1. Baseline white blood cell count has been obtained
2. Patient registered with the Clozaril National Registry
3. 12.5 mg of clozapine on the first day and then increased by 12.5mg per day for three days 2 times per day. Then the dose should be 25mg per day until the target 300mg per day is reached. It should be administered at night to minimize adverse effects. 
- Elderly patient dosing should be connservative with initiation at half the regular dose. 
- Most useful in nonresponse to therapeutic dosage
- Clozapine available in 25 and 100 mg scored tablets.

University of South Florida

Clozapine the conventional antipsychotic loxapine was the first atypical drug to become available widely in the US.

Clozapine

Markowitz, J. S., Brown, C. S., &amp; Moore, T. R. (1999). Atypical antipsychotics part I: Pharmacology, pharmacokinetics, and efficacy. Annals of Pharmacotherapy, 33(1), 73–85. https://doi.org/10.1345/aph.17215 

Atypical Antipsychotics; Part 1: Pharmacology, Pharmacokinetics, and Efficacy

There is a selective nature that this drug exhibits for the mesolimbic region. Not only that but there is also a significant affinity that it has on a number of receptors, including; dopaminergic, serotonergic, and muscarinic receptors. An effect of an alpha blockade may lead to orthostatic hypotension and sexual dysfunction. A blockage of H1 causes sedation.

Pharmacology

Clozapine is absorbed after oral administration, however, it can undergo extensive metabolism. With bioavailability from 12-81%, the administration of clozapine can be seen to have an effect with or without food. The peak time of plasma concentration is approximately 3-4 hours. As it is metabolized in the liver, clozapine may exceed concentrations of parent compounds. There is activity at the D2 and 5-HT2 receptors. 

Pharmacokinetics

Dosing Guidelines

Although fatalities have occurred following an overdose, it is generally at doses of >2500mg. Patients have survived an excess of 4 grams. 
Signs and symptoms: 
1. Drowsiness
2. Hypersalivation
3. Delirium
4. Tachycardia
5. Hypotension
6. Respiratory depression/failure

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