Clozapine
Toxicology Overview / Directory
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.
Test PDF
Standard Kch Clozapine Request Form V2.pdf
Sample Requirements
2mL of EDTA whole blood preferred. Serum or plasma can be used if required.
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 above (Test PDF) 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): A special request form is available to download below. Do not use this form if you are not registered with CPMS!
PDF Request Form
Download Clozapine Request Form
Turnaround Time
Results are available within 2 working days of receipt in the laboratory.
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)
Contacts
Clinical Advice & Interpretation
Dr Bob Flanagan
T 020 3299 5881
Fax 020 3299 5888
Laboratory
Simon Handley
T 020 3299 5883
F 020 3299 5888
References
Bowskill S, Couchamn L, MacCabe J, Flanagan R. Plasma clozapine and norclozapine in relation to prescribed dose and other factors in patients aged 65 years and over: data from a therapeutic drug monitoring service, 1996–2010. Human Psychopharmacology: Clinical & Experimental, 2012.
Couchman L, Morgan P, Spencer E, Flanagan J. Plasma Clozapine, Norclozapine, and the Clozapine:Norclozapine Ratio in Relation to Prescribed Dose and Other Factors: Data From a therapeutic Drug monitoring Service, 1993-2007. Therapeutic Drug Monitoring, 2010.
Couchman L, Morgan P, Spencer E, Johnston A, Flanagan R. Plasma Clozapine and Norclozapine in Parients Prescribed Different Brands of Clozapine (Clozaril, Denzapine, Zaponex). Therapeutic Drug Monitoring, 2010.
Couchman L, Bowskill S, Handley S, Patel M, Flanagan R. Plasma clozapine and norclozapine in relation to prescribed dose and other factors in patients aged <18 years: Data from a Therapeutic Drug Monitoring service, 1994-2010. Early Intervention in Psychiatry, 2012; doi: 10.1111/j.1751-7893.2012.00374.x. [Epub ahead of print]
Flanagan RJ, Spencer E, Morgan P, Barnes T, Dunk L. Suspected clozapine poisoning in the UK/Eire, 1992–2003. Forensic Science International, 2005; 155:91-99.
Flanagan RJ. Therapeutic Monitoring of Antipsychotic Drugs. CPD Clinical Biochemistry, 2006.
Hiemke C et al. AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011. Pharmacopsychiatry, 2011; 44: p195-235
Fisher DS et al. LC-MS/MS of some atypical antipsychotics in human plasma, serum, oral fluid and haemolysed whole blood. Forensic Science International, 2013 (epub ahead of print)
Fisher DS et al. Stability of some atypical antipsychotics in human plasma, haemolysed whole blood, oral fluid, human serum and calf serum. Forensic Science International, 2013 (epub ahead of print)
Fisher DS et al. Plasma, Oral Fluid, and Whole Blood Distribution of Antipsychotics and Metabolites in Clinical Samples. Therapeutic Drug Monitoring, 2013 (epub ahead of print)
