Basic Information
ID DDInter419 and DDInter2136
Interaction Coadministration with viloxazine may increase the plasma concentrations and risk of adverse effects, including agranulocytosis and QT prolongation, of clozapine. The proposed mechanism is viloxazine inhibition of the CYP450 3A4-mediated metabolism of clozapine. Inhibition of CYP450 2D6 and 3A4 may also contribute.
Management Concomitant use of viloxazine with clozapine is not recommended; however, if coadministration is necessary, pharmacologic response and plasma clozapine concentrations should be monitored closely and the clozapine dosage adjusted as necessary. Patients should be advised to report symptoms such as somnolence, disorientation, slurred speech, seizures, uncontrolled movements, dizziness, irregular heartbeat, palpitations, fever, or hypersalivation to their doctor.
References [1] "Product Information. Qelbree (viloxazine)." Supernus Pharmaceuticals Inc (2021):
Alternative for Clozapine N05A
Amisulpride Loxapine Prochlorperazine Thiothixene Mesoridazine Molindone
Methotrimeprazine Paliperidone Trifluoperazine Triflupromazine Promazine Fluphenazine
Alternative for Viloxazine N06A
Oxitriptan Tryptophan Vilazodone Vortioxetine
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.