Trexan Drug Interactions

Methotrexate is extensively protein bound and may displace, or be displaced by, other acidic drugs. The concurrent administration of agents such as diphenylhydantoins, acidic anti-inflammatory agents, salicylates, phenylbutazone, phenytoin, barbiturates, tranquilisers, oral contraceptives, amidopyrine derivatives, p-aminobenzoic acid, thiazide diuretics, oral hypoglycaemics, doxorubicin,, tetracyclines, probenecid or sulfinpyrazone or oral hypoglycaemics will decrease the methotrexate transport function of renal tubules, thereby reducing excretion and almost certainly increasing methotrexate toxicity.
Since probenecid and weak organic acids, such as "loop-diuretics" as well as pyrazoles reduce tubular secretion, great caution should be exercised when these medicinal products are coadministered with methotrexate.
Concurrent use of other, potentially nephro-, hemato- or hepatotoxic agents (e.g. sulphasalazine, leflunomide and alcohol) should be avoided. Special caution should be exercised when observing patients receiving methotrexate therapy in combination with azathioprine or retinoids.
Methotrexate in combination with leflunomide can increase the risk for pancytopenia.
Enhancement of nephrotoxicity may be seen if high-dose methotrexate is administered in combination with a potentially nephrotoxic chemotherapeutic agent (e.g. cisplatin).
Antibiotics, like penicillin, glycopeptides, sulfonamides, ciprofloxacin and cefalotin can, in individual cases, reduce the renal clearance of methotrexate, so that increased serum concentrations of methotrexate with simultaneous haematological and gastro-intestinal toxicity may occur.
Oral antibiotics such as tetracyclines, chloramphenicol and non-absorbable broad-spectrum antibiotics may reduce intestinal methotrexate absorption or interfere with the enterohepatic circulation, due to inhibition of the intestinal flora or suppression of bacterial metabolism.
Methotrexate dosage should be monitored if concomitant treatment with aspirin, ibuprofen or indomethacin (NSAID's) is commenced, as concomitant use of NSAID's has been associated with fatal methotrexate toxicity.
Hepatic, hematotoxic and nephrotoxic drugs should be avoided.
Vitamin preparations or other products containing folic acid or its derivatives may impair methotrexate efficacy.
Under (pre-) treatment with substances that may have adverse effects on the bone marrow (e.g. sulfonamides, trimethoprim-sulfamethoxazole, chloramphenicol, pyrimethamine), the possibility of marked haematopoietic disorders should be considered.
Co-administration of medicinal products which cause folate deficiency (e.g. sulfonamides, trimethoprim-sulfamethoxazole) can lead to increased methotrexate toxicity. Particular caution should therefore also be exercised in the presence of existing folic acid deficiency.
Acitretin (a treatment for psoriasis) is metabolised to etretinate. Methotrexate levels may be increased by etretinate and severe hepatitis has been reported following concomitant use.
Bone marrow suppression and decreased folate levels have been described in the concomitant administration of triamterene and methotrexate.
Administration of additional haematotoxic medicinal products (e.g. metamizole) increases the probability of severe haematoxic effects of methotrexate.
There is evidence that co-administration of methotrexate and omeprazole prolongs the elimination of methotrexate via kidneys. Co-administration of proton pump inhibitors such as omeprazole or pantoprazole can cause interactions. In combination with pantoprazole, inhibited renal elimination of the 7-hydroxymethotrexate metabolite, with myalgia and shivering, was reported in one case.
Methotrexate may decrease the clearance of theophylline; theophylline levels should be monitored when used concurrently with methotrexate. Excessive consumption of beverages containing caffeine or theophylline (coffee, soft drinks containing caffeine, black tea) should be avoided during methotrexate therapy since the efficacy of methotrexate may be reduced due to possible interaction between methotrexate and methylxanthines at adenosine receptors.
One should be aware of pharmacokinetic interactions between methotrexate, anticonvulsant medicinal products (reduced methotrexate blood levels), and 5-fluorouracil (increased t½ of 5--fluorouracil).
The use of nitrous oxide potentiates the effect of methotrexate on folate metabolism, yielding increased toxicity such as severe, unpredictable myelosuppression and stomatitis. Whilst this effect can be reduced by administering calcium folinate, the concomitant use of nitrous oxide and methotrexate should be avoided.
Colestyramine can increase the non-renal elimination of methotrexate by interrupting the enterohepatic circulation.
Delayed methotrexate clearance should be considered in combination with other cytostatic medicinal products.
The application of procarbazine during high-dose methotrexate therapy increases the risk of impairment or renal function.
Radiotherapy during use of methotrexate can increase the risk of soft tissue or bone necrosis.
Methotrexate increases plasma levels of mercaptopurine. Combinations of methotrexate and mercaptopurine may therefore require dose adjustment.
Vaccination with a live vaccine in patients receiving chemotherapeutic agents may result in severe and fatal infections (see Contraindications). On account of its possible effect on the immune system, methotrexate can falsify vaccinal and test results (immunological procedures to record the immune reaction). During methotrexate therapy concurrent vaccination with live vaccines must not be carried out (see Contraindications and Precautions).
Cytotoxic agents may impair absorption of phenytoin, which may decrease efficacy of phenytoin and increase the risk for exacerbation of convulsions. Risk of toxicity enhancement or loss of efficacy of the cytotoxic drug due to increased hepatic metabolism by phenytoin is possible.
Ciclosporin may potentiate methotrexate efficacy and toxicity. There is a risk of excessive immunosuppression with risk of lymphoproliferation when the combination is used.
Particularly in the case of orthopaedic surgery where susceptibility to infection is high, a combination of methotrexate with immune-modulating medicinal products must be used with caution.
Concomitant administration of levetiracetam and methotrexate has been reported to decrease methotrexate clearance, resulting in increased/prolonged blood methotrexate concentration to potentially toxic levels. Blood methotrexate and levetiracetam levels should be carefully monitored in patients treated concomitantly with the two drugs.