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Drug Interactions between deferasirox and Rheumatrex Dose Pack

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

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Interactions between your drugs

Major

methotrexate deferasirox

Applies to: Rheumatrex Dose Pack (methotrexate) and deferasirox

MONITOR CLOSELY: Theoretical concerns exist regarding the potential for increased risk of renal impairment during coadministration of deferasirox with other nephrotoxic agents. The use of deferasirox has been associated with postmarketing reports of acute renal failure, in some cases resulting in dialysis or even fatality. Most fatalities occurred in patients with multiple comorbidities and who were in advanced stages of their hematological disorders. In clinical studies, patients treated with deferasirox experienced dose-dependent increases in serum creatinine. These increases occurred at a greater frequency than in deferoxamine-treated patients (38% vs. 14%, respectively, in one study and 36% vs. 22%, respectively, in another study). Most of the creatinine elevations remained within the normal range. There have also been reports of renal tubulopathy in patients treated with deferasirox. The majority of these patients were children and adolescents with beta-thalassemia and serum ferritin levels below 1500 mcg/L. Deferasirox has not been studied for use in patients with baseline serum creatinine above the upper limit of normal.

MANAGEMENT: Caution is advised if deferasirox is used in combination with other potentially nephrotoxic agents (e.g., aminoglycosides; polypeptide, glycopeptide, and polymyxin antibiotics; amphotericin B; adefovir; cidofovir; tenofovir; foscarnet; cisplatin; gallium nitrate; lithium; mesalamine; certain immunosuppressants; intravenous bisphosphonates; intravenous pentamidine; high intravenous dosages of methotrexate; high dosages and/or chronic use of nonsteroidal anti-inflammatory agents). Serum creatinine and/or creatinine clearance should be closely monitored (e.g., prior to initiation of deferasirox therapy, then weekly during the first month after initiation or modification of therapy and monthly thereafter), especially in the elderly and patients with preexisting renal impairment, comorbid conditions, dehydration, or severe infections. Dosage reduction, interruption, or discontinuation should be considered in the presence of creatinine elevations. A progressive increase in serum creatinine beyond the age-appropriate upper limit of normal may warrant an interruption of therapy. Once the creatinine has returned to within the normal range, therapy may be reinitiated at a lower dose followed by a gradual dose escalation according to the product labeling, provided the clinical benefit is expected to outweigh potential risks. In clinical studies, the daily dosage of deferasirox was reduced by 10 mg/kg for increases of serum creatinine on two consecutive measures (i.e., >33% in patients older than 15 years of age, or >33% and greater than the age-appropriate upper limit of normal in patients younger than 15 years of age). Care should be taken to maintain adequate hydration in patients who develop diarrhea or vomiting.

References

  1. "Product Information. Exjade (deferasirox)." Novartis Pharmaceuticals (2005):
  2. Rafat C, Fakhouri F, Ribeil JA, Delarue R, Le Quintrec M "Fanconi Syndrome Due to Deferasirox." Am J Kidney Dis (2009):

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Drug and food interactions

Moderate

methotrexate food

Applies to: Rheumatrex Dose Pack (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

deferasirox food

Applies to: deferasirox

ADJUST DOSING INTERVAL: According to product labeling, the bioavailability of deferasirox was variably increased when taken with a meal.

MANAGEMENT: To ensure consistent plasma drug levels, deferasirox should be taken on an empty stomach 30 minutes before eating preferably at the same time everyday.

References

  1. "Product Information. Exjade (deferasirox)." Novartis Pharmaceuticals (2005):

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Moderate

methotrexate food

Applies to: Rheumatrex Dose Pack (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: Rheumatrex Dose Pack (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.

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