Clozapine: Difference between revisions

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[[Category: Drugs]][[Category: Antipsychotics, typical; Antipsychotic 2nd Generation]]
[[Category: Drugs]][[Category: Atypical antipsychotic ]]
'''Clozapine'''  (中文:[[      ]])is an atypical antipsychotic or 2nd Generation antipsychotic medication. It is specifically used to treat treatment resistant schizophrenia (TRS), which affects approximately 1 in 3 people with the condition. These people include those who:
*Have tried at least 2 other antipsychotic medications that did not work
*Are unable to tolerae other antipsychotics because of their side-effects
It may also be used to treat psychoses secondary to Parkinson’s disease.


==Pronunciation==
[[:Category: Antipsychotic Drug | '''Antipsychotic Drug''']]


==Drug Names==
'''Drug class: [[:Category: Atypical antipsychotic  | Atypical Antipsychotic]]
{| class="wikitable"
 
!Generic Name 藥名
'''Clozapine (CLOZARIL)'''（中文：[[氯氮平]]）
!HA Code 藥物代碼
 
!Classification藥物分類
==Common Strengths of Clozapine Tablet==
|-
Clozapine are available in the following strengths:
|Clozapine Tab 25 mg
*25 mg and 100 mg tablets
|CLOZ01
 
|P1S1S3
==Drug Trade Names of Clozapine Tablet==
|-
Clozaril
|Clozapine Tab 100 mg
 
|CLOZ02
==Drug Usage==
|P1S1S3
Clozapine is used for:
|}
*Treatment-resistant schizophrenia.
*Reducing risk of recurrent suicidal behavior in schizophrenia or schizoaffective disorder.


==Mechanism of Action==
==Mechanism of Action==
Clozapine has only weak dopamine-receptor-blocking activity at D1, D2, D3 and D5 receptors, but shows high potency for the D4 receptor.
Partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and antagonist at serotonin 5-HT2A receptors.
It is also an antagonist at the serotonin 5-HT2A receptors, improving depression, anxiety and the negative cognitive symptoms associated with schizophrenia.


==Dosage==
==Route of ADministration==
Oral
 
==Dosages==
*Initial dose: 12.5 mg once or twice daily
*Target dose: 300 - 450 mg/day in divided doses
*Maximum dose: 900 mg/day
 
==Side Effects==
{| class="wikitable"
{| class="wikitable"
!style="text-align: left"| Indication
!style="text-align: left"| Frequency
!style="text-align: left"| Dose
!Adverse reactions
|-
| rowspan="5" | '''Common
| Drowsiness and sedation: Many patients experience significant drowsiness or sedation, which can impact daily activities
|-
| Weight gain: Clozapine can lead to substantial weight gain, which may increase the risk of metabolic syndrome
|-
| Increased salivation
|-
| Constipation
|-
| Dizziness and lightheadedness: Espeically when standing up quickly, due to orthostatic hypotension
|-
| rowspan="7" | '''Uncommon
| Agranlocytosis: Clozapine can cause a significant decrease in white blood cells, leading to a higher risk of infections. Regular blood monitoring is required
|-
| Seizures: The risk of seizures increase with higher doses of clozapine
|-
| Myocarditis and cardiomyopathy
|-
| Neuroleptic Malignant Syndrome (NMS): This is a rare but potentially fatal condition characterized by high fever, muscle stiffness, and altered mental status
|-
|-
!style="text-align: left"| Schizophrenia 
| Tardive dyskinesia: This is a movement disorder that may become irreversible with prolonged use, particularly in older adults
|By ''mouth
ADULT:
ADULT (18 – 59 YEARS):
*12.5 mg 1- 2 times daily on day 1,
*25 – 50 mg on day 2
*Then increased by 25 – 50 mg daily over 14 – 21 days up to 300 mg daily in divided doses
*Usual dose 200 – 450 mg daily
*Maximum 900 mg daily
ADULT (≧ 60 years)
*12.5 ng daily on day 1
*25 – 37.5 mg on day 2,  
*Then increased by 25 mg daily over 14 – 21 days up to 300 mg daily in divided doses,
*Usual dose 200 – 450 mg daily
*Maximum 900 mg daily
|-
|-
!style="text-align: left"| Psychosis in Parkinson’s disease
| QT prolongation
|By ''mouth
|-
ADULT:
| Liver issues: Symptoms may include jaundice, dark urine, and abdominal pain
*12.5 mg at bedtime
*Increased by 12.5 mg up to twice weekly
*Usual dose range 25 – 37.5 mg at bedtime
*Maximum 100 mg daily in 1 – 2 divided doses
|}
|}


DOSE ADJUSTMENTS DUE TO INTERACTIONS
==Pharmacokinetics==
Dose adjustment may be necessary if smoking started or stopped during treatment.
*Pharmacologic effects (e.g. sedation) are apparent within 15 minutes
*Peak plasma concentrations are typically attained within 1.5 to 2.5 hours after single or multiple doses of clozapine tablets
*Elimination half-life: 8 hours (single dose), 12 hours (multiples doses)
*Approximately 50% excreted in urine, 30% in feces
 
==Drug Precautions==
'''Pregnancy
 
Use caution; potential risks to the fetus should be considered
 
'''Breastfeeding
 
Contraindicated during lactation


How long will it take before clozapine begins to work?
'''Children & Elderly
Some people feel the benefit of clozapine within a few days, others may need a few months or even a year.
*Contraindicated in children before puberty
*1 in 3 people with TRS have an improvement within 6 weeks
*Use caution in elderly patients
*2 in 3 people with TRS have an improvement after one year of treatment.


==Side Effects==
'''Monitoring Requirements
Clozapine is associated with a relatively high risk of low white blood cells. It specifically affects a type of white blood cell called neutrophil. Neutrophils help the body to fight infections. A small fall in neutrophil levels leads to a condition called neutropenia, while a big fall is called agranulocytosis. Agranulocytosis and neutropenia are uncommon. However, if they occur, it is usually within the first 18 weeks of clozapine treatment.
 
It is recommended that the white blood cell count be regularly monitored.
Patients on clozapine require regular monitoring, including:
*Frequent blood test to monitor white blood cell counts.
*Cardiac monitoring to detect any changes in heart rhythm.
*Regular metabolic assessments to check for weight gain, blood sugar levels, and lipid profiles.
 
'''Drug Interactions
 
Interactions with strong CYP1A2 inhibitors, CYP2D6 inhibitors, and CYP3A4 inducers
*CYP1A2 Inhibitors
**Drugs such as fluvoxamine, ciprofloxacin, and hormonal contraceptives can increase clozapine levels, raising the risk of adverse effects
*CYP1A2 inducers
**Substances like omeprazole can decrease clozapine levels, potentially reducing its efficacy
*Lamotrigine
**THis anticonvulsant can increase clozapine levels, requiring close monitoring
*Caffeine
**Can increase clozapine levels due to CYP1A2 inhibition
*Grapefruit Juice
**May increase clozapine levels bhy inhibiting CYP3A4
*Smoking
**Can decrease clozapine levels; cessation can lead to increase plasma levles and potential toxicity
 
==FAQ==
'''How Should I Take the Tablet?
 
Take with or without food.
 
'''What should I avoid while taking?
 
Avoid activities requiring mental alertness until you know how the medication affects you.


All side-effects are listed by system organ and frequency:
'''What Happens if I Miss a Dose?
*Very common (≥ 1/10)
*Common ( ≥ 1/100 to < 1/10)
*Uncommon (≥ 1/1000 to < 1/100)
*Rare (≥ 1/10,000 to < 1/1000)
*Very rare (<1/10,000)


{| class = "wikitable"
Take the missed dose as soon as you remember unless it is almost time for your next dose. Do not double doses.
!style="text-align: left"| Blood and lymphatic system disorders
|
Common: neutropenia
Uncommon: agranulocytosis
Rare: anaemia
Very rare: thrombocytopenia
|-
!style="text-align: left"| Metabolism and nutrition disorders
|
Common: weight gain
Rare: diabetes mellitus
|-
!style="text-align: left"| Psychiatric disorders
|Common: dysarthria
|-
!style="text-align: left"| Nervous system disorders
|
Very common:
*Drowsiness/sedation
*Dizziness
Common:
*Seizures
*Extrapyramidal symptoms
*Akathisia
*Tremor
*Rigidity
*headache
Uncommon:
*neuroleptic malignant syndrome
Rare:
*confusion
*delirium
|-
!style="text-align: left"| Eye disorders
|Common: blurred vision
!style="text-align: left"| Cardiac disorders
|
Very common: tachycardia
Common: ECG changes
Rare:
*arrhythmias
*myocarditis
*pericarditis
!style="text-align: left"| Vascular disorders
|
Common:
*syncope
*postural hypotension
*hypertension
!style="text-align: left"| Gastrointestinal disorders
|
Very common:
*constipation
*hypersalivation
Common:
*nausea
*vomiting
*anorexia
*dry mouth
!style="text-align: left"| Hepatobiliary disorders
|
Common: elevated liver enzymes
Rare:
*pancreatitis
*hepatitis
*cholestatic jaundice
!style="text-align: left"| Renal and urinary disorders
|Common: urinary retention
|}

Latest revision as of 22:11, 21 July 2024


Antipsychotic Drug

Drug class: Atypical Antipsychotic

Clozapine (CLOZARIL)（中文：氯氮平）

Common Strengths of Clozapine Tablet[edit]

Clozapine are available in the following strengths:

  • 25 mg and 100 mg tablets

Drug Trade Names of Clozapine Tablet[edit]

Clozaril

Drug Usage[edit]

Clozapine is used for:

  • Treatment-resistant schizophrenia.
  • Reducing risk of recurrent suicidal behavior in schizophrenia or schizoaffective disorder.

Mechanism of Action[edit]

Partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and antagonist at serotonin 5-HT2A receptors.

Route of ADministration[edit]

Oral

Dosages[edit]

  • Initial dose: 12.5 mg once or twice daily
  • Target dose: 300 - 450 mg/day in divided doses
  • Maximum dose: 900 mg/day

Side Effects[edit]

Frequency Adverse reactions
Common Drowsiness and sedation: Many patients experience significant drowsiness or sedation, which can impact daily activities
Weight gain: Clozapine can lead to substantial weight gain, which may increase the risk of metabolic syndrome
Increased salivation
Constipation
Dizziness and lightheadedness: Espeically when standing up quickly, due to orthostatic hypotension
Uncommon Agranlocytosis: Clozapine can cause a significant decrease in white blood cells, leading to a higher risk of infections. Regular blood monitoring is required
Seizures: The risk of seizures increase with higher doses of clozapine
Myocarditis and cardiomyopathy
Neuroleptic Malignant Syndrome (NMS): This is a rare but potentially fatal condition characterized by high fever, muscle stiffness, and altered mental status
Tardive dyskinesia: This is a movement disorder that may become irreversible with prolonged use, particularly in older adults
QT prolongation
Liver issues: Symptoms may include jaundice, dark urine, and abdominal pain

Pharmacokinetics[edit]

  • Pharmacologic effects (e.g. sedation) are apparent within 15 minutes
  • Peak plasma concentrations are typically attained within 1.5 to 2.5 hours after single or multiple doses of clozapine tablets
  • Elimination half-life: 8 hours (single dose), 12 hours (multiples doses)
  • Approximately 50% excreted in urine, 30% in feces

Drug Precautions[edit]

Pregnancy

Use caution; potential risks to the fetus should be considered

Breastfeeding

Contraindicated during lactation

Children & Elderly

  • Contraindicated in children before puberty
  • Use caution in elderly patients

Monitoring Requirements

Patients on clozapine require regular monitoring, including:

  • Frequent blood test to monitor white blood cell counts.
  • Cardiac monitoring to detect any changes in heart rhythm.
  • Regular metabolic assessments to check for weight gain, blood sugar levels, and lipid profiles.

Drug Interactions

Interactions with strong CYP1A2 inhibitors, CYP2D6 inhibitors, and CYP3A4 inducers

  • CYP1A2 Inhibitors
    • Drugs such as fluvoxamine, ciprofloxacin, and hormonal contraceptives can increase clozapine levels, raising the risk of adverse effects
  • CYP1A2 inducers
    • Substances like omeprazole can decrease clozapine levels, potentially reducing its efficacy
  • Lamotrigine
    • THis anticonvulsant can increase clozapine levels, requiring close monitoring
  • Caffeine
    • Can increase clozapine levels due to CYP1A2 inhibition
  • Grapefruit Juice
    • May increase clozapine levels bhy inhibiting CYP3A4
  • Smoking
    • Can decrease clozapine levels; cessation can lead to increase plasma levles and potential toxicity

FAQ[edit]

How Should I Take the Tablet?

Take with or without food.

What should I avoid while taking?

Avoid activities requiring mental alertness until you know how the medication affects you.

What Happens if I Miss a Dose?

Take the missed dose as soon as you remember unless it is almost time for your next dose. Do not double doses.

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