WARNING

Clozapine is an antipsychotic medication used to treat severe schizophrenia that has not responded to other treatments. While effective, it also carries significant risks:

• Agranulocytosis: This is a potentially life-threatening condition where the bone marrow decreases production of white blood cells, leaving the body vulnerable to infections.
• Seizures: Clozapine lowers the seizure threshold, increasing the risk of seizures, particularly at higher doses.
• Myocarditis: Inflammation of the heart muscle can occur, which may be fatal if not promptly recognized and treated.
• Metabolic Changes: Clozapine can cause significant weight gain, elevated blood sugar levels (leading to diabetes), and abnormal lipid levels.
• Constipation: This is a common side effect that can lead to bowel complications if not managed.
• Orthostatic Hypotension: Sudden drop in blood pressure upon standing, which can cause dizziness or fainting.
• Increased Risk of Mortality in Elderly Patients with Dementia: Elderly patients with dementia-related psychosis treated with antipsychotic drugs like clozapine are at an increased risk of death.
• Other Side Effects: These may include sedation, hypersalivation, and urinary incontinence.

Due to these risks, clozapine is usually reserved for patients who have not responded to other antipsychotic medications and requires careful monitoring with regular blood tests and medical check-ups.

Why is this medication prescribed?

Clozapine is prescribed primarily for the treatment of severe schizophrenia that has not responded adequately to other antipsychotic medications. It is considered when other treatments have failed due to its unique effectiveness in treating symptoms that may not be controlled by other medications.

How should this medicine be used?

Now, regarding how Clozapine should be used:

• Initiation and Titration: Clozapine therapy typically starts at a low dose and is gradually increased to an effective dose. This process helps minimize side effects such as sedation and dizziness. The titration schedule is closely monitored by healthcare providers.
• Dosage: The usual starting dose is 12.5 to 25 mg once or twice daily. Over several weeks, the dose is increased gradually up to a target dose, which typically ranges from 300 to 900 mg per day, divided into two or more doses. The exact dose varies based on individual response and tolerability.
• Monitoring: Regular monitoring is crucial due to the potential for serious side effects like agranulocytosis and myocarditis. Blood tests to monitor white blood cell counts and other parameters are required:
  • Weekly blood tests: During the first 6 months of treatment.
  • Every 2 weeks: From 6 months to 1 year of treatment.
  • Every 4 weeks: After 1 year of treatment and beyond.
• Long-term Use: Clozapine is often used long-term to maintain symptom control in patients with treatment-resistant schizophrenia. It is important to continue regular monitoring even after the patient has been stabilized on the medication.
• Administration: Clozapine is available in tablet form and should be taken with water. It can be taken with or without food.
• Stopping Treatment: If clozapine needs to be stopped for any reason, it should be done gradually under the guidance of a healthcare provider to avoid withdrawal symptoms or symptom recurrence.
• Additional Considerations: Clozapine may interact with other medications, so it’s essential to inform healthcare providers about all medications being taken. It should not be used concurrently with other medications that lower the seizure threshold unless absolutely necessary and under close supervision.

Clozapine treatment requires careful management and monitoring to balance its effectiveness in managing schizophrenia symptoms with the potential risks associated with its use.

Other uses for this medicine

• Treatment-Resistant Bipolar Disorder: In cases where standard mood stabilizers and antipsychotics have not been effective.
• Schizoaffective Disorder: Especially when psychotic symptoms are prominent.
• Reduction of Suicidal Behavior: Clozapine has shown efficacy in reducing suicidal behavior in schizophrenia patients who are at high risk.

What special precautions should I follow?

Special Precautions for Clozapine:

• Blood Monitoring: Regular blood tests are essential to monitor for potential serious side effects, particularly agranulocytosis (a decrease in white blood cell count) and myocarditis (inflammation of the heart muscle).
• Seizure Risk: Clozapine lowers the seizure threshold. Caution is needed when prescribing to individuals with a history of seizures or other factors that increase seizure risk.
• Orthostatic Hypotension: Clozapine can cause a sudden drop in blood pressure upon standing, leading to dizziness or fainting. Patients should be advised to rise slowly from sitting or lying positions.
• Metabolic Effects: Regular monitoring of weight, blood sugar levels, and lipid profiles is recommended due to potential metabolic changes (e.g., weight gain, elevated blood glucose, and lipid levels).
• Constipation: Clozapine can cause severe constipation, which may require intervention to prevent complications such as bowel obstruction.
• Cardiovascular Monitoring: Given the risk of myocarditis, symptoms such as chest pain, shortness of breath, and palpitations should be promptly evaluated.
• Pregnancy and Breastfeeding: Clozapine should be used with caution during pregnancy and breastfeeding. The potential risks to the fetus or infant should be weighed against the benefits of treatment.
• Other Medications: Clozapine may interact with other medications, including those that affect the central nervous system or those that lower the seizure threshold. Healthcare providers should be informed about all medications being taken.
• Smoking: Smoking can increase the metabolism of clozapine, potentially reducing its effectiveness. Adjustments in dosage may be necessary for smokers.
• Regular Follow-Up: Patients on clozapine require ongoing monitoring and follow-up visits to assess response to treatment, manage side effects, and ensure compliance with blood monitoring requirements.

Clozapine is a powerful medication that can be highly effective for certain psychiatric conditions, but its use requires careful management and monitoring to mitigate risks and maximize benefits.

What special dietary instructions should I follow?

• Dietary Restrictions: There are no specific dietary restrictions for clozapine. However, maintaining a healthy and balanced diet is important to manage potential metabolic side effects such as weight gain and elevated blood sugar levels.
• Hydration: Since constipation can be a side effect of clozapine, adequate hydration (drinking enough water) is recommended to help prevent this issue.

What should I do if I forget a dose?

• If you miss a dose of clozapine, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule.
• Do not double the dose to catch up. Taking more than the prescribed amount can increase the risk of side effects.
• Notify your healthcare provider if you frequently forget doses or have trouble remembering to take your medication regularly. They can offer guidance on managing your medication schedule effectively.

What side effects can this medication cause?

Clozapine, like all medications, can cause side effects. These can range from mild to severe. Some of the common and potentially serious side effects of clozapine include:

• Agranulocytosis: A serious condition where the bone marrow decreases production of white blood cells, leaving the body vulnerable to infections. Regular blood tests are necessary to monitor for this.
• Seizures: Clozapine lowers the seizure threshold, increasing the risk of seizures, particularly at higher doses.
• Myocarditis: Inflammation of the heart muscle, which can be life-threatening if not promptly recognized and treated.
• Orthostatic Hypotension: Sudden drop in blood pressure upon standing, which can cause dizziness or fainting.
• Metabolic Changes: These can include significant weight gain, elevated blood sugar levels (leading to diabetes), and abnormal lipid levels.
• Constipation: A common side effect that can lead to bowel complications if not managed.
• Sedation: Many individuals experience drowsiness or sedation, especially when starting clozapine or when the dose is increased.
• Hypersalivation: Excessive saliva production, which can be bothersome for some patients.
• Urinary Incontinence: Difficulty controlling urination.
• Tachycardia: Rapid heart rate.
• Dizziness: Feeling lightheaded or dizzy.
• Fever: Elevated body temperature.
• Sialorrhea: Excessive drooling.
• Gastrointestinal Issues: Nausea, vomiting, and indigestion.
• Hypersensitivity Reactions: Rarely, severe allergic reactions can occur.

It’s important for patients taking clozapine to be aware of these potential side effects and to promptly report any unusual symptoms to their healthcare provider. Clozapine treatment requires close monitoring, especially during the initial phases of therapy, to detect and manage any adverse effects early on.

What should I know about storage and disposal of this medication?

Storage and Disposal of Clozapine:

• Storage: Store clozapine tablets at room temperature away from moisture and heat. Keep the medication in its original packaging or container to protect it from light.
• Disposal: Dispose of unused or expired clozapine tablets properly to prevent accidental ingestion by children, pets, or others. Follow local guidelines or ask your pharmacist about the best way to dispose of medications safely.

In case of emergency/overdose

• Emergency: If you or someone else may have overdosed on clozapine and is experiencing severe symptoms such as difficulty breathing or loss of consciousness, call emergency services immediately (911 in the United States).
• Symptoms of Overdose: Symptoms of clozapine overdose may include severe drowsiness, confusion, agitation, rapid heartbeat, seizures, or fainting.
• Treatment: Emergency medical treatment for clozapine overdose typically involves supportive care to manage symptoms and ensure adequate ventilation and cardiovascular function. Activated charcoal may be administered to reduce absorption if the overdose was recent and ingestion is confirmed.

What other information should I know?

• Regular Monitoring: Clozapine treatment requires regular monitoring of blood counts and other parameters to detect and manage potential side effects such as agranulocytosis and myocarditis.
• Follow-Up Visits: Attend scheduled follow-up visits with your healthcare provider to assess your response to treatment, adjust medication dosage if necessary, and address any concerns or side effects.
• Driving and Machinery: Clozapine may cause drowsiness or dizziness. Avoid driving or operating machinery until you know how this medication affects you.
• Pregnancy and Breastfeeding: Inform your healthcare provider if you are pregnant, planning to become pregnant, or breastfeeding. The risks and benefits of using clozapine during pregnancy or breastfeeding should be discussed with your doctor.
• Smoking: Smoking can affect the metabolism of clozapine. If you smoke, inform your healthcare provider as adjustments in dosage may be needed.
• Other Medications: Inform your healthcare provider about all medications, supplements, or herbal products you are taking, as they may interact with clozapine.
• Patient Support: Joining a support group or working closely with healthcare providers experienced in clozapine treatment can provide valuable information and support throughout your treatment journey.

Clozapine is a potent medication that can be highly effective for managing certain psychiatric conditions, but it requires careful monitoring and management to minimize risks and optimize therapeutic benefits. Always follow your healthcare provider’s instructions and report any concerns promptly.