Concomitant use of clozapine is not recommended however if a strong cyp450 3a4 inducer is necessary a dose increase of clozapine dose may be needed.
Clozapine dose range.
Clozapine dosage modification may be required if coadministered with drugs that inhibit or induce metabolism of clozapine eg cyp 1a2 2d6 and 3a4 inhibitors qt prolongation.
4 to12 hours compared to a mean elimination half life of 12 hours range.
To assess compliance plasma clozapine and norclozapine in the expected range only guarantees adherence over the previous few days.
Reduce clozapine dose based on clinical response.
For dose optimisation.
Clozapine has been associated with varying degrees of impairment of intestinal peristalsis see cautions and contra indications for further information.
If well tolerated the dose can be increased gradually typically by 12 5 to 25 mg every one to two days with the target dose and frequency determined by the plasma clozapine level and adverse effects.
Understanding plasma clozapine and norclozapine measurement can be helpful.
Recommended maximum daily dose is 600mg.
The maximum dose is 900 mg per day.
When interpreting blood levels low clozapine levels can result from low dose non adherence or rapid metabolism.
Clozapine associated with qt prolongation.
The mean elimination half life of clozapine after a single 75 mg dose was 8 hours range.
Doses 450 mg increase the possibility of side effects and adverse events including seizures.
Clozapine is a substrate for many cytochrome p450 isozymes in particular cyp1a2 cyp2d6 and cyp3a4.
Most agree that clozapine levels provide the most value while others suggest norclozapine levels should also be considered.
Subsequently the dose can be increased once weekly or twice weekly in increments of up to 100 mg.
His clozapine level is 100 ng ml ie low range and his norclozapine level is 50 ng ml.
4 66 hours after achieving steady state with 100mg twice daily dosing.
A clozapine plasma level can be checked after an initial target dose is reached generally after two weeks in the inpatient setting.
Monitor for decreased effectiveness when discontinuing a strong cyp450 3a4 inducer and continuing clozapine.
To assess the effect of changes in smoking habit tobacco and cannabis on clozapine.
If a clozapine level is high check the patient for dose related side effects.
If you halve the dose you halve the level.
For example consider the case of a schizophrenia patient who remains psychotic despite a clozapine dose of 200 mg bid 400 mg d.
Patients and their carers should be advised to seek immediate medical advice before taking the next dose of clozapine if constipation develops.
Clozapine page 14 therapeutic dose range of clozapine usual dosage range is 200 450 mg day divided dose.
