Precautions

Clozaril is contraindicated in patients with a previous hypersensitivity to Clozapine or any other component of this drug, in patients withmyeloproliferative disorders, uncontrolled epilepsy, paralytic ileus, or a history of Clozaril-induced agranulocytosis or severe granulocytopenia. As with more typical antipsychotic drugs, Clozaril is contraindicated in severe central nervous system depression or comatose states from any cause.

 

Among elderly patients with dementia-related psychosis, treatment with Clozapine is associated with an increased risk of death for unclear reasons. Clozapine is not approved for use in dementia-related psychosis.

 

Seizures have occurred in approximately 1 of every 20 to 30 persons receiving clozapine. Patients receiving higher doses seem to be at higher risk. Clozapine may cause a severe reduction in white blood cell count. White blood cells fight infections. If there is a severe reduction in white blood cells it can result in severe infections. Early detection may avoid fatality. Therefore, the white blood cell count should be measured.

 

There are no adequate studies of Clozapine in pregnant women, If you are pregnant or thinking about becoming pregnant, talk your doctor to see if the benefits outweighs the adverse effects. It is not recommended to breastfeed while on this medication.

 

Clozapine also may cause sudden, often jerky, uncontrollable motions of the body and eyes. The risk of such reactions appears to be lower withClozapine than with older anti-psychotics, perhaps due to its weaker effects on dopamine type-2 receptors. Patients ought to be tested during treatment for elevated blood-sugars. In addition, patients with risk factors for diabetes, including obesity or a family history of diabetes, should have their fasting levels of blood sugar tested before they start treatment and periodically throughout treatment to detect the onset of diabetes. Any patient developing symptoms that suggest diabetes during treatment should be tested for diabetes.

 

Clozapine is eliminated from the body by enzymes P450 in the liver. Many medications can increase or decrease the activities of these enzymes leading to low (potentially ineffective) or highly toxic levels of Clozapine in the blood.  When used with these medications, the dose of Clozapine may need to be reduced or increased.

 

The possibility of increased hazardous seizures and other adverse reactions at higher dosages, patients should ordinarily be given adequate time to respond to any given dose level before increasing the allocated dosage.

 

Patients should be advised to report immediately the appearance of lethargy, weakness, fever, sore throat or any other signs of infection occurring at any time during Clozaril (clozapine) therapy. Such patients should have a WBC count and ANC performed promptly. 

 

Hyperglycemia, in some cases extreme and associated with ketoacidosis or coma or death, has been reported in patients treated with atypicalantipsychotics including Clozaril. A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported with antipsychotic drugs. This syndrome manifests as muscle rigidity, altered mental status and evidence of autonomic instability.

 

A syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may  also develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly - especially elderly women.

 

If signs and symptoms of tardive dyskinesia appear in a patient on Clozaril, drug discontinuation should be considered.

 

Gradual reduction in dose is recommended over a 1-2-week period. However, should a patient's medical condition require abrupt discontinuation (leukopenia), the patient should be carefully observed for the recurrence of psychotic symptoms and symptoms related tocholinergic rebound such as headache, nausea, vomiting, and diarrhea. If you are pregnant or thinking about becoming pregnant, do not take this drug without speaking to a physician first.

 

Drug Interactions

Enzymes may decrease the plasma levels of Clozapine. Phenytoin, tobacco smoke, and rifampin may decrease Clozaril plasma levels, resulting in a decrease in effectiveness of a previously effective Clozaril dose. Cimetidine, caffeine, citalopram, ciprofloxacin, and erythromycin may increase plasma levels of Clozaril.

 

Fluvoxamine, debrisoquin, dextromethorphan, and tricyclic antidepressants may interact. In addition, certain drugs that are metabolized by thisisozyme, including many antidepressants (Clozapine, selective serotonin reuptake inhibitors, and others), may inhibit the activity of this isozyme.Requireing lower doses than usually prescribed for either Clozapine or the other drug. Therefore, co-administration of Clozapine with other drugs that are metabolized by this isozyme, which include antidepressants, phenothiazines, carbamazepine, and Type 1c antiarrhythmics, propafenone, flecainide,  encainide, or that inhibit this enzyme like quinidine, should be approached with caution.

 

Risperidone (Risperdal) may cause an increase in the amount of Clozapine in the blood. This could lead to an increased risk of side effects fromClozapine. Always tell you doctor about your medical history and about any drugs or supplements you may be taking.

 

Adverse/Side Effects

The most common side effect of Clozapine is drowsiness. Central nervous system complaints, including drowsiness/sedation, dizziness/vertigo, headache and tremor; autonomic nervous system complaints, including salivation, sweating, dry mouth along with the possibility of visual disturbances; cardiovascular findings, including tachycardia, hypotension and syncope; and gastrointestinal complaints, including constipation and nausea; and fever are all potential side effects. Complaints of drowsiness/sedation tend to subside with continued therapy or dose reduction. Salivation may be profuse, especially during sleep, but may be diminished with dose reduction.

 

Tell your doctor immediately if you experience any of the following side effects: stomach and intestinal inflammation, bloody vomit, rectal bleeding, nervous stomach, abnormal stools, gastric ulcer, bitter taste, belching causing regurgitation, loss of speech, lack of brain development, poor coordination, delusions/hallucinations, involuntary movement, stuttering, dysarthria, amnesia, memory loss, histrionic movements, libido increase or decrease, paranoia, shakiness, parkinsonism, irritability, edema, palpitations, vein inflammation, bluish colour skin, prematureventriculation contraction, bradycardia, nosebleeds, abdominal swelling, bitter taste, dysmenorrhea, impotence, breast pain/discomfort, and vaginal itch/infection, numbness, hot flashes, excessive thirst, pupil dilation, dry throat, allergic itching, eczema, erythema, bruising, dermatitis, twitching, joint pain, coughing, pneumonia/pneumonia-like symptoms, rhinorrhea, hyperventilation, wheezing, bronchitis, laryngitis, anemia andleukocytosis, chills/chills with fever, malaise, appetite increase, ear disorder, hypothermia, eyelid disorder, bloodshot eyes, and nystagmus.

 

Other side effects include: increased heart rate, tremers, low blood pressure, increased salivation, headache, and fever. Clozapine hasanticholinergic effects that interfere with the function of smooth muscles.  This can lead to blurred vision and difficulty urinating (when there is enlargement of the prostate) due to effects on the muscles of the eye and bladder.  Clozapine slows the intestine and leads to constipation in approximately 14% of patients.  Paralysis of the intestinal muscles can lead to paralytic ileus, a condition in which the intestine stops working.

 

Other rare side effects that may occur include: irregular heart rhythm, edema, acute pancreatitis, dysphagia, fecal impaction; intestinal obstruction/paralytic ileus; and salivary gland swelling. inability of bile to flow from liver, hapitits, jaunice, acute interstitial nephritis, inability of penis or clitori to return to facid state, photosensitivity, inflammatory destruction of blood cells, superficial microvasculature of the skinhypercholesterolemia, new onset diabetes, myasthenic syndrome, rhabdomyolysis, aspiration, pleural effusion, and pneumonia and lower respiratory tract infection which may be fatal, deep vein thrombosis, elevated hemoglobin/hematocrit; ESR increased; pulmonary embolism  sepsis, thrombocytosis , thrombocytopnia, narrow angle glaucoma,  CPK elevation, hyperglycemia, hyperuricemia, hypoartemia and weight loss. If any of these side effects occur immediately consult your doctor.

 

Overdose

In case of overdose contact local poison control or emergency room. Symptoms of Clozaril overdose include: coma, delirium, drowsiness, excess salivation, low blood pressure, faintness, pneumonia, rapid heartbeat, seizures, shallow breathing or absence of breathing.

 

Storage Instructions

Store at room temperature, away from moisture and light, and out of reach of children and pets.