Roxithromycin Theophylline

The effect of macrohdes on serum theophylline concentration and clearance has been investigated in 53 patients with moderate asthma treated with theophylline (400 mg/day) in a randomized trial reference. Erythromycin (500 mg bd) and roxithromycin (150 mg bd), but not clarithromycin (250 mg bd) or azithromycin (250 mg bd), caused increased serum theophylline concentrations and reduced clearance. 

Roxithromycin altered the pharmacokinetics of theophylline, mainly increasing the C ax, prolonging the half-life, and increasing the renal clearance (15). However, while these changes were statistically significant, they were considered clinically irrelevant. There was no effect of roxithromycin on trough concentrations of theophylline. 

Saint-Salvi B, Tremblay D, Surjus A, Lefebvre MA. A study of the interaction of roxithromycin with theophylline and carbamazepine. J Antimicrob Chemother 1987 20(Suppl B) 121-9. 

Suijus, A., Tremblay, D., Saint-Salvi, B., Granier, J., and Lefebvre, M. A. (1986). Pharmacokinetic interaction of a new macrolide, roxithromycin (RU 28965) with theophyllin. Presented at the Third World Conference on Clinical Pharmacology and Therapeutics (Stockholm). Abstr. No. 1203. 

Troleandomycin can increase serum theophylline levels, causing toxicity if the dosage is not reduced. Azithromycin, clarithromycin, dirithromycin, josamycin, midecamycin, rokitamycin, spiramycin, and telithromycin normally only cause modest changes in theophylline levels or do not interact at all. There are unexplained and isolated case reports of theophylline toxicity with josamycin and clarithromycin. Roxithromycin usually has no relevant interaction but a significant increase in theophylline levels was seen in one study. See also Theophylline + Macrolides Erythromycin , p.ll87. 

One study in 12 healthy subjects and another in 16 patients with chronic obstructive pulmonary disease found only minor increases in steady-state theophylline levels, which were not considered clinically relevant, when they were given roxithromycin 150 mg twice daily.Another study in 5 healthy subjects similarly showed that roxithromycin 300 mg twice daily did not affect the pharmacokinetics of theophylline." However, further study reported a significant increase in serum theophylline levels in 14 patients with asthma who were given roxithromycin 150 mg twice daily, but since the rise was not quantified it is difficult to assess the clinical relevance of this finding. ... 

It is believed that troleandomycin forms inactive cytochrome P450-metab-olite complexes within the liver, the effect of which is to reduce the metabolism (A/-demethylation and 8-hydroxylation) of theophylline, thereby reducing its clearance and increasing its levels. Clarithromycin, josamycin, midecamycin, and roxithromycin are thought to rarely form complexes, and azithromycin, dirithromycin, rokitamycin and spiramycin are not thought to inactivate cytochrome P450. ... 

The interaction between theophylline and troleandomycin is established and well documented. If troleandomycin is given, monitor the levels of theophylline closely and adjust the dose as necessary. Reductions of 25 to 50% may be needed. The situation with roxithromycin is uncertain since only 1 of 4 studies suggested an interaction, but it would be prudent to be alert for the need to reduce the theophylline dosage. Alternative mac-rolides that usually interact only moderately, or not at all are azithromycin, clarithromycin, dirithromycin, josamycin, midecamycin, rokitamycin and spiramycin. Telithromycin may also he a suitable alternative. However, even with these macrolides it would still be prudent to monitor the outcome because a few patients, especially those with theophylline levels at the high end of the range, may need some small theophylline dosage adjustments. In the case of azithromycin, care should be taken in adjusting the dose based on theophylline levels taken after about 5 days of concurrent use, as they may only he a reflection of a transient drop. In addition, acute infection perse may alter theophylline pharmacokineties. 

Bandera M, Fioretti M, Rimoldi R, Lazzarini A, Anelli M. Roxithromycin and controlled release theophylline, an interaction study. Chemioterapia ( 9SS) 7,313-16. 

Hashiguchi K, Niki Y, Soejima R. Roxithromycin does not raise serum theophylline levels. Cto( 1992) 102,653-4. 

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