Nortriptyline drug interactions

Gannon RH, Anderson ML. Fluconazole-nortriptyline drug interaction. Ann Pharmacother (1992) 26, 1456-7. 

Neuroleptic and antidepressant drugs interact with a number of different receptors in the brain, which may partly explain their PK-PD relationships. Figure 9 shows the bell shaped concentration-response relationship for the antidepressant drug nortriptyline. 

Determination of nortriptyline plasma concentrations is not routinely recommended but may be useful in identifying toxicity, drug interactions, or noncompliance (adjustments in dosage should be made according to clinical response, not plasma concentrations) therapeutic range is 50-150 ng/ml... 

Jerling, M., Bertilsson, L., and Sjoqvist, F. (1994) The use of therapeutic drug monitoring data to document kinetic drug interactions an example with amitriptyline and nortriptyline. Ther Drug Monit 16 1-12. 

FIGURE 7—54. Heroic combo 10 SSRI plus NRI. Here, 5HT and NE are both single-boosted. The preferred NRI is selective reboxetine, as there are no drug interactions. Nonselective TCAs that are preferential NRIs such as desipramine, maprotilene, nortriptyline, or protriptyline can be combined if plasma drug levels of the TCA are monitored, especially if fluoxetine or paroxetine is the SSRI chosen. 

St John s wort can cause drug interactions by inducing hepatic microsomal drug-metabolizing enzymes or the drug transporter P-glycoprotein, which causes a net efflux of substrates, such as amitriptyline, from intestinal epithelial cells into the gut lumen (SEDA-24,12). In 12 patients (9 women, 3 men) the addition of St John s wort 900 mg/ day to amitriptyline 150 mg/day led to a 20% reduction in plasma amitriptyline concentrations, while nortriptyline concentrations were almost halved (210). 

Desipramine and nortriptyline are the least problematic in terms of drug interaction, being weak inhibitors of CYP2D6 inhibitors. 

Loomis CW, Racz WJ, Drug interactions of amitriptyline and nortriptyline with warfarin in the rat. Res Commun Chem Pathol Pharmacol (1980) 30, 41-58,... 

Bebchuk JM, Stewart DE. Drug interaction between rifampin and nortriptyline a case report. IntJPsychiatry Med 99 )2, 183-7. 

Drug-drug interactions In a placebo-controlled study evaluating the combination of topiramate and nortriptyline for headache prophylaxis, 44 patients were given topiramate 100 mg/day and nortriptyline 30 mg/day, while 17 took topiramate 100 mg/day plus placebo [174 ]. Side effects reported by those taking both medications, as opposed to topiramate alone, included dry mouth (18%), somnolence (9%), hair loss (2.3%), heartburn (2.3%), dry mouth (4.5%), and memory disturbance (6.8%). 

Interaction with drug metabolism liquorices, which are the most commonly used herbs in TCM can increase metabolites (e.g., nortriptyline, desipramine, and norclomipramine) of tricyclic antidepressants (TCAs) and may produce more side effects (such as dry mouth, constipation, palpitation, etc.) (Xu, 2004 Zhu Huang, 2004). 

The selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment of depression in the elderly. Compared with tricyciic antidepressants (TCAs), they are much safer in overdose and, for the most part, their side-effects are better tolerated. The antidepressants that have been shown, in controlled studies, to be effective in geriatric major depression are the SSRIs fluoxetine, paroxetine, and sertraline, the TCAs clomipramine and nortriptyline, and the serotonin and norepinephrine reuptake inhibitor (SNRi) venlafaxine. Given that most antidepressants are effective in the elderly, the choice of drug is based on its side-effect profile and its potential to interact with other medications. 

The absorption of a single 400-mg dose of phenylbutazone in 4 depressed women was considerably delayed (time to maximum level, 4 to 10 hours compared with 2 hours), but the total amount absorbed (measured by the urinary excretion of oxyphenbutazone) remained unchanged when they were pretreated with desipramine 75 mg daily for 7 days. In another 5 depressed women the half-life of oxyphenbutazone was found to be unaltered by 75 mg of desipramine or nortriptyline dailyAnimal studies have confirmed that the absorption of phenylbutazone and oxyphenbutazone are delayed by the tricyclic antidepressants, probably because their antimuscarinic effects reduce the motility of the gut, - but there seems to be no direct clinical evidence that the antirheumatic effects of either drug are reduced by this interaction. No particular precautions appear to be needed. 

---