Drug Interaction Report

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 treosulfan may increase the plasma concentrations of drugs that are substrates of CYP450 3A4, 2C19, and/or the efflux transporter P-glycoprotein (P-gp). The proposed mechanism is decreased clearance due to inhibition of these routes of elimination due to treosulfan. According to physiologically-based pharmacokinetic modeling, treosulfan is predicted to be a weak to moderate CYP450 3A4 inhibitor and weak inhibitor of CYP450 2C19, with negligible inhibitory effects on P-gp. However, according to the manufacturer, in vitro studies were unable to exclude potential drug-drug interactions with high plasma concentrations of treosulfan and CYP450 3A4, 2C19, and/or P-gp substrates.

MANAGEMENT: Caution is recommended if treosulfan is coadministered with substrates of CYP450 3A4, 2C19, and/or P-gp, particularly those with a narrow therapeutic range. Some authorities advise that if concomitant use is required, the dosage of these substrates should be administered either 2 hours before or 8 hours after administration of the treosulfan infusion. The prescribing information of the substrates may be consulted for potential dose reductions.

Limited data suggest that chemotherapy with antineoplastic agents may reduce the plasma concentrations of oral quinolone antibiotics. The proposed mechanism is decreased quinolone absorption secondary to alteration of intestinal mucosa by cancer chemotherapy. In six patients with newly diagnosed hematologic malignancy, treatment with various antineoplastic agents (cyclophosphamide, cytarabine, daunorubicin, doxorubicin, mitoxantrone, prednisolone, vincristine) decreased the mean peak serum concentration (Cmax) and area under the concentration-time curve (AUC 0 to 4 hours) of ciprofloxacin by approximately 46% each. Data are not available for other quinolone antibiotics.