Drug Interactions between dexamethasone / moxifloxacin and idelalisib

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 inducers of CYP450 3A4 may decrease the plasma concentrations of idelalisib, which is a substrate of the isoenzyme. In healthy volunteers, administration of a single 150 mg dose of idelalisib with the potent CYP450 3A4 inducer rifampin (600 mg daily for 8 days) decreased mean idelalisib peak plasma concentration (Cmax) by 58% and systemic exposure (AUC) by 75%. Data are not available for idelalisib in combination with other, less potent CYP450 3A4 inducers.

MANAGEMENT: Patients receiving idelalisib with CYP450 3A4 inducers should be monitored for potentially diminished pharmacologic response to idelalisib. Concomitant use should be avoided if an interaction is suspected.

GENERALLY AVOID: Coadministration of idelalisib with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. The use of idelalisib has been associated with elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 5 times the upper limit of normal. Serious and fatal hepatotoxicity occurred in 14% of patients treated with idelalisib in premarketing trials. Liver enzyme elevations were generally observed within the first 12 weeks of treatment and were reversible with dose interruption. Following treatment resumption at a lower dose, 26% of patients had recurrence of ALT and AST elevations.

MANAGEMENT: The use of idelalisib with other potentially hepatotoxic agents should be avoided whenever possible (e.g., acetaminophen; alcohol; amiodarone; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; methotrexate; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; tetracyclines; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients treated with idelalisib should have serum ALT, AST, and bilirubin measured prior to initiation of treatment and regularly during treatment in accordance with the product labeling, and the dosing adjusted or interrupted as necessary. Permanent discontinuation of idelalisib is recommended in those who experience recurrent hepatotoxicity following dosage reduction. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice.