Naclo-R Drug Interactions

Aceclofenac: Lithium: NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.
Cardiac Glycoside: Through their renal effects, NSAIDs may increase plasma glycoside (including digoxin) levels, exacerbate cardiac failure and reduce the glomerular filtration rate in patients receiving glycosides.
Diuretics: Aceclofenac, like other NSAIDs, may inhibit the activity of diuretics. Although it was not shown to affect blood pressure control when co-administered with bendrofluazide, interactions with other diuretics cannot be ruled out. When concomitant administration with potassium-sparing diuretics is employed, serum potassium should be monitored. Diuretics can increase the risk of nephrotoxicity of NSAIDs.
Anticoagulants: Like other NSAIDs, aceclofenac may enhance the activity of anticoagulants. Close monitoring of patients on combined anticoagulant and aceclofenac therapy should be undertaken. The effects of warfarin and NSAIDs on gastrointestinal bleeding are synergistic, such that users of both drugs together have a risk of serious gastrointestinal bleeding higher than users of either drug alone.
Antidiabetic Agents: Clinical studies have shown that diclofenac can be given together with oral antidiabetic agents without influencing their clinical effect. However, there have been isolated reports of hypoglycaemic and hyperglycaemic effects. Thus with aceclofenac, consideration should be given to adjustment of the dosage of hypoglycaemic agents.
Methotrexate: Caution should be exercised if NSAIDs and methotrexate are administered within 24 hrs of each other, since NSAIDs may increase plasma levels, resulting in increased toxicity.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
Other NSAIDs and Steroids: Concomitant therapy with aspirin, other NSAIDs and steroids may increase the bleeding.
Cyclosporine: Cyclosporine nephrotoxicity may be increased by the effect of NSAIDs on renal prostaglandins.
Quinolone Antimicrobials: Convulsions may occur due to an interaction between quinolones and NSAIDs. This may occur in patients with or without previous history of epilepsy or convulsions. Therefore, caution should be exercised when considering the use of a quinolone in patients who are already receiving NSAIDs.
ACE Inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE inhibitors.
Rabeprazole: Rabeprazole is metabolized by the CYP450 drug metabolizing enzyme system. Studies in healthy subjects have shown that rabeprazole does not have clinically significant interactions with other drugs metabolized by the CYP450 system eg, warfarin and theophylline given as single oral doses, diazepam as a single IV dose, and phenytoin given as a single IV dose (with supplemental oral dosing). Steady-state interactions with rabeprazole and other drugs metabolized by this enzyme system have not been studied in patients; There have been reports of increased INR and prothrombin time may lead to abnormal bleeding and even death.
In vitro incubations employing human liver microsomes indicated that rabeprazole inhibited cyclosporine metabolism with an IC50 of 62 micromolar, a concentration that is over 50 times higher than the C_max in healthy volunteers following 14 days of dosing with 20 mg of rabeprazole. This degree of inhibition is similar to that by omeprazole at equivalent concentrations.
Rabeprazole sodium produces a profound and long lasting inhibition of gastric acid secretion. An interaction with compounds whose absorption is pH-dependent may occur. Co-administration of rabeprazole sodium with ketoconazole or itraconazole may result in a significant decrease in antifungal plasma levels. Therefore, individual patients may need to be monitored to determine if a dosage adjustment is necessary when ketoconazole or itraconazole are taken concomitantly with rabeprazole. For example, in normal subjects, co-administration of rabeprazole 20 mg 4 times a day. resulted in approximately 30% decrease in the bioavailability of ketoconazole and increase in the AUC and C_max for digoxin of 19% and 29%, respectively. Therefore, patients may need to be monitored when such drugs are taken concomitantly with rabeprazole. Co-administration of rabeprazole and antacids produced no clinically relevant changes in plasma rabeprazole concentrations.
Concomitant use of atazanavir and PPIs is not recommended. Co-administration of atazanavir with PPIs is expected to substantially decrease atazanavir plasma concentrations and thereby reduce its therapeutic effect.
In a clinical study in Japan evaluating rabeprazole in patients categorized by CYP2C19 genotype (n=6 per genotype category), gastric and suppression was higher in poor metabolizers as compared to extensive metabolizers. This could be due to higher rabeprazole plasma levels in poor metabolizers. Whether or not interactions of rabeprazole sodium with other drugs metabolized by CYP2C19 would be different between extensive metabolizers and poor metabolizers has not been studied. Combined administration consisting of rabeprazole, amoxicillin, and clarithromycin resulted in increases in plasma concentrations of rabeprazole and 14-hydroxyclarithromycin.