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Drug Interactions between Folex PFS and Maximum Strength Stress

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

methotrexate bismuth subsalicylate

Applies to: Folex PFS (methotrexate) and Maximum Strength Stress (bismuth subsalicylate)

GENERALLY AVOID: Salicylates may interfere with the renal elimination of methotrexate and may displace it from binding sites. The pharmacologic effect and toxicity of methotrexate may be increased. Patients receiving high-dose methotrexate are at a greater risk of developing toxicity.

MANAGEMENT: If these agents must be used concomitantly, caution should be exercised and the patient should be monitored closely for signs and symptoms of bone marrow suppression and nephrotoxicity. Patients should be advised to report possible symptoms of toxicity including nausea, vomiting, diarrhea, stomatitis, sore throat, chills, fever, rash, unusual bruising or bleeding, jaundice, dark urine, swelling of the extremities, or shortness of breath to their physician. Patients should also be counseled to avoid any other over-the-counter salicylate products.

References

  1. Frenia ML, Long KS "Methotrexate and nonsteroidal antiinflamatory drug interactions." Ann Pharmacother 26 (1992): 234-7
  2. Skeith KJ, Russell AS, Jamali F, Coates J, Friedman H "Lack of significant interaction between low dose methotrexate and ibuprofen or flurbiprofen in patients with arthritis." J Rheumatol 17 (1990): 1008-10
  3. Maiche AG "Acute renal failure due to concomitant action of methotrexate and indomethacin." Lancet 1 (1986): 1390
  4. Singh RR, Malaviya AN, Pandey JN, Guleria JS "Fatal interaction between methotrexate and naproxen." Lancet 1 (1986): 1390
  5. Dupuis LL, Koren G, Shore A, Silverman ED, Laxer RM "Methotrexate-nonsteroidal antiinflammatory drug interaction in children with arthritis." J Rheumatol 17 (1990): 1469-73
  6. Stewart CF, Fleming RA, Germain BF, et al. "Aspirin alters methotrexate disposition in rheumatoid arthritis patients." Arthritis Rheum 34 (1991): 1514-20
  7. Stewart CF, Fleming RA, Arkin CR, Evans WE "Coadministration of naproxen and low-dose methotrexate in patients with rheumatoid arthritis." Clin Pharmacol Ther 47 (1990): 540-6
  8. Liegler DG, Henderson ES, Hahn MA, Oliverio VT "The effect of organic acids on renal clearance of methotrexate in man." Clin Pharmacol Ther 10 (1969): 849-57
  9. Ellison NM, Servi RJ "Acute renal failure and death following sequential intermediate-dose methotrexate and 5-FU: a possible adverse effect due to concomitant indomethacin administration." Cancer Treat Rep 69 (1985): 342-3
  10. Kraus A, Alarcon-Segovia D "Low dose MTX and NSAID induced "mild" renal insufficiency and severe neutropenia." J Rheumatol 18 (1991): 1274
  11. Dixon RL, Henderson ES, Rall DP "Plasma protein binding of methotrexate and its displacement by various drugs." Fed Proc 24 (1965): 454
  12. Baker H "Intermittent high dose oral methotrexate therapy in psoriasis." Br J Dermatol 82 (1970): 65-9
  13. Mandel MA "The synergistic effect of salicylates on methotrexate toxicity." Plast Reconstr Surg 57 (1976): 733-7
  14. Taylor JR, Halprin KM "Effect of sodium salicylate and indomethacin on methotrexate-serum albumin binding." Arch Dermatol 113 (1977): 588-91
  15. "Product Information. Methotrexate (methotrexate)." Lederle Laboratories PROD (2002):
  16. Tracy TS, Krohn K, Jones DR, Bradley JD, Hall SD, Brater DC "The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis." Eur J Clin Pharmacol 42 (1992): 121-5
View all 16 references

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Drug and food interactions

Moderate

methotrexate food

Applies to: Folex PFS (methotrexate)

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.

References

  1. Nesher G, Mates M, Zevin S "Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis." Arthritis Rheum 48 (2003): 571-572

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Moderate

methotrexate food

Applies to: Folex PFS (methotrexate)

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.

References

  1. "Product Information. Methotrexate (methotrexate)." Lederle Laboratories PROD (2002):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. "Product Information. Methotrexate (methotrexate)." Hospira Inc (2023):

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Moderate

methotrexate food

Applies to: Folex PFS (methotrexate)

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.

References

  1. Nesher G, Mates M, Zevin S "Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis." Arthritis Rheum 48 (2003): 571-572

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.