Half-Life of Clozapine in Pediatric Overdose
The elimination half-life of clozapine in this 35 kg pediatric patient who ingested 300mg is approximately 14 hours, though this represents steady-state kinetics and may differ in acute overdose settings where the half-life can be prolonged.
Pharmacokinetic Properties of Clozapine
The half-life of clozapine varies depending on dosing patterns:
- Single-dose half-life: Approximately 8-10 hours 1
- Multiple-dose (steady-state) half-life: Approximately 14.1 hours 1
- Bioavailability: 27% (0.27) after oral administration 1
Clinical Implications for This Overdose
Expected Timeline for This Patient
This 35 kg child ingested 300mg (3 × 100mg tablets), which represents a significant overdose requiring careful monitoring despite potentially mild initial symptoms 2, 3:
- Peak plasma concentrations typically occur 2.5-4 hours post-ingestion 4
- Using the 14-hour half-life, approximately 50% of the drug would be eliminated every 14 hours
- Complete symptom resolution typically occurs within 4 days following pediatric ingestion 2
- Monitoring should continue for at least 5 days to detect late-onset complications 4
Dose-Severity Relationship
The 300mg ingestion (approximately 8.6 mg/kg for this 35 kg patient) places this child at risk for moderate to severe toxicity 3:
- Minimal dose for moderate/severe intoxication: 100mg 3
- This patient's dose is 3-fold higher than the minimal toxic dose
- Pediatric patients may experience complete symptom resolution with supportive care alone 2
Expected Clinical Course
Anticipated Symptoms (in order of frequency)
Monitor this patient closely for 3:
- Central nervous system depression (63% of cases) - most common finding
- Tachycardia (40% of cases) - sinus tachycardia expected
- Altered mental status with periods of somnolence and intermittent agitation 4
- Anticholinergic syndrome with mild hypotension 4
- Respiratory depression (9.6% of cases) 3
- QTc prolongation (8.2% of cases) - requires cardiac monitoring 3
Critical Monitoring Parameters
Continuous monitoring for 24-48 hours minimum, extending to 5 days if complications develop 4:
- Continuous cardiac telemetry for dysrhythmias and QTc prolongation 3
- Frequent vital signs with attention to blood pressure and respiratory rate 3
- Serial neurological assessments for level of consciousness 4
- Seizure precautions, as clozapine lowers seizure threshold in dose-dependent manner 5, 6
Plasma Level Interpretation
If serum clozapine levels are obtained 2, 4:
- Therapeutic adult range: 350-600 mcg/L (or 0.35-0.6 mcg/mL) 2
- Toxic levels: >3.8 mcg/mL have been survived with supportive care 4
- A 5-year-old child had detectable levels (17 mcg/L) at 85 hours post-ingestion, demonstrating prolonged elimination 2
- Plasma levels do not always correlate with severity - high levels are not universally lethal 4
Important Clinical Caveats
Age does not appear to significantly affect toxicity risk in pediatric patients, unlike adults over 50 years 3:
- Patients >50 years have 6.4-fold increased risk of severe intoxication (not applicable here) 3
- Pediatric cases have shown favorable outcomes with supportive care alone 2
- Decontamination measures and pretreatment status do not significantly correlate with severity 3
The half-life may be prolonged in overdose situations due to saturation of hepatic metabolism, though specific pediatric overdose pharmacokinetic data are limited 1.