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Itraconazole and Tofranil

Determining the interaction of Itraconazole and Tofranil and the possibility of their joint administration.

Check result:
Itraconazole <> Tofranil
Relevance: 15.12.2022 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Using imipramine together with itraconazole can increase your blood levels of imipramine. This combination may cause side effects such as drowsiness, dry mouth, blurred vision, constipation, or urinating less than usual. Talk with your doctor before using these medications together. You may need a dose adjustment or special tests to safely take both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

MONITOR: The coadministration with azole antifungal agents may increase the plasma concentrations of some tricyclic antidepressants (TCAs). Elevated TCA levels may result in CNS toxicity, anticholinergic symptoms, and QT interval prolongation. The mechanism is decreased TCA clearance due to azole-related inhibition of the CYP450 3A4 isoenzyme, which is partially responsible for the metabolism of TCAs like amitriptyline, clomipramine, imipramine, and possibly others. Fluconazole additionally inhibits CYP450 2C19, which is another secondary route of metabolism for several TCAs. The effect of a single dose of fluconazole on TCA pharmacokinetics has not been reported. In a pharmacokinetic study involving six healthy subjects, ketoconazole (200 mg/day for 14 days) increased the half-life and area under the plasma concentration-time curve (AUC) of a single dose of imipramine (100 mg) by 15% and 20%, respectively, but did not affect the pharmacokinetics of desipramine or its metabolite.

MANAGEMENT: During concomitant therapy with azole antifungal agents, patients stabilized on their TCA regimen should be observed for increased pharmacologic response to the TCA, and the dosage adjusted accordingly if necessary. Serum TCA levels should be monitored following initiation or discontinuation of azole antifungal therapy. Patients should be advised to notify their caregiver if they experience excessive dry mouth, visual disturbances, urinary retention, dizziness, syncope, fast or irregular heartbeat, constipation, or seizures.

References
  • Gannon RH "Fluconazole-nortriptyline drug interaction." Ann Pharmacother 26 (1992): 1456
  • Dorsey ST, Biblio LA "Prolonged QT interval and torsades de pointes caused by the combination of fluconazole and amitriptyline." Am J Emerg Med 18 (2000): 227-9
  • Spina E, Avenoso A, Campo GM, Scordo MG, Caputi AP, Perucca E "Effect of ketoconazole on the pharmacokinetics of imipramine and desipramine in healthy subjects." Br J Clin Pharmacol 43 (1997): 315-8
  • Spina E, Avenoso A, Campo GM, Scordo MG, Caputi AP, Perucca E "Effect of ketoconazole on the pharmacokinetics of imipramine and desipramine in healthy subjects." Br J Clin Pharmacol 43 (1997): 315-8
  • Robinson RF, Nahata MC, Olshefski RS "Syncope associated with concurrent amitriptyline and fluconazole therapy." Ann Pharmacother 34 (2000): 1406-9
  • Newberry DL, Bass SN, Mbanefo CO "A fluconazole/amitriptyline drug interaction in three male adults." Clin Infect Dis 24 (1997): 270-1
Itraconazole

Generic Name: itraconazole

Brand name: Onmel, Sporanox, Sporanox PulsePak, Tolsura

Synonyms: n.a.

Tofranil

Generic Name: imipramine

Brand name: Tofranil, Tofranil-PM

Synonyms: n.a.

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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