine may be released into your blood too quickly. If this happens, you may experience a serious problem called Post-injection Delirium Sedation Syndrome (PDSS). If you develop PDSS, you may experience dizziness, confusion, difficulty thinking clearly, anxiety, irritability, aggressive behavior, weakness, slurred speech, difficulty walking, muscle stiffness or shaking, seizures, drowsiness, and coma (loss of consciousness for a period of time). You are most likely to experience these symptoms during the first 3 hours after you receive the medication. You will receive olanzapine extended-release injection in a hospital, clinic, or other medical facility where you can receive emergency medical treatment if it is needed. You will need to remain in the facility for at least 3 hours after you receive the medication. While you are in the clinic, the medical staff will watch you closely for signs of PDSS. When you are ready to leave the facility, you will need a responsible person to be with you, and you should not drive a car or operate machinery for the rest of the day. Get emergency medical help right away if you experience any symptoms of PDSS after you leave the facility.
A program has been set up to help people receive olanzapine extended-release injection safely. You will need to register and agree to the rules of this program before you receive olanzapine extended-release injection. Your doctor, the pharmacy that dispenses your medication, and the medical facility where you receive your medication will also need to register. Ask your doctor if you have any questions about this program.
For people being treated with olanzapine extended-release injection or olanzapine injection:
Studies have shown that older adults with dementia (a brain disorder that affects the ability to remember, think clearly, communicate, and perform daily activities and that may cause changes in mood and personality) who take antipsychotics (medications for mental illness) such as olanzapine have an increased chance of death during treatment. Older adults with dementia may also have a greater chance of having a stroke or ministroke during treatment.
Olanzapine injection and olanzapine extended-release injection are not approved by the Food and Drug Administration (FDA) for the treatment of behavior disorders in older adults with dementia. Talk to the doctor who prescribed this medication if you, a family member, or someone you care for has dementia and is being treated with olanzapine injection or olanzapine extended-release injection. For more information visit the FDA website: http://www.fda.gov/Drugs
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with olanzapine extended-release injection and each time you receive an injection. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.
Talk to your doctor about the risks of receiving olanzapine injection or olanzapine extended-release injection.
Why is this medication prescribed?
Olanzapine extended-release injection is used to treat schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions). Olanzapine injection is used to treat episodes of agitation in people who have schizophrenia or in people who have bipolar I disorder (manic depressive disorder; a disease that causes episodes of depression, episodes of severe mania, and other abnormal moods) and are experiencing an episode of mania (abnormally excited or irritated mood). Olanzapine is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain.
How should this medicine be used?
Olanzapine injection and olanzapine extended-release injection come as powders to be mixed with water and injected into a muscle by a healthcare provider. Olanzapine injection is usually given as needed for agitation. If you are still agitated after you receive your first dose, you may be given one or more additional doses. Olanzapine extended-release injection is usually given once every 2 to 4 weeks.
Olanzapine extended-release injection may help control your symptoms but will not cure your condition. Continue to keep appointments to receive olanzapine extended-release injection even if you feel well. Talk to your doctor if you do not feel like you are getting better during your treatment with olanzapine extended-release injection.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before receiving olanzapine injection or olanzapine extended-release injection,
- tell your doctor and pharmacist if you are allergic to olanzapine, any other medications, or any of the ingredients in olanzapine injection or olanzapine extended-release injection. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: antihistamines (in cough and cold medications); carbamazepine (Carbatrol, Equetro, Tegretol); diazepam (Valium); fluvoxamine (Luvox); dopamine agonists such as bromocriptine (Parlodel), cabergoline (Dostinex), levodopa (Dopar, Laradopa); pramipexole (Mirapex), and ropinirole (Requip); medications for anxiety, high blood pressure, irritable bowel disease, mental illness, motion sickness, pain, Parkinson's disease, ulcers, or urinary problems; omeprazole (Prilosec, in Zegerid); rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); sedatives; sleeping pills, and tranquilizers. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor if you have a low number of white blood cells or if any other medication has ever caused a decrease in your white blood cells. Also tell your doctor if you use or have ever used street drugs or have overused prescription medications and if you have or have ever had a stroke, a ministroke, heart disease, a heart attack, heart failure, an irregular heartbeat, seizures, breast cancer, any condition that makes it difficult for you to swallow, high or low blood pressure, a high level of fats (cholesterol and triglycerides) in your blood, paralytic ileus (condition in which food cannot move through the intestine); glaucoma (an eye condition), high blood sugar, diabetes, or liver or prostate disease. Tell your doctor if you have severe vomiting, diarrhea or signs of dehydration now, or if you develop these symptoms at any time during your treatment. Also tell your doctor if you have ever had to stop taking a medication for mental illness because of severe side effects or have or have had thoughts about harming or killing yourself.
- tell your doctor if you are pregnant, especially if you are in in the last few months of your pregnancy, if you plan to become pregnant, or if you are breastfeeding. If you become pregnant during your treatment with olanzapine injection, call your doctor.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are being treated with olanzapine injection.
- you should know that receiving olanzapine injection or olanzapine extended-release injection may make you drowsy and may affect your ability to think clearly, make decisions, and react quickly. Do not drive a car or operate machinery for the rest of the day after you receive olanzapine extended-release injection. Do not drive a car or operate machinery at other times during your treatment with olanzapine extended-release injection or during your treatment with olanzapine injection until you know how this medication affects you.
- you should know that alcohol can add to the drowsiness caused by this medication. Do not drink alcohol during your treatment with olanzapine.
- tell your doctor if you use tobacco products. Cigarette smoking may decrease the effectiveness of this medication.
- you should know that olanzapine injection and olanzapine extended-release injection may cause dizziness, lightheadedness, fast or slow heartbeat, and fainting when you get up too quickly from a lying position, especially right after you receive your injection. If you feel dizzy or drowsy after you receive your injection, you will need to lie down until you feel better. During your treatment, you should get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
- you should know that you may experience hyperglycemia (increases in your blood sugar) while you are taking this medication, even if you do not already have diabetes. If you have schizophrenia, you are more likely to develop diabetes than people who do not have schizophrenia, and receiving olanzapine injection, olanzapine extended-release injection or similar medications may increase this risk. Tell your doctor immediately if you have any of the following symptoms during your treatment: extreme thirst, frequent urination, extreme hunger, blurred vision, or weakness. It is very important to call your doctor as soon as you have any of these symptoms, because high blood sugar can cause a serious condition called ketoacidosis. Ketoacidosis may become life-threatening if it is not treated at an early stage. Symptoms of ketoacidosis include dry mouth, nausea and vomiting,shortness of breath, breath that smells fruity, and decreased consciousness.
- you should know that olanzapine injection or olanzapine extended-release injection may make it harder for your body to cool down when it gets very hot. Tell your doctor if you plan to do vigorous exercise or be exposed to extreme heat. Be sure to drink plenty of water and call your doctor if you experience any of the following symptoms: feeling very hot, sweating heavily, not sweating even though it is hot, dry mouth, excessive thirst, or decreased urination.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do if I forget a dose?
If you forget to keep an appointment to receive olanzapine extended-release injection, call your doctor to schedule another appointment as soon as possible.
What side effects can this medication cause?
Olanzapine injection and olanzapine extended-release injection may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- increased appetite
- weight gain
- stomach pain
- dry mouth
- back or joint pain
- vaginal discharge
- missed menstrual periods
- breast enlargement or discharge
- decreased sexual ability
- pain, hardness, or a lump in the place where the medication was injected
Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:
- sore throat, fever, chills, or other signs of infection
- excessive sweating
- muscle stiffness
- fast or irregular heartbeat
- uncontrollable unusual movements of your face or body
- difficulty swallowing
- chest pain
Olanzapine injection and olanzapine extended-release injection may cause other side effects. Call your doctor if you have any unusual problems while you are receiving this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
In case of emergency/overdose
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Symptoms of overdose may include the following:
- slurred speech
- difficulty walking
- slowed or uncontrollable movements
- muscle stiffness
- aggressive behavior
- fast heartbeat
- coma (loss of consciousness for a period of time)
What other information should I know?
Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests to check your body's response to olanzapine injection or olanzapine extended-release injection.
Ask your pharmacist any questions you have about olanzapine injection or olanzapine extended-release injection.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
- Zyprexa Relprevv®