clozapine Flashcards
6 indications de clozapine à part schizophrénie résistante
manie résistante (add)
psychose chez parkinson
agressivité
suicidalité
polydipsie psychogène
dyskinésie tardive
traitement de non réponse a la clozapine
verifier adhérence
verifier niveaux plasmatiques et augmenter la dose (seuil minimal 350 ng/ml, aller ad 1000 ng/ml si toléré)
ajouter un AP avec D2 effect
ajouter ECT
work up avant debuter clozapine
signes vitaux
BMI
constipation? smoking? seizures?
labs: FSC (neutro, eosino), E+/creat/liver/HbA1C/lipids
ECG (QT)
abd XR if needed
insciption au programme de suivi de clozapine
QT correction error: how to estimate the true QT at rate >72/sec
current formula (Bazett) overestimates QT
Fridericia formula QTc=QT/racine cube du RR
titration clozapine inpatient smoker/non smoker
titration pour smoker (non smoker - 50%)
se rendre à 200 en 1 sem et 400 en 2 sem
25-50-100-150-200
ensuite par increment de 50 mg (par 2-3 jours) ad 400
dosage clozapine 7 jours apres 400mg
titration clozapine pour outpatient smoker/non smoker
doses pour smoker (non smoker - 50% de la dose)
ad 100 jour6
ad 200 jour12
ad 300 jour18
ad 400 jour24
dosage plasmatique 7 jours apres 300mg
à quel delais d’attendre de la myocardite?
1-7 weeks after initiation of Tx, most cases - within 4 weeks
monitoring after initiaion of clozapine
within 3 months - possible side effects
then - FSC
8 side effects of clozapine
neutropenia
constipation - ileus
sedation
orthostasis - tachycardia
sialorrhea
seizure
metabolic syndrome
DRESS syndrome
constipating medications - psychotrops
chlorpromazine +++
olanzapine
quetiapine >600
TCA
antiparkinsonian: cogentin, diphenhydramine
constipating medications - non psychotrops
opiods
iron
managing cholinergic rebound
si possible, baisser la dose par 100 mg die ad 100mg die
ensuite - par increments de 25 mg q 4-7 jours
if sleep disturbance - 25-50 mg benadryl HS
if abrupt d/c - strart cogentin (benztropine) at equivalent dose (50 mg clozapine in nonsmoker = 1 mg cogentin = 25 mg benadryl) for at least 2 weeks
options pour pts parkinson sous clozapine si d/c
pimavanserin (nuplazid) - a first-in-class atypical antipsychotic that does not induce clinically significant antagonism of dopaminergic, adrenergic, histaminergic, or muscarinic receptors. It is the first FDA-approved drug indicated for the treatment of the hallucinations and delusions in PD-associated psychosis
possibly - quetiapine
ECT
options pour pts parkinson sous clozapine si d/c
pimavanserin (nuplazid) - a first-in-class atypical antipsychotic that does not induce clinically significant antagonism of dopaminergic, adrenergic, histaminergic, or muscarinic receptors. It is the first FDA-approved drug indicated for the treatment of the hallucinations and delusions in PD-associated psychosis
possibly - quetiapine
ECT
mechanisme d’action - clozapine
alpha 1 antagonist
H1 antagonist
M1 et M3 antagonism
norclozapine - agonist M1-M5 exept M3 (donne sialorrhea via agonisme muscarinique)
D2 antagost (low affinity)
5HT2A - inverse agonist
conditions qui affectent le metabolisme de la clozapine (activité CYP 1A2)
tabagisme (hydrocarbons, pas la nicotine, CYP 1A2 inducers)
infections (augmentent niveaux de clozapine x3)
caffeine (heavy intake can increase clozapine level)
polymorphisme génétique
vrai ou faux: individus avec la neutropénie ethnique bénigne sont plus grand risque de développer la neutropénie sévère
faux
quand le risque de neutropénie est le plus élévé?
6 premiers mois
quel est le temps de résolution de la neutropénie après la d/c de la clozapine?
12 jours (médiane)
seuil neutrophiles pour débuter/continuer clozapine
ANC égal ou plus que 2000/mm3
BEN: 1000
eosinophiles et clozaril: seuil d’alerte
700/mm3
qui est à risque de BEN?
origine africaine
première action si low ANC and no BEN
vérifier Rx (épival, ab + bcp autres très courants)
US guidelines in case of low ANC under clozapine
if more than 1500 - continue
if 1000-1499 - continue
if moderate neutropenia (500-999) - interrupt and consult hematology
if severe neutropenia - d/c Tx and no rechallenge if risks>benefits
vrai ou faux: lithium peux être utilisé comme prévention de neutropénie
oui, à doses autour de 300 HS
clozapine induced constripation management
avoid opioids, iron and other cholinergic drugs
start PEG (level 1) and docusate (no evidence) and stimulant (bisacodyl - moderate evidence) at the beginning of Tx
do not use psyllium - exacerbates constipation
vrai ou faux: mortalité d’ileus dépasse celle de neutropénie chez pts sous clozapine
vrai
ileus - 15-27%
neutropenie - 2.2-4.2%
clozapine: how to manage sedation?
reduce dose if high
adjunct aripiprazole or modafinil (if other methods failed - data weak)
vrai ou faux: sedation is the cause no1 of clozarilTx discontinuation by pts
vrai
Clozaril: management of orthostasis
fluid and salt intake
slowing titration
manage alpha 1 antagonists and antihypertensive drugs
last method - fludrocortisone
Clozaril: management of tachycardia
rule out orthostasis
rule out other causes
atenolol
Clozaril: management of sialorrhea
atropine drops 1% (1st line)
botulinum toxin-B (2nd line)
amilsulpride or clonidine
avoid anticholinergic - risk of ileus
Clozapine: management of seizures
Do NOT stop clozapine
Valproate - the most studied and recommended (risk of neutropenia/thrombocytemia/hyperNH3)
manage as epilepsy
Clozapine: management of metabolic effects
all patients are candidates for metformin (weight gain early)
monitor BMI/lipid profile/Hb1Ac
Clozapine: rate and onset of fever, myocarditis, interstitial nephritis, DRESS, cardiomyopathy
Fever - in 20%, within first 8 wks
Myocarditis - up to 3% within the first 6-8 wks
Intestitial nephritis, serosostis and DRESS - less common, within first 60 days
Cardiomyopathy - many months after
Clozapine: rate of incontinence and enuresis and their management
up to 40% early in Tx
20% - persistent
manage other antipsychotics
do not use anticholinergic
vrai ou faux: si clozapine donne élevation des enzymes hépatiques il faut d/c
faux
élevation x2 du baseline est normale chez 30%
clozapine: rate and management of thrombocytopenia
3%
no action needed unless less than 50K - risk of bleeding - d/c
