Clozapine - 1 Flashcards
when was clozapine first made?
1950’s
the europian journey of clozapine?
Introduced in 1970’s
withdrawn despite affecitveness in 1976
Reintroduced in 1990 with mandatory blood monitoringg
cause of withdrawal of clozpaine in europe in 1976?
some death due to agranulocytosis
Indication for clozpane in schizo?
treatment-resistant schizophrenia
how is treatment-resistant schizophrenia (TRS) defined?
Ongoing symptoms and functional impairments despite two adequate trials of different antipsychotics with proper adherence.
% of TRS?
20-33%
% of TRS responding to clozapine?
a whopping 60%
what are those who don’t respond to even clozapine called?
Ultra Resistant ( no response to trial of 2 antipsychotic and clozapine)
% of schizophrenia that will be ultra Resistant?
12-20%
how long should you wait after clozapine administration to monitor blood level?
12 hours ideally
how many days should patients be on clozapine before monitoring is performed and why?
7 days
to achieve a steady state
what is average clozapine dose in the UK
450 mg / day
- - -
in what range of clozapine dose is response seen?
150-900 mg / day
what threshold most studies have suggested for clozapine?
0.34-0.42 mg/l
(can be as high as .5 mg/l)
is there an established threshold for clozapine?
No!!!!
what does a threshould above 0.5 mg/l mean?
-should be treated with caution
-there is a risk of @@@Seizure@@@
what patients might need lower dose?
non-smokers
elderly
females
patients on SSRs (enzyme inhibitors)
can inflammations affect clozapine level?
Yes, it increased.
what does Maudsley 14th edition say if the clozapine plasma level is < 0.35?
if poor response, increase.
if good response, maintain.
what does Maudsley 14th edition say if the clozapine plasma level is 0.35-0.5?
if good response, maintain
If poor, increase to >0.5 mg/l and consider prophylactic anticonvulsants
what does Maudsley 14th edition say if the clozapine plasma level is 0.5-1 mg/l?
*if there is a poor response, consider prophylactic anticonvulsant and consider augmentation.
if that is poorly tolerated, reduce the dose if augmentation worked.
*If good response and well tolerated, just consider prophylactic anticonvulsant and maintain the dose.
*If good response and poorly tolerated, consider prophylactic, reduce the dose ( if there is no history of poor response in low doses)
so when clozapine is between 0.5 to 1 mg/l, additing what agent must be considered?
prophylactic anticonulsant
what does Maudsley 14th edition say if the clozapine plasma level is > 1mg/l?
*if poor response, attempt augmentation and add anticonvulsant, then reduce the dose ( to >1 mg/l)…Consider abandoning clozapine
*If there is a good response but poorly tolerated, add anticonvulsant and slowly reduce the dose
*If there is good response and well tolerated, add anticonvulsant and monitor closely…only attempt dose reduction if toleration declined
when should clozapine abandoning be considered?
if blood level is above 1 mg/l and there is poor response to current dose and reduction.
what is the name of major metabolite of clozapine
Nor clozapine (norclozapine)
how is norclozapine different than clozapine?
Longer half life
Factuate less
Can be used to indicate recent compliance
the average ratio of clozapine and norclozapine?
1.3
can clozapine and norclozapine ratio be used for?
to assess compliance and enzyme induction
what clozapine norclozpine ratio range means good compliance and no
0.5-2.5
what can >2.5 clozpaine norclozpine ratio mean?
either
-the blood is taken less than 11 hours after last administration or
-metabolism of clozapine is saturated or
-or enzyme inhitors are added
-or patient has stopped smoking
what does it mean if the clozapine norclozapine ratio is <.5
either
- blood is taken after 13 hours of last administration
- poor compliance
- enzyme induction ( smoking or rifampicin)
Green code in clozapine monitoring for blood cells?
WBC > 3.5
Neutrophil >2
Amber code in clozapine monitoring for blood cells
WBC 3.0 - 3.5
Neutrophil 1.5-2
Red code in clozapine monitoring for blood cells
WBC < 3
Neutrophil < 1.5
How is neutropenia is defined?
absolute neutrophil count of less than 1.5 * 10^9/L
prevalence of neutropenia in clozpine takers?
2.7%
Onset of Neutropenia in clozapine therapy?
half of 2.7% in the first 18 weeks and 3 quarter in first year.
RISK factor for neutropenia
younger age
Afro-Caribbean 77%
Low baseline WBC count
Is risk for neutropenia in clozapine therapy dose dependent?
Nope!
Neutropenia dose dependent?
No!!!
How is agranulocytosis defined?
Absolute neutrophil count of less than .5 * 10^9/L
Prevalence of agranulocytosis in clozapine therapy?
0.8%
is agranulocytosis fatal if not treated
yes
death rate in those who develop agranulocytosis?
3%
why can’t clozapine used with drugs like carbamazepine?
both have risk of agranulocytosis
Risk for agranulocytosis?
Older age
Asians (2.4 times more than Caucasians)
age risk difference between neutropenia and agranulocytosis
neutropenia risk decreases with age
agranulocytosis risk increases with age
racial risk difference between neutropenia and agranulocytosis
neutropenia more in afro-Caribbeans (77% more risk)
agranulocytosis more in Asians ( 2.4 times more than Caucasians)
Rechallenge blood dyscrasia prevalence
one third of those who stop clozapine due to neutropenia or agranul.
how is blood dyscrasia on rechallence descriped?
Rapid onset
More severe
Last longer
