Drug Interactions between dexamethasone / moxifloxacin and praziquantel

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 with inducers of CYP450 3A4 may decrease the plasma concentrations of praziquantel, which is a substrate of the isoenzyme. In a crossover study with a 2-week washout period, plasma praziquantel concentrations were undetectable in 7 out of 10 subjects who ingested a single 40 mg/kg dose of praziquantel following pretreatment with the potent CYP450 3A4 inducer, rifampin, given at 600 mg daily for 5 days. When the same dose of praziquantel was administered two weeks after discontinuation of rifampin, the mean praziquantel peak plasma concentration (Cmax) and systemic exposure (AUC) were only 35% and 23% lower, respectively, than when praziquantel was given alone. The oral bioavailability of praziquantel has also been shown to decrease significantly in patients treated with carbamazepine or phenytoin, both of which are known potent CYP450 3A4 inducers. In one study, maximum plasma praziquantel concentrations in epileptic patients receiving stable carbamazepine (n=10) and phenytoin (n=10) therapy were 8% and 24%, respectively, of those observed in control subjects following administration of a single 25 mg oral dose of praziquantel. The extent to which other, less potent CYP450 3A4 inducers may interact with praziquantel is unknown.

MANAGEMENT: Concomitant use of praziquantel with CYP450 3A4 inducers should generally be avoided, since therapeutically effective blood levels of praziquantel may not be achieved. Alternative agents for schistosomiasis should be considered whenever possible in patients receiving treatment with a CYP450 3A4 inducer. Otherwise, clinical response to praziquantel should be closely monitored.