Documentation of Clozapine Hold Due to Missing Laboratory Monitoring
Clozapine must be interrupted immediately when required absolute neutrophil count (ANC) monitoring is not available, as continuation without current hematologic data creates unacceptable risk of undetected life-threatening agranulocytosis.
Mandatory Documentation Elements
Primary Safety Rationale
Document that clozapine therapy is being held because current ANC and complete blood count with differential are not available within the required monitoring timeframe, creating inability to detect potentially fatal agranulocytosis. 1
State explicitly that clozapine-induced agranulocytosis occurs in approximately 0.8–1% of patients and carries risk of serious and potentially fatal infection when ANC falls below 500/μL. 2, 3, 4
Note that the risk of neutropenia is greatest during the first 18 weeks of treatment but persists throughout therapy, making continuous monitoring non-negotiable. 1
Specific Monitoring Requirements Not Met
Specify which monitoring interval was missed: weekly monitoring (first 6 months), biweekly monitoring (months 6–12), or monthly monitoring (after 12 months of continuous therapy). 3, 1
Document the date of the last available ANC value and the date by which the next monitoring was required per FDA guidelines. 1
State that without current laboratory data, you cannot determine if the patient's ANC remains in the safe range (≥1500/μL for general population or ≥1000/μL for benign ethnic neutropenia). 1
Clinical Decision Framework
Document that FDA labeling mandates interruption of clozapine when ANC monitoring cannot be performed as scheduled, as the drug's risk-benefit profile depends entirely on timely detection of neutropenia. 1
Note that clozapine-induced agranulocytosis typically manifests as rapid decline over approximately 2 weeks to ANC <0.5 × 10⁹/L, making even brief lapses in monitoring potentially catastrophic. 3
State that continuation without monitoring violates the mandatory Risk Evaluation and Mitigation Strategy (REMS) program requirements for clozapine prescribing. 1
Sample Documentation Language
"Clozapine therapy is being held effective [date] due to absence of required hematologic monitoring. Patient's last ANC was [value] on [date]. Per FDA guidelines, [weekly/biweekly/monthly] monitoring is required, with next laboratory draw due by [date]. This monitoring has not been completed as of today. Clozapine carries approximately 1% risk of potentially fatal agranulocytosis (ANC <500/μL), with highest risk in first 18 weeks but persistent risk throughout treatment. Without current ANC data, I cannot determine if patient has developed neutropenia requiring immediate intervention. Continuation of clozapine without mandated monitoring creates unacceptable risk of undetected life-threatening hematologic toxicity. Clozapine will remain held until current CBC with differential and ANC are obtained and reviewed. If ANC ≥1500/μL (or ≥1000/μL for documented benign ethnic neutropenia) with no signs of infection, clozapine may be resumed with monitoring schedule determined by duration of interruption per FDA guidelines." 1
Resumption Criteria to Document
State that clozapine may be resumed only after obtaining current ANC and confirming it meets safety thresholds: ANC ≥1500/μL for general population or ANC ≥1000/μL for patients with documented benign ethnic neutropenia. 1
Document the monitoring schedule upon resumption: if interruption <30 days, continue previous monitoring frequency; if interruption ≥30 days, restart as new patient with weekly monitoring for 6 months. 1
Note that if the delayed laboratory work reveals ANC 1000–1499/μL, clozapine should remain interrupted with weekly monitoring until ANC ≥1500/μL, then weekly for 4 additional weeks before returning to prior monitoring interval. 2, 1
Critical Thresholds to Reference
ANC <500/μL: Severe neutropenia requiring permanent discontinuation (do not rechallenge unless benefits clearly outweigh risks), daily monitoring until ANC ≥1000/μL, then three times weekly until ANC ≥1500/μL, with hematology consultation recommended. 2, 1
ANC 500–999/μL: Moderate neutropenia requiring interruption, three times weekly monitoring until ANC ≥1500/μL, then weekly for 4 weeks before resuming prior monitoring schedule. 1
ANC 1000–1499/μL: Mild neutropenia requiring interruption, weekly monitoring until ANC ≥1500/μL, then weekly for 4 additional weeks. 2, 1
Additional Safety Considerations
Document that monitoring must continue for 4 weeks after any clozapine discontinuation, as agranulocytosis risk persists after drug cessation. 3, 4
Note that fever (temperature ≥38.5°C or 101.3°F) in any patient on clozapine requires immediate ANC measurement, as fever is often the first sign of neutropenic infection. 1
State that if patient develops fever with ANC <1000/μL, immediate workup for infection and hematology consultation are indicated. 1