Leponex Drug Interactions

Pharmacodynamic-related interactions: Anticipated pharmacodynamic interactions resulting in concomitant use not being recommended: Medicinal products known to have a substantial potential to depress bone marrow function should not be used concurrently with clozapine (Leponex) (see Precautions).
As with other antipsychotics, caution should be exercised when clozapine is prescribed with medicines known to increase the QTc interval or causing electrolyte imbalance.
Observed pharmacodynamic interactions to be considered: Particular caution is recommended when clozapine therapy is initiated in patients who are receiving (or have recently received) a benzodiazepine or any other psychotropic agent, as these patients may have an increased risk of circulatory collapse, which, on rare occasions, can be profound and may lead to cardiac and/or respiratory arrest.
Concomitant use of lithium or other CNS-active agents may increase the risk of development of neuroleptic malignant syndrome (NMS).
Rare but serious reports of seizures, including onset of seizures in non-epileptic patients, and isolated cases of delirium where clozapine was co-administered with valproic acid have been reported. These effects are possibly due to a pharmacodynamic interaction, the mechanism of which has not been determined.
Anticipated pharmacodynamic interactions to be considered: Clozapine may enhance the central effects of alcohol, MAO inhibitors and CNS depressants such as narcotics, antihistamines, and benzodiazepines.
Because of the possibility of additive effects, caution is essential when substances possessing anticholinergic, hypotensive, or respiratory depressant effects are given concomitantly.
Owing to its anti-alpha-adrenergic properties, clozapine may reduce the blood pressure-increasing effect of norepinephrine or other predominantly alpha-adrenergic agents and reverse the pressor effect of epinephrine.
Pharmacokinetic-related interactions: Clozapine is a substrate for many CYP 450 isoenzymes, in particular 1A2 and 3A4. The risk of metabolic interactions caused by an effect on an individual isoform is therefore minimized. Nevertheless, caution is called for in patients receiving concomitant treatment with other substances that are either inhibitors or inducers of these enzymes.
No clinically relevant interactions have been observed thus far with tricyclic antidepressants, phenothiazines or type 1_C anti-arrhythmics, which are known to bind to cytochrome P450 2D6.
Observed pharmacokinetic interactions to be considered: Concomitant administration of substances known to induce cytochrome P450 enzymes may decrease the plasma levels of clozapine: Substances known to induce the activity of 3A4 and with reported interactions with clozapine include, for instance, carbamazepine, phenytoin and rifampicin.
Concomitant administration of substances known to inhibit the activity of cytochrome P450 isozymes may increase the plasma levels of clozapine: Substances known to inhibit the activity of the major isozymes involved in the metabolism of clozapine and with reported interactions include, for instance, cimetidine, erythromycin (3A4), fluvoxamine (1A2), perazine (1A2) ciprofloxacin (1A2) and oral contraceptives (1A2, 3A4, 2C19).
The plasma concentration of clozapine is increased by caffeine (1A2) intake and decreased by nearly 50% following a 5-day caffeine-free period.
Elevated clozapine plasma concentrations also have been reported in patients receiving the substances in combination with selective serotonin re-uptake inhibitors (SSRIs) such as paroxetine (1A2), sertraline, fluoxetine or citalopram.
Anticipated pharmacokinetic interactions to be considered: Concomitant administration of substances known to induce cytochrome P450 enzymes may decrease the plasma levels of clozapine: Known inducers of 1A2 include, for instance, omeprazole and tobacco smoke. In cases of sudden cessation of tobacco smoking, the plasma clozapine concentration may be increased, thus leading to an increase in adverse effects.
Concomitant administration of substances known to inhibit the activity of cytochrome P450 isozymes may increase the plasma levels of clozapine: Potent inhibitors of CYP3A, such as azole antimycotics and protease inhibitors, could potentially also increase clozapine plasma concentrations; no interactions have been reported to date, however.