Pronunciation:

KLOE-za-peen

Brand Names:

• Clozaril
• FazaClo

Dosage Forms:

• Tablet, Disintegrating
• Tablet

Warnings:

• Agranulocytosis
  • Clozaril(R):
    • Because of a significant risk of agranulocytosis, a potentially life-threatening adverse event, Clozaril(R) should be reserved for use in (1) the treatment of severely ill patients with schizophrenia who fail to show an acceptable response to adequate courses of standard antipsychotic drug treatment, or (2) for reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at risk of reexperiencing suicidal behavior .
  • FazaClo(R):
    • Because of a significant risk of agranulocytosis, a potentially life-threatening adverse event, FazaClo(R) should be reserved for use in the treatment of severely ill patients with schizophrenia who fail to show an acceptable response to adequate courses of standard antipsychotic drug treatment .
  • Patients being treated with clozapine must have a baseline white blood cell (WBC) count and absolute neutrophil count (ANC) before initiation of treatment as well as regular WBC counts and ANCs during treatment and for at least 4 weeks after discontinuation of treatment.
  • Clozapine is available only through a distribution system that ensures monitoring of WBC count and ANC according to the schedule described below prior to delivery of the next supply of medication.
• Seizures
  • Seizures have been associated with the use of clozapine. Dose appears to be an important predictor of seizure, with a greater likelihood at higher clozapine doses. Caution should be used when administering clozapine to patients having a history of seizures or other predisposing factors. Patients should be advised not to engage in any activity where sudden loss of consciousness could cause serious risk to themselves or others.
• Myocarditis
  • Analyses of post-marketing safety databases suggest that clozapine is associated with an increased risk of fatal myocarditis, especially during, but not limited to, the first month of therapy. In patients in whom myocarditis is suspected, clozapine treatment should be promptly discontinued.
• Other Adverse Cardiovascular and Respiratory Effects
  • Orthostatic hypotension, with or without syncope, can occur with clozapine treatment. Rarely, collapse can be profound and be accompanied by respiratory and/or cardiac arrest. Orthostatic hypotension is more likely to occur during initial titration in association with rapid dose escalation. In patients who have had even a brief interval off clozapine, i.e., 2 or more days since the last dose, treatment should be started with 12.5 mg once or twice daily.
  • Since collapse, respiratory arrest and cardiac arrest during initial treatment has occurred in patients who were being administered benzodiazepines or other psychotropic drugs, caution is advised when clozapine is initiated in patients taking a benzodiazepine or any other psychotropic drug.
• Increased Mortality in Elderly Patients with Dementia-related Psychosis
  • Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Analysis of seventeen placebo-controlled trials (modal duration of 10 weeks) in these patients revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that seen in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Clozapine is not approved for the treatment of patients with dementia-related psychosis .

Risks associated with the use of clozapine include agranulocytosis, seizures, myocarditis, orthostatic hypotension, and respiratory and/or cardiac arrest. Patients being treated with clozapine must have a baseline white blood cell (WBC) count and absolute neutrophil count (ANC) before initiation of treatment as well as regular WBC counts and ANCs during treatment and for at least 4 weeks after discontinuation of treatment. Clozapine is only available through a distribution system that ensures monitoring of WBC count and ANC according to the schedule prior to delivery of the next supply of medication. Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death; most appeared to be cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Not approved for the treatment of patients with dementia-related psychosis .

Classifications:

Therapeutic—

Antipsychotic

Chemical—

Dibenzodiazepine

Uses of This Medicine:

Clozapine is used to treat schizophrenia in patients who have not been helped by or are unable to take other medicines. This medicine should NOT be used to treat behavioral problems in older adult patients who have dementia.

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.

Before Using This Medicine:

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 this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

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. This medicine should not be used for behavioral problems in older adults with dementia.

Pregnancy—

	Pregnancy Category	Explanation
All Trimesters	B	Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Droperidol

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• 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

Proper Use of This Medicine:

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 this medicine 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 this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine 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 the medical problem for which you are using the medicine.

• 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—

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using This Medicine:

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.

Side Effects of This Medicine:

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

Some 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. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

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 may also occur in some patients. If you notice any other effects, check with your healthcare professional.