Drug Interactions between fluconazole and moxifloxacin / triamcinolone

GENERALLY AVOID: Certain quinolones, including gatifloxacin and moxifloxacin, may cause dose-related prolongation of the QT interval in some patients. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. During postmarketing surveillance, rare cases of torsade de pointes have been reported in patients taking gatifloxacin. These cases primarily involved patients with underlying medical conditions for which they were receiving concomitant medications known to prolong the QTc interval. Rare cases of tachycardia have been reported with moxifloxacin. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Coadministration of gatifloxacin or moxifloxacin with other drugs that can prolong the QT interval should generally be avoided. Caution and clinical monitoring are recommended if concomitant use is required. Since the magnitude of QTc prolongation increases with increasing plasma concentrations of the quinolone, recommended dosages and intravenous infusion rates should not be exceeded. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

MONITOR CLOSELY: Concomitant administration of corticosteroids may potentiate the risk of tendinitis and tendon rupture associated with fluoroquinolone treatment. The mechanism is unknown. Tendinitis and tendon rupture have most frequently involved the Achilles tendon, although cases involving the rotator cuff (the shoulder), the hand, the biceps, and the thumb have also been reported. Some have required surgical repair or resulted in prolonged disability. Tendon rupture can occur during or up to several months after completion of fluoroquinolone therapy.

MANAGEMENT: Caution is recommended if fluoroquinolones are prescribed in combination with corticosteroids, particularly in patients with other concomitant risk factors (e.g., age over 60 years; recipient of kidney, heart, and/or lung transplant). Patients should be advised to stop taking the fluoroquinolone, avoid exercise and use of the affected area, and promptly contact their physician if they experience pain, swelling, or inflammation of a tendon. In general, fluoroquinolones should only be used to treat conditions that are proven or strongly suspected to be caused by bacteria and only if the benefits outweigh the risks.

MONITOR: Coadministration with fluconazole may increase the plasma concentrations of drugs that are substrates of CYP450 3A4. The mechanism is decreased clearance due to inhibition of CYP450 3A4-mediated metabolism by fluconazole, a moderate inhibitor of the isoenzyme. A 30% increase in serum carbamazepine has been observed during coadministration with fluconazole according to the product labeling. There have also been a few isolated case reports in the medical literature describing an approximate doubling of carbamazepine levels following the addition of fluconazole, resulting in toxicity. Other drugs metabolized by CYP450 3A4 whose plasma levels reportedly are increased by fluconazole include oral contraceptives (ethinyl estradiol and levonorgestrel), cyclosporine, tacrolimus, and cisapride. These interactions have usually been observed with higher dosages of fluconazole (200 mg/day or more).

MANAGEMENT: Caution is advised when fluconazole is used with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever fluconazole is added to or withdrawn from therapy.