There is some limited evidence to suggest that erythromycin mayincrease effects of doxofylline, but clinical importance ofthis is uncertain. Digoxin initially raises, then lowers serum doxofylline levels, but bronchodilator effects do not appear to besignificantly affected. Allopurinol and lithium carbonate appearto have no significant effects on doxofylline.
Clinical evidence,mechanism, importance and management
Healthy subjects were given doxofylline 400mg three times daily,either alone, or with allopurinol 100mg once daily, erythromycin 400mg three times daily or lithium carbonate 300mg three times daily. None of pharmacokinetic parameters measured, including maximum serum levels, were significantly altered by any of these drugs apart from AUC of doxofylline, which was raised by about 40 % by allopurinol, 70 % by erythromycin, and 35 % by lithium carbonate. Only erythromycin result was statistically significant (See reference number 1). The clinical significance of these changes is uncertain,and their mechanism is not understood. Until situation is much clearer it would be prudent to check outcome of addingerythromycin to established treatment with doxofylline, being alert for evidence of increased effects.
In a comparative study in 9 patients taking doxofylline 800mg daily,digoxin 500 micrograms daily was given to 5 patients. It was found that digoxin increased serum levels of doxofylline by 50 % on first day of treatment, 3 hrs after administration but then reduced doxofylline levels by about 30 % at steady-state (day 30). Nevertheless, bronchodilating effects of doxofylline were little different between two groups. It was concluded that concurrent use is normally safe and effective, but initial doxofylline dose should be chosen to avoid too high a serum level on first day, and pulmonary function should be well monitored (See reference number 2).
Harning R,Sekora D, O’Connell K, Wilson J. A crossover study of the effect of erythromycin,lithium carbonate, and allopurinol on doxofylline pharmacokinetics. Clin Pharmacol Ther (1994) 55, 158.
Provvedi D,Rubegni M, Biffignandi P. Pharmacokinetic interaction between doxofylline anddigitalis in elderly patients with chronic obstructive bronchitis. Acta Ther (1990) 16, 239–46.