MARVIL

Adults

Olanzapine is indicated in the treatment of schizophrenia.

Olanzapine is effective for maintaining clinical improvement during continuation of treatment in patients who initially responded to treatment.

Olanzapine is indicated in the treatment of moderate to severe manic episodes.

In patients with bipolar disorders who have responded to treatment with olanzapine during a manic episode, olanzapine is indicated in the prevention of relapses (see section 5.1).

Interaction studies have been conducted only in adults.

Potential interactions having an effect on olanzapine: as olanzapine is metabolized by CYP1A2, substances that can specifically induce or inhibit this isoenzyme may also affect the pharmacokinetics of olanzapine.

Induction of CYP1A2: the metabolism of olanzapine can be induced by smoking and carbamazepine, which may lead to a decrease in olanzapine concentrations. Only a slight to moderate increase in olanzapine clearance has been observed. Clinical consequences should be limited, but clinical monitoring is recommended and an increase in the olanzapine dose may be considered if necessary (see section 4.2).

Inhibition of CYP1A2: It has been shown that fluvoxamine, a specific inhibitor of CYP1A2, significantly inhibits the metabolism of olanzapine. The mean increase in C max of olanzapine after administration of fluvoxamine was 54 % in non-smoking women and 77 % in smoking men. The mean increase in ASC of olanzapine was 52 and 108 %, respectively. It may be appropriate to consider choosing a lower initial dose of olanzapine for patients taking fluvoxamine or other CYP1A2 inhibitors such as ciprofloxacin. A decrease in the olanzapine dose should be considered when starting treatment with a CYP1A2 inhibitor.

Decrease in bioavailability: activated charcoal decreases the oral bioavailability of olanzapine by 50 to 60 % and it must be taken at least two hours before or after olanzapine.

No significant alteration in the pharmacokinetics of olanzapine has been observed with fluoxetine (CYP2D6 inhibitor), single doses of antacids (aluminium, magnesium) or cimetidine.

Potential effects of olanzapine on other drugs: olanzapine is likely to antagonize the effects of direct and indirect dopaminergic agonists.

Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e.g. 1A2, 2D6, 2C9, 2C19, 3A4). Consequently, no particular interaction is expected, as verified by in vivo studies in which no inhibition of the metabolism of the following active substances was detected: tricyclic antidepressants (mainly representing the CYP2D6 pathway), warfarin (CYP2C9), theophylline (CYP1A2) or diazepam (CYP3A4 and 2C19).

No interaction has been observed in the case of concomitant administration of olanzapine and lithium or biperiden.

Therapeutic monitoring of valproate plasma concentrations has not shown the need to adjust the valproate dose after introduction of concomitant olanzapine.

General activity on the CNS

Caution is advised for patients who consume alcohol or take medicines that may produce depression of the central nervous system.

Concomitant use of olanzapine with anti-parkinsonian drugs in patients with Parkinson's disease and dementia is not recommended (see section 4.4).

QTc interval

Caution is required if olanzapine is administered concomitantly with medicines known to prolong the QTc interval (see section 4.4).

The effects on the ability to drive vehicles and use machines have not been studied. As olanzapine can cause somnolence and dizziness, patients should be warned of this risk when using machines and driving motor vehicles.