Methotrexate Aminoglycosides

Drugs that may be affected by NSAIDs include the following Aminoglycosides, anticoagulants, ACE inhibitors, beta blockers, cyclosporine, dextromethorphan, digoxin, dipyridamole, hydantoins, lithium, loop diuretics, methotrexate, penicillamine, potassium-sparing diuretics, sympathomimetics, theophylline, thiazide diuretics. 

Drugs that may be affected by aminoglycosides include anticoagulants, digoxin, methotrexate, neuromuscular blockers (depolarizing and nondepolarizing). 

Drugs that may affect methotrexate include oral aminoglycosides, charcoal, chloramphenicol, folic acid, NSAIDs, PCNs, probenecid, salicylates, sulfonamides, TCN, trimethoprim. 

METHOTREXATE -ORAL NEOMYCIN 1 plasma concentrations following oral methotrexate Oral aminoglycosides 1 absorption of oral methotrexate by 30-50% Separate doses of each drug by at least 2-4 hours... 

However, renal toxicity occurs with high-dose methotrexate and more likely to occur with concomitant administration of other nephrotoxic agents, such as aminoglycosides, cephalosporins, NSAIDs, and diuretics (60). 

Tubular cell toxicity This involves the cellular transport systems mentioned previously and is thus dose dependent to a degree. Examples of tubular cell toxins include aminoglycosides, calcineurin inhibitors, amphotericin, antiviral agents, cisplatin, methotrexate, contrast agents and cocaine. 

Clinically important, potentially hazardous interactions with altretamine, amikacin, aminoglycosides, antineoplastics, bleomycin, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, corticosteroids, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, docetaxel, doxorubicin, estramustine, etoposide, fludarabine, fluorouracil, gemcitabine, gentamicin, hydroxyurea, idarubicin, ifosfamide, indomethacin, kanamycin, levamisole, lomustine, mechlorethamine, melphalan, mercaptopurine, methotrexate, mitomycin, mitotane, mitoxantrone, neomycin, pentostatin, plicamycin, procarbazine, streptomycin, streptozocin, thioguanine, thiotepa, tobramycin, tretinoin, uracil, vinblastine, vincristine, vinorelbine... 

Probenecid but not cidofovir alters zidovudine pharmacokinetics such that zidovudine doses should be reduced when probenecid is present, as should the doses of drugs similarly affected by probenecid fe.g., /i-lactam antibiotics, nonsteroidal anti-inflammatory drugs [NSAIDs], acyclovir, lorazepam, furosemide, methotrexate, theophylline, and rifampin). Concurrent nephrotoxic agents are contraindicated, and an interval of 1 week before beginning cidofovir treatment is recommended after prior exposure to aminoglycosides, intravenous pentamidine, amphotericin foscamet, NSAIDs, or contrast dye. Cidofovir and oral ganciclovir in combination are poorly tolerated at full doses. 

There is evidence that the gastrointestinal absorption of methotrexate can be reduced by paromomycin, neomycin and possibly other oral aminoglycosides, but increased by kanamycin. 

Oral aminoglycosides reduce the activity of the gut flora, which metabo-lise methotrexate so that more is available for absorption. However, paromomycin and neomycin, in common with other oral aminoglycosides, can cause a malabsorption syndrome, which reduces drug absorption and presumably negates any effect altering the gut flora has. Kanamycin may possibly be different because it causes less malabsorption. 

The documentation of these interactions is sparse, but it would seem prudent to be on the alert for a reduction in the response to methotrexate if patients are given oral aminoglycosides such as paromomycin or neomycin. An increased response may possibly occur with kanamycin. No interaction would be expected if aminoglycosides are given parenterally. 

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