Patients initiating and continuing treatment with clozapine
Clozapine
This medication is used to treat certain mental/mood disorders. Clozapine is a psychiatric medication that works by helping to restore the balance of certain natural substances in the brain. Clozapine decreases hallucinations and helps prevent suicide in people who are likely to try to harm themselves.
Can clozapine be taken before or after a blood test?
When to take blood sample for clozapine plasma levels: • No sooner than two to three weeks after treatment initiation and only where dose has been stable for at least the preceding 5 days. • To ensure the result represents a trough level, take sample immediately before the morning dose or 10-12
When to check clozapine level?
- Meyer, J.M. & Stahl, S.M. (2020). The clozapine handbook. ...
- Nielsen J, et al. (2013). Termination of clozapine treatment due to medical reasons: When is it warranted and how can it be avoided? Journal of Clinical Psychiatry, 74, 603-613.
- Schoretsanitis, G., Kane, J.M., Ruan, C.-J., Spina, E., Hiemke, C. (2019). ...
- Williams, A.M. & Park, S.H. (2015). ...
What are possible side effects of Clozaril?
- Seizures or convulsions: The higher the dosage, the greater the risk of seizures. ...
- Fast or irregular heartbeat: If this happens, the dosage may be reduced, or this side effect may be treated with another medication.
- Myocarditis (an inflammation of a muscle in the heart): The risk is greatest during the first month of CLOZARIL therapy.
What to expect from Clozaril?
Common side effects of Clozaril include: hypotension, fever, tachycardia, constipation, dizziness, headache, nausea, sedated state, vomiting, and weight gain. Other side effects include: syncope, and diaphoresis.
What lab tests are required when a patient is taking clozapine?
You will need to have an initial blood test to check that you have a normal level of white blood cells before you first start on Clozapine. If this is OK and you begin treatment with Clozapine, you will need to have a blood test on day 3 of treatment and then every week for 18 weeks.
Why do you need blood tests for clozapine?
People usually will have a blood test at least every four weeks. This could be more frequent when clozapine is started or if their blood level is not stable. The blood test is used to check the persons' white blood cell count.
Does clozapine require lab monitoring?
The side effects are also the potential reasons for clozapine discontinuation. A mandatory requirement for its use is regular monitoring of white blood cell count and absolute neutrophil count.
What are the requirements for a physician to order clozapine for a patient?
Prescribers who prescribe clozapine for outpatient use must:Certify in the Clozapine REMS Program. ... Enroll patients in the Clozapine REMS Program. ... Obtain an absolute neutrophil count (ANC) for patients in accordance with the clozapine Prescribing Information and aligned with the patient's monitoring frequency.
What labs need to be monitored with antipsychotics?
Recommended assessments at baseline include: pulse, blood pressure, weight, height, calculation of body mass index, fasting blood glucose or hemoglobin A1C, lipid panel, CBC, electrolytes, renal function tests, hepatic function tests, TSH.
Does clozapine cause high platelets?
Clozapine is known to cause blood dyscrasias, typically neutropenia and agranulocytosis. A raised platelet count, with clozapine as the sole implicated agent, had been reported to the Committee on Safety of Medicines in three cases.
Does clozapine affect white blood cells?
Unfortunately, clozapine is also associated with a number of adverse effects, with agranulocytosis being one of the chief concerns. Interestingly, patients who receive clozapine treatment may occasionally experience elevations in their total white blood cell count (WBC).
What is ANC in blood test?
A measure of the number of neutrophils in the blood. Neutrophils are a type of white blood cell. They help the body fight infection. An ANC may be used to check for infection, inflammation, leukemia, and other conditions.
How often should clozapine levels be checked?
No sooner than two to three weeks after treatment initiation and only where dose has been stable for at least the preceding 5 days. To ensure the result represents a trough level, take sample immediately before the morning dose or 10-12 hours post-dose where only one dose is taken per day.
What is RDA for clozapine REMS?
An RDA is an electronic code that indicates the Clozapine REMS has verified that all safe use conditions have been met. dashboard. identify the patient in the REMS system. Enter as much patient information as you have.
How do I enroll a patient in clozapine REMS?
To receive treatment, a patient must be enrolled in the Clozapine REMS program by a certified doctor. Pharmacies must be certified in the Clozapine REMS to receive and dispense clozapine. If you are the designated authorized representative of a pharmacy, you can certify below.
How does clozapine cause agranulocytosis?
The exact mechanism of clozapine induced agranulocytosis is unclear. It has been postulated that clozapine is metabolised to a nitrenium ion. The binding of this ion to neutrophils may result in agranulocytosis. Antineutrophil antibodies may be involved in mediating agranulocytosis.
What Is Clozapine Level Blood Test? (Background Information)
1. Clozapine is an antipsychotic drug used to treat schizophrenia and bipolar disorder 2. Schizophrenia is a complex mental disorder characterized...
What Are The Clinical Indications For Performing The Clozapine Level Blood Test?
The clinical indications for performing a Clozapine Level Blood Test include monitoring clozapine therapy.
How Is The Specimen Collected For Clozapine Level Blood Test?
Following is the specimen collection process for Clozapine Level Blood Test:Sample required: BloodProcess of obtaining blood sample in adults: 1. A...
What Is The Significance of The Clozapine Level Blood Test result?
The significance of the Clozapine Level Blood Test is explained: 1. Excessive clozapine levels may indicate clozapine toxicity, which is marked by:...
Additional and Relevant Useful Information
1. Clozapine is mainly used when more classical schizophrenia and bipolar disorder medications, such as haloperidol, cannot be used 2. Schizophreni...
Why is Clozapine kept in the blood?
Like every other drug, clozapine must be kept within a certain range to prevent unwanted effects. If levels are too high, toxicity may result; if levels are too low, the drug may not successfully treat the condition. The Clozapine Level Blood Test assesses the levels of clozapine in blood.
When is clozapine used for schizophrenia?
Additional and Relevant Useful Information: Clozapine is mainly used when more classical schizophrenia and bipolar disorder medications , such as haloperidol, cannot be used.
Why is it important to inform your healthcare provider of the complete list of medications?
Hence, it is important to inform your healthcare provider of the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.
Can laboratory results be interpreted as stand alone?
The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information.
How long does it take to prescribe Clozapine?
This generally takes less than an hour.
How often is ANC measured for Clozapine?
When starting clozapine, ANC is measured every week for 6 months, then every other week for 6 months, then monthly, if all ANC results are adequate.
What is the side effect of Clozapine?
An uncommon but serious side effect of clozapine is severe neutropenia, defined as an absolute neutrophil count (ANC) less than 500/μL. Neutrophils are a type of white blood cell that combats infection.
How long does it take for neutropenia to develop after taking Clozapine?
The most dangerous form of neutropenia is agranulocytosis, which occurs in 1% or less of patients taking clozapine, most commonly between 6 and 18 weeks after starting the medication.
Is Clozapine safe for neutropenia?
Any severe neutropenia can be fatal if not detected and managed, since it makes people vulnerable to infection. With required monitoring, clozapine is safe and fatalities from neutropenia are very rare.
What is Clozapine used for?
Uses for Clozaril. Clozapine is used to treat severely ill patients with schizophrenia who have used other medicines that did not work well. It is also used to lower risk of suicidal behavior in patients with schizophrenia or schizoaffective disorder.
What are some examples of CNS depressants?
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, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics.
Can clozapine cause stomach pain?
If this problem continues or gets worse, check with your doctor. Clozapine may cause stomach or bowel problems (eg, gastrointestinal hypomotility). Tell your doctor right away if you have severe constipation, nausea, vomiting, or stomach pain or swelling.
Can clozapine be used in elderly?
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of clozapine in the elderly. However, elderly patients are more likely to have constipation, trouble passing urine, uncontrolled movements, or age-related liver, kidney, or heart problems, which may require caution in patients receiving clozapine.
Can you take Sparfloxacin with Ziprasidone?
Saquinavir. Sparfloxacin. Terfenadine. Thioridazine. Ziprasidone. Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Can Clozapine cause blood problems?
Clozapine can cause some very serious blood problems that you will not be able to feel. Your doctor will check your blood at regular visits and it is important that you have your blood tests done when they are scheduled. The pharmacy will give you this medicine only if your blood tests show that it is safe for you to take it. Your doctor will make sure the medicine is working properly and change the dosage if needed.
Can Clozapine cause severe neutropenia?
Severe Neutropenia; Orthostatic Hypotension; Bradycardia, and Syncope; Seizure; Myocarditis and Cardiomyopathy; Increased Mortality in Elderly Patients with Dementia-related PsychosisSevere Neutropenia: Clozapine can cause severe neutropenia, which can lead to serious and fatal infections. Patients initiating and continuing treatment with clozapine must have a baseline blood absolute neutrophil count (ANC) measured before treatment initiation and regular ANC monitoring during treatment.Clozapine is available only through a restricted program called the Clozapine Risk Evaluation Mitigation Strategy (REMS).Orthostatic Hypotension, Bradycardia, and Syncope: Risk is dose related. Starting dose is 12.5 mg. Titrate gradually and use divided dosages.Seizure: Risk is dose-related. Titrate gradually and use divided doses. Use with caution in patients with history of seizure or risk factors for seizure.Myocarditis, Cardiomyopathy and Mitral Valve Incompetence: Can be fatal. Discontinue and obtain cardiac evaluation if findings suggest these cardiac reactions.Increased Mortality in Elderly Patients with Dementia-Related Psychosis: Clozapine is not approved for this condition .
Why is clozapine monitored?
Patients who are taking clozapine require ongoing monitoring because of the risk of serious blood dyscrasias. What should pharmacists be checking before they dispense the medicine?
How many people respond to Clozapine?
Some 30–60% of patients with treatment-resistant schizophrenia will respond to clozapine.1,2The decision to prescribe clozapine is usually made for patients who have been treated unsuccessfully with at least two other antipsychotic medicines (one of which is another atypical antipsychotic).
What is clozapine used for?
Clozapine is an atypical antipsychotic that is used for treatment-resistant schizophrenia. The drug is subject to strict monitoring requirements because it is associated with serious side effects, such as neutropenia, agranulocytosis, seizures, ...
How many brands of Clozapine are there in the UK?
The prescribing consultant, patient and supplying pharmacy each have to be registered with the clozapine manufacturer. There are three brands of clozapine currently available in the UK, namely:u0001
What is FBC in blood work?
The frequency of full blood count (F BC) tests and when the last one was taken. The current dose of clozapine. The patient’s adherence to clozapine treatment — specifically, whether he or she has missed a dose more than 48 hours beforehand. Who currently supplies the patient’s clozapine.
Can a community pharmacy supply Clozapine?
A community pharmacy may be supplying clozapine under a service level agreement for patients receiving monthly blood tests. Contact the supplying pharmacy to find out the patient’s current dose of clozapine, when he or she last collected supplies, the brand of clozapine and the directions prescribed.
Does rifampicin increase clozapine?
Check that none of the new medicines prescribed interacts with clozapine (eg, erythromycin and ciprofloxacin can increase clozapine levels, rifampicin can greatly reduce clozapine levels). Patients who stop smoking while an inpatient will need to have their doses reduced because smoking induces clozapine metabolism.
What is clozapine used for?
Clozapine is an atypical antipsychotic used for treatment-resistant schizophrenia. A number of serious adverse reactions are associated with its use including: agranulocytosis, myocarditis, cardiomyopathy, and severe constipation (ileus).
How often should you monitor for trophonins?
Patients should be monitored at least weekly for the first four months, and/or co-prescribed a laxative, to avoid constipation.
When does agranulocytosis develop?
Agranulocytosis tends to develop during the first six months of treatment , whereas neutropenia (ANC between 500 and 1500/µL) may occur at any time 1. Agranulocytosis is a medical emergency and clozapine should be stopped immediately and patients referred for acute medical assessment 2.
How often should I be evaluated for heart failure?
Patients should be assessed at least four times a year for symptoms of heart failure and constipation. Any patients with new symptoms consistent with heart failure/cardiomyopathy or constipation should be investigated further.
Does clozapine cause constipation?
More deaths are caused by clozapine-induced ileus/megacolon than by agranulocytosis 1. The most commonly reported signs and symptoms associated with severe constipation include moderate to severe abdominal pain, abdominal distension, vomiting, paradoxical ‘overflow’ diarrhoea, reduced appetite and nausea.
Is clozapine a hypersensitivity reaction?
The pathophysiology of clozapine -associated myocarditis is poorly understood but may be a hypersensitivity reaction and as such is not dose-dependent 4. Myocarditis has a variety of non-specific presenting symptoms. Those most commonly reported include fever, tachycardia and chest pain 3.
Is Clozapine effective for schizophrenia?
Key Messages. Clozapine is effective in treatment-resistant schizophrenia, but is associated with significant adverse reactions. Close monitoring, particularly in the first few months of treatment, is essential to reduce the occurrence of serious, sometimes fatal adverse reactions. Permanent discontinuation of clozapine treatment is recommended ...
What is the temperature of a patient on clozaril?
During CLOZARIL therapy, patients may experience transient temperature elevations above 100.4°F (38°C), with the peak incidence within the first 3 weeks of treatment. While this fever is generally benign and self-limiting, it may necessitate discontinuing patients from treatment. On occasion, there may be an associated increase or decrease in WBC count. Patients with fever should be carefully evaluated to rule out the possibility of an underlying infectious process or the development of agranulocytosis. In the presence of high fever, the possibility of Neuroleptic Malignant Syndrome (NMS) must be considered. There have been several reports of NMS in patients receiving CLOZARIL, usually in combination with lithium or other CNS-active drugs. (See Neuroleptic Malignant Syndrome [NMS], under WARNINGS.)
How much Clozaril should I take daily?
It is recommended that treatment with CLOZARIL begin with one-half of a 25-mg tablet (12.5 mg) once or twice daily and then be continued with daily dosage increments of 25-50 mg/day, if well tolerated, to achieve a target dose of 300-450 mg/day by the end of 2 weeks. Subsequent dosage increments should be made no more than once or twice weekly, in increments not to exceed 100 mg. Cautious titration and a divided dosage schedule are necessary to minimize the risks of hypotension, seizure, and sedation.
What are the adverse effects of Clozaril?
Adverse events observed in association with the use of CLOZARIL in clinical trials at an incidence of greater than 5% were: central nervous system complaints, including drowsiness/sedation, dizziness/vertigo, headache and tremor; autonomic nervous system complaints, including salivation, sweating, dry mouth and visual disturbances; cardiovascular findings, including tachycardia, hypotension and syncope; and gastrointestinal complaints, including constipation and nausea; and fever. 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.
How long to retitrate Clozaril?
However, any patient who has previously experienced respiratory or cardiac arrest with initial dosing, but was then able to be successfully titrated to a therapeutic dose, should be retitrated with extreme caution after even 24 hours of discontinuation. Certain additional precautions seem prudent when reinitiating treatment. The mechanisms underlying CLOZARIL-induced adverse reactions are unknown. It is conceivable, however, that reexposure of a patient might enhance the risk of an untoward event’s occurrence and increase its severity. Such phenomena, for example, occur when immune-mediated mechanisms are responsible. Consequently, during the reinitiation of treatment, additional caution is advised. Patients discontinued for WBC counts below 2000/mm3 or an ANC below 1000/mm3 must not be restarted on CLOZARIL. (See WARNINGS.)
What are the reasons for discontinuing Clozapine?
The more common events considered to be causes of discontinuation included: CNS, primarily drowsiness/sedation, seizures, dizziness/syncope; cardiovascular, primarily tachycardia, hypotension and ECG changes; gastrointestinal, primarily nausea/vomi ting; hematologic, primarily leukopenia/ granulocytopenia/ agranulocytosis; and fever. None of the events enumerated accounts for more than 1.7% of all discontinuations attributed to adverse clinical events.
What is clozaril used for?
CLOZARIL is indicated for reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at chronic risk for reexperiencing suicidal behavior , based on history and recent clinical state. Suicidal behavior refers to actions by a patient that puts him/herself at risk for death.
Can Clozapine be used for agranulocytosis?
Although it is not known whether the risk would be increased, it is prudent either to avoid CLOZARIL® (clozapine) or use it cautiously in patients with a previous history of agranulocytosis induced by other drugs.
Can you take more than prescribed meds?
Do not take more than your prescribed dosage. Do not make up missed doses, instead contact your health care provider. Do not stop taking this drug suddenly; gradual reduction of dosage is needed to prevent side effects. If you think you are pregnant or wish to become pregnant, contact your health care provider.
Does Clozapine block dopamine?
Clozapine has relatively weak dopamine receptor-blocking activity at D 1, D 2, D 3 and D 5 receptors but has high affinity for the D4 receptor. It has also blocking effects on serotonin, α-adrenergic histamine H 1 and cholinergic receptors.
Heparin
Heparin is not given to break up a clot. Know that this would be given to prevent fibrin from forming a clot. The two things that should come to your mind is deep vein thrombosis and pulmonary emboli being prevented. Here’s a question for you. How does fibrin get prevented from forming a clot?
Coumadin
The lab report for Coumadin is PT. The antidote for Coumadin is vitamin K. The easy way to remember that is that Coumadin starts with the letter C. C and K sounds alike.
Medical uses
- Clozaril is indicated for the treatment of severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment. Because of the risks of severe neutropenia and of seizure associated with its use, Clozaril should be used only in patients who …
Research
- The effectiveness of Clozaril in treatment-resistant schizophrenia was demonstrated in a 6-week, randomized, double-blind, active-controlled study comparing Clozaril and chlorpromazine in patients who had failed other antipsychotics [see Clinical Studies (14.1)]. The effectiveness of Clozaril in reducing the risk of recurrent suicidal behavior was demonstrated over a two-year tre…
Side effects
- The starting dose is 12.5 mg once daily or twice daily. The total daily dose can be increased in increments of 25 mg to 50 mg per day, if well-tolerated, to achieve a target dose of 300 mg to 450 mg per day (administered in divided doses) by the end of 2 weeks. Subsequently, the dose can be increased once weekly or twice weekly, in increments of up to 100 mg. The maximum dose is 90…
Prognosis
- Generally, patients responding to Clozaril should continue maintenance treatment on their effective dose beyond the acute episode. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a r…
Administration
- When restarting Clozaril in patients who have discontinued Clozaril (i.e., 2 days or more since the last dose), re-initiate with 12.5 mg once daily or twice daily. This is necessary to minimize the risk of hypotension, bradycardia, and syncope [see Warnings and Precautions (5.3)]. If that dose is well-tolerated, the dose may be increased to the previously therapeutic dose more quickly than r…
Interactions
- Dose adjustments may be necessary in patients with concomitant use of: strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin); moderate or weak CYP1A2 inhibitors (e.g., oral contraceptives, or caffeine); CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, …
Description
- Clozaril (clozapine) is available as 25 mg and 100 mg round, pale-yellow, uncoated tablets with a facilitated score on one side.
Contraindications
- Clozaril is contraindicated in patients with a history of serious hypersensitivity to clozapine (e.g., photosensitivity, vasculitis, erythema multiforme, or Stevens-Johnson Syndrome) or any other component of Clozaril [see Adverse Reactions (6.2)]. Use Clozaril cautiously in patients with cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conductio…
Definition
- Clozaril can cause neutropenia (a low absolute neutrophil count (ANC)), defined as a reduction below pre-treatment normal levels of blood neutrophils. The ANC is usually available as a component of the complete blood count (CBC), including differential, and is more relevant to drug-induced neutropenia than is the white blood cell (WBC) count. The ANC may also be calculated …
Management
- Two separate management algorithms are provided below, the first for patients in the general population, and the second for patients identified to have baseline neutropenia. Obtain a CBC, including the ANC value, prior to initiating treatment with Clozaril to ensure the presence of a normal baseline neutrophil count (equal to or greater than 1500/µL) and to permit later comparis…
Results
- * Confirm all initial reports of ANC less than 1500/ µL with a repeat ANC measurement within 24 hours
Epidemiology
- Benign ethnic neutropenia (BEN) is a condition observed in certain ethnic groups whose average ANC values are lower than standard laboratory ranges for neutrophils. It is most commonly observed in individuals of African descent (approximate prevalence of 25-50%), some Middle Eastern ethnic groups, and in other non-Caucasian ethnic groups with darker skin. BEN is more c…
Prevention
- For some patients who experience severe Clozaril-related neutropenia, the risk of serious psychiatric illness from discontinuing Clozaril treatment may be greater than the risk of rechallenge (e.g., patients with severe schizophrenic illness who have no treatment options other than Clozaril). A hematology consultation may be useful in deciding to rechallenge a patient. In …
Qualification
- If a patient will be rechallenged, the clinician should consider thresholds provided in Tables 2 and 3, the patients medical and psychiatric history, a discussion with the patient and his/her caregiver about the benefits and risks of Clozaril rechallenge, and the severity and characteristics of the neutropenic episode.
Adverse effects
- Hypotension, bradycardia, syncope, and cardiac arrest have occurred with clozapine treatment. The risk is highest during the initial titration period, particularly with rapid dose-escalation. These reactions can occur with the first dose, at doses as low as 12.5 mg. These reactions can be fatal. The syndrome is consistent with neurally mediated reflex bradycardia (NMRB). Clozaril may cau…
Signs and symptoms
- Consider the possibility of myocarditis or cardiomyopathy in patients receiving Clozaril who present with chest pain, dyspnea, persistent tachycardia at rest, palpitations, fever, flu-like symptoms, hypotension, other signs or symptoms of heart failure, or electrocardiographic findings (low voltages, ST-T abnormalities, arrhythmias, right axis deviation, and poor R wave pr…
Risks
- QT prolongation, Torsade de Pointes and other life-threatening ventricular arrhythmias, cardiac arrest, and sudden death have occurred with Clozaril treatment. When prescribing Clozaril, consider the presence of additional risk factors for QT prolongation and serious cardiovascular reactions. Conditions that increase these risks include the following: history of QT prolongation, …