Clozapine, Serum or Plasma

CPT: 80159
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Synonyms

  • Clozaril®
  • FazaClo®

Expected Turnaround Time

2 - 4 days


Related Documents


Specimen Requirements


Specimen

Serum or plasma


Volume

1 mL


Minimum Volume

0.3 mL


Container

Red-top tube, lavender-top (EDTA) tube, or green-top (heparin) tube. Do not use a gel-barrier tube. The use of gel-barrier tubes is not recommended due to slow absorption of the drug by the gel. Depending on the specimen volume and storage time, the decrease in drug level due to absorption may be clinically significant.


Collection

Transfer separated serum or plasma to a plastic transport tube.


Storage Instructions

Room temperature


Stability Requirements

Temperature

Period

Room temperature

14 days

Refrigerated

14 days

Frozen

14 days

Freeze/thaw cycles

Stable x3


Causes for Rejection

Gel-barrier tube


Test Details


Use

Evaluate toxicity; monitor therapeutic levels


Limitations

This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.


Methodology

Liquid chromatography/tandem mass spectrometry (LC/MS-MS)


Reference Interval

Patients dosed with 400 mg clozapine daily for four weeks were most likely to exhibit a therapeutic effect when the sum of clozapine and norclozapine concentrations was at least 450 ng/mL.


Additional Information

Clozapine is absorbed rapidly, with peak plasma concentrations occurring within 30 minutes to six hours. Terminal half-life in humans is in the range of 5.5 to 33 hours. Determination of clozapine in plasma is needed to correlate efficacy with plasma concentration. However, pharmacogenomics and coadministration of other agents can complicate the correlation between dose and plasma concentration. Changes in the activity of the cytochrome P450 mixed-function oxidases, especially CYP1A2 and CYP3A4 can affect clozapine levels.1 These oxidases can be induced by drugs such as carbamazepine, with the resulting increase in activity causing 50% decrease in clozapine concentration.2 An additional report3 has indicated some patients may be ultrarapid metabolizers of clozapine due to genetically induced CYP1A2 activity levels. Conversely, clozapine plasma (serum) concentrations may be increased by inhibitors of the P450 oxidases. Amiodarone, cimetidine, ciprofloxacin, fluoxetine, fluvoxamine, indinavir, paroxetine, quinidine, ritonavir, and saquinavir are examples of inhibiting drugs which may cause increases in clozapine levels when coadministered.

A review of adverse metabolic effects4 has indicated clozapine can significantly increase mean levels of glucose and C-peptide, as well as increase in triglyceride levels. Additionally, the Federal Drug Administration and drug provider have issued the following: Patients being treated with clozapine must have a baseline white blood cell (WBC) count and absolute neutrophil count (ANC) before initiation of treatment as well as regular WBC counts and ANCs during treatment and for at least four weeks after discontinuation of treatment.5


Footnotes

1. Spina E, Perucca E. Clinical significance of pharmacokinetic interactions between antiepileptic and psychotropic drugs. Epilepsia. 2002; 43(Suppl 2):37-44. 11903482
2. Jerling M, Lindstrom L, Bondesson U, Bertilsson L. Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: Evidence from a therapeutic drug monitoring service. Ther Drug Monit. 1994 Aug; 16(4):368-374. 7974626
3. Eap CB, Bender S, Sirot EJ, et al. Nonresponse to clozapine and ultrarapid CYP1A2 activity. Clinical data and analysis of CYP1A2 gene. J Clin Psychopharmacol. 2004 Apr; 24(2):214-219. 15206669
4. Melkersson K, Dahl ML. Adverse metabolic effects associated with atypical antipsychotics. Literature review and clinical implications. Drugs. 2004; 64(7):701-723. 15025545
5. MedWatch Safety Alerts for Human Medical Products. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/default.htm. Accessed: September 5, 2006.

References

Hiemke C, Baumann P, Bergemann N, et al. AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: Update 2011, Pharmacopsychiatry. Sep 2011; 44(6):195-235. 22053351
Lovdahl MJ, Perry PJ, Miller DD. The assay of clozapine and N-desmethylclozapine in human plasma by high-performance liquid chromatography. Ther Drug Monit. 1991 Jan; 13(1):69-72. 2057995
Meeker JE, Herrmann PW, Som CW, Reynolds PC. Clozapine tissue concentrations following an apparent suicidal overdose of Clozaril®. J Anal Toxicol. 1992 Jan-Feb; 16(1):54-56. 1640699
Perry PJ, Miller DD, Arndt SV, Cadoret RJ. Clozapine and norclozapine plasma concentrations and clinical response of treatment—refractory schizophrenic patients. Am J Psychiatry. 1991 Feb; 148(2):231-235. 1670979

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
706440 Clozapine (Clozaril), Serum 706443 Total(Cloz+Norcloz) ng/mL 12375-2
706440 Clozapine (Clozaril), Serum 706441 Clozapine, Serum ng/mL 6896-5
706440 Clozapine (Clozaril), Serum 706442 Norclozapine, Serum ng/mL 10992-6

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