Drug · FAERS side-effect profile with label screen
Clozapine side effects: what 124,826 FDA adverse event reports show
Who reports
124,826 reports · 95% serious · 22,310 with death outcome · 39% female
openFDA FAERS counts, all years, deduplication not applied
Used for
Clozapine orally disintegrating tablets (Clozapine ODT) is an atypical antipsychotic indicated for: Treatment of severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment. Because of the risks of severe.
FDA label, Indications and Usage
What it is
Clozapine is a benzodiazepine that is 5H-dibenzo[b,e][1,4]diazepine substituted by a chloro group at position 8 and a 4-methylpiperazin-1-yl group at position 11.
PubChem CID 135398737 (ChEBI)
Boxed warning
WARNING: SEVERE NEUTROPENIA; ORTHOSTATIC HYPOTENSION, BRADYCARDIA, AND SYNCOPE; SEIZURE; MYOCARDITIS, PERICARDITIS, AND CARDIOMYOPATHY; INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Severe N.
FDA label
How to read this page. FAERS is a spontaneous-reporting system: counts are not incidence rates and a signal is not proof of causation.
Each reaction below is run through an automated screen — is the term in the FDA label (known), in the indications (the disease being treated), an administrative/coding term, or none of these (unlabeled)?
That screen is mechanical text matching, not a causality assessment. The 30 hand-written Bradford Hill assessments are on the causality assessment page. Not medical advice.
Causality screen of the 40 strongest signals
Labeled — boxed warning 2Labeled adverse reaction 3Labeled (related wording) 1Likely indication confounding 4Reporting / coding artifact 7Lab value / disease marker 15Not in label — unassessed 8
What the badges mean
- Labeled — boxed warning The term (or its clinical synonym) appears in the FDA boxed warning: causality is regulator-recognised and considered serious.
- Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Likely indication confounding The term appears in the label's indications: reports probably describe the disease being treated (or its progression), not a drug effect. Classic confounding by indication.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only (and, for the 300 most-reported drugs, adjusted for age band), and flags pairs whose reports are unusually skewed by sex or come mostly from consumers. Each row also shows the PRR against the other drugs of the same FDA class, which removes most confounding by the condition being treated, and a calibrated p-value: on validation, known non-causes average an ROR of about 2, so significance is judged against that empirical null (✓ = p < 0.05 after calibration). 1,239 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
Show:
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Neutrophil count normal | 335 | 6,133.0 3,163.4–11,890.3ROR 6,149.5 · calibrated p 3e-23 ✓ | 160.0 EB05 146.1 · IC025 +6.8 3/3 methods agree vs other Atypical Antipsychotics: only this drug | Reporting / coding artifact | 94% clinician | not reported in cached trials |
| Benign ethnic neutropenia | 114 | 1,565.3 863.5–2,837.4ROR 1,566.7 · calibrated p 5e-17 ✓ | 146.3 EB05 125.2 · IC025 +6.2 3/3 methods agree vs other Atypical Antipsychotics: only this drug | Labeled — boxed warning exact term | serious n=108 · 100% clinician | not reported in cached trials |
| Differential white blood cell count abnormal | 1,500 | 1,462.4 1,247.5–1,714.4ROR 1,480.2 · calibrated p 3e-19 ✓ | 148.7 EB05 142.5 · IC025 +7.1 3/3 methods agree vs other Atypical Antipsychotics: only this drug | Lab value / disease marker | serious n=1,483 | not reported in cached trials |
| Antipsychotic drug level decreased | 420 | 659.1 532.2–816.2ROR 661.3 · calibrated p 5e-15 ✓ | 131.8 EB05 121.6 · IC025 +6.7 3/3 methods agree vs other Atypical Antipsychotics: PRR 39.6 (33.6–46.6) | Lab value / disease marker | serious n=414 · 93% clinician | not reported in cached trials |
| Anosognosia | 498 | 310.8 267.8–360.8ROR 312.1 · calibrated p 8e-12 ✓ | 107.9 EB05 100.2 · IC025 +6.5 3/3 methods agree vs other Atypical Antipsychotics: PRR 3.0 (2.8–3.3) | Not in label — unassessed | serious n=495 · ♀ 77% (drug 39%) | not reported in cached trials |
| Refusal of examination | 83 | 291.0 203.5–416.1ROR 291.2 · calibrated p 5e-11 ✓ | 103.4 EB05 86.0 · IC025 +5.7 3/3 methods agree vs other Atypical Antipsychotics: PRR 32.6 (23.1–46.1) | Reporting / coding artifact | serious n=80 · ♀ 60% (drug 39%) · 100% clinician | not reported in cached trials |
| Radiation inflammation | 50 | 274.6 174.6–431.8ROR 274.7 · calibrated p 2e-10 ✓ | 99.8 EB05 78.6 · IC025 +5.2 3/3 methods agree vs other Atypical Antipsychotics: only this drug | Not in label — unassessed | serious n=50 · ♀ 0% (drug 39%) | not reported in cached trials |
| Antipsychotic drug level below therapeutic | 424 | 266.6 228.6–311.0ROR 267.6 · calibrated p 4e-11 ✓ | 102.0 EB05 94.1 · IC025 +6.4 3/3 methods agree vs other Atypical Antipsychotics: PRR 7.5 (6.7–8.4) | Lab value / disease marker | serious n=419 · ♀ 16% (drug 39%) · 91% clinician | not reported in cached trials |
| Antipsychotic drug level increased | 1,615 | 228.6 212.1–246.5ROR 231.6 · calibrated p 1e-10 ✓ | 96.2 EB05 92.4 · IC025 +6.5 3/3 methods agree vs other Atypical Antipsychotics: PRR 28.1 (26.1–30.3) | Lab value / disease marker | serious n=1,589 · 91% clinician | not reported in cached trials |
| Investigation noncompliance | 57 | 191.7 130.8–280.8ROR 191.8 · calibrated p 2e-9 ✓ | 86.6 EB05 69.3 · IC025 +5.2 3/3 methods agree vs other Atypical Antipsychotics: only this drug | Reporting / coding artifact | 100% clinician | not reported in cached trials |
| Blood prolactin abnormal | 432 | 165.9 145.2–189.6ROR 166.5 · calibrated p 2e-9 ✓ | 82.9 EB05 76.5 · IC025 +6.1 3/3 methods agree vs other Atypical Antipsychotics: PRR 2.3 (2.1–2.5) | Lab value / disease marker | serious n=429 · ♀ 79% (drug 39%) | not reported in cached trials |
| Neutrophilia | 2,602 | 142.9 135.6–150.6ROR 145.9 · calibrated p 6e-9 ✓ | 77.0 EB05 74.5 · IC025 +6.2 3/3 methods agree vs other Atypical Antipsychotics: PRR 135.7 (122.1–150.8) | Likely indication confounding shares a disease stem with the indications wording | serious n=2,057 | not reported in cached trials |
| Eosinophil count decreased | 1,060 | 141.4 130.3–153.5ROR 142.6 · calibrated p 7e-9 ✓ | 76.5 EB05 72.7 · IC025 +6.1 3/3 methods agree vs other Atypical Antipsychotics: PRR 38.6 (34.8–42.7) | Lab value / disease marker | serious n=1,013 | not reported in cached trials |
| Granulocytopenia | 2,616 | 141.2 134.1–148.8ROR 144.2 · calibrated p 6e-9 ✓ | 76.5 EB05 74.0 · IC025 +6.2 3/3 methods agree vs other Atypical Antipsychotics: PRR 63.4 (58.7–68.4) | Labeled adverse reaction exact term | serious n=2,069 | not reported in cached trials |
| Antipsychotic drug level above therapeutic | 399 | 135.0 118.3–154.1ROR 135.4 · calibrated p 1e-8 ✓ | 74.4 EB05 68.5 · IC025 +5.9 3/3 methods agree vs other Atypical Antipsychotics: PRR 17.5 (15.3–20.0) | Lab value / disease marker | serious n=392 · 91% clinician | not reported in cached trials |
| Neutrophil count increased | 4,168 | 114.9 110.5–119.5ROR 118.9 · calibrated p 3e-8 ✓ | 68.1 EB05 66.4 · IC025 +6.0 3/3 methods agree vs other Atypical Antipsychotics: PRR 55.1 (52.1–58.4) | Lab value / disease marker | serious PRR 42.4 | not reported in cached trials |
| Withdrawal catatonia | 91 | 114.5 87.6–149.5ROR 114.5 · calibrated p 7e-8 ✓ | 67.0 EB05 56.3 · IC025 +5.3 3/3 methods agree vs other Atypical Antipsychotics: only this drug | Not in label — unassessed | serious n=91 · 100% clinician | not reported in cached trials |
| Schizophrenia | 4,690 | 105.7 101.9–109.6ROR 109.8 · calibrated p 6e-8 ✓ | 64.8 EB05 63.2 · IC025 +6.0 3/3 methods agree vs other Atypical Antipsychotics: PRR 8.7 (8.5–9.0) | Likely indication confounding term in indications; also in warnings | serious PRR 40.8 | not reported in cached trials |
| Rebound psychosis | 79 | 99.4 75.2–131.4ROR 99.4 · calibrated p 2e-7 ✓ | 61.5 EB05 50.9 · IC025 +5.1 3/3 methods agree vs other Atypical Antipsychotics: PRR 201.9 (97.6–417.7) | Labeled (related wording) related wording | serious n=79 | not reported in cached trials |
| Schizoaffective disorder | 610 | 86.6 78.6–95.6ROR 87.1 · calibrated p 3e-7 ✓ | 57.0 EB05 53.3 · IC025 +5.6 3/3 methods agree vs other Atypical Antipsychotics: PRR 4.6 (4.2–5.1) | Likely indication confounding term in indications; also in warnings | serious n=609 · ♀ 67% (drug 39%) | not reported in cached trials |
| Metamyelocyte count increased | 50 | 84.1 59.8–118.2ROR 84.1 · calibrated p 8e-7 ✓ | 54.9 EB05 43.3 · IC025 +4.7 3/3 methods agree vs other Atypical Antipsychotics: PRR 48.7 (29.2–81.0) | Lab value / disease marker | serious n=49 | not reported in cached trials |
| Immature granulocyte count increased | 90 | 80.2 62.3–103.1ROR 80.2 · calibrated p 8e-7 ✓ | 53.7 EB05 45.0 · IC025 +5.0 3/3 methods agree vs other Atypical Antipsychotics: only this drug | Lab value / disease marker | serious n=76 | not reported in cached trials |
| Schizoaffective disorder bipolar type | 69 | 71.5 53.9–94.8ROR 71.5 · calibrated p 2e-6 ✓ | 49.5 EB05 40.5 · IC025 +4.8 3/3 methods agree vs other Atypical Antipsychotics: PRR 67.2 (41.2–109.5) | Likely indication confounding shares a disease stem with the indications wording | serious n=68 · 100% clinician | not reported in cached trials |
| Delusion of grandeur | 121 | 62.1 50.4–76.5ROR 62.2 · calibrated p 4e-6 ✓ | 45.1 EB05 38.7 · IC025 +5.0 3/3 methods agree vs other Atypical Antipsychotics: PRR 5.0 (4.1–6.1) | Not in label — unassessed | serious n=120 · ♀ 19% (drug 39%) | not reported in cached trials |
| Myelocyte count increased | 47 | 55.7 40.0–77.5ROR 55.7 · calibrated p 1e-5 ✓ | 41.2 EB05 32.3 · IC025 +4.4 3/3 methods agree vs other Atypical Antipsychotics: PRR 43.7 (26.3–72.4) | Lab value / disease marker | serious n=46 | not reported in cached trials |
| Psychiatric decompensation | 465 | 52.4 47.3–58.2ROR 52.6 · calibrated p 1e-5 ✓ | 40.0 EB05 37.0 · IC025 +5.1 3/3 methods agree vs other Atypical Antipsychotics: PRR 6.9 (6.2–7.7) | Not in label — unassessed | serious n=454 | not reported in cached trials |
| Mean cell haemoglobin concentration decreased | 385 | 50.5 45.0–56.6ROR 50.6 · calibrated p 1e-5 ✓ | 38.8 EB05 35.7 · IC025 +5.0 3/3 methods agree vs other Atypical Antipsychotics: PRR 109.3 (85.0–140.5) | Lab value / disease marker | serious n=320 | not reported in cached trials |
| Mean cell haemoglobin decreased | 420 | 49.7 44.6–55.4ROR 49.8 · calibrated p 1e-5 ✓ | 38.3 EB05 35.4 · IC025 +5.0 3/3 methods agree vs other Atypical Antipsychotics: PRR 35.2 (30.1–41.2) | Lab value / disease marker | serious n=379 | not reported in cached trials |
| Mean cell volume decreased | 321 | 43.9 38.8–49.6ROR 44.0 · calibrated p 3e-5 ✓ | 34.8 EB05 31.7 · IC025 +4.9 3/3 methods agree vs other Atypical Antipsychotics: PRR 82.0 (64.2–104.8) | Lab value / disease marker | serious n=304 | not reported in cached trials |
| Pre-existing disease | 101 | 43.1 34.6–53.7ROR 43.1 · calibrated p 4e-5 ✓ | 34.2 EB05 28.9 · IC025 +4.6 3/3 methods agree vs other Atypical Antipsychotics: only this drug | Reporting / coding artifact | serious n=101 · 100% clinician | not reported in cached trials |
| Myocarditis | 2,231 | 41.1 39.2–43.0ROR 41.8 · calibrated p 4e-5 ✓ | 33.1 EB05 31.9 · IC025 +5.0 3/3 methods agree vs other Atypical Antipsychotics: PRR 16.8 (15.9–17.7) | Labeled — boxed warning exact term | age-adj. PRR 36.2 · serious PRR 20.1 · 91% clinician | NCT02404155: 1/274 (0.4%) on Clozapine (serious AE) |
| Living in residential institution | 366 | 40.4 36.1–45.3ROR 40.5 · calibrated p 5e-5 ✓ | 32.6 EB05 29.9 · IC025 +4.8 3/3 methods agree vs other Atypical Antipsychotics: only this drug | Reporting / coding artifact | serious n=161 | not reported in cached trials |
| Delusional disorder, persecutory type | 82 | 40.2 31.6–51.2ROR 40.2 · calibrated p 6e-5 ✓ | 32.3 EB05 26.8 · IC025 +4.4 3/3 methods agree vs other Atypical Antipsychotics: PRR 5.8 (4.5–7.4) | Not in label — unassessed | serious n=82 · ♀ 0% (drug 39%) | not reported in cached trials |
| Malignant catatonia | 49 | 39.2 28.7–53.5ROR 39.2 · calibrated p 9e-5 ✓ | 31.5 EB05 24.8 · IC025 +4.1 3/3 methods agree vs other Atypical Antipsychotics: PRR 8.8 (6.3–12.3) | Not in label — unassessed | serious n=49 · ♀ 0% (drug 39%) · 100% clinician | not reported in cached trials |
| Wrong patient | 91 | 38.0 30.2–47.7ROR 38.0 · calibrated p 9e-5 ✓ | 30.9 EB05 25.9 · IC025 +4.4 3/3 methods agree vs other Atypical Antipsychotics: PRR 27.0 (19.7–36.9) | Reporting / coding artifact | serious n=91 | not reported in cached trials |
| Sinus rhythm | 81 | 37.9 29.8–48.3ROR 37.9 · calibrated p 9e-5 ✓ | 30.8 EB05 25.6 · IC025 +4.3 3/3 methods agree vs other Atypical Antipsychotics: PRR 8.2 (6.4–10.7) | Not in label — unassessed | serious n=78 · ♀ 100% (drug 39%) · 90% clinician | not reported in cached trials |
| Salivary hypersecretion | 1,844 | 37.9 36.0–39.9ROR 38.5 · calibrated p 7e-5 ✓ | 31.0 EB05 29.8 · IC025 +4.9 3/3 methods agree vs other Atypical Antipsychotics: PRR 10.3 (9.7–10.8) | Labeled adverse reaction exact term | age-adj. PRR 38.8 · serious PRR 24.6 | not reported in cached trials |
| Disturbance in social behaviour | 435 | 37.7 34.0–41.8ROR 37.8 · calibrated p 7e-5 ✓ | 30.8 EB05 28.5 · IC025 +4.7 3/3 methods agree vs other Atypical Antipsychotics: PRR 2.6 (2.4–2.9) | Reporting / coding artifact | serious n=432 · ♀ 80% (drug 39%) | not reported in cached trials |
| Monocyte count increased | 663 | 37.3 34.3–40.6ROR 37.5 · calibrated p 8e-5 ✓ | 30.6 EB05 28.7 · IC025 +4.8 3/3 methods agree vs other Atypical Antipsychotics: PRR 30.3 (26.9–34.1) | Lab value / disease marker | serious n=592 | not reported in cached trials |
| Psychotic symptom | 370 | 37.1 33.2–41.5ROR 37.2 · calibrated p 8e-5 ✓ | 30.4 EB05 27.9 · IC025 +4.7 3/3 methods agree vs other Atypical Antipsychotics: PRR 3.9 (3.5–4.4) | Labeled adverse reaction exact term | serious n=367 | not reported in cached trials |
Clinical concept groups
MedDRA splits one clinical problem across several terms (e.g. "neutropenia", "neutrophil count decreased", "agranulocytosis"), which dilutes term-level signals. These rows count reports with any term in a concept group (an exact union, not a sum), compared with all other drugs. Groups are hand-built and listed in the methods.
| Concept | Reports | PRR 95% CI | Reading |
|---|---|---|---|
| Neutropenia / agranulocytosis | 23,271 | 17.317.1–17.6 | signal |
| Extrapyramidal | 3,326 | 5.45.3–5.6 | signal |
| Rhabdomyolysis / myopathy | 1,535 | 3.23.1–3.4 | signal |
| Anaemia | 4,855 | 2.72.7–2.8 | signal |
| Thrombocytopenia | 3,294 | 2.52.5–2.6 | signal |
| Suicidality | 3,563 | 2.52.4–2.5 | signal |
| Seizure | 2,183 | 1.91.8–2.0 | raised |
| Arrhythmia / qt | 2,102 | 1.81.8–1.9 | raised |
| Serious infection | 7,273 | 1.61.6–1.6 | raised |
| Hyponatraemia | 679 | 1.41.3–1.5 | raised |
| Hyperglycaemia / diabetes | 2,768 | 1.31.3–1.4 | raised |
| Fall / fracture | 2,957 | 1.31.3–1.4 | raised |
| Heart failure | 1,063 | 1.00.9–1.1 | no difference |
| Myocardial infarction | 1,194 | 1.00.9–1.0 | no difference |
| Pancreatitis | 461 | 1.00.9–1.1 | no difference |
| Malignancy | 2,091 | 0.90.9–1.0 | lower than other drugs |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Clozapine as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (1 of 40 signal terms matched).
- NCT02404155 — Biomarker and Safety Study of Clozapine in Patients With Benign Ethnic Neutropenia (BEN) (N=274, NA; 49 AE terms posted; arms: Clozapine)
Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Neutropenia (low neutrophils (infection-fighting cells)) | 18,898 | 27.1 26.7–27.5ROR 31.8 · calibrated p 2e-4 ✓ | 23.4 EB05 23.2 · IC025 +4.5 3/3 methods agree vs other Atypical Antipsychotics: PRR 62.6 (61.0–64.3) | Labeled — boxed warning exact term | age-adj. PRR 33.7 · serious PRR 14.7 · 91% clinician | NCT02404155: 1/274 (0.4%) on Clozapine (serious AE) |
| Hospitalisation | 12,426 | 14.8 14.6–15.1ROR 16.4 · calibrated p 0.005 ✓ | 13.7 EB05 13.5 · IC025 +3.7 3/3 methods agree vs other Atypical Antipsychotics: PRR 39.5 (38.4–40.6) | Reporting / coding artifact | age-adj. PRR 10.2 · serious PRR 8.5 | not reported in cached trials |
| Death | 12,035 | 2.4 2.3–2.4ROR 2.5 · calibrated p 0.808 | 2.3 EB05 2.3 · IC025 +1.2 3/3 methods agree vs other Atypical Antipsychotics: PRR 23.5 (23.0–24.1) | Outcome field, not a reaction boxed warning mentions mortality | age-adj. PRR 2.9 · serious PRR 1.4 | not reported in cached trials |
| Schizophrenia | 4,690 | 105.7 101.9–109.6ROR 109.8 · calibrated p 6e-8 ✓ | 64.8 EB05 63.2 · IC025 +6.0 3/3 methods agree vs other Atypical Antipsychotics: PRR 8.7 (8.5–9.0) | Likely indication confounding term in indications; also in warnings | serious PRR 40.8 | not reported in cached trials |
| White blood cell count increased | 4,506 | 22.2 21.5–22.9ROR 23.0 · calibrated p 0.001 ✓ | 19.7 EB05 19.2 · IC025 +4.2 3/3 methods agree vs other Atypical Antipsychotics: PRR 37.7 (35.9–39.5) | Lab value / disease marker | age-adj. PRR 22.9 · serious PRR 13.5 · 91% clinician | not reported in cached trials |
| White blood cell count decreased | 4,480 | 7.2 7.0–7.4ROR 7.4 · calibrated p 0.083 | 6.9 EB05 6.8 · IC025 +2.7 3/3 methods agree vs other Atypical Antipsychotics: PRR 22.3 (21.4–23.2) | Labeled (related wording) related wording | age-adj. PRR 7.5 · serious PRR 5.8 | not reported in cached trials |
| Neutrophil count increased | 4,168 | 114.9 110.5–119.5ROR 118.9 · calibrated p 3e-8 ✓ | 68.1 EB05 66.4 · IC025 +6.0 3/3 methods agree vs other Atypical Antipsychotics: PRR 55.1 (52.1–58.4) | Lab value / disease marker | serious PRR 42.4 | not reported in cached trials |
| Drug ineffective (drug did not work) | 3,967 | 0.5 0.5–0.5ROR 0.5 · calibrated p 0.045 ✓ | 0.5 EB05 0.5 · IC025 -1.0 PRR-only: not supported by EBGM or IC vs other Atypical Antipsychotics: PRR 2.1 (2.1–2.2) | Reporting / coding artifact | age-adj. PRR 0.7 · serious PRR 0.8 | not reported in cached trials |
| Malaise (feeling unwell) | 3,849 | 1.5 1.4–1.5ROR 1.5 · calibrated p 0.635 | 1.5 EB05 1.4 · IC025 +0.5 vs other Atypical Antipsychotics: PRR 8.4 (8.2–8.7) | Labeled adverse reaction exact term | age-adj. PRR 1.1 · serious PRR 1.5 | NCT02404155: 144/274 (52.6%) on Clozapine |
| Off label use (used outside approved label) | 3,764 | 0.7 0.7–0.8ROR 0.7 · calibrated p 0.140 | 0.7 EB05 0.7 · IC025 -0.5 PRR-only: not supported by EBGM or IC vs other Atypical Antipsychotics: PRR 2.0 (2.0–2.1) | Reporting / coding artifact | age-adj. PRR 0.8 · serious PRR 0.8 | not reported in cached trials |
| Treatment noncompliance | 3,293 | 10.8 10.4–11.2ROR 11.0 · calibrated p 0.023 ✓ | 10.2 EB05 9.9 · IC025 +3.3 3/3 methods agree vs other Atypical Antipsychotics: PRR 7.1 (6.8–7.4) | Reporting / coding artifact | age-adj. PRR 6.8 · serious PRR 9.3 · 90% clinician | not reported in cached trials |
| Pneumonia (lung infection) | 3,266 | 1.7 1.6–1.8ROR 1.7 · calibrated p 0.784 | 1.7 EB05 1.6 · IC025 +0.7 vs other Atypical Antipsychotics: PRR 9.0 (8.7–9.4) | Labeled — boxed warning synonym match | age-adj. PRR 1.7 · serious PRR 1.1 | NCT02404155: 1/274 (0.4%) on Clozapine (serious AE) |
| Neutrophil count decreased | 3,169 | 14.2 13.7–14.7ROR 14.5 · calibrated p 0.008 ✓ | 13.1 EB05 12.8 · IC025 +3.7 3/3 methods agree vs other Atypical Antipsychotics: PRR 29.6 (28.1–31.2) | Labeled — boxed warning synonym match | age-adj. PRR 13.7 · serious PRR 8.7 | not reported in cached trials |
| Drug interaction | 3,153 | 3.4 3.3–3.5ROR 3.4 · calibrated p 0.498 | 3.3 EB05 3.2 · IC025 +1.7 3/3 methods agree vs other Atypical Antipsychotics: PRR 3.4 (3.3–3.5) | Reporting / coding artifact | age-adj. PRR 3.4 · serious PRR 2.2 · 91% clinician | not reported in cached trials |
| Haemoglobin decreased | 3,132 | 5.2 5.1–5.4ROR 5.4 · calibrated p 0.200 | 5.1 EB05 5.0 · IC025 +2.3 3/3 methods agree vs other Atypical Antipsychotics: PRR 25.8 (24.6–27.2) | Labeled (related wording) related wording | age-adj. PRR 6.1 · serious PRR 3.4 | not reported in cached trials |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Anosognosia — n=498, PRR 310.8
- Radiation inflammation — n=50, PRR 274.6
- Withdrawal catatonia — n=91, PRR 114.5
- Delusion of grandeur — n=121, PRR 62.1
- Psychiatric decompensation — n=465, PRR 52.4
- Delusional disorder, persecutory type — n=82, PRR 40.2
- Malignant catatonia — n=49, PRR 39.2
- Sinus rhythm — n=81, PRR 37.9
✓ A hand-written Bradford Hill causality assessment exists for this drug: Clozapine ↔ Agranulocytosis / severe neutropenia.
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Clozapine?
In FDA FAERS, the most frequently co-reported reaction terms for Clozapine are neutropenia, schizophrenia, white blood cell count increased, white blood cell count decreased, neutrophil count increased, malaise. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Clozapine have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: WARNING: SEVERE NEUTROPENIA; ORTHOSTATIC HYPOTENSION, BRADYCARDIA, AND SYNCOPE; SEIZURE; MYOCARDITIS, PERICARDITIS, AND CARDIOMYOPATHY; INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Severe N.
Do FAERS signals prove that Clozapine causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID 09231d80-6343-4a34-bd5b-100c547fd3c9, effective 20260313; matched on
openfda.generic_name.exact:"CLOZAPINE") - PubChem CID 135398737 description (ChEBI)
- Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 1,279 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath - ClinicalTrials.gov API v2 (query
CLOZAPINE, results-bearing studies sorted by enrollment)
Page generated 2026-10-14. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.