Clozapine Dose Range

For dose optimisation.

Clozapine dose range.

Understanding plasma clozapine and norclozapine measurement can be helpful. 4 66 hours after achieving steady state with 100mg twice daily dosing. For example consider the case of a schizophrenia patient who remains psychotic despite a clozapine dose of 200 mg bid 400 mg d. The maximum dose is 900 mg per day.

Clozapine associated with qt prolongation. Monitor for decreased effectiveness when discontinuing a strong cyp450 3a4 inducer and continuing clozapine. 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. A clozapine plasma level can be checked after an initial target dose is reached generally after two weeks in the inpatient setting.

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. If you double the dose you double the level. 4 to12 hours compared to a mean elimination half life of 12 hours range. If you halve the dose you halve the level.

Dosing up to but not exceeding 900mg day has been used for exceptional cases only. To assess compliance plasma clozapine and norclozapine in the expected range only guarantees adherence over the previous few days. If a clozapine level is high check the patient for dose related side effects. To assess the effect of changes in smoking habit tobacco and cannabis on clozapine.

Subsequently the dose can be increased once weekly or twice weekly in increments of up to 100 mg. Recommended maximum daily dose is 600mg. 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. The mean elimination half life of clozapine after a single 75 mg dose was 8 hours range.

The total daily dose can be increased in increments of 25 mg to 50 mg per day if well tolerated to achieve a target dose of 300 mg to 450 mg per day administered in divided doses by the end of 2 weeks. 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.

His clozapine level is 100 ng ml ie low range and his norclozapine level is 50 ng ml. Reduce clozapine dose based on clinical response. Patients and their carers should be advised to seek immediate medical advice before taking the next dose of clozapine if constipation develops.