Is clozapine associated with neutropenia?

Is clozapine associated with neutropenia?

Clozapine is the only effective antipsychotic for treatment-resistant schizophrenia but remains widely under prescribed, at least in part due to its potential to cause agranulocytosis and neutropenia.

How is clozapine metabolism?

Clozapine is primarily metabolized in the liver by the CYP450 superfamily of enzymes. The primary metabolic steps are demethylation to form norclozapine and oxidation to clozapine n-oxide. The major enzymes involved in clozapine demethylation are CYP3A4 and CYP1A2, with CYP2D6 playing a minor role.

How is clozapine absorbed in the body?

Clozapine is quickly and almost completely absorbed after oral administration with time to maximum plasma concentration (Tmax) of 1.5–2 h in which the maximum effect of the drug appears approximately 4 h after administration [1, 10]. However, its bioavailability is only about 27%–50% due to the first-pass metabolism.

Is clozapine a prodrug?

It is a prodrug of clozapine; the fatty acid docosahexaenoic acid (DHA) was added to clozapine in order to increase penetration of the blood–brain barrier….DHA-clozapine.

Clinical data
Chemical and physical data
Formula C40H49ClN4O
Molar mass 637.31 g·mol−1
3D model (JSmol) Interactive image

What is ANC level for clozapine?

The US Food and Drug Administration requires patients in the United States to have a minimum absolute neutrophil count (ANC) greater than or equal to 1500/microL to initiate clozapine [1]. An exception is made for patients with benign ethnic neutropenia, who are subject to a lower ANC level.

What is clozapine toxicity?

Toxic Mechanism: Clozapine is an antagonist to dopamine (D1 and D2 in the mesolimbic system), serotonin, peripheral alpha receptors, muscarinic, histamine and GABA receptors. This combination of antagonism results in CNS depression, tachycardia, orthostatic hypotension and anticholinergic toxidrome.

How do you monitor clozapine?

Monitoring clozapine patients Baseline blood tests should check white cell count, troponins, CRP and possibly BNP3. Patients with a history of cardiac disease or abnormal cardiac findings on examination (such as QT prolongation) should be referred to a cardiologist7.

What causes high clozapine levels?

Clozapine has wide intraindividual and interindividual variation in plasma concentration with a given dose. Many factors may affect clozapine plasma levels including genetic variants of drug-metabolizing enzymes and transporting proteins, smoking habits, sex, age, concurrent use of other drugs, and food.

Why do you need blood tests for clozapine?

Blood tests are important because the drop in the number of white cells may not cause any symptoms until you have actually developed an infection. Checking the number of white blood cells on a regular basis helps to detect any changes early on before they cause problems.

When do you Retitrate clozapine?

Rapid retitration of clozapine may be necessary to reduce the known high risk of mental state destabilisation in patients who have had a 48 h treatment break. It may carry a high risk of complications, including seizures and myocarditis.

What labs do you monitor for clozapine?

What is a normal clozapine level?

Levels of around 0.6-0.8 mg/L have been proposed as the upper therapeutic limit. There is a clearer link between seizures and plasma levels over 1.0 mg/L and other types of toxicity with levels over 0.75 mg/L. For levels >1mg/L, consider cautious dose reduction and LFT (Liver Function Test) measurement.

What happens when clozapine levels are too high?

High Clozapine Levels (>1000 ng/ml) If there is clozapine toxicity, the patient should obtain urgent care that includes symptomatic treatment and assessment for serious problems such as cardiac arrhythmias, seizure activity, or systemic infection.

What are normal clozapine levels?

When do you measure clozapine levels?

Clozapine reaches a steady-state concentration at 5-7 days. Levels should be drawn 12 hours (± 2 h) after the last dose. Clozapine blood levels are correlated with both clozapine effectiveness and side effects.

What is a good clozapine level?

Levels of around 0.6-0.8 mg/L have been proposed as the upper therapeutic limit. There is a clearer link between seizures and plasma levels over 1.0 mg/L and other types of toxicity with levels over 0.75 mg/L.