Methotrexate Aminophylline

Bleomycin Bleomycin is incompatible and loses its potency if it is administered with solutions of benzylpenicillin sodium, carbenicillin, cephazolin or cephalothin sodium, hydrocortisone sodium succinate, mitomycin, methotrexate, nafcillin sodium, aminophylline, ascorbic acid, terbutaline, divalent and trivalent cations (especially copper), compounds containing sulfhydryl groups, and precipitation by hydrophobic anions, essential amino acids, riboflavine, dexamethasone, and frusemide. 

Clinically important, potentially hazardous interactions with aminophylline, carbamazepine, cyclosporine, mercaptopurine, methotrexate, phenobarbital, prednisone, vincristine, warfarin... 

Clinically important, potentially hazardous interactions with aluminum, aminophylline, carbamazepine, carbimazole, cyclosporine, daclizumab, diuretics, etoposide, etretinate, grapefruit juice, indomethacin, isoniazid, itraconazole, ketoconazole, licorice, live vaccines, methotrexate, naproxen, oral contraceptives, pancuronium, phenobarbital, phenytoin, rifampicin, troleandomycin... 

The apparent elearanee of theophylline (given as oral aminophylline, eholine theophyllinate or theophylline) was reduced by 19% in 8 patients with severe, steroid-dependent asthma after 6 weeks of treatment with in-tramuseular methotrexate 15 mg weekly. Three patients complained of nausea and the theophylline dosage was reduced in one of them as the theophylline level was more than 20 mierograms/mL. ... 

Four of 6 patients aged 3 to 16 years with acute lymphoblastic leukaemia and high-dose methotrexate-induced neurotoxicity had a complete resolution of their symptoms when they were given a 2.5-mg/kg aminophylline infusion over 1 hour. The other 2 had some improvement in symptoms. One patient also had symptom relief with rapid-release theophylline. Similar results were reported for another child who developed neurotoxicity after receiving high-dose methotrexate. In this case, aminophylline was reported not to alter methotrexate levels. A patient with methotrexate-induced leukoencephalopathy recovered after being given a combination of intravenous folinic acid with intravenous aminophylline 145 mg daily for 7 days. ... 

The clinical importance of the small reduction in theophylline elearanee is uncertain, although it may be worth bearing this in mind in patients maintained at the higher end of the therapeutic levels for theophylline, as they may be more likely to develop toxicity. Aminophylline may reduce methotrexate-induced neurotoxicity, and, dthough there is some evidence that theophylline does not alter the cytotoxic effects of methotrexate, this requires confirmation. One UK manufacturer of methotrexate (licenced for... 

Bernini JC, Fort DW, Griener JC, Kane BJ, Chappell WB, Kamen BA. Aminophylline for methotrexate-induced neurotoxicity. Lancet (1995) 345, 544-7. 

Peyriere H, Poiree M, Cociglio M, Margueritte G, Hansel S, Hillaire-Buys D. Reversal of neu-rolc ic disturbances related to high-dose methotrexate by aminophylline. MedPediatr Oncol (2001) 36, 662-4. 

---