This panel provides information on interacting drugs and their ADRs along with references
| Interacting drug |
Toxicity |
Interaction Type |
Mechanism |
Reference |
|---|
| Acetylsalicylic acid (50-78-2) | Pancytopenia | Synergistic | salicylates competitively inhibit the tubular secretion of methotrexate, which would further reduce its clearance | The effect of organic acids on renal clearance of methotrexate in man
|
| Aminopyrine (58-15-1) | Pancytopenia | Synergistic | Methotrexate is largely cleared unchanged from the body by renal excretion. The NSAIDs as a group inhibit the synthesis of the prostaglandins (PGE2) resulting in a fall in renal perfusion, which could lead to a rise in serum methotrexate levels | Megaloblastic pancytopenia in a female patient with rheumatoid arthritis given methotrexate and amidopyrine simultaneously
|
| Amoxicillin (26787-78-0) | Aplastic Anaemia | Synergistic | compete with methotrexate in the kidney tubules for excretion so that the methotrexate is retained, | Pharmacokinetic interaction between high-dose methotrexate and amoxycillin
|
| Amoxicillin (26787-78-0) | Pneumonitis | Synergistic | compete with methotrexate in the kidney tubules for excretion so that the methotrexate is retained, | Pharmacokinetic interaction between high-dose methotrexate and amoxycillin
|
| Amoxicillin (26787-78-0) | Thrombocytopenia | Synergistic | compete with methotrexate in the kidney tubules for excretion so that the methotrexate is retained, | Pharmacokinetic interaction between high-dose methotrexate and amoxycillin
|
| Amphotericin B (1397-89-3) | Renal Impairment | Synergistic | Not clear | Renal function and methotrexate clearance in children with newly diagnosed leukemia
|
| Apazone (13539-59-8) | Bone Marrow Failure | Synergistic | The NSAIDs as a group inhibit the synthesis of the prostaglandins (PGE2) resulting in a fall in renal perfusion, which could lead to a rise in serum methotrexate levels | Methotrexate toxicity precipitated by azapropazone
|
| Apazone (13539-59-8) | Genital Ulceration | Synergistic | The NSAIDs as a group inhibit the synthesis of the prostaglandins (PGE2) resulting in a fall in renal perfusion, which could lead to a rise in serum methotrexate levels | Methotrexate toxicity precipitated by azapropazone
|
| Apazone (13539-59-8) | Oral Ulceration | Synergistic | The NSAIDs as a group inhibit the synthesis of the prostaglandins (PGE2) resulting in a fall in renal perfusion, which could lead to a rise in serum methotrexate levels | Methotrexate toxicity precipitated by azapropazone
|
| Cefotiam (61622-34-2) | Pancytopenia | Synergistic | Not understood | Pancytopenia and Colitis with Clostridium difficile in a Rheumatoid Arthritis Patient Taking Methotrexate, Antibiotics and Non-steroidal Anti-inflammatory Drugs
|
| Ciprofloxacin (85721-33-1) | Renal Impairment | Synergistic | Not fully understood. Ciprofloxacin may displace methotrexate from its plasma-protein binding sites resulting in a rise in levels of unbound methotrexate. Ciprofloxacin may also cause a decrease in renal clearance of methotrexate | Interaction Between Methotrexate and Ciprofloxacin
|
| Ciprofloxacin (85721-33-1) | Skin Toxicity | Synergistic | Not fully understood. Ciprofloxacin may displace methotrexate from its plasma-protein binding sites resulting in a rise in levels of unbound methotrexate. Ciprofloxacin may also cause a decrease in renal clearance of methotrexate | Interaction Between Methotrexate and Ciprofloxacin
|
| Cisplatin (15663-27-1) | Renal Failure | Synergistic | Not clear | Methotrexate-related deaths in patients previously treated with cis-diamminedichloride platinum
|
| Dexamethasone (50-02-2) | Hepatotoxicity | Antagonistic | Not understood | Dexamethasone increases hepatotoxicity of MTX in children with brain tumors
|
| Doxorubicin (23214-92-8) | Cardiotoxicity | Synergistic | Not understood | Adriamycin and mitomycin C: possible synergistic cardiotoxicit
|
| Doxycycline (564-25-0) | Diarrhoea | Synergistic | Displacement of the methotrexate from its binding sites | High-dose methotrexate-doxycycline interaction
|
| Doxycycline (564-25-0) | Ulcerative Stomatitis | Synergistic | Displacement of the methotrexate from its binding sites | High-dose methotrexate-doxycycline interaction
|
| Etretinate (54350-48-0) | Hepatotoxicity | Synergistic | Not understood | Methotrexate and retinoids in combination for psoriasis
|
| Flurbiprofen (5104-49-4) | Haematemesis | Synergistic | The NSAIDs as a group inhibit the synthesis of the prostaglandins (PGE2) resulting in a fall in renal perfusion, which could lead to a rise in serum methotrexate levels | Methotrexate and nonsteroidal antiinflammatory drug interactions
|
| Flurbiprofen (5104-49-4) | Neutropenia | Synergistic | The NSAIDs as a group inhibit the synthesis of the prostaglandins (PGE2) resulting in a fall in renal perfusion, which could lead to a rise in serum methotrexate levels | Methotrexate and nonsteroidal antiinflammatory drug interactions
|
| Flurbiprofen (5104-49-4) | Thrombocytopenia | Synergistic | The NSAIDs as a group inhibit the synthesis of the prostaglandins (PGE2) resulting in a fall in renal perfusion, which could lead to a rise in serum methotrexate levels | Methotrexate and nonsteroidal antiinflammatory drug interactions
|
| Ibuprofen (15687-27-1) | Nephrotoxicity | Synergistic | The NSAIDs as a group inhibit the synthesis of the prostaglandins (PGE2) resulting in a fall in renal perfusion, which could lead to a rise in serum methotrexate levels | Serious methotrexate toxicity caused by interaction with ibuprofen
|
| Indomethacin (53-86-1) | Renal Failure | Synergistic | The NSAIDs as a group inhibit the synthesis of the prostaglandins (PGE2) resulting in a fall in renal perfusion, which could lead to a rise in serum methotrexate levels | Acute renal failure and death following sequential intermediate-dose methotrexate and 5-FU: a possible adverse effect due to concomitant indomethacin administration
|
| Nitrous oxide (10024-97-2) | Stomatitis | Additive | the effects of methotrexate on tetrahydrofolate metabolism are increased by nitrous oxide | Toxicity of methotrexate in rats preexposed to nitrous oxide
|
| Pantoprazole (102625-70-7) | Myalgia | Synergistic | Proton pump inhibitors may affect renal, and possibly hepatic, clearance of methotrexate by inhibition of methotrexate transporter proteins | Drug points: Severe myalgia from an interaction between treatments with pantoprazole and methotrexate
|
| Paromomycin (7542-37-2) | Malabsorption Syndrome | Antagonistic | Oral aminoglycosides reduce the activity of the gut flora, which metabolise methotrexate so that more is available for absorption. | Malabsorption due to paromomycin
|
| Phenylbutazone (50-33-9) | Bone Marrow Depression | Synergistic | The NSAIDs as a group inhibit the synthesis of the prostaglandins (PGE2) resulting in a fall in renal perfusion, which could lead to a rise in serum methotrexate levels | Drug interaction in psoriasis
|
| Phenylbutazone (50-33-9) | Septicaemia | Synergistic | The NSAIDs as a group inhibit the synthesis of the prostaglandins (PGE2) resulting in a fall in renal perfusion, which could lead to a rise in serum methotrexate levels | Drug interaction in psoriasis
|
| Pristinamycin (11006-76-1) | Anus Abnormal | Synergistic | Not understood | Severe Interaction Between Methotrexate and a Macrolide-Like Antibiotic
|
| Pristinamycin (11006-76-1) | Balanitis | Synergistic | Not understood | Severe Interaction Between Methotrexate and a Macrolide-Like Antibiotic
|
| Pristinamycin (11006-76-1) | Mucositis Oral | Synergistic | Not understood | Severe Interaction Between Methotrexate and a Macrolide-Like Antibiotic
|
| Pristinamycin (11006-76-1) | Neutropenia | Synergistic | Not understood | Severe Interaction Between Methotrexate and a Macrolide-Like Antibiotic
|
| Pristinamycin (11006-76-1) | Thrombocytopenia | Synergistic | Not understood | Severe Interaction Between Methotrexate and a Macrolide-Like Antibiotic
|
| Probenecid (57-66-9) | Pancytopenia | Synergistic | Probenecid inhibits the renal excretion of methotrexate | Inhibition of renal tubular transport of methotrexate by probenecid
|
| Triamterene (396-01-0) | Mucosal Ulceration | Additive | Triamterene is structurally similar to folate and has anti-folate activity, which may therefore have been additive with the effects of methotrexate | Methotrexate and triamterene--a potentially fatal combination?
|
| Triamterene (396-01-0) | Pancytopenia | Additive | Triamterene is structurally similar to folate and has anti-folate activity, which may therefore have been additive with the effects of methotrexate | Methotrexate and triamterene--a potentially fatal combination?
|
| Triamterene (396-01-0) | Renal Impairment | Additive | Triamterene is structurally similar to folate and has anti-folate activity, which may therefore have been additive with the effects of methotrexate | Methotrexate and triamterene--a potentially fatal combination?
|
| Trimethoprim (738-70-5) | Bone Marrow Depression | Synergistic | Not fully understood. Both drugs can suppress the activity of dihydrofolate reductase and it seems possible that they can act additively to produceproduce folate deficiency | Methotrexate and trimethoprim: a fatal interaction
|
| Vancomycin (1404-90-6) | Mucositis | Synergistic | Not understood | Significant impairment of high-dose methotrexate clearance following vancomycin administration in the absence of overt renal impairment
|