Troleandomycin Theophylline

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Macrolide Antibiotics. Erythromycin may significantly increase serum concentrations of medications such as theophylline by inhibiting their hepatic metabolism. Clarithromycin (Biaxin) and troleandomycin appear to interact with other medications in a manner similar to erythromycin, whereas azithromycin (Zithromax) is unlikely to interact with these agents. 

Increased effects (P450 3A4 inhibitors) cimetidine, danazol, diltiazem, erythromycin, troleandomycin, clarithromycin, fluoxetine, isoniazid, niacinamide, nicotinamide, propoxyphene, ketoconazole, itraconazole, verapamil,and valproate Decreased effects (P450 3A4 inducers) cisplatin, doxorubicin, felbamate, rifampin, phenobarbital, phenytoin, primidone, theophylline... 

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

When used concomitantly, theophylline increases the excretion of lithium. Also, cimetidine, allopurinol (high dose), propranolol, erythromycin, and troleandomycin may cause an increase in serum concentrations of theophylline by decreasing the hepatic clearance. Barbiturates and phenytoin enhance hepatic clearance and hepatic metabolism of theophylline, decreasing plasma levels. Beta-adrenergic blockers exert an antagonistic pharmacologic effect. 

Troleandomycin Inhibits hepatic drug metabolism examples include carbamazepine, corticosteroids, and theophylline. 

Increased serum theophylline, usually beginning only after several days of erythromycin effect is modest in many cases, but severe toxicity has occurred. Clarithromycin and troleandomycin also inhibit theophylline metabolism. 

Concomitant administration of recombinant human a-interferon decreased theophylline clearance by 15%. Most macrolides are potent inhibitors of CYP3A4. Erythromycin and its salts as well as troleandomycin reduce theophylline Cl concentrahon-dependently 20-40% reduction after 5—7 days of therapy" " with erythromycin, 50% after 10 days with troleandomycin." Results for clarithromycin are similar to those for erythromycin." Azithromycin does not seem to influence theophylline metabolism, although reported results are contradictory. " ... 

Increase in theophylline serum concentrations is generally not more than 25% after erythromycin. Dose reduction by 25% might be appropriate. Use of other antibiotics should be considered, especially if troleandomycin is used. 

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. 

A series of 8 patients with severe ehronic asthma found that troleandomycin 250 mg four times daily caused an average reduction in the clearance of theophylline (given as intravenous aminophylline) of 50%. One patient had a theophylline-induced seizure after 10 days, with a serum theophylline level of 43 mg/mL (reference range 10 to 20 mg/L). The theophylline half-life in this patient had increased from 4.6 to 11.3 hours. Other studies in healthy subjects and patients given oral theophylline with troleandomycin have also found reductions in theophylline clearance and marked rises in serum theophylline levels and half-life, even at low troleandomycin doses. ... 

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. 

Brazier JL, Kofman J, Faucon G, Perrin-Fayolle M, Lepape A, Lanoue R Retard d ehmina-tion de la theophylline du a la troleandomycine. Absence d effet de la josamycine. Therc ie (1980) 35,545-9. 

Weinberger M, Hudgel D, Spector S, Chidsey C. Inhibition of theophylline clearance by troleandomycin. J Allergy Clin Immunol 917) 59,228-31. 

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