Clozapine, also known as Clozaril, Denzapine and Zaponex, is an antipsychotic drug mainly used to treat severe schizophrenia in adults, usually when other treatments have not worked. Clozapine is prescribed after consulting with your doctor, and you will be closely monitored whilst taking the medication, as harmful complications can occur if you have underlying health issues or are taking other medications.

Clozapine brand names

Clozapine is also known by other brand names, including Clozaril, FazalClo ODT, Versacloz, Denzapine and Zaponex.

What is clozapine prescribed for?

Clozapine is mainly used to treat severe schizophrenia in adults (18+), typically when other medications have not worked. [1] It is also used to treat patients with schizophrenia or schizoaffective disorder who have recurring episodes of suicide ideation and/or behavior.

Clozapine is sometimes prescribed for violent or paranoid personality disorders, which occur when a person has an unrelenting mistrust or suspicion of others for no apparent reason. [2] However, this is ‘off-label,’ meaning there is not enough research to formally recommend its use, but there is some evidence it has worked for some people. 

Clozapine is also the only treatment licensed to treat adults with Parkinson’s Disease Psychosis, which includes delusional thoughts and tremors occurring due to having Parkinson’s disease. [3]

How does clozapine work?

Clozapine changes the chemicals in the brain that are thought to cause psychosis and delusional thoughts in the brain. [4]

Clozapine treats schizophrenia by interrupting the chemicals that lead to the symptoms of schizophrenia. For example, by affecting the brain chemistry, Clozapine prevents or reduces disturbed thinking, delusions, withdrawal, or loss of interest from life, and strong or inappropriate feelings.

How is clozapine usually taken?

Clozapine is prescribed by your doctor to meet your individual needs and should be taken exactly as instructed - never take clozapine without medical advice. It is important to read all the information on the prescription label and follow the instructions given by your healthcare team. [1]

Clozapine is a drug that needs to be titrated. This means that when the medication is started, changed, or stopped, it should be done gradually to reduce the potential for harmful side effects.

Clozapine is dispensed either as a liquid (oral suspension) or in tablets that disintegrate in the mouth.

How long does clozapine stay in your system?

Clozapine stays in your system about 15 days, or 360 hours. Rapid withdrawal from Clozapine can cause rebound psychosis.

Clozapine side effects

Clozapine can be a very effective drug, but it has some dangerous side effects, meaning that risks will have to be balanced with benefits before prescribing it. The side effects that you experience will depend on the individual and the dose that you take. [4]

There are some common side effects that you do not need to worry about as much, but report to your doctor if they persist or have an adverse effect on your life. These are:

Common side effects

  • Gastric discomfort, including acid reflux, heartburn, or belching
  • Feeling sleepy
  • Relaxed feeling with a mild feeling of spinning
  • Mild constipation

Less common

  • Vision problems, including distorted color, tunnel vision, blurred vision, double vision, halos around lights, or loss of vision
  • Restlessness, an inability to sit still, or increased body movements
  • Muscle problems, including severe stiffness, aches, pain, or weakness
  • Nightmares
  • Pain in the back, neck, or legs
  • Feeling unusually drowsy, tired, weak, or sluggish
  • Ejaculation problems
  • A sore tongue, ulcers or white spots in the mouth
  • A blocked or stuffy nose
  • Pain in the chest

There are other side effects that have been reported, but it is not known how common they are, including:

  • Skin problems, including lesions (often red with a purple center); blistering, peeling or loosening of the skin; increased sensitivity to sunlight leading to sunburn; hives; or welts
  • Severe abdominal pain
  • Swelling of the face, nose, and eyes, or salivary glands
  • Irritated red eyes
  • Painful or long-lasting erections

Major side effects

Clozaril also has some very serious side effects that should be reported to a doctor as soon as they occur. [5]

These are:

  • Weakened immune system

One of the major side effects of Clozapine is that it can weaken your immune system by reducing your white blood cell production (neutropenia). This means that you may contract infections more easily, or have more serious and even fatal infections. If you have any symptoms of an infection, such as a high temperature, flu-like symptoms, feelings of weakness or fatigue, a sore throat, or common symptoms of a vaginal, kidney, skin, or lung infection, it is important that you contact your doctor.

  • Seizures

Clozapine can increase the risk of seizures, especially when you are taking a high dose of the drug. If you are taking Clozapine, you may have to avoid activities that could be dangerous if were to lose consciousness during a seizure, such as driving, rock climbing, or outdoor swimming. If you begin having seizures whilst taking Clozapine, make sure you let your doctor know.

  • Heart problems

Clozapine can also cause heart problems and lead to cardiac arrest or pulmonary embolism. It is important that if you have any chest pain, shortness of breath, dizziness, or fast and pounding heartbeat, contact your doctor immediately.

  • Metabolic problems

Clozapine causes metabolic problems, such as weight gain, type two diabetes and blood sugar problems, high blood pressure, and raised cholesterol. It is known to cause weight gain in 30% of people who take it. These side effects can cause long-term harm and need to be managed.

Clozapine precautions

You should only take Clozapine if you have been prescribed the medication from your doctor or medical team. The doctor will ask you questions before prescribing Clozapine, as there are many potential adverse reactions and side effects. Do not take Clozapine if you have ever had an allergic reaction to any of its ingredients.

Before you take Clozapine, you will also have blood work done to check your blood count, blood sugar level, and cholesterol. This is to ensure that you do not have any underlying conditions that may interact negatively with Clozapine. 

Due to increased risk factors, Clozapine is not prescribed to older adults with dementia-related psychosis, people under 18, pregnant or breastfeeding women, people with epilepsy, people with a heart condition or high blood pressure, and people with a wide range of health conditions, including those that affect the lungs, liver, and kidneys.

It is important to be honest with your medical team about all the drugs you take (prescribed or not) to avoid harm to yourself, as Clozapine interacts with many other drugs in ways that could put you at risk. [1], [4], [5]

The doctor will take a full medical history to ensure you do not have any underlying health issues that may increase the risk of having a bad reaction to Clozapine.

The doctor will also talk to you about Clozapine side effects to watch for, and when to contact your doctor. Whilst taking Clozapine, you will be regularly monitored to make sure that you do not develop an illness that could cause an adverse reaction with Clozapine, and to monitor any side effects, including a weakened immune system.

It is important that you do not suddenly stop taking Clozapine, as there can be severe side effects. This includes if you are pregnant. Although it is not recommended to take Clozapine in the last three months of pregnancy, it can also be dangerous to stop taking it suddenly, so discuss any plans for cessation with your doctor so that you can be monitored.

Clozapine interactions

Clozapine is a drug that can have harmful interactions with a substantial number of prescribed, over-the-counter, and recreational drugs, including alcohol and caffeine. There are 445 major and 415 minor drug interactions listed for Clozapine, which indicates just how many drugs it interacts with. When you are taking Clozapine, it is vital to discuss any additional medication or drug that you take with your doctor.

Clozapine can cause serious heart problems if taken with certain other medications, including some for infections, heart problems, depression, malaria, HIV, cancer, asthma, and high blood pressure. 

Most drugs will affect how Clozapine works, including over-the-counter medications (such as cough medicines), herbal medicines (especially St John’s Wort), and vitamins. 

There can be dangerous side effects from drinking alcohol and taking Clozapine, and alcohol use should be avoided. Clozapine levels can also be affected by nicotine, so it is important to tell your doctor if you have recently stopped smoking or changed your smoking habits. 

Clozapine storage

Clozapine needs to be stored at room temperature and in a dark and dry place. Direct sunlight and moisture can damage the medication, so do not store it in a bathroom. If the medication is damaged, you may experience side effects, as the Clozapine may not work as expected.

Clozapine can be dangerous for anyone without a prescription, so keep the medication out of reach from others, especially children or pets. 

The best place to store the medication is in an airtight container in a high cupboard.

Clozapine has an expiration date that should be heeded. If the product has expired, do not take it, as it may no longer be the right dose for you. 

What to do if you overdose on Clozapine

It is very dangerous to take more Clozapine than you have been prescribed, and an overdose can cause a change in your heartbeat or breathing, fainting and dizziness, loss of consciousness, or even death.

If you take too much Clozapine, you should seek help immediately and call the poison helpline on 1-800-222-1222. If you are having trouble breathing, call 911 (or the emergency services number in your country).

If you think someone has had an overdose of Clozapine, you should seek medical attention and call 911 (or the emergency services number in your country) if they have collapsed, had a seizure, are having difficulty breathing, or cannot be awakened.

Frequently asked questions about Clozapine

Is Clozapine addictive?

Stopping or reducing clozapine causes withdrawal symptoms and sometimes a relapse of symptoms of psychosis; therefore, it may be difficult to cease. However, it is not considered a risk for recreational drug abuse.

Are there any alternatives to Clozapine?

You will only usually be prescribed clozapine if you have already tried other antipsychotic medications that have not worked. These include olanzapine, risperidone, aripiprazole, and quetiapine. Talk to your doctor about alternative medications that might be an option for you.

Resources:

  1. Warnez, S., Alessi-Severini, S. Clozapine (2014). A review of clinical practice guidelines and prescribing trends. BMC Psychiatry 14, 102.
  2. Brown, D., Larkin, F., Sengupta, S., Romero-Ureclay, J. L., Ross, C. C., Gupta, N., Vinestock, M., & Das, M. (2014). Clozapine: an effective treatment for seriously violent and psychopathic men with antisocial personality disorder in a UK high-security hospital. CNS Spectrums19(5), 391–402.
  3. Joyce, E. (2022) Adults with Parkinson's disease and hallucinations or delusions can have treatment with clozapine if they need to. BJPsych Advances,28(2), 99-101.
  4. Dragoi, A. M., Radulescu, I., Năsui, B. A., Pop, A. L., Varlas, V. N., & Trifu, S. (2020). Clozapine: an updated overview of pharmacogenetic biomarkers, risks, and safety-particularities in the context of COVID-19. Brain Sciences10(11).
  5. Iqbal E, Govind R, Romero A, Dzahini O, Broadbent M, Stewart R, et al. (2020) The side effect profile of Clozapine in real world data of three large mental health hospitals. PLoS ONE, 15(12): e0243437.