Allopurinol interaction

Cummins D, Sekar M, Halil C, Banner N. Myelosuppression associated with azathioprine-allopurinol interaction after heart and lung transplantation. Transplantation (1996) 61,1661-2. 

A study in 5 kidney transplant patients with gouty arthritis, who were switched from azathioprine to myeophenolate mofetil 2 g daily (to avoid the risk of an azathioprine/allopurinol interaction), found that no adverse effects occurred when they were given allopurinol 100 or 200 mg daily. On average, 10 weeks after the switch had taken place, uricaemia had fall-... 

Azathioprine, mycophenolate mofetil, and enteric-coated MPA are not metabolized through the CYP isozyme system therefore, they do not experience the same DDI profiles as cyclosporine, tacrolimus, and sirolimus. Azathioprine s major DDIs involve allopurinol, angiotensin-converting enzyme (ACE) inhibitors, aminosalicylates (e.g., mesalamine and sulfasalazine), and warfarin.11 The interaction with allopurinol is seen frequently and has clinical significance. Allopurinol inhibits xanthine oxidase, the enzyme responsible for metabolizing azathioprine. Combination of azathioprine and allopurinol has resulted in severe toxicities, particularly myelosuppression. It is recommended that concomitant therapy with azathioprine and allopurinol be avoided, but if combination therapy is necessary, the azathioprine doses must be reduced to one-third or one-fourth of the current dose. Use of azathioprine with the ACE inhibitors or aminosalicylates also can result in enhanced myelosuppression.11 Some case reports exist demonstrating that warfarin s therapeutic effects may be decreased by azathioprine.43-45... 

There are several important drug-drug interactions with allopurinol. The effects of both theophylline and warfarin may be potentiated by allopurinol. Azathioprine and 6-mercaptopurine are purines whose metabolism is inhibited... 

Oral allopurinol (Zyloprim ) Adult 600-800 mg/day in 2-3 divided doses Child 10 mg/kg per day or 200-300 mg/m2 per day Adult 200-400 mg/m2 per day Child 200 mg/m2 per day 0.48/day (generic) Adjust dose for renal impairment. Avoid drug interactions (mercaptopurine). Monitor for skin rash. 

Evaluate the patient for drug interactions, allergies, and adverse effects of allopurinol or rasburicase. 

Mercaptopurine [6-MP] (Purinethol) [Antineoplastic/ Antimeta lite] Uses Acute leukemias, 2nd-line Rx of CML NHL, maint ALL in children, immunosuppressant w/ autoimmune Dzs (Crohn Dz) Action Antimetabolite, mimics hypoxanthine Dose Adults. 80-100 mg/mVd or 2.5-5 mg/kg/d maint 1.5-2.5 mg/kg/d Peds. Per protocol X w/ renal/hepatic insuff on empty stomach Caution [D, ] Contra Severe hepatic Dz, BM suppression, PRG Disp Tabs SE Mild hematotox, mucositis, stomatitis, D rash, fever, eosinophilia, jaundice. Hep Interactions T Effects W/ allopurinol T risk of BM suppression W/ trimethoprim-sulfamethoxazole X effects OF warfarin EMS May falsely T glucose OD May cause NA and liver necrosis symptomatic and supportive Meropenem (Merrem) [Antibiotic/Carbapenem] Uses lntra-abd Infxns, bacterial meningitis Action Carbapenem X cell wall synth, a [3-lactam Dose Adults. 1 to 2 g IV q8h Peds. >3 mo, <50 kg 10-40 mg/kg IV q 8h in renal insuff Caution [B, ] Contra [3-Lactam sensitivity Disp Inj 500 mg, 1 g SE Less Sz potential than imipenem D, thrombocytopenia Interactions T Effects W/ probenecid EMS Monitor for signs of electrolyte disturbances and... 

Phenytoin (Dilantin) [Anticenvulsant/Hydantoin] Uses Sz disorders Action X Sz spread in the motor cortex Dose Load Adults Peds. 15-20 mg/kg IV, 25 mg/min max or PO in 400-mg doses at 4-h intervals Maint Adults. Initial, 200 mg PO or IV bid or 300 mg hs then follow levels Peds. 4-7 mg/kg/24h PO or IV -s- daily-bid avoid PO susp (erratic absorption) Caution [D, +] Contra Heart block, sinus bradycardia Disp Caps, susp, inj SE Nystag-mus/ataxia early signs of tox gum hyperplasia w/ long-term use. IV BP, bradycardia, arrhythmias, phlebitis peripheral neuropathy, rash, blood dyscrasias, Stevens-Johnson synd Notes Levels Trough Just before next dose Therapeutic Peak 10-20 mcg/mL Toxic >20 mcg/mL phenytoin albumin bound, levels = bound free phenytoin w/ i albumin azotemia, low levels may be therapeutic (nl free levels) Interactions T Effects W/ amiodarone, allopurinol, chloramphenicol, disulfiram, INH, omeprazole, sulfonamides, quinolones, trimethoprim t... 

MP is converted to an inactive metabolite (6-thiouric acid) by an oxidation reaction catalyzed by xanthine oxidase, whereas 6-TG undergoes deamination. This is an important issue because the purine analog allopurinol, a potent xanthine oxidase inhibitor, is frequently used as a supportive care measure in the treatment of acute leukemias to prevent the development of hyperuricemia that often occurs with tumor cell lysis. Because allopurinol inhibits xanthine oxidase, simultaneous therapy with allopurinol and 6-MP would result in increased levels of 6-MP, thereby leading to excessive toxicity. In this setting, the dose of mercaptopurine must be reduced by 50-75%. In contrast, such an interaction does not occur with 6-TG, which can be used in full doses with allopurinol. 

Drug Interactions Allopurinol Agents affecting myelopoiesis Angiotensin converting enzyme inhibitors... 

Probenecid has been reported to inhibit renal elimination of many drugs acyclovir (325,326), allopurinol (327), bumetanide (328), cephalosporins (329-334), cidofovir (335), ciprofloxacin (336), famotidine (337), fexofenadine (338), furosemide (339), and oseltamivir (Ro 64-0802) (340). Recent studies have elucidated that probenecid is a potent inhibitor of renal organic anion transporters (OAT1 and OAT3) with the Ki values lower than the unbound plasma concentration of probenecid, indicating the interaction with probenecid includes inhibition of the basolateral uptake process mediated by OAT1 and/or OAT3. 

Kennedy DT, Hayney MS, Lake KD. Azathioprine and allopurinol the price of an avoidable drag interaction. Ann Pharmacother 1996 30 951-954. 

The retinal lesions caused by direct visual sun exposure are similar to those caused by less direct ultraviolet light, as well as by mild but repeated solar interactions over many years, which occur in many of the elderly. In addition, the recent diminishing level of atmospheric ozone may add to these problems, especially in the future if its concentration continues to diminish. Moreover, numerous drugs, including phenothiazines, tetracycline, and allopurinol, are photosensitizers, which may further add to the problem in some individuals. 

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