Mercaptopurine Methotrexate

Although the published data are not consistent, there is evidence to suggest that azathioprine, mercaptopurine, methotrexate, infliximab, and adalimumab are effective in maintaining remission in Crohn s disease. 

Hydrolysis azathioprine benorylate diazepam diphenhydramine frusemide furazolidone nitrofurantoin menaquinone-4 mercaptopurine methotrexate nalidixic acid nicotinamide nicotine nicotinic acid nifedipine... 

Reduction chloramphenicol cinchonidine cinchonine nitrazepam physostigmine pyrithione quinidine quinine benzoxaprofen chlortetracycline demeclocycline dithranol menadione mercaptopurine methotrexate nalidixic acid oxolinic acid... 

Schmiegelow K, Bjork O, Glomstein A et al. Intensification of mercaptopurine/methotrexate maintenance chemotherapy may increase the risk of relapse for some children with acute lymphoblastic leukemia. JC/rri Onco/2003 21 1332-1339. 

Andersen JB, Szumlanski C, Weinshilboum RM et al. Pharmacokinetics, dose adjustments, and 6-mercaptopurine/methotrexate drug interactions in two patients with thiopurine methyltransferase deficiency. Acta Paediatr 1998 87 108-111. 

Therapeutic pyramid approach to inflammatory bowel diseases. Treatment choice is predicated on both the severity of the illness and the responsiveness to therapy. Agents at the bottom of the pyramid are less efficacious but carry a lower risk of serious adverse effects. Drugs may be used alone or in various combinations. Patients with mild disease may be treated with 5-aminosalicylates (with ulcerative colitis or Crohn s colitis), topical corticosteroids (ulcerative colitis), antibiotics (Crohn s colitis or Crohn s perianal disease), or budesonide (Crohn s ileitis). Patients with moderate disease or patients who fail initial therapy for mild disease may be treated with oral corticosteroids to promote disease remission immunomodulators (azathioprine, mercaptopurine, methotrexate) to promote or maintain disease remission or anti-TNF antibodies. Patients with moderate disease who fail other therapies or patients with severe disease may require intravenous corticosteroids, anti-TNF antibodies, or surgery. Natalizumab is reserved for patients with severe Crohn s disease who have failed immunomodulators and TNF antagonists. Cyclosporine is used primarily for patients with severe ulcerative colitis who have failed a course of intravenous corticosteroids. TNF, tumor necrosis factor. 

Purine analogs and antimetabolites, eg, 6-mercaptopurine, methotrexate Mechanism uncertain may promote apoptosis of immune cells Generalized suppression of immune processes Moderately severe to severe Crohn s disease and ulcerative colitis GI upset, mucositis myelosuppression purine analogs may cause hepatotoxicity, but rare with methotrexate at the low doses used... 

Acute lymphocytic leukemia Induction vincristine plus prednisone. Remission maintenance mercaptopurine, methotrexate, and cyclophosphamide in various combinations Asparaginase, daunorubicin, carmustine, doxorubicin, cytarabine, allopurinol,1 craniospinal radiotherapy... 

Antineoplastic drugs such as 6-mercaptopurine, methotrexate, cyclophosphamide, and aminopterin administered in early pregnancy have produced various congenital malformations. Cytotoxic drugs also have induced fetal malformation and early abortion of malformed fetuses (4-6). 

Mercaptopurine Methotrexate Oral contraceptives p-Ami nosalicylate Phenobarbital Phenyloin Primidone Pyrimethamine Sulfasalazine Tetracycline Vinblastine... 

MERCAPTOPURINE METHOTREXATE-ORAL t plasma concentrations of mercaptopurine (t AUC by 30%) and t risk of myelotoxicity Methotrexate t oral bioavailability of mercaptopurine 1 dose of oral 6-mercaptopurine when used with doses of methotrexate >20 mg/m2 or higher doses of methotrexate given intravenously... 

A 36-year-old man with Crohn s disease became refractory to standard anti-inflammatory treatment (glucocorticoids, mercaptopurine, methotrexate, ciclosporin, tacrolimus) (33). Remission over 8 months was achieved with a single infusion of infliximab. With the onset of relapse he was given another infusion of infliximab and had an anaphylactic-Uke reaction within 1 minute. 

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... 

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

Reabsorption of purine metabolites occurs at high urinary pH An adult patient is being treated for acute leukemia with a combination of anticancer dmgs that includes cyclophosphamide, mercaptopurine, methotrexate, vincristine, and prednisone. He is also using dronabinol for emesis, a chlorhexidine mouthwash to reduce mucositis, and laxatives. The patient complains of pins and needles sensations in the extremities and muscle weakness. He is not able to execute a deep knee bend or get up out of a chair without using his arm muscles. He is also very constipated. If these problems are related to the chemotherapy, the most likely causative agent is (A) Cyclophosphamide Dronabinol Mercaptopurine Prednisone Vincristine... 

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