In the U.S.—

In Canada—

• Antipsychotic

Clozapine (KLOE-za-peen) is used to treat schizophrenia in patients who have not been helped by or are unable to take other medicines.

Clozapine is available only from pharmacies that agree to participate with your doctor in a plan to monitor your blood tests. You will need to have blood tests done every week for at least 6 months. After that, your doctor will decide if it is safe for you to have blood tests every other week. You will receive enough clozapine to last until your next blood test, but only if the results of your blood tests show that it is safe for you to take this medicine. If any of your blood tests are not normal, you may need to have blood tests more often than every week until they return to normal.

Clozapine is available in the following dosage form:

Oral
• Tablets (U.S. and Canada)

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For clozapine, the following should be considered:

Allergies—Tell your doctor if you have ever had any unusual or allergic reaction to clozapine. Also tell your health care professional if you are allergic to any other substances, such as foods, preservatives, or dyes.

Pregnancy—Clozapine has not been studied in pregnant women. However, clozapine has not been shown to cause birth defects or other problems in animal studies.

Breast-feeding—Clozapine may pass into breast milk and cause drowsiness, trouble in nursing, restlessness or irritability, convulsions (seizures), or heart or blood vessel problems in nursing babies.

Children—Studies on this medicine have been done only in adult patients, and there is no specific information comparing use of clozapine in children with use in other age groups.

Older adults—Many medicines have not been tested in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Clozapine may be more likely to cause side effects in the elderly, including dizziness and fainting, low blood pressure, and confusion or excitement.

Other medicines—Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking clozapine, it is especially important that your health care professional know if you are taking any of the following:

• Alcohol or
• Central nervous system (CNS) depressants (medicines that cause drowsiness) or
• Tricyclic antidepressants (amitriptyline [e.g., Elavil], amoxapine [e.g., Asendin], clomipramine [e.g., Anafranil], desipramine [e.g., Pertofrane], doxepin [e.g., Sinequan], imipramine [e.g., Tofranil], nortriptyline [e.g., Aventyl], protriptyline [e.g., Vivactil], trimipramine [e.g., Surmontil])—Using these medicines or alcohol with clozapine may cause increased drowsiness, low blood pressure, or trouble in breathing

• Amantadine (e.g., Symmetrel) or
• Antihypertensives (high blood pressure medicine) or
• Antipsychotics (medicine for mental illness) or
• Bromocriptine (e.g., Parlodel) or
• Certain eye drops used to treat glaucoma (carteolol [e.g., Ocupress], levobunolol [e.g., Betagan], metipranolol [e.g., OptiPranolol], timolol [e.g., Timoptic]) or
• Diuretics (water pills) or
• Levodopa (e.g., Dopar) or
• Medicine for heart disease or
• Nabilone (e.g., Cesamet) (with high doses) or
• Narcotic pain medicine or
• Pentamidine (e.g., Pentam) or
• Pimozide (e.g., Orap) or
• Promethazine (e.g., Phenergan) or
• Trimeprazine (e.g., Temaril)—Using these medicines with clozapine may cause low blood pressure, which can cause dizziness or fainting

• Amphotericin B by injection (e.g., Fungizone) or
• Antineoplastics (cancer medicine) or
• Antithyroid agents (medicine for overactive thyroid) or
• Azathioprine (e.g., Imuran) or
• Chlorambucil (e.g., Leukeran) or
• Chloramphenicol (e.g., Chloromycetin) or
• Colchicine or
• Cyclophosphamide (e.g., Cytoxan) or
• Flucytosine (e.g., Ancobon) or
• Ganciclovir (e.g., Cytovene) or
• Interferon (e.g., Intron A, Roferon-A) or
• Mercaptopurine (e.g., Purinethol) or
• Methotrexate (e.g., Mexate) or
• Plicamycin (e.g., Mithracin) or
• Zidovudine (e.g., AZT, Retrovir)—Taking clozapine with any of these medicines may increase the chance that very serious blood problems will occur

• Lithium—Using clozapine with lithium may increase the chance that convulsions (seizures), confusion or problems with movement will occur

• Selective serotonin reuptake inhibitors (fluoxetine [e.g., Prozac], fluvoxamine [e.g., Luvox], paroxetine [e.g., Paxil], sertraline [e.g., Zoloft])—These medicines can increase the blood levels of clozapine, which increases the chance that unwanted effects will occur

• Blood diseases or
• Enlarged prostate or difficult urination or
• Gastrointestinal problems or
• Glaucoma, narrow angle or
• Heart or blood vessel problems—Clozapine may make these conditions worse

• Epilepsy or other seizure disorder—Clozapine may increase the chance that seizures will occur

• Kidney or liver disease—Higher blood levels of clozapine may occur, increasing the chance that unwanted effects will occur

Take this medicine exactly as directed. Do not take more of this medicine and do not take it more often than your doctor ordered. Do not miss any doses.

This medicine has been prescribed for your current medical problem only. It must not be given to other people or used for other problems unless you are directed to do so by your doctor.

Dosing—

The dose of clozapine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of clozapine. If your dose is different, do not change it unless your doctor tells you to do so.

The number of tablets that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on your special needs.

• For oral dosage form (tablets):
  • For schizophrenia:
    • Adults—At first, 12.5 milligrams (mg) (one half of a 25-mg tablet) once or twice a day. Your doctor may increase your dose as needed. However, the dose usually is not more than 900 mg a day.
    • Children younger than 16 years of age—Use and dose must be determined by your doctor.

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss 2 or more days of clozapine doses, talk to your doctor before you start taking it again. You may need to restart this medicine at a lower dose than you were taking before.

Storage—

To store this medicine:

• Keep out of the reach of children.
• Store away from heat and direct light.
• Do not store in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the medicine to break down.
• Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of the reach of children.

It is important that you have your blood tests done when they are scheduled, and that your doctor check your progress at regular visits . Clozapine can cause some very serious blood problems that you may not be able to feel or see. The pharmacy will give you this medicine only if your blood tests show that it is safe for you to take clozapine. Also, your doctor will make sure the medicine is working properly and change the dosage if needed.

If you do not take clozapine for 2 or more days, talk to your doctor about what to do. You may need to take a lower dose when you first start taking this medicine again.

If you have been using this medicine regularly, do not stop taking it without first checking with your doctor. Your doctor may want you to reduce gradually the amount you are taking before stopping completely. This is to help prevent the illness from suddenly returning.

This medicine will add to the effects of alcohol and other CNS depressants (medicines that slow down the nervous system, possibly causing drowsiness). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; barbiturates; medicine for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using this medicine.

Contact your doctor as soon as possible if you develop unusual tiredness or weakness, fever, sore throat, or other symptoms of infection. These can be symptoms of a very serious blood problem.

Contact your doctor as soon as possible if you have chest pain or discomfort, a fast heartbeat, trouble breathing, or fever and chills. These can be symptoms of a very serious problem with your heart.

Clozapine may cause drowsiness, blurred vision or convulsions (seizures). Do not drive, climb, swim, operate machines or do anything else that could be dangerous while you are taking this medicine.

Dizziness, lightheadedness, or fainting may occur, especially when you get up from a lying or sitting position. Getting up slowly may help. If this problem continues or gets worse, check with your doctor.

In some patients, clozapine may cause increased watering of the mouth. Other patients, however, may get dryness of the mouth. For temporary relief of mouth dryness, use sugarless gum or candy, melt bits of ice in your mouth, or use a saliva substitute. However, if your mouth continues to feel dry for more than 2 weeks, check with your medical doctor or dentist. Continuing dryness of the mouth may increase the chance of dental disease, including tooth decay, gum disease, and fungus infections.

Along with its needed effects, a medicine may cause some unwanted effects. Some side effects may not have signs or symptoms that you can see or feel. Clozapine can cause some very serious blood problems. Your doctor will watch for these by doing blood tests every week or two for as long as you are taking clozapine and for 4 weeks after you stop taking it. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• More common
  • Fast or irregular heartbeat;  fever;  low blood pressure 
  
  

• Less common
  • High blood pressure (severe or continuing headache) 
  
  

• Rare
  • Chest pain or discomfort;  chills;  convulsions (seizures);  cough;  difficult or fast breathing or sudden shortness of breath;  fainting;  increased sweating;  loss of bladder control;  muscle stiffness (severe);  sore throat;  sores, ulcers, or white spots on lips or in mouth;  swelling or pain in leg;  trouble breathing;  unusual bleeding or bruising;  unusual tiredness or weakness;  unusually pale skin 
  
  

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

• More common
  • Dizziness, especially when getting up from a lying or sitting position 
  
  

• Less common
  • Blurred vision;  confusion;  restlessness or need to keep moving;  unusual anxiety, nervousness, or irritability 
  
  

• Rare
  • Absence of or decrease in movement;  decreased sexual ability;  high blood sugar (increased appetite, increased thirst, increased urination, weakness);  lip smacking or puckering;  liver problems (dark urine, decreased appetite, nausea, vomiting, yellow eyes or skin);  mental depression;  puffing of cheeks;  rapid or worm-like movements of tongue;  trembling or shaking;  trouble in sleeping;  trouble in urinating;  uncontrolled chewing movements;  uncontrolled movements of arms and legs  
  
  

• Symptoms of overdose
  • Convulsions (seizures);  dizziness or fainting;  drowsiness (severe) or coma;  fast, slow, or irregular heartbeat;  hallucinations (seeing, hearing, or feeling things that are not there);  increased watering of mouth (severe);  slow, irregular, or troubled breathing;  unusual excitement, nervousness, or restlessness 
  
  

Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, check with your doctor if any of the following side effects continue or are bothersome:

• More common
  • Constipation;  dizziness or lightheadedness (mild);  drowsiness;  headache (mild);  increased watering of mouth;  nausea or vomiting;  unusual weight gain  
  
  

• Less common
  • Abdominal discomfort or heartburn;  dryness of mouth 
  
  

Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor.