Theophylline interaction with other drugs

Drug interactions Cimetidine is a CYP450 inhibitor and can inhibit the metabolism of phenytoin, warfarin, and theophylline. Famotidine, nizatidine, and ranitidine are unlikely to cause clinically significant drug interactions. All antagonists have the potential to interact with other drugs that require gastric acid for absorption (e.g., ketoconazole, itraconazole). 

Some cytochrome P-450 isozymes, such as CYP lAl are inhibited by enoxacin, resulting in potentially important interactions with other drugs. For example, enoxacin has been reported to decrease theophylline clearance, causing increas plasma levels and increa.sed toxicity. Enoxacin forms insoluble chelates with divalent metal ions present in antacids and hcmalinic.s. which reduce its oral bioavailabilily. 

Pharmacokinetics. Carbamazepine is extensively metabolised one of the main products, an epoxide (a chemically reactive form), has anticonvulsant activity similar to that of the parent drug but may also cause some of its adverse effects. The t) of carbamazepine falls from 35 h to 20 h over the first few weeks of therapy due to induction of hepatic enzymes that metabolise it as well as other drugs, including corticosteroids (adrenal and contraceptive), theophylline and warfarin. Cimetidine and valproate inhibit its metabolism. There are complex interactions with other antiepilepsy drugs, which constitute a reason for monodrug therapy. 

One of the important limitations to the widespread use of the macrolides has been the propensity to interact with other commonly administered medications. Serious, sometimes life-threatening, consequences have resulted from the administration of macrolides to patients receiving routine medications including theophylline, carbamazepine, terfenadine, and other frequently prescribed medications [4-6]. Most of these interactions involve inhibition of drug metabolism via cytochrome P-450 microsomal enzyme. However, not all macrolides have been associated with such drug interactions. 

Caffeine, like theophylline, also undergoes extensive hepatic metabolism, principally by CYP1A2, and interacts with many drugs, but it has a wider therapeutic range. However, other xanthines may act differently (e.g. diprophylline does not undergo hepatic metabolism), so it should not be assumed that they all share common interactions. 

Although many patients believe that dietary supplements will not interact with medications, recent literature suggests otherwise. Recently, many St. John s wort-drug interactions have been reported in the literature. Cases of patients developing symptoms of serotonin syndrome have been reported with St. John s wort alone and in concomitant therapy with other antidepressants such as monoamine oxidase inhibitors, serotonin reuptake inhibitors, and venlafaxine. St. John s wort may exacerbate the sedative effects of benzodiazepines, alcohol, narcotics, and other sedatives. St. John s wort may decrease the levels of protease inhibitors, cyclosporine, digoxin, and theophylline. 

Pharmacokinetic interactions Preliminary evidence suggests that Saint-John s-wort induces the cytochrome oxidase enzyme isoform CYP3A4 (Ernst 1999). This raises the potential for pharmacokinetic interactions with drugs metabolized by the same enzyme. A few cases have been reported of reduced warfarin levels (Yue et al. 2000). Similar interactions have also been reported for concurrent use with digoxin, theophylline, and cyclosporin (Nebel et al. 1999 Ruschitzka et al. 2000 Johne et al. 1999). As with any other medication, potential interactions should be considered when taking a combination of drugs. 

All quinolones interact with multivalent cations, forming chelation complexes resulting in reduced absorption. Major offenders are antacids vitamins containing calcium and iron can also be problematic. All fluoroquinolones interact with warfarin, didanosine (ddi), and phenytoin, resulting in decreased absorption or metabolism. Ciprofloxacin and other second-generation drugs interact with theophylline by decreasing its clearance, which leads to theophylline toxicity. 

Hypericum has been found to also interact with drugs metabolized via other pathways. For example, it decreases serum levels of digoxin, which is metabolized via the P-glycoprotein drug transporter, and reduces levels of theophylline and warfarin, which are metabolized via CYP1A2 and CYP2C9 pathways, respectively. It is possible that St. John s wort might also induce those enzymes via the steroid X receptor (Wentworth et ah, 2000). 

Drug Interactions According to the product label, interactions between Intron A and other drugs have not been fully evaluated. Caution should be exercised when administering Intron A therapy in combination with other potentially myelo-suppressive agents such as zidovudine. Concomitant use of alfa interferon and theophylline decreases theophylline clearance, resulting in a 100% increase in serum theophylline levels. 

A retrospective analysis of 3995 patients treated with azithromycin did not show any pharmacokinetic interactions in patients who were also taking various other drugs, including theophylline (1,45). 

The overall safety record of the currently marketed agents, particularly cimetidine and ranitidine, which have had extensive worldwide use, is excellent, and in practice safety issues seldom affect drug choice (1), except perhaps when it is necessary to avoid interactions with phenytoin, theophylline, or warfarin. Surveillance studies, which have been going on for a quarter of a century (including 10-year studies in many patients, mainly involving cimetidine and ranitidine), have failed to detect any serious adverse effects other than those recognized by 1980, or any adverse effect on mortality (2). 

After influenza immunization there was a reduction in blood theophylline concentrations in patients and healthy volunteers (58). The authors concluded that flu vaccine may influence the pharmacokinetics of several drugs, and a second group found that theophylline oxidation was significantly reduced at 1 day, but not at 7 days, after immunization (57). However, others did not confirm these effects (55,59). The lack of a clinical interaction with theophylline has also been confirmed by a report of the US Immunization Practices Advisory Committee (9). 

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