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Clozapine is an atypical antipsychotic medication.It is mainly used for schizophrenia that does not improve following the use of other antipsychotic medications. In those with schizophrenia and schizoaffective disorder it may decrease the rate of suicidal behavior.It is more effective than typical antipsychotics and effective for those who are treatment resistant.It is taken by mouth.
Mechanism of action of Clozapine
Clozapine’s antipsychotic action is likely mediated through a combination of antogistic effects at D2 receptors in the mesolimbic pathway and 5-HT2A receptors in the frontal cortex. D2 antagonism relieves positive symptoms while 5-HT2A antagonism alleviates negative symptoms. Clozapine is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Clozapine acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other therapeutic and side effects of Clozapine. Clozapine’s antagonism of muscarinic M1-5 receptors may explain its anticholinergic effects. Clozapine’s antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Clozapine’s antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug.
Indications of Clozapine
- Suicidal Behaviour
- Treatment-resistant schizophrenia
- Advanced dopaminomimetic psychosis
- Schizophrenia
- Paranoid disorder
- Borderline personality disorder
Contra-Indications of Clozapine
- Diabetes
- excessive fat in the blood
- low amount of magnesium in the blood
- Extreme Loss of Body Water
- low amount of potassium in the blood
- Overweight
- Decreased Function of Bone Marrow
- Deficiency of Granulocytes a Type of White Blood Cell
- Increased Eosinophils in the Blood
- Abnormal Movements of Face Muscles and Tongue
- Neuroleptic Malignant Syndrome
- Lower Seizure Threshold
- closed angle glaucoma
- lung embolism
- Very Rapid Heartbeat – Torsades de Pointes
- Slow Heartbeat
- Sinus Tachycardia
- prolonged QT interval on EKG
- infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">Inflammation of the Middle Tissue Heart Muscle
- Abnormal EKG with QT changes from Birth
- Stroke
- Disorder of the Blood Vessels of the Brain
- A blood clot in a deep vein of the extremities
- Blood Pressure Drop Upon Standing
- abnormally low blood pressure
- Paralysis of the Intestines
- Impacted Stool
- constipation
- Liver Problems
- Acute infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">Inflammation of the Pancreas
- Enlarged Prostate
- seizures
- Weight Gain
- Cannot Empty Bladder
- High Blood Sugar
- Abnormal Liver Function Tests
- Susceptible to Breathing Fluid Into Lungs
- A Mother who is Producing Milk and Breastfeeding
- Severely Decreased Levels of Neutrophils in the Blood
- Dilated Cardiomyopathy
- Tobacco Smoking
- Metabolic Syndrome X
- Dementia in an Elderly Person
- Decreased Motility Function of Stomach or Intestines
Dosages of Clozapine
Strengths: 25 mg; 100 mg; 12.5 mg; 150 mg; 200 mg; 50 mg; 50 mg/mL
Schizophrenia
- Initial dose – 12.5 mg orally once or twice a day
- Titration and Maintenance dose – May increase total daily dose in increments of 25 mg to 50 mg per day to a target dose of 300 mg to 450 mg per day (administered in divided doses) by the end of week 2. Subsequent dose increases can be in increments of up to 100 mg once or twice weekly.
- Maximum dose – 900 mg per day
Side Effects of Clozapine
The most common
- abdominal pain,
- physical weakness (asthenia)
- diarrhea
- gas (flatulence)
- Low blood pressure (hypotension)
- Fast heart rate
- Fever, sedation, seizures (with high doses)
- Appetite increased
- Constipation
- symptoms of weakness, muscle pain (myalgia)
- upper respiratory tract infection
- abdominal pain (GI complaints), lactic acidosis (rare)
- low blood levels of vitamin B-12
- nausea, vomiting
- chest discomfort
- chills, dizziness
- bloating/abdominal distention
- constipation
- heartburn
More common
- Abdominal or stomach discomfort
- cough or hoarseness
- decreased appetite
- diarrhea
- fast or shallow breathing
- fever or chills
- Acid or sour stomach
- the feeling of constant movement of self or surroundings
- heartburn
- the relaxed and calm sensation of spinning
- sleepiness
Less common
- Blurred or loss of vision
- change or problem with discharge of semen
- disturbed color perception
- double vision
- halos around lights
- inability to sit still
- increase in body movements
- muscle ache or pain
- muscle weakness
- night blindness
Drug Interaction of Clozapine
- antacids (e.g., aluminum hydroxide, calcium carbonate, magnesium hydroxide)
- antihistamines (e.g, cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
- anti-Parkinson’s agents (e.g., amantadine, bromocriptine, levodopa)
- antipsychotics (e.g., chlorpromazine, haloperidol, olanzapine, quetiapine, risperidone)
- “azole” antifungals (e.g., fluconazole, ketoconazole, voriconazole)
- barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
- benzodiazepines (e.g., clonazepam, diazepam, lorazepam)
- buprenorphine
- captopril
- corticosteroids (e.g., budesonide, dexamethasone, hydrocortisone, fluticasone, prednisone)
- insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।" data-rx-term="diabetes" data-rx-definition="Diabetes is a condition where blood sugar stays too high because insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।">diabetes medications (e.g., chlorpropamide, glipizide, glyburide, insulin, metformin, nateglinide, rosiglitazone)
- dronedarone
- ergot alkaloids (e.g., ergotamine, dihydroergotamine)
- general anesthetics (medications used to put people to sleep before surgery)
- HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., delavirdine, efavirenz, etravirine, nevirapine)
- ipratropium
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- medications that can suppress the immune system (e.g., azathioprine, biologics, cancer medications, cyclosporine, hydroxyurea, mycophenolate, tacrolimus)
- metronidazole
- metyrosine
- mirabegron
- mirtazapine
- monoamine oxidase inhibitors (MAOIs; moclobemide, phenelzine, rasagiline, selegiline, tranylcypromine)
- muscle relaxants (e.g., cyclobenzaprine, methocarbamol, orphenadrine)
- narcotics (e.g., codeine, fentanyl, morphine, oxycodone)
- omeprazole
- propafenone
- quinolone antibiotics (e.g., ciprofloxacin, norfloxacin, ofloxacin)
- serotonin antagonists (anti-emetic medications; e.g., granisetron, ondansetron)
- serotonin/norepinephrine reuptake inhibitors (SNRIs; e.g., desvenlafaxine, duloxetine, venlafaxine)
- seizure medications (e.g., carbamazepine, clobazam, felbamate, levetiracetam, phenobarbital, phenytoin, primidone, topiramate, valproic acid, zonisamide)
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine)
Pregnancy & Lactation
FDA Pregnancy Category B
Pregnancy
Clozapine should be used only if the benefits clearly outweigh the risks. If you become pregnant or intend to become pregnant while taking this medication, contact your doctor immediately.
Lactation
This medication may pass into breast milk. If you are a breastfeeding mother and are taking clozapine, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. The safety and efficacy of this medication for use by children and adolescents below age 18 have not been established.
References
