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Drug Interactions between Azo-Truxazole and Xatmep

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

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Interactions between your drugs

Moderate

methotrexate sulfiSOXAZOLE

Applies to: Xatmep (methotrexate) and Azo-Truxazole (phenazopyridine / sulfisoxazole)

MONITOR: Sulfonamide antibiotics may potentiate the toxicities of methotrexate, possibly by interfering with the plasma protein binding and/or renal clearance of methotrexate and its toxic metabolite. In a study of nine children with acute lymphoblastic leukemia given intravenous or oral methotrexate, a single dose of sulfamethoxazole-trimethoprim (SMX-TMP) increased the free fraction of methotrexate (MTX) from an average of 37.4% to 52.2%. In addition, plasma clearance and renal clearance of free MTX decreased by nearly 40% and 54%, respectively, in the presence of SMX-TMP. These changes were determined to increase systemic exposure to MTX by an average of 66%. On the contrary, two other studies found no significant effect of SMX-TMP on the pharmacokinetics of MTX. The interaction has not been studied with other sulfonamide antibiotics. Because changes in renal function can sometimes occur during sulfonamide therapy, reduced MTX clearance is a possibility regardless of whether or not a pharmacokinetic interaction has been demonstrated.

MANAGEMENT: Caution is advised when methotrexate is used with sulfonamides. Complete blood counts, liver enzymes, and serum creatinine levels should be performed at baseline and periodically during treatment. Patients should be closely monitored for increased methotrexate adverse effects including nausea, vomiting, diarrhea, stomatitis, alopecia, anemia, bone marrow suppression (e.g., aplastic anemia, leukopenia, neutropenia, thrombocytopenia., pancytopenia), hepatotoxicity, and nephrotoxicity.

References

  1. Thomas MH, Gutterman LA "Methotrexate toxicity in a patient receiving trimethoprim-sulfamethoxazole." J Rheumatol 13 (1986): 440-1
  2. Frain JB "Methotrexate toxicity in a patient receiving trimethoprim-sulfamethoxazole." J Rheumatol 14 (1987): 176-7
  3. 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
  4. Thomas DR, Dover JS, Camp RD "Pancytopenia induced by the interaction between methotrexate and trimethoprim-sulfamethoxazole." J Am Acad Dermatol 17 (1987): 1055-6
  5. Jeurissen ME, Boerbooms AM, van de Putte LB "Pancytopenia and methotrexate with trimethoprim-sulfamethoxazole." Ann Intern Med 111 (1989): 261
  6. 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
  7. Beach BJ, Woods WG, Howell SB "Influence of co-trimoxazole on methotrexate pharmacokinetics in children with acute lymphoblastic leukemia." Am J Pediatr Hematol Oncol 3 (1981): 115-9
  8. Verbov JL "Methotrexate and trimethoprim-sulfamethoxazole." Clin Exp Dermatol 16 (1991): 231
  9. Govert JA, Patton S, Fine RL "Pancytopenia from using trimethoprim and methotrexate." Ann Intern Med 117 (1992): 877-8
  10. "Product Information. Rheumatrex (methotrexate)." Lederle Laboratories PROD (2002):
  11. "Product Information. Bactrim (sulfamethoxazole-trimethoprim)." Roche Laboratories (2022):
  12. "Product Information. Sulfadiazine (sulfadiazine)." Eon Labs Manufacturing Inc PROD (2001):
  13. Ferrazzini G, Klein J, Sulh H, Chung D, Griesbrecht E, Koren G "Interaction between trimethoprim-sulfamethoxazole and methotrexate in children with leukemia." J Pediatr 117 (1990): 823-6
  14. Bannwarth B, Pehourcq F, Schaeverbeke T, Dehais J "Clinical pharmacokinetics of low-dose pulse methotrexate in rheumatoid arthritis." Clin Pharmacokinet 30 (1996): 194-210
  15. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
View all 15 references

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Moderate

methotrexate phenazopyridine

Applies to: Xatmep (methotrexate) and Azo-Truxazole (phenazopyridine / sulfisoxazole)

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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Drug and food interactions

Moderate

methotrexate food

Applies to: Xatmep (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: Xatmep (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: Xatmep (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.

See also

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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.

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