Klaryth Drug Interactions

Increased rifabutin toxicity has been reported in patients receiving Clarithromycin and rifabutin. There has been also a report of delirium following concurrent use with fluoxetine.
Antiretroviral drugs: Concomitant administration of the HIV - protease inhibitor ritonavir inhibit the metabolism of Clarithromycin producing elevated plasma concentrations and a prolonged half-life. It has been suggested that other HIV - protease inhibitors and non-nucleoside reverse transcriptase inhibitors may also affect the metabolism of Clarithromycin. Concurrent use of efavirenz with Clarithromycin has resulted in decrease in the plasma concentration of Clarithromycin and increases in its hydroxyl metabolite. This combination has been associated with a high incidence of skin rashes. Decreased concentrations of zidovudine have been reported in patients also taking Clarithromycin. It is recommended that the doses of these two drugs should be separated by 1 to 2 hours.
Administration of cimetidine with Clarithromycin may alter some of the pharmacokinetic parameters of Clarithromycin. The clinical significance of such changes is unknown.
Concomitant administration of omeprazole with Clarithromycin resulted in increased concentrations of Clarithromycin and its active metabolite. There is also an increased and prolonged plasma concentrations of omeprazole. This interaction could account for the synergistic action with the combination when used for eradication of Helicobacter pylori.
Activity with other antimycobacterials: Clarithromycin has been reported to enhance the activity of a number of antimycobacterials including ethambutol, isoniazid, pyrazinamide, and rifampicin against Mycobacterium tuberculosis.
The use of Clarithromycin in patients receiving theophylline may be associated with an increase of serum theophylline concentrations. Monitoring of serum theophylline concentrations should be considered for patients receiving high doses of theophylline or with base line concentrations in the upper therapeutic range.
Concurrent use of single doses of Clarithromycin and carbamazepine has been shown to result in increased plasma concentrations of carbamazepine. Blood level monitoring of carbamazepine may be considered.
When Clarithromycin and terfenadine were co-administered, plasma concentrations of the active acid metabolite of terfenadine were threefold higher, an average, than the values observed when terfenadine was administered alone. The pharmacokinetics of Clarithromycin and the 14-hydroxylclarithromycin were not significantly affected by co-administration of terfenadine once Clarithromycin reached steady-state conditions.
Co-administration of fluconazole and Clarithromycin increased the mean steady-state Clarithromycin C_min of 33% and AUC of 18%. Steady-state concentrations of 14-hydroxylclarithromycin were not significantly affected by the concomitant administration of fluconazole.
Concurrent use of Clarithromycin and oral anticoagulants may potentiate the effects of the oral anticoagulants. Prothrombin time should be carefully monitored.
There have been reports on increased digoxin serum concentrations when Clarithromycin is co-administered with digoxin. Monitoring of serum digoxin concentrations should be considered.
Colchicine toxicity have been reported with concomitant use of Clarithromycin and colchicine, especially in the elderly, some of which occurred in patients with renal insufficiency.
Clarithromycin is a substrate and inhibitor of the 3A isoform subfamily of the cytochrome P450 enzyme system (CYP3A). Co-administration of Clarithromycin and a drug primarily metabolized by CYP3A may be associated with elevations in drug concentrations that could increase or prolong both the therapeutic and adverse effects of the concomitant drug. The following are examples of clinically significant CYP3A based drug interactions observed with Clarithromycin: Antiarrhythmics: There have been post marketing reports of Torsades de Pointes occurring with concurrent use of Clarithromycin and quinidine or disopyramide. Electrocardiograms should be monitored for QTc prolongation during co-administration of Clarithromycin with these drugs. Serum concentrations of these medications should also be monitored.
Post-marketing reports indicate that co-administration of Clarithromycin with ergotamine or dihydroergotamine has been associated with acute toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system. Concomitant administration of Clarithromycin with ergotamine or dihydroergotamine is contraindicated.
Drug interactions and CNS effects (e.g. somnolence and confusion) have been reported with the concomitant use of Clarithromycin and triazolobenzodiazepines (such as triazolam and alprazolam) and other related benzodiazepines (such as midazolam).
Clarithromycin has been reported to increase concentrations of HMG-CoA reductase inhibitors (e.g. lovastatin and simvastatin). There have been rare reports of rhabdomyolysis in patients taking these drugs concomitantly.
Clarithromycin has been reported to increase the systematic exposure (AUC) of sildenafil. Reduction of sildenafil dosage should be considered.
There have been published reports of CYP3A based interactions of Clarithromycin with cyclosporine, carbamazepine, tacrolimus, alfentanil, disopyramide, rifabutin, quinidine, methylprednisolone, cilostazol, and bromocriptine. In addition, there also have been reports of interactions of Clarithromycin with drugs not thought to be metabolized by CYP3A, including hexobarbital, phenytoin and valproate.