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Toxicology Overview / Directory

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Purpose of the test

Clozapine is an atypical antipsychotic used to treat schizophrenia resistant to conventional therapy. Because of the risk of agranulocytosis, white blood cell counts (WBC) are monitored weekly in the early stages of therapy and monthly thereafter. It is recommended that therapy is withheld if the WBC is less than 3,500 mm-3 and abandoned if the WBC falls below 3000 mm-3 or the granulocyte count below 1,500 mm-3.

Side-effects of clozapine include lethargy, hypersalivation, constipation and somnolence. There is a risk of hypo-tension and seizure at higher doses. A single dose of 300-400 mg may be life-threatening in a clozapine-naïve subject. Clozapine is metabolised by N-demethylation, hydroxylation and N-oxidation. The N-demethylated metabolite, nor-clozapine, is present in plasma at similar concentrations to the parent compound, but has a longer plasma half-life.

Plasma clozapine concentrations of 0.35 mg/L and above have been associated with a good response, with the risk of convulsions increasing above 1.0 mg/L.

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Sample Requirements

2mL of EDTA whole blood preferred. Serum or plasma can be used if required.

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Storage and Transport

Please refrigerate (if possible) if not sending immediately. Send by first class post to:

Toxicology Unit

Top Floor, Bessemer Wing

King’s College Hospital

Denmark Hill

London

SE5 9RS

If possible, please COMPLETE (details can be completed electronically) & PRINT the request form below and send as a hard copy (DO NOT SEND ELECTRONICALLY) with the sample. This will ensure all relevant information is available and will aid us in processing your test.

Important note for patients currently registered with the Clozaril Patient Monitoring Service (CPMS): special request forms are available via the CPMS. Do not use this form.

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PDF Request Form

Download Clozapine Request Form

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Turnaround Time

Results are available within 2 working days of receipt in the laboratory.

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Price

Price available on application - please contact adrianturner1@nhs.net. Discounts could be available for significant workloads.

(for patients registered with the Clozaril® Patient Monitoring Service, CPMS or the Denzapine® Monitoring Service, DMS please contact the respective supplier for details of sample transport arrangements and assay cost)

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Contacts

Clinical Advice & Interpretation

Dr Bob Flanagan

E robert.flanagan@nhs.net

T 020 3299 5881

Fax 020 3299 5888

Laboratory

Simon Handley

E simon.handley@nhs.net

T 020 3299 5883

F 020 3299 5888

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References

Rostami-Hodjegan, A; Amin, AM; Spencer, EP; Lennard, MS; Tucker, GT; Flanagan, RJ. (2004) Influence of Dose, Cigarette Smoking, Age, Sex, and Metabolic Activity on Plasma Clozapine Concentrations: A Predictive Model and Nomograms to Aid Clozapine Dose Adjustment and to Assess Compliance in Individual Patients. Journal of Clinical Psychopharmacology. 24(1):70-78

RJ. Flanagan, E. Spencer, P. Morgan, T. Barnes, L. Dunk. (2005) Suspected clozapine poisoning in the UK/Eire, 1992–2003. Forensic Science International, 155 (2-3) 91-99

RJ. Flanagan (2006) Therapeutic Monitoring of Antipsychotic Drugs CPD Clinical Biochemistry 7(1): 3-18

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