International reference: 2 US FDA recalls for this ingredient
Microbial Contamination of Non-Sterile Products (clozapine)
Failed Tablet/Capsule Specifications; potential presence of broken tablets. (clozapine)
US-market enforcement records (OpenFDA), shown for reference - not specific to this product in Zimbabwe.
NONE
CLOZAPINE
What it does
Clozapine is an antipsychotic medication used to treat severe mental health conditions.
Commonly used for: schizophrenia, severe mental disorders
Read more in plain English ↓Plain-language summary for general understanding - not medical advice. Always follow your pharmacist/doctor.
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Answers come only from this medicine's registration record, BNF monograph and interaction data - not medical advice.
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Sourcing - Kenya onlyRegistration & product details
Source: Medicines Control Authority of Zimbabwe · fetched 2026-04-29 04:30:10 · updated 2026-09-16 04:30:09
Drug Interactions
54Pharmacodynamic Warnings
Clozapine appears in TABLE 8: Drugs that cause hypotension
Clozapine appears in TABLE 10: Drugs with antimuscarinic effects
Clozapine appears in TABLE 11: Drugs with CNS depressant effects
Severe (3)
Clozapine - increases risk of myelosuppression
Carbamazepine is predicted to increase the risk of myelosuppression when given with antipsychotics, second generation (clozapine). Avoid.
Clozapine - affects exposure
Ritonavir is predicted to affect the exposure to antipsychotics, second generation (clozapine). Avoid.
Clozapine - increases exposure
Deferasirox is predicted to increase the exposure to antipsychotics, second generation (clozapine). Avoid.
Moderate (6)
Clozapine - increases concentration
Mexiletine increases the concentration of clozapine. Monitor adverse effects and adjust dose.
Clozapine - increases concentration
Osilodrostat increases the concentration of clozapine. Monitor adverse effects and adjust dose.
Clozapine - increases concentration
Rucaparib increases the concentration of clozapine. Monitor adverse effects and adjust dose.
Clozapine - increases concentration
Vemurafenib increases the concentration of clozapine. Monitor adverse effects and adjust dose.
Clozapine - increases concentration
Ciprofloxacin increases the concentration of antipsychotics, second generation (clozapine). Monitor adverse effects and adjust dose.
Clozapine - increases concentration
Fluvoxamine increases the concentration of antipsychotics, second generation (clozapine). Monitor adverse effects and adjust dose.
Unknown (45)
Aclidinium - additive effect
Clozapine can cause constipation, as can aclidinium; concurrent use might increase the risk of developing intestinal obstruction. Also see TABLE 10 p. 1519
Antiarrhythmics - additive effect
Clozapinecancauseconstipation,ascanantiarrhythmics (disopyramide,propafenone);concurrentusemightincrease theriskofdevelopingintestinalobstruction.r Theoretical →AlsoseeTABLE10p.1519
Antihistamines - additive effect
Clozapinecancauseconstipation,ascanantihistamines, sedating(chlorphenamine,clemastine,cyclizine, 1xidneppA|snoitcaretnI A1 https://www.facebook.c (Books-Courses-Medic
Antipsychotics - additive effect
Antipsychotics,secondgeneration(clozapine)cancause constipation,ascanantipsychotics,secondgeneration (olanzapine,quetiapine);concurrentusemightincreasethe riskofdevelopingintestinalobstruction.rAnecdo
Atropine - additive effect
Clozapine can cause constipation, as can atropine; concurrent use might increase the risk of developing intestinal obstruction. Also see TABLE 10 p. 1519.
Data from BNF 85 (British National Formulary). This is not a substitute for professional medical advice. Matched via: exact
About this medicine
Clozapine is an antipsychotic medication used to treat severe mental health conditions.
What it treats
- schizophrenia
- severe mental disorders
How it works
Clozapine helps to balance certain chemicals in the brain that affect mood and behavior.
Who it's for
This medication is prescribed for individuals with treatment-resistant schizophrenia or those who have not responded well to other treatments.
Drug class
Antipsychotics
Cautions
- • Be careful if taking medications that lower blood pressure.
- • Avoid drugs that may cause dry mouth or other antimuscarinic effects.
- • Use caution with medications that can cause drowsiness or sedation.
AI-assisted summary grounded in BNF data - general information only, not medical advice. Always confirm with your pharmacist or doctor.
Clinical monograph: Clozapine
BNF-referencedClozapine is an atypical antipsychotic that is primarily used for the treatment of schizophrenia, particularly in patients who are treatment-resistant or intolerant to conventional antipsychotic medications. It is effective in reducing symptoms of psychosis, such as delusions and hallucinations, and is associated with a lower risk of extrapyramidal side effects compared to typical antipsychotics. However, clozapine carries a significant risk of agranulocytosis, necessitating careful monitoring of white blood cell counts.
Indications
- Schizophrenia in patients unresponsive to, or intolerant of, conventional antipsychotic drugs
Dosage
Adults: Initial dose: 12.5 mg once daily on Day 1. Increase to 25-37.5 mg on Day 2, then increase gradually in steps of 25-50 mg daily over 14-21 days. Usual maintenance dose
Mechanism of action
The precise mechanism of action of clozapine remains unknown. However, it is believed that its therapeutic effects in schizophrenia are largely mediated through the antagonism of dopamine D2 and serotonin 5-HT2A receptors. Additionally, clozapine exhibits antagonistic properties at various other receptors, including adrenergic, cholinergic, and histaminergic receptors, which may contribute to its pharmacological profile and side effects.
Pharmacodynamics
Clozapine is recognized as a highly effective treatment for treatment-resistant schizophrenia. It interacts with multiple neurotransmitter systems, which may explain its efficacy in alleviating psychotic symptoms. The drug is associated with a risk of agranulocytosis, which is a potentially life-threatening reduction in white blood cell counts, primarily occurring within the first few months of treatment. Patients on clozapine require regular blood monitoring to detect any hematological abnormalities promptly.
Pharmacokinetics
Clozapine is well absorbed after oral administration, with peak plasma concentrations typically occurring within 1-2 hours. It has a high volume of distribution and is extensively metabolized in the liver, primarily by CYP1A2 and CYP3A4 enzymes. The drug exhibits a long half-life, allowing for once or twice daily dosing. Its clearance may be affected by various factors, including smoking status and the use of certain medications that induce or inhibit liver enzymes.
Contra-indications
- Agranulocytosis
- Severe bone marrow disorders
- History of circulatory collapse
- Severe cardiac disorders (e.g. myocarditis)
- Coma
- Alcoholic and toxic psychoses
- History of neutropenia
- Paralytic ileus
- Severe CNS depression
Adverse effects
- Agranulocytosis
- Myocarditis
- Cardiomyopathy
- Seizures
- Sedation
- Hypotension
- Constipation
- Increased salivation
- Weight gain
- Metabolic syndrome
- Dizziness
- Somnolence
Interactions
- Carbamazepine: Severe (increases risk of myelosuppression)
- Ritonavir: Severe (affects exposure)
- Deferasirox: Severe (increases exposure)
- Mexiletine: Moderate (increases concentration)
- Osilodrostat: Moderate (increases concentration)
- Rucaparib: Moderate (increases concentration)
- Vemurafenib: Moderate (increases concentration)
- Ciprofloxacin: Moderate (increases concentration)
- Fluvoxamine: Moderate (increases concentration)
- Enzalutamide: Unknown (decreases exposure)
Precautions
- Regular monitoring of white blood cell counts due to risk of agranulocytosis
- Monitor for signs of infection, especially in the first 3-6 months of therapy
- Caution in patients with previous respiratory or cardiac arrest
- Consider individual risks in elderly patients
Pregnancy
Clozapine is not recommended during pregnancy unless the potential benefits outweigh the risks. Consult relevant guidelines.
Breast-feeding
Clozapine is excreted in breast milk; breastfeeding is not recommended during treatment.
Storage
Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.
Formulations
- Clozapine 25 mg capsules
- Clozapine 100 mg capsules
- Clozapine 200 mg capsules
AI-synthesized from BNF references - general information only, not a substitute for professional medical advice or the current BNF. Verify doses with a pharmacist.
Molecular reference: Clozapine
PubChem CID 135398737Molecular formula: C18H19ClN4
Mechanism of action
The mechanism of action of clozapine is unknown. However, it has been proposed that the therapeutic efficacy of clozapine in schizophrenia is mediated through antagonism of the dopamine type 2 (D<sub>2</sub>) and the serotonin type 2A (5-HT<sub>2A</sub>) receptors. Clozapine also acts as an antagonist at adrenergic, cholinergic, histaminergic, and other dopaminergic and serotonergic receptors. Clozapine demonstrated binding affinity to the following receptors: histamine H1 (Ki 1.1 nM), adrenergic α1A (Ki 1.6 nM), serotonin 5-HT6 (Ki 4 nM), serotonin 5-HT2A (Ki 5.4 nM), muscarinic M1 (Ki 6.2 nM), serotonin 5-HT7 (Ki 6.3 nM), serotonin 5-HT2C (Ki 9.4 nM), dopamine D4 (Ki 24 nM), adrenergic α2A (Ki 90 nM), serotonin 5-HT3 (Ki 95 nM), serotonin 5-HT1A (Ki 120 nM), dopamine D2 (Ki 160 nM), dopamine D1 (Ki 270 nM), dopamine D5 (Ki 454 nM), and dopamine D3 (Ki 555 nM). Clozapine acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT<sub>2</sub> with similar receptor affinities may explain some of the other therapeutic and side effects of clozapine. Clozapine's antagonism of muscarinic M1-5 receptors may explain its anticholinergic effects. Clozapine's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Clozapine's antagonism of adrenergic α1 receptors may explain the orthostatic hypotension observed with this drug. Clozapine is classified as an 'atypical' antipsychotic drug because its profile of binding to dopamine receptors and its effects on various dopamine mediated behaviors differ from those exhibited by more typical antipsychotic drug products. In particular, although clozapine does interfere with the binding of dopamine at D1, D2, D3 and D5 receptors, and has a high affinity for the D4 receptor, it does not induce catalepsy nor inhibit apomorphine-induced stereotypy. This evidence, consistent with the view that clozapine is preferentially more active at limbic than at striatal dopamine receptors, may explain the relative freedom of clozapine from extrapyramidal side effects. Clozapine also acts as an antagonist at adrenergic, cholinergic, histaminergic and serotonergic receptors.
Pharmacodynamics
Clozapine is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives that is universally regarded as the treatment of choice for treatment-resistant schizophrenia. Although it is thought to mediate its pharmacological effect through antagonism of the dopamine type 2 (D<sub>2</sub>) and the serotonin type 2A (5-HT<sub>2A</sub>) receptors, research have shown that clozapine can act on various types of receptors. Patients should be counseled regarding the risk of hypersensitivity reactions such as agranulocytosis and myocarditis with clozapine use. Clozapine-induced agranulocytosis, which is a reduction in the absolute neutrophil count or white blood cell count, places the patient at an increased risk for infection. Agranulocytosis is most likely to occur in the first 3-6 months of therapy, but it can still occur after years of treatment. The mechanism is thought to be a dose-independent and immune-mediated reaction against neutrophils. Patients are strictly monitored by lab testing (complete blood count with differential) to ensure agranulocytosis is detected and treated if it occurs. Testing is initially completed at one-week intervals but is expanded to two-week intervals at six months, and then four-week intervals at twelve months if lab results have been within an appropriate range. Monitoring parameters may change if there is any break in therapy. In Canada, the patient's lab values are reported to the manufacturer for hematological monitoring, and in the USA, the patient's lab values are reported to the REMS (Risk Evaluation and Mitigation Strategy) program. These programs function to notify the care provider of any significant drop in WBC/neutrophil count, or if there is a drop below a threshold level. Patients who enter the "Red" zone (WBC<2x109/L or ANC<1.5x109/L) should normally not be re-challenged. Clozapine-induced myocarditis is a hypersensitivity reaction that usually occurs in the third week of clozapine therapy and about 2% of clozapine patients. Monitor the patient's troponin, CRP, and ECG at baseline, and 28 days into treatment. Follow guidelines for appropriate next steps according to the patient's lab results. If myocarditis occurs, the patient should not be re-challenged with clozapine.
Biological pathways
Source: PubChem (NCBI) · pathways from PathBank, Reactome, WikiPathways & PharmGKB.
This drug in other countries
The same active ingredient registered across other registries we cover - including different brands.