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Clozapine

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clozapine
Type antipsychotic
Group atypical antipsychotics
links
ATC-code N05AH02
CAS-number 5786-21-0
Medscape 342972
FDA 094303
PubChem 2818
PubMed clozapine
Drugs.com clozapine
drugbank APRD00470
Kompas (nl) clozapine
Wikipedia clozapine
more info
Dmin 300mg [1]
DDD 300mg [2]
Dmax 900mg [1]
Cth 300-600μg/L [3]
Ctox 800μg/L [4][3]
EQ-dosage 0.025[5][6] haloperidol
T1/2 10h [7]
metabolites 5[7]
bioavailability 55%[7]
administration oral
tablets 25,100,200 mg
Price/day 1 [8]

clozapine is an antipsychotic in the group atypical antipsychotics.


Caution area Value Ref Description
Lactation 6 [7][9][10] Possibly unsafe
Pregnancy 5 [10] possibly unsafe - B3* - animal studies have shown fetal damage, significance in humans unknown
Diabetes mellitus 8 [1][10][11][12] strong influence on diabetes - only applicable with frequent monitoring
Hepatic insufficiency 8 [7] Unsafe with mild hepatic impairment (Child-Pugh classification A - monitoring required)
Children 2 [13] applicable - not registered for pediatric use, but well studied
Elderly 8 [7][9][14] unsafe - adapt dosage or substitute drug
Dementia 10 [10] not approved for patients with dementia
Chronic Obstructive Pulmonary Disease 8 [15][10] unsafe - adapt dosage or substitute drug
Hypertension 8 [22] common (between 1 in 10 and 1 in 100 patients: 1% - 10%)
Hypotension 8 [22] common (between 1 in 10 and 1 in 100 patients: 1% - 10%)
Heart failure 8 [7] strong influence on HF - rather unsafe, continue only if absolutely necessary
Long QT-syndrome 4 [16][17] Possible Risk of QT prolongation Arizona Scale - Possible Risk of TdP
Seizures 8 [10][9] common (between 1 in 10 and 1 in 100 patients: 1% - 10%)
Cerebrovascular accidents 6 [7] average influence on CVA - frequent monitoring recommended
Renal insufficiency 2 [18] generally safe - unsafe when MDRD < 10 (end stage renal disease (ESRD))
Dyskinesia 2 [1][10] very rare (less then 1 in 10,000 patients: < 0,01% )
Movement disorders 8 [22] common (between 1 in 10 and 1 in 100 patients: 1% - 10%)
Haematology 8 [1][10][19] common (between 1 in 10 and 1 in 100 patients: 1% - 10%)
Anticholinergic effects 8 [7][1][10] common (between 1 in 10 and 1 in 100 patients: 1% - 10%)
Male sexual dysfunction 6 [10][9] uncommon (between 1 in 100 and 1 in 1,000 patients: 0,1% - 1%)
Female sexual dysfunction 3 [21] rare (between 1 in 1,000 and 1 in 10,000 patients: 0,01% - 0,1%)
Traffic 6 [7][22][23] medium influence (category II) 0,5-0,8 g/l (0,5–0,8‰)
Weight 10 [7][1][12]\ very common (over 1 in 10 patients: > 10%)
Weight gain 10 [7][1][12] weight gain is very common (over 1 in 10 patients: >10%)
Weight loss 0 unknown/unverified
Photosensitivity 7 [24] There is a potential risk for photosensitivity reactions
Sedation 10 [9] very common (over 1 in 10 patients: > 10%)
Poor CYP2D6 metabolizer 1 [25] No substrate of this enzyme – safe
Ultra rapid CYP2D6 metabolizer 1 [25] No substrate of this enzyme – safe
Poor CYPC19 metabolizer 1 [25] No substrate of this enzyme – safe
Ultra rapid CYP2C19 metabolizer 1 [25] No substrate of this enzyme – safe


  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 CVZ; Farmacotherapeutisch Kompas - clozapine (dutch)
  2. WHO Collaborating Centre for Drug Statistics Methodology ATC=N05AH02
  3. Universitair Medisch Centrum Groningen, Referentiewaarden klinisch farmacologisch bepalingen
  4. VU Medisch Centrum, Referentiewaarden klinisch farmacologisch bepalingen
  5. Farmacotherapeutisch Kompas; Inleidende Tekst Antipsychotica (dutch)
  6. average of FTK-mentioned 0.02-0.03
  7. 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 7.13 7.14 KNMP; Informatorium Medicamentorum 2009; Monografie "clozapine" (Dutch)
  8. oraal 37.42/maand/DDD cf FTK: results in €1.25
  9. 9.0 9.1 9.2 9.3 9.4 Drugs.com clozapine
  10. 10.00 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 10.10 DailyMed Current Medication Information - 8681
  11. Nielsen J, Skadhede S, Correll CU. Antipsychotics associated with the development of type 2 diabetes in antipsychotic-naïve schizophrenia patients. Neuropsychopharmacology 2010: 1-8 (advance online publ.)  (pubmed-id 20520598)
  12. 12.0 12.1 12.2 Cahn W, Ramlal D, Bruggeman R, de Haan L, Scheepers FE, van Soest MM et al. Prevention and treatment of somatic complications arising from the use of antipsychotics. Tijdschr Psychiatr 2008;50(9):579-91  (pubmed-id 18785105)
  13. NKFK Kinderformularium ID=306 (dutch)
  14. Oberholzer AF, Hendriksen C, Monsch AU, Heierli B, Stähelin HB. Safety and effectiveness of low-dose clozapine in psychogeriatric patients: a preliminary study. Int Psychogeriatr. 1992 Fall;4(2):187-95  (pubmed-id 1477306)
  15. Trifirò G, Gambassi G, Sen EF, Caputi AP, Brea J, Sturkenboom MC; Association of community-acquired pneumonia with antipsychotic drug use in elderly patients: a nested case-control study; Ann Intern Med 2010;152(7):418-25  (pubmed-id 20368647)
  16. Stöllberger C, Huber JO, Finsterer J; Antipsychotic drugs and QT prolongation; Int Clin Psychopharmacol 2005;20:243-251  (pubmed-id 16096514)
  17. Arizona Scale
  18. Taylor D, Paton C, Kapur S. The Maudsley prescribing guidelines, 10th edition. London: Informa Healthcare; 2009
  19. Alvir JM, Lieberman JA, Safferman AZ, Schwimmer JL, Schaaf JA. Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med. 1993 Jul 15;329(3):162-7  (pubmed-id 8515788)
  20. 20.0 20.1 ToxNet, Hazardous Substances Data Bank - 6478
  21. Cutler AJ. Sexual dysfunction and antipsychotic treatment. Psychoneuroendocrinology. 2003 Jan; 28 Suppl 1: 69-82.  (pubmed-id 12504073)
  22. 22.0 22.1 22.2 22.3 Novartis Pharmaceuticals UK Ltd; SPC Clozaril 25mg and 100mg Tablets
  23. ICADTS Reports Medicinal Drug List 2007
  24. UptoDate - clozapine
  25. 25.0 25.1 25.2 25.3 Roo, M. de; CYP2D6 and CYP2C19 scores.