Kanamycin Methotrexate

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... 

Macrocyclic antibiotics The multiple chiral atoms and several functional groups allow multiple interactions with the analytes to enable chiral recognition. The primary interaction is ionic secondary interactions include hydrogen bonding, dipole-dipole, n-n, hydrophobic interactions, and steric repulsion. Rifamycin B, rifamycin SV, ristocetin A, teicoplanin, fradiomycin, kanamycin, ansamycins, avoparcin, and vancomycin. Amephoterin, a-aminoadipic acid, flurbiprofen, fenoprofen, methionine, methotrexate, ketoprofen, and suprofen, etc. 

Noninterfering acetaminophen, allopurinol, amikacin, amoxapine, amytal, bretylium, caffeine, carbamazepine, carisoprodol, chloramphenicol, chlordiazepoxide, chlorpropamide, clonazepam, codeine, diazepeun, disop30 amide, droperidol, ethinamate, ethinamate, etho-suximide, fluphenazine, flurazepam, furosemide, gentamicin, haloperidol, hydrochlorothiazide, hydro yzine, ibuprofen, kanamycin, lidocaine, loxapine, meperidine, mepho-barbital, meprobamate, methaqualone, methotrexate, morphine, nafcUlin, naloxone, neomycin, perphenazine, phenacetin, phenobarbital, phenytoin, prazepam, primidone, procaine, propoxyphene, reserpine, salicylamide, salicylic acid, secobarbital, spironolactone, theophyUine, thiopental, thioridazine, tobramycin, valproic acid, verapeunil... 

Noninterfering acetaminophen, N-acetylprocainamide, amikacin, caffeine, carbamaze-pine, chloramphenicol, clonazepam, cyclosporine, diazepam, digoxin, disopyramide, etho-suximide, flurazepam, gentamicin, haloperidol, kanamycin, lidocaine, meprobamate, methapyriline, methaqualone, methotrexate, methyprylon, netilmicin, pentazocine, pentobarbital, phenobarbital, phenytoin, prazepam, primidone, procainamide, propranolol, quinidine, salicylic acid, secobarbital, streptomycin, theophylline, tobramycin, tocainide, valproic acid, vancomycin... 

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

A study in 10 patients with small cell bronchogenic carcinoma taking methotrexate found that when they were also given a range of oral anti-in-feetives (paromomycin, vancomycin, polymyxin B, nystatin) the urinary recovery of methotrexate was reduced by over one-third (from 69% to 44%). The paromomycin was believed to have been responsible. In another study the concurrent use of neomycin 500 mg four times a day for 3 days reduced the methotrexate AUC and the 72-hour cumulative excretion by 50%. In contrast, the same report suggests that kanamycin can increase the absorption of methotrexate, but no details are given. 

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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