The metabolism and pharmacokinetics of Paroxetine may be affected by the induction or inhibition of drug metabolising enzymes.
When Paroxetine is to be co-administered with a known drug metabolising enzyme inhibitor, consideration should be given to using doses at the lower end of the range. No initial dosage adjustment is considered necessary when the drug is to be co-administered with known drug metabolising enzyme inducers (e.g. carbamazepine, rifampicin, phenobarbital, phenytoin). Any subsequent dosage adjustment should be guided by clinical effect (tolerability and efficacy).
Fosamprenavir/ritonavir: Co-administration of fosamprenavir/ritonavir with Paroxetine significantly decreased plasma levels of Paroxetine. Any dose adjustment should be guided by clinical effect (tolerability and efficacy).
Procyclidine: Daily administration of Paroxetine increases significantly the plasma levels of procyclidine. If anti-cholinergic effects are seen, the dose of procyclidine should be reduced.
Anticonvulsants: Carbamazepine, phenytoin, sodium valproate. Concomitant administration does not seem to show any effect on pharmacokinetic/dynamic profile in epileptic patients.
Paroxetine should not be used in combination with thioridazine, because, as with other drugs, which inhibit the hepatic enzyme CYP450 2D6, Paroxetine can elevate plasma levels of thioridazine. Administration of thioridazine alone can lead to QTc interval prolongation with associated serious ventricular arrhythmia such as torsades de pointes, and sudden death.
Paroxetine should not be used in combination with pimozide.