How does this medication work? What will it do for me?

Clozapine belongs to a family of medications called antipsychotics. It is used to treat schizophrenia when other medications are not effective. Schizophrenia is related to imbalances in certain brain chemicals such as dopamine. This medication helps to balance these chemicals.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

What form(s) does this medication come in?

Apo-Clozapine is no longer being manufactured for sale in Canada. For brands that may still be available, search under clozapine.  This article is being kept available for reference purposes only. If you are using this medication, speak with your doctor or pharmacist for information about your treatment options.

How should I use this medication?

The recommended dose varies widely based on need but is usually started at 12.5 mg taken once or twice daily and adjusted gradually upwards according to the doctor's instructions.

Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

Do not stop taking this medication without talking to your doctor. If it becomes necessary to stop this medication, the dose should be reduced gradually to prevent withdrawal effects. Stopping clozapine too quickly can cause a return of the symptoms you originally started taking the medication for as well as headache, nausea, vomiting, and diarrhea.

It is important to take this medication exactly as prescribed. If you miss a dose of this medication and remember within 2 hours, take it as soon as possible. However, if it has been more than 2 hours, skip the missed dose and go back to your regular dosing schedule. If you miss 2 or more days of clozapine doses, talk to your doctor before restarting the medication. You may need to start taking the medication at a lower dose than you were taking previously.

Store this medication in its original container at room temperature and keep it out of the reach of children.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not take this medication if you:

  • are allergic to clozapine or any ingredients of this medication
  • are unable to undergo regular blood tests
  • have active liver disease associated with nausea, loss of appetite, or jaundice (yellowing of skin)
  • have certain blood disorders (e.g., platelet disorders, low white blood cells)
  • have obstruction of the bowels
  • have severe heart disease (e.g., myocarditis) or heart failure
  • have severe kidney disease
  • have uncontrolled epilepsy

Do not give this medication to people who are in a severely sedated or comatose state.

What side effects are possible with this medication?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

  • abdominal discomfort or heartburn
  • constipation
  • diarrhea
  • dizziness or lightheadedness (mild)
  • drowsiness
  • dry mouth
  • falls
  • headache (mild)
  • increased watering of mouth
  • increased sweating
  • joint pain
  • nausea or vomiting
  • nighttime bedwetting
  • patchy skin colour changes
  • rash or itchy skin
  • stuffy nose
  • weight gain

Although most of the side effects listed below don't happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

  • abnormal heart rhythms (such as fast or slow heart rate, palpitations, shortness of breath)
  • blurred vision
  • change in thoughts or behaviours (unusual anxiety, nervousness, irritability, excitement, nervousness, or restlessness)
  • confusion
  • constipation that is new or worsening
  • decreased sexual ability
  • diarrhea (severe)
  • difficulty reading
  • difficulty speaking
  • dizziness, especially when getting up from a lying or sitting position
  • drowsiness (severe)
  • fainting
  • muscle spasms
  • muscle weakness or stiffness
  • problems swallowing
  • restlessness or need to keep moving
  • signs of anemia (low red blood cells; e.g., dizziness, pale skin, unusual tiredness or weakness, shortness of breath)
  • signs of a blood clot in the arm or leg (tenderness, pain, swelling, warmth, or redness in the arm or leg) or lungs (difficulty breathing, sharp chest pain that is worse when breathing in, coughing, coughing up blood, sweating, or passing out)
  • signs of bleeding (e.g., unusual nosebleeds, bruising, blood in urine, coughing blood, bleeding gums, cuts that don't stop bleeding)
  • signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
  • signs of heart problems (e.g., fast, irregular heartbeat or pulse, chest pain, sudden weight gain, difficulty breathing, leg swelling)
  • signs of inflammation of the heart muscle (e.g., chest pain, fast heartbeat, fever, shortness of breath, flu-like symptoms)
  • signs of kidney problems (e.g., change in the amount or colour of urine, decreased urination, increased urination at night, blood in the urine, swelling in the feet or legs)
  • signs of neuroleptic malignant syndrome (e.g., confusion, reduced consciousness, high fever, or muscle stiffness)
  • signs of pancreatitis (e.g., abdominal pain on the upper left side, back pain, nausea, fever, chills, rapid heartbeat, swollen abdomen)
  • signs of pneumonia (e.g., fever, chills, shortness of breath, cough)
  • signs of heart failure (e.g., shortness of breath; fatigue; swelling in legs, ankles, feet)
  • symptoms of high blood sugar (increased appetite, increased thirst, increased urination, weakness)
  • symptoms of increased pressure in the eyes (e.g., decreased or blurred vision, eye pain, red eye, swelling of the eye)
  • symptoms of infections (symptoms may include fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness)
  • symptoms of liver problems (dark urine, decreased appetite, nausea, vomiting, yellow eyes or skin)
  • symptoms of movement disorders (e.g., continuous muscle spasms and contractions, slow movements, irregular, jerky movements, tremor, inability to move eyes, increased blinking, puffing of cheeks, shuffling walk, tremor)
  • stomach pain
  • trouble sleeping

Stop taking the medication and seek immediate medical attention if any of the following occur:

  • an erection that lasts more than 4 hours
  • convulsions (seizures)
  • signs of a serious allergic reaction (e.g., abdominal cramps, difficulty breathing, nausea and vomiting, swelling of the face and throat)
  • signs of a heart attack (e.g., chest pain or pressure, pain extending through shoulder and arm, nausea and vomiting, sweating)
  • signs of a severe skin reaction such as blistering, peeling, a rash covering a large area of the body, a rash that spreads quickly, or a rash combined with fever or discomfort
  • signs of stroke (e.g., sudden or severe headache; sudden loss of coordination; vision changes; sudden slurring of speech; or unexplained weakness, numbness, or pain in arm or leg)
  • symptoms of severely increased blood pressure (e.g., chest pain, blurred vision, dizziness, excessive tiredness, headache, stronger or faster heartbeat)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for this medication?

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Blood clots: This medication may increase the chance of blood clot formation, causing reduction of blood flow to organs or the extremities.

If you have a history of clotting you may be at increased risk of experiencing blood clot-related problems such as heart attack, stroke, or clots in the deep veins of your leg. Discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

If you experience symptoms such as sharp pain and swelling in the leg, difficulty breathing, chest pain, blurred vision, or difficulty speaking, contact your doctor immediately.

Blood disorders: Because of the significant risk of serious blood disorders, including life-threatening decrease in white blood cell counts, clozapine should only be used by people for whom other medications do not work or for whom other medications cause intolerable side effects.

Blood work must be performed weekly for the first 26 weeks of treatment, then every 2 weeks for the next 26 weeks, in order to monitor the effect of the medication on the number of white blood cells. After this time, blood tests should be done at least every 4 weeks and continue for 4 weeks after the medication is stopped. If you notice lethargy (a tired and groggy feeling), weakness, fever, sore throat, flu-like complaints, or any other signs of infection, contact a doctor immediately.

For safety reasons, lab test results are recorded in patient registries. A patient registry is a database of health-related information collected from people with a particular medical condition for the purposes of safety and research. Different drug companies that make clozapine have different registries. If you switch from one brand of clozapine to another, your name will be entered into a different registry, and it will make it difficult to monitor your history of clozapine use and your safety. To ensure that this does not happen, new information will be added to the Patient Registration Form. This will help improve the way your health information is collected and shared between registries.

Cholesterol: Clozapine can cause increases in cholesterol and other lipids in the blood. If you have increased cholesterol or are at risk of developing increased cholesterol, discuss with your doctor whether any special monitoring is needed.

Constipation: This medication may cause constipation, possibly resulting in obstruction or blockage of the intestines. If you have abdominal or stomach problems, or are talking other medications that cause constipation, discuss with your doctor whether any special monitoring is needed.

Diabetes: Clozapine may cause an increase in blood sugar levels and glucose tolerance may change. People with diabetes may find it necessary to monitor their blood sugar more frequently while using this medication.

If you have diabetes or are at risk for developing diabetes, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Drowsiness/reduced alertness: Clozapine may affect the mental or physical abilities needed to drive or operate machinery, particularly during the first few days of taking this medication. Avoid driving, operating machinery, or performing other hazardous tasks until you have determined how this medication affects you.

Enlarged prostate: This medication may worsen symptoms of an enlarged prostate, such as reduced urine flow. If you have a prostate condition, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Glaucoma: People with glaucoma (increased pressure in the eyes) may find that this medication makes the symptoms of glaucoma worse. If you have glaucoma, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Heart and lung problems: Clozapine may increase the risk of heart and lung problems. If you have heart disease, you should not use this medication. Get medical attention immediately if you notice chest pain; shortness of breath; fast, irregular, or pounding heartbeat; extreme fatigue; flu-like symptoms; unexplained fever; more noticeable neck veins when standing or sitting; or fainting.

Heart rhythm: Clozapine can cause changes to the normal rhythm of the heart, including an irregular heartbeat called QT prolongation. QT prolongation is a serious, life-threatening condition that can cause fainting, seizures, and sudden death. If you are at risk for heart rhythm problems (e.g., if you have heart failure, angina, or low potassium or magnesium levels), discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Interruption of treatment: If you stop taking clozapine for 2 days or more, do not restart your medication at the same dosage; contact your doctor for dosage instructions.

Kidney function: Kidney disease or reduced kidney function may cause this medication to build up in the body, causing side effects. If you have reduced kidney function or kidney disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Liver function: Clozapine is broken down by the liver. Liver disease or reduced liver function may cause this medication to build up in the body, causing side effects. If you have liver problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Your doctor may want to test your liver function regularly with blood tests while you are taking this medication.

This medication may also cause a decrease in liver function. If you experience symptoms of liver problems such as fatigue, feeling unwell, loss of appetite, nausea, yellowing of the skin or whites of the eyes, dark urine, pale stools, abdominal pain or swelling, and itchy skin, contact your doctor immediately.

Low blood pressure: Extreme lowering of blood pressure when moving from a lying or sitting to a standing position, with or without loss of consciousness, can occur with clozapine, especially at the beginning of therapy when doses are being increased. To reduce the possibility of this being problematic, move slowly when rising from a sitting or lying position.

Movement disorder: People taking clozapine may develop tardive dyskinesia, a disorder of uncontrolled muscle movements, mainly in the face, tongue, mouth, or jaw. The risk increases with longer treatment and is higher in seniors, especially senior women. Tardive dyskinesia is more likely to be irreversible with long-term treatment (over 12 weeks). If you develop signs and symptoms of tardive dyskinesia, including sticking the tongue out, smacking the lips, pursing or puckering of lips, or other involuntary movements, contact your doctor as soon as possible.

Neuroleptic malignant syndrome: A rare but serious effect called neuroleptic malignant syndrome has been reported with antipsychotic medications such as clozapine. You should monitor for the following symptoms: altered mental status, heart palpitations, high fever, irregular pulse or blood pressure, muscle rigidity (muscle stiffness), and sweating. If you notice these symptoms, contact your doctor immediately.

Seizures: Clozapine may cause seizures. The dosing prescribed by the doctor should be carefully followed and activities requiring alertness (e.g., driving, operating machinery, swimming, climbing) should be avoided.

Severe skin reactions: This medication has been associated with several life-threatening allergic skin reactions. If you experience any skin reactions, such as peeling, shedding, or scaling of the skin, a rash that forms blisters, or you have symptoms that affect the body (e.g., fever, nausea, swollen lymph glands, joint swelling or pain, yellowing of the skin or eyes, dry cough, or shortness of breath), contact your doctor immediately.

Pregnancy: Clozapine should be used only if the benefits clearly outweigh the risks. If you become pregnant or intend to become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding: This medication may pass into breast milk. If you are breast-feeding and are taking clozapine, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and efficacy of this medication for use by children and adolescents below age 18 have not been established.

Seniors: People over the age of 60 years may have an increased risk of developing side effects from this medication. Studies with antipsychotic medications have shown that seniors with dementia taking antipsychotic medications have an increased rate of death. Seniors with dementia should not take clozapine.

What other drugs could interact with this medication?

There may be an interaction between clozapine and any of the following:

  • abiraterone
  • aclidinium
  • acyclovir
  • alcohol
  • aldesleukin
  • aliskiren
  • alpha-agonists (e.g., clonidine, methyldopa)
  • alpha-blockers (e.g., alfuzosin, doxazosin, tamsulosin)
  • amiodarone
  • amphetamines (e.g., dextroamphetamine, lisdexamfetamine)
  • angiotensin converting enzyme inhibitors (ACEIs; captopril, enalapril, ramipril)
  • angiotensin receptor blockers (ARBs; e.g., candesartan, irbesartan, losartan)
  • antacids (e.g., aluminum hydroxide, calcium carbonate, magnesium hydroxide)
  • antihistamines (e.g., azelastine, cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
  • anti-Parkinsons medications (e.g., amantadine, apomorphine, bromocriptine, levodopa, pramipexole, ropinirole)
  • other antipsychotics (e.g., chlorpromazine, haloperidol, olanzapine, quetiapine, risperidone)
  • apalutamide
  • atropine
  • "azole" antifungals (e.g., fluconazole, ketoconazole, voriconazole)
  • barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
  • benzodiazepines (e.g., clonazepam, diazepam, lorazepam)
  • benztropine
  • beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
  • bosentan
  • botulinum toxin
  • brimonidine
  • buprenorphine
  • bupropion
  • cabergoline
  • caffeine
  • calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
  • cannabis
  • chloral hydrate
  • chloroquine
  • cimetidine
  • cinacalcet
  • cobicistat
  • conivaptan
  • darifenacin
  • deferasirox
  • dexamethasone
  • dexmethylphenidate
  • diabetes medications (e.g., acarbose, canagliflozin, glyburide, insulin, linagliptin, lixisenatide, metformin, rosiglitazone)
  • diazoxide
  • disopyramide
  • diuretics (water pills; e.g., furosemide, hydrochlorothiazide, triamterene)
  • domperidone
  • donepezil
  • dronedarone
  • echinacea
  • elagolix
  • eluxadoline
  • entacapone
  • enzalutamide
  • eplerenone
  • esketamine
  • estrogens (e.g., ethinyl estradiol, birth control pills)
  • fesoterodine
  • flavoxate
  • flecainide
  • formoterol
  • galantamine
  • general anaesthetics (medications used to put people to sleep before surgery)
  • gingko biloba
  • glecaprevir and pibrentasvir
  • glucagon
  • glycopyrrolate
  • grapefruit juice
  • guanfacine
  • HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., efavirenz, etravirine, nevirapine)
  • HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir, saquinavir)
  • interferons
  • ipratropium
  • isoniazid
  • leflunomide
  • lemborexant
  • letermovir
  • leuprolide
  • lithium
  • lumacaftor and ivacaftor
  • macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
  • medications that can suppress the immune system (e.g., azathioprine, biologics, cancer medications, cyclosporine, hydroxyurea, mycophenolate, tacrolimus)
  • methadone
  • methoxsalen
  • methylphenidate
  • metoclopramide
  • mexiletine
  • mifepristone
  • minoxidil
  • mirabegron
  • mirtazapine
  • modafinil
  • monoamine oxidase inhibitors (MAOIs; moclobemide, phenelzine, rasagiline, selegiline, tranylcypromine)
  • muscle relaxants (e.g., cyclobenzaprine, methocarbamol, orphenadrine, tizanidine)
  • nabilone
  • narcotics (e.g., codeine, fentanyl, morphine, oxycodone, tramadol)
  • nitrates (e.g., nitroglycerin, isosorbide dinitrate, isosorbide mononitrate)
  • obinutuzumab
  • omeprazole
  • oxybutynin
  • pentamidine
  • pentoxifylline
  • phenylephrine
  • phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
  • potassium chloride
  • procainamide
  • propafenone
  • quinidine
  • quinine
  • quinolone antibiotics (e.g., ciprofloxacin, levofloxacin, norfloxacin, ofloxacin)
  • rifampin
  • rifabutin
  • riociguat
  • rivastigmine
  • romidepsin
  • St. John's wort
  • salmeterol
  • sarilumab
  • scopolamine
  • serotonin antagonists (anti-emetic medications; e.g., granisetron, ondansetron)
  • serotonin/norepinephrine reuptake inhibitors (SNRIs; e.g., desvenlafaxine, duloxetine, venlafaxine)
  • seizure medications (e.g., carbamazepine, clobazam, levetiracetam, phenobarbital, phenytoin, primidone, rufinamide, topiramate, valproic acid, zonisamide)
  • selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, fluvoxamine, paroxetine)
  • serotonin-norepinephrine reuptake inhibitors (SNRIs; e.g., desvenlafaxine, duloxetine, venlafaxine)
  • siltuximab
  • solifenacin
  • terbinafine
  • teriflunomide
  • tetrabenazine
  • thalidomide
  • tiotropium
  • tobacco smoke
  • tocilizumab
  • tolterodine
  • trazodone
  • tretinoin
  • tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
  • tryptophan
  • tyrosine kinase inhibitors (e.g., bosutinib, dasatinib, imatinib, nilotinib, osimertinib, vandetanib)
  • umeclidinium
  • valacyclovir
  • zidovudine
  • zolpidem
  • zopiclone

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

  • stop taking one of the medications,
  • change one of the medications to another,
  • change how you are taking one or both of the medications, or
  • leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

All material copyright MediResource Inc. 1996 – 2024. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: