Since<unk>  and its active metabolite nortriptyline are primarily metabolized by cytochromes CYP2D6 and CYP2C19 (see<unk> #Pharmacology), the inhibitors of these enzymes are expected to exhibit pharmacokinetic interactions with<unk> . According to the prescribing information, the interaction with CYP2D6 inhibitors may increase the plasma level of<unk> . However, the results in the other literature are inconsistent: the co-administration of<unk>  with a potent CYP2D6 inhibitor paroxetine does increase the plasma levels of<unk>  two-fold and of the main active metabolite nortriptyline 1.5-fold, but combination with less potent CYP2D6 inhibitors thioridazine or levomepromazine does not affect the levels of<unk>  and increases nortriptyline by about 1.5-fold; a moderate CYP2D6 inhibitor fluoxetine does not seem to have a significant effect on the levels of<unk>  or nortriptyline. A case of clinically significant interaction with potent CYP2D6 inhibitor terbinafine has been reported. A potent inhibitor of CYP2C19 and other cytochromes fluvoxamine increases the level of<unk>  two-fold while slightly decreasing the level of nortriptyline. Similar changes occur with a moderate inhibitor of CYP2C19 and other cytochromes cimetidine:<unk>  level increases by about 70%, while nortriptyline decreases by 50%. CYP3A4 inhibitor ketoconazole elevates<unk>  level by about a quarter. On the other hand, cytochrome P450 inducers such as carbamazepine and St. John's Wort decrease the levels of both<unk>  and nortriptyline Oral contraceptives may increase the blood level of<unk>  by as high as 90%. Valproate moderately increases the levels of<unk>  and nortriptyline through an unclear mechanism. The prescribing information warns that the combination of<unk>  with monoamine oxidase inhibitors may cause potentially lethal serotonin syndrome; however, this has been disputed. The prescribing information cautions that some patients may experience a large increase in<unk>  concentration in the presence of topiramate. However, other literature states that there is little or no interaction: in a pharmacokinetic study topiramate only increased the level of<unk>  by 20% and nortriptyline by 33%.<unk>  counteracts the antihypertensive action of guanethidine. When given with<unk> , other anticholinergic agents may result in hyperpyrexia or paralytic ileus. Co-administration of<unk>  and disulfiram is not recommended due to the potential for the development of toxic delirium.<unk>  causes an unusual type of interaction with the anticoagulant phenprocoumon during which great fluctuations of the prothrombin time have been observed.
Amitriptyline
Nortriptyline
Venlafaxine
Trazodone
Guanfacine
Nabilone
Citalopram
Atomoxetine