Drug Interaction Report

MONITOR: Probiotic use during immunosuppressant or intense antineoplastic therapy may theoretically increase the risk of infections from the live microorganisms contained in probiotic products. Patients may be immunosuppressed if they have recently received or are receiving alkylating agents, antimetabolites, radiation, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents, or long-term topical or inhaled corticosteroids. Although probiotics are generally considered safe, with minimal to low pathogenicity, infections such as bacteremia and endocarditis with various strains commonly found in probiotics (e.g., lactobacilli, bifidobacteria, Bacillus subtilis) have been rarely reported, primarily in critically ill patients or patients with significant underlying medical conditions such as malignancy, organ transplantation, AIDS, valvular heart disease, diabetes mellitus, recent surgery, or compromised immune system. Lactobacillus bacteremia has also been reported following endoscopy. In addition, cases of lactobacillus pneumonia and liver abscess, as well as Saccharomyces fungemia, pneumonia, liver abscess, peritonitis and vaginitis, have been described in the medical literature.

MANAGEMENT: Caution is advised when probiotics are used during immunosuppressant or intense antineoplastic therapy. It may be advisable to avoid using probiotics, particularly products containing saccharomyces boulardii, in patients who are significantly immunosuppressed unless benefits are anticipated to outweigh the potential risk of infection.

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MONITOR: Probiotic use during immunosuppressant or intense antineoplastic therapy may theoretically increase the risk of infections from the live microorganisms contained in probiotic products. Patients may be immunosuppressed if they have recently received or are receiving alkylating agents, antimetabolites, radiation, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents, or long-term topical or inhaled corticosteroids. Although probiotics are generally considered safe, with minimal to low pathogenicity, infections such as bacteremia and endocarditis with various strains commonly found in probiotics (e.g., lactobacilli, bifidobacteria, Bacillus subtilis) have been rarely reported, primarily in critically ill patients or patients with significant underlying medical conditions such as malignancy, organ transplantation, AIDS, valvular heart disease, diabetes mellitus, recent surgery, or compromised immune system. Lactobacillus bacteremia has also been reported following endoscopy. In addition, cases of lactobacillus pneumonia and liver abscess, as well as Saccharomyces fungemia, pneumonia, liver abscess, peritonitis and vaginitis, have been described in the medical literature.

MANAGEMENT: Caution is advised when probiotics are used during immunosuppressant or intense antineoplastic therapy. It may be advisable to avoid using probiotics, particularly products containing saccharomyces boulardii, in patients who are significantly immunosuppressed unless benefits are anticipated to outweigh the potential risk of infection.

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MONITOR: Limited data suggest that consumption of greater than 180 mg/day of caffeine may interfere with the efficacy of methotrexate (MTX) in patients with rheumatoid arthritis. The exact mechanism of interaction is unknown but may be related to the antagonistic effect of caffeine on adenosine receptors, as anti-inflammatory properties of MTX is thought to result from the accumulation of adenosine. In a study of 39 patients treated with MTX 7.5 mg/week (without folate supplementation) for 3 months, patients with high caffeine intake (more than 180 mg/day) experienced significantly less improvement in morning stiffness and joint pain from baseline than patients with low caffeine intake (less than 120 mg/day). There were no significant differences between the responses of patients with moderate caffeine intake (120 to 180 mg/day) and those of the other 2 groups. In an interview of 91 patients treated with MTX, 26% of patients who discontinued the drug were regular coffee drinkers compared to only 2% of those still receiving the drug. Because treatment failure was the reason for MTX discontinuation in 80% of patients who discontinued, the investigators suggested that caffeine may have interfered with MTX efficacy.

MANAGEMENT: Until further information is available, the potential for interaction should be considered in patients who consume substantial amounts of caffeine and caffeine-containing foods and are prescribed methotrexate for rheumatoid arthritis. It may be appropriate to limit caffeine intake if an interaction is suspected in cases of treatment failure.

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GENERALLY AVOID: Coadministration of methotrexate with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Methotrexate, especially at higher dosages or during prolonged treatment, has been associated with severe hepatotoxicity including acute hepatitis, chronic fibrosis, cirrhosis, and fatal liver failure.

MANAGEMENT: The risk of hepatic injury should be considered when methotrexate is used with other potentially hepatotoxic agents (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Baseline and periodic monitoring of hepatic function is recommended, while liver biopsy may be warranted during long-term use of methotrexate. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, pale stools, and jaundice.

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MONITOR: Limited data suggest that consumption of greater than 180 mg/day of caffeine may interfere with the efficacy of methotrexate (MTX) in patients with rheumatoid arthritis. The exact mechanism of interaction is unknown but may be related to the antagonistic effect of caffeine on adenosine receptors, as anti-inflammatory properties of MTX is thought to result from the accumulation of adenosine. In a study of 39 patients treated with MTX 7.5 mg/week (without folate supplementation) for 3 months, patients with high caffeine intake (more than 180 mg/day) experienced significantly less improvement in morning stiffness and joint pain from baseline than patients with low caffeine intake (less than 120 mg/day). There were no significant differences between the responses of patients with moderate caffeine intake (120 to 180 mg/day) and those of the other 2 groups. In an interview of 91 patients treated with MTX, 26% of patients who discontinued the drug were regular coffee drinkers compared to only 2% of those still receiving the drug. Because treatment failure was the reason for MTX discontinuation in 80% of patients who discontinued, the investigators suggested that caffeine may have interfered with MTX efficacy.

MANAGEMENT: Until further information is available, the potential for interaction should be considered in patients who consume substantial amounts of caffeine and caffeine-containing foods and are prescribed methotrexate for rheumatoid arthritis. It may be appropriate to limit caffeine intake if an interaction is suspected in cases of treatment failure.

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