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Drug Interactions between Methotrexate LPF Sodium and Motrin Pediatric

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

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Interactions between your drugs

Major

ibuprofen methotrexate

Applies to: Motrin Pediatric (ibuprofen) and Methotrexate LPF Sodium (methotrexate)

MONITOR CLOSELY: Coadministration with nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the plasma concentrations and toxicities of methotrexate. The proposed mechanism is NSAID inhibition of the renal elimination of methotrexate and its metabolite, 7-hydroxymethotrexate, although data from pharmacokinetic studies are inconsistent and conflicting. Displacement of methotrexate binding to serum albumin by certain NSAIDs may also play a secondary role. Unexpectedly severe and sometimes fatal bone marrow suppression, aplastic anemia, gastrointestinal toxicity, and nephrotoxicity have been reported during concomitant administration of methotrexate with NSAIDs. The risk is greatest in patients receiving high dosages of methotrexate and those with renal impairment. In clinical studies, methotrexate at dosages of 7.5 to 15 mg/week has been used without apparent problems in patients with rheumatoid arthritis who also received constant dosage regimens of NSAIDs. However, there have been occasional reports of stomatitis, pneumonitis, bone marrow toxicity, and fatality in patients receiving low-dose weekly methotrexate with daily NSAIDs.

MANAGEMENT: NSAIDs should generally not be administered prior to or concomitantly with high dosages of methotrexate, such as those used to treat osteosarcoma. Caution should be exercised when NSAIDs are administered concomitantly with lower dosages of methotrexate. Close monitoring for signs and symptoms of bone marrow suppression, nephrotoxicity, and hepatotoxicity is recommended during treatment. Patients should be advised to contact their physician if they develop stomatitis, nausea, vomiting, diarrhea, rash, anorexia, jaundice, dark urine, dry cough, shortness of breath, and/or signs and symptoms of myelosuppression such as pallor, dizziness, fatigue, lethargy, fainting, easy bruising or bleeding, fever, chills, sore throat, body aches, and other influenza-like symptoms. Patients should also be counseled to avoid any other over-the-counter NSAID products.

References

  1. 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
  2. Bloom EJ, Ignoffo RJ, Reis CA, Cadman E "Delayed clearance (CL) of methotrexate (MTX) associated with antibiotics and antiinflammatory agents." Clin Res 34 (1986): a560
  3. Thyss A, Milano G, Kubar J, Namer M, Schneider M "Clinical and pharmacokinetic evidence of a life-threatening interaction between methotrexate and ketoprofen." Lancet 1 (1986): 256-8
  4. Maiche AG "Acute renal failure due to concomitant action of methotrexate and indomethacin." Lancet 1 (1986): 1390
  5. Singh RR, Malaviya AN, Pandey JN, Guleria JS "Fatal interaction between methotrexate and naproxen." Lancet 1 (1986): 1390
  6. Ng HW, Macfarlane AW, Graham RM, Verbov JL "Near fatal drug interactions with methotrexate given for psoriasis." Br Med J (Clin Res Ed) 295 (1987): 752-3
  7. 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
  8. Frenia ML, Long KS "Methotrexate and nonsteroidal antiinflammatory drug interactions." Ann Pharmacother 26 (1992): 234-7
  9. Stewart CF, Fleming RA, Germain BF, Seleznick MJ, Evans WE "Aspirin alters methotrexate disposition in rheumatoid arthritis patients." Arthritis Rheum 34 (1991): 1514-20
  10. 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
  11. Mayall B, Poggi G, Parkin JD "Neutropenia due to low-dose methotrexate therapy for psoriasis and rheumatoid arthritis may be fatal." Med J Aust 155 (1991): 480-4
  12. 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
  13. Kraus A, Alarcon-Segovia D "Low dose MTX and NSAID induced "mild" renal insufficiency and severe neutropenia." J Rheumatol 18 (1991): 1274
  14. Adams JD, Hunter GA "Drug interaction in psoriasis." Australas J Dermatol 17 (1976): 39-40
  15. Baker H "Intermittent high dose oral methotrexate therapy in psoriasis." Br J Dermatol 82 (1970): 65-9
  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
  17. Anaya JM, Fabre D, Bressolle F, Bologna C, Alric R, Cocciglio M, Dropsy R, Sany J "Effect of etodolac on methotrexate pharmacokinetics in patients with rheumatoid arthritis." J Rheumatol 21 (1994): 203-8
  18. Tracy TS, Worster T, Bradley JD, Greene PK, Brater DC "Methotrexate disposition following concomitant administration of ketoprofen, piroxicam and flurbiprofen in patients with rheumatoid arthritis." Br J Clin Pharmacol 37 (1994): 453-6
  19. Brouwers JRBJ, Desmet PAGM "Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs." Clin Pharmacokinet 27 (1994): 462-85
  20. Combe B, Edno L, Lafforgue P, Bologna C, Bernard JC, Acquaviva P, Sany J "Total and free methotrexate pharmacokinetics, with and without piroxicam, in rheumatoid arthritis patients." Br J Rheumatol 34 (1995): 421-8
  21. Wallace CA, Smith AL, Sherry DD "Pilot investigation of naproxen/methotrexate interaction in patients with juvenile rheumatoid arthritis." J Rheumatol 20 (1993): 1764-8
  22. Franck H, Rau R, Herborn G "Thrombocytopenia in patients with rheumatoid arthritis on long-term treatment with low dose methotrexate." Clin Rheumatol 15 (1996): 163-7
  23. "Product Information. Arthrotec (diclofenac-misoprostol)." Searle PROD (2001):
  24. Karim A, Tolbert DS, Hunt TL, Hubbard RC, Harper KM, Geis GS "Celecoxib, a specific COX-2 inhibitor, has no significant effect on methotrexate pharmacokinetics in patients with rheumatoid arthritis." J Rheumatol 26 (1999): 2539-43
  25. Matheson AJ, Figgitt DP "Rofecoxib - A review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis." Drugs 61 (2001): 833-65
  26. Schwartz JI, Agrawal NG, Wong PH, et al. "Lack of pharmacokinetic interaction between rofecoxib and methotrexate in rheumatoid arthritis patients." J Clin Pharmacol 41 (2001): 1120-30
  27. Hartmann SN, Rordorf CM, Milosavljev S, et al. "Lumiracoxib does not affect methotrexate pharmacokinetics in rheumatoid arthritis patients." Ann Pharmacother 38 (2004): 1582-7
  28. Vakily M, Amer F, Kukulka MJ, Andhivarothai N "Coadministration of lansoprazole and naproxen does not affect the pharmacokinetic profile of methotrexate in adult patients with rheumatoid arthritis." J Clin Pharmacol 45 (2005): 1179-86
  29. EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid" (2007):
View all 29 references

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Drug and food interactions

Moderate

methotrexate food

Applies to: Methotrexate LPF Sodium (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

ibuprofen food

Applies to: Motrin Pediatric (ibuprofen)

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn PROD (2002):

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Moderate

methotrexate food

Applies to: Methotrexate LPF Sodium (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: Methotrexate LPF Sodium (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.

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