Drug Interactions between dexamethasone / moxifloxacin and fosaprepitant

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.

ADJUST DOSE: Coadministration with aprepitant or its prodrug, fosaprepitant, may increase the plasma concentrations of some corticosteroids. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by aprepitant. According to the product labeling, coadministration of aprepitant (125 mg on day 1 and 80 mg/day on days 2 through 5) and dexamethasone (20 mg orally on day 1 and 8 mg on days 2 through 5) resulted in an increase in the area under the plasma concentration-time curve (AUC) of dexamethasone by 2.2-fold on days 1 and 5. Similarly, aprepitant (125 mg on day 1 and 80 mg/day on days 2 and 3) increased the AUC of methylprednisolone (125 mg intravenously on day 1 and 40 mg orally on days 2 and 3) by 1.34-fold on day 1 and 2.5-fold on day 3. In contrast, coadministration with a single 40 mg dose of aprepitant increased the AUC of oral dexamethasone (20 mg) by just 45%, indicating a weaker inhibition of CYP450 3A4 during low-dose, single administration. The effect of aprepitant on the pharmacokinetics of CYP450 3A4 substrates is also expected to be smaller when the substrates are administered intravenously as opposed to orally, and may be altered following prolonged administration.

MANAGEMENT: Oral dexamethasone and methylprednisolone dosage should be reduced by approximately 50% when coadministered with the aprepitant 125 mg/80 mg regimen, and intravenous methylprednisolone dosage should be reduced by approximately 25%. The daily dosage of dexamethasone administered in clinical chemotherapy-induced nausea and vomiting studies with aprepitant was reduced to account for the drug interaction. No dosage adjustment for the corticosteroid is necessary during coadministration with aprepitant in a single 40 mg dose for prevention of postoperative nausea and vomiting. Chronic, continuous use of aprepitant for prevention of nausea and vomiting is not recommended, as it has not been studied and the drug interaction profile may change during long-term use.