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January 14, 2018
platelet count below 100,000/mm3, reticulocyte count below 0.3 percent, and a serum iron concen...
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treatment of schizophrenia
most effective drug treatment for patients who have failed to respond to standard therapies,
clozapine has been shown to benefit patients with severe
tardive dysk...
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treatment-resistant mania, severe psychotic depression, idiopathic Parkinson’s disease, Huntington’s disease, and suicidal patients with schizophrenia or schizoaffective disorder.
pervasive developmental disorder, autism of childhood, and OCD (either alone or in combination with an SSRI).
clozapine may very rarely induce obsessive-comp...
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Studies have found that plasma concentrations greater than 350 μg/mL are associated with a better likelihood of response.
agranulocytosis or bone marrow suppression.
include carbamazepine, phenytoin, propylthiouracil, sulfonamides, and captopril
Lithium combined with clozapine may increase the risk of seizures, confusion,...
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Lithium should not be used in combination with clozapine by persons who have experienced...
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malignant sy...
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Clomipramine (Anafranil) can increase the risk of seizure by lowering the seizure threshold and by increasing ...
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Risperidone, fluoxetine, paroxetine, and fluvoxamine increase serum concentrations of clozapine. Addition of paroxetine may precipit...
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most common
sedation, dizziness, syncope, tachycardia, hypotension, electrocardiography (ECG) changes, nausea, and vomiting.
fatigue, weight gain, various GI symptoms (most commonly constipation), anticholinergic effects, and subjective muscle weakness. Sialorrhea, or hypersalivation, is a side effect that begins early in treatment and is most evident at night. Patients report that their pillows are drenched with saliva. This side effect is most likely the result of impairment of swallowing. Although there are reports that clonidine or ...
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The risk of seizures is about 4 percent in patients taking dosages grea...
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Leukopenia, granulocytopenia, agranulocytosis, and fever occur in about ...
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During the first year of treatment, there is a 0.73 percent risk of clozapine-...
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during the second year is 0....
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For neutropenia, the risk is 2.32 percent and 0.69 percent, respectively, during the first an...
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The only contraindications to the use of clozapine are a white blood cell (WBC) count below 3,500 cells per mm3; a previous bone marrow disorder; a history of agranulocytosis during clozapine treatment; or the use of another drug that is kno...
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the first 6...
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weekly WBC...
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Clozapine should be discontinued if the WBC count is below 3,000 cells per mm3 or the granulocyte count is below 1,500 per mm3.
Persons with agranulocytosis should not be re-exposed to the drug.
clozapine cannot be dispensed without proof of monitoring.
Patients exhibiting symptoms of chest pain, shortness of breath, fever, or tachypnea should be immediately evaluated for myocarditis or cardiomyopathy, an infrequent but serious adverse effect ending in death.
(creatine phosphokinase with myocardial band fractions), troponin levels, and EKG studies are recommended, with immed...
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approved for the treatment of manic episodes associated with bipolar I disorder
It has a rapid onset of action and is well tolerated, and numerous studies suggest that it reduces the frequency and intensity of recurrent manic episodes over extended periods of time.
absorbed 1 to 2 hours after oral administration, with peak concentrations occurring 4 to 5 hours
The plasma half-life of valproate is 10 to 16 hours.
concentrations of therapeutically effective free valproate increase at serum concentrati...
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Antimanic response is generally associated with levels greater than 50 μg/mL, in a range of 50 to 150 μg/mL.
DRAs. Numerous studies have suggested that the irritable manic subtype respond significantly better to divalproex than lithium or placebo.
valproate is preferred to lithium for treatment of acute mania in children and elderly persons.
prophylactic treatment of bipolar I disorder, resulting in fewer, less severe, and shorter manic episodes.
affect the pancreas and liver.
potentially fatal hepatotoxicity include young age (younger than 3 years); concurrent use of phenobarbital; and the presence of neurologic disorders, especially inborn errors of metabolism.
oral loading strategy of initiation with 20 to 30 mg/kg a day can be used to accelerate control of symptoms.
