Fluconazole Amitriptyline

Duggal HS. Delirium associated with amitriptyline/fluconazole drug. Gen Hasp Psychiatry (2003) 25, 297-8. 

Dorsey ST, Biblo LA. Prolonged QT interval and torsades de pointes caused by the combination of fluconazole and amitriptyline. Am J Emerg Med 2000 18(2) 227-9. 

Robinson RF, Nahata MC, Olshefski RS. Syncope associated with concurrent amitriptyline and fluconazole therapy. Ann Pharmacother 2000 34(12) 1406-9. 

PROPAFENONE I. ANTIARRHYTHMICS - disopyra-mide, procainamide 2. ANTIBIOTICS - macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS - TCAs, venlafaxine 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES - terfenadine, hydroxyzine, mizolastine 8. ANTI-M ALARIALS - artemether with lumefantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS - pentamidine isetionate 10. ANTIPSYCHOTICS-atypicals, phenothiazines, pimozide II. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS -parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs prolong the Q-T interval. Also, amitriptyline, clomipramine and desipramine levels may be t by propafenone. Amitriptyline and clomipramine may t propafenone levels. Propafenone and these TCAs inhibit CYP2D6-mediated metabolism of each other Avoid co-administration... 

ITRACONAZOLE, KETOCONAZOLE, MICONAZOLE, FLUCONAZOLE, VORICONAZOLE TCAs Possible t plasma concentrations of TCAs All TCAs are metabolized primarily by CYP2D6. Other pathways include CYP1A2 (e.g. amitriptyline, clomipramine, imipramine), CYP2C9 and CYP2C19(e.g. clomipramine, imipramine). Ketoconazole and voriconazole are documented inhibitors of CYP2C19. Fluconazole and voriconazole are reported to inhibit CYP2C9 Warn patients to report t side-effects of TCAs such as dry mouth, blurred vision and constipation, which may be an early sign of t TCA levels. In this case, consider 1 dose of TCA... 

An interaction of fluconazole with amitriptyline has been reported (69). 

A 12-year-old boy with prostatic rhabdomyosarcoma had episodes of syncope periodically over 7 months while taking fluconazole for chemotherapy-induced mucositis. He had taken fluconazole in the past without problems but had also taken a stable dose of amitriptyline for neuropathic pain. On withdrawal of amitriptyline he had no further episodes. The effect was confirmed by re administration. 

Concurrent administration of fluconazole probably causes increased exposure to amitriptyline. Three reports of adults have shown increased amitriptyline plasma concentrations with concurrent administration of fluconazole in one patient, a 57-year-old woman, the QT interval was prolonged and torsade de pointes occurred (70). 

CYP2C9 20 10 Celecoxib Diclofenac Fluoxetine Fluvastatin Ibuprofen Irbesarten Naproxen Amitriptyline Phenytoin Tolbutamide Torsemide S-warfarin Rosiglitazone Amiodarone Fluconazole Fluvoxamine Fluvastatin Isoniazid Sertraline Sulfaphenazole Trimethoprin Zafirlukast Rifampin Clotrimazole Carbamazepine Hyperforin Phenobarbital Ritonavir... 

Noninterfering acetaminophen, N-acetylprocainamide, amikacin, amitriptyline, amlodi-pine, carbamazepine, cefotaxime, ceftazidime, chloramphenicol, ciprofloxacin, cisapride, clindamycin, clonidine, codeine, cyclosporine, digoxin, diphenhydramine, disopyramide, ethosuximide, fluconazole, gentamicin, gentamicin, heparin, labetalol, levothyroxine, li-docaine, lithium, methotrexate, metronidazole, minoxidil, nafcillin, nifedipine, phenobar-bital, phenobarbital, phenytoin, phenytoin, primidone, procainamide, propranolol, quini-dine, ranitidine, salicylic acid, theophylline, tobramycin, tobramycin, valproic acid, warfarin... 

Markedly increased serum amitriptyline levels developed in five patients and increased serum nortriptyline levels in another patient when they took fluconazole. Mental changes, syncope, and prolonged QTc interval occurred in some of these patients and there is also a report of prolonged QT interval and torsades de pointes associated with the concurrent use of amitriptyline and fluconazole in a further patient. 

Other reports similarly describe increased amitriptyline levels when fluconazole was given in a child who developed syncope as a result and in... 

Newberry DL, Bass SN, Mbanefo CO. A fluconazole/amitriptyline drug interaction in three male adidts. Clin Infect bis (1997) 24, 270-1. 

There is also a report of the serotonin syndrome occurring in a 21-year-old patient when amitriptyline 10 mg at night was added to the range of medications she was receiving, which included venlafaxine 37.5 mg daily, pethidine (meperidine) 400 mg daily and fluconazole 200 mg daily. There are fwo ofher reporfs offhe serotonin syndrome in patients who had discontinued venlafaxine 3 days and 2 weeks, respectively, before starting amitriptyline. ... 

The serotonin syndrome , (p.9), has been reported in patients taking venlafaxine and amitriptyline alone or with other serotonergic drugs. Both can increase serotonergic activity by inhibition of serotonin re-uptake at presynaptic neurones. In addition, one of the cases described above is complicated by the fact that pethidine also has serotonergic activity and the metabolism of amitriptyline can be inhibited by fluconazole , (p.l230). 

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