Drug Interactions between dexamethasone / moxifloxacin and temsirolimus

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.

GENERALLY AVOID: Coadministration of temsirolimus with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of sirolimus, a major active metabolite of temsirolimus and known substrate of CYP450 3A4. According to the product labeling, administration of temsirolimus in combination with the CYP450 3A4 inducer rifampin resulted in a 65% and 56% decrease in sirolimus peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration of temsirolimus alone. No significant effect on the pharmacokinetics of temsirolimus was reported.

MANAGEMENT: Concomitant use of temsirolimus with potent CYP450 3A4 inducers should generally be avoided. If coadministration is required in patients treated with temsirolimus for renal cell carcinoma, the manufacturer recommends increasing the temsirolimus dosage from 25 mg to 50 mg once a week depending on patient tolerability. Based on pharmacokinetic studies, this dosage is predicted to adjust the sirolimus systemic exposure (AUC) to the range observed without inducers. However, clinical data are lacking. The dosage should be reduced to the normally recommended dosage (i.e., 25 mg once a week) following discontinuation of the potent CYP450 3A4 inducer.