Probenecid Cisplatin

Drugs that may interact with zalcitabine include antacids, chloramphenicol, cisplatin, dapsone, didanosine, disulfiram, ethionamide, glutethimide, gold, hydralazine, iodoquinol, isoniazid, metronidazole, nitrofurantoin, phenytoin, ribavirin, vincristine, cimetidine, metoclopramide, amphotericin, aminoglycosides, foscarnet, antiretroviral nucleoside analogs, pentamidine, and probenecid. 

Uses w/ cisplatin in nonresectable mesothelioma NSCLC Action Antifolate antineoplastic Dose 500 mg/m IV over 10 min q3wk hold if CrCl <45 mLAnin give w/ vit Bi2 (1000 meg IM q9wk) folic acid (350-1000 meg PO daily) start 1 wk before dexamethasone 4 mg PO bid x 3 start 1 d before each Rx Caution [D, -] w/ renal/hepatic/ BM impair Contra Component sensitivity Disp IV SE Neutropenia, thrombocytopenia, N/V/D, anorexia, stomatitis, renal failure, neuropathy, fevCT, fatigue, mood changes, dyspnea, anaphylactic Rxns Interactions t Effects W/ NSAIDs, probenecid d/t decreased pemetrexed EMS Monitor for S/Sxs of Infxn OD May cause profound BM suppression, mucous membrane irritation, D, and rash symptomatic and supportive... 

Uses Edema, HTN, CHF, h atic cirrhosis Action Loop diuretic -1- reabsorption of Na Cr in ascending loop of Henle distal tubule Dose 5-20 mg/d PO or IV 200 mg/d max Caution [B, ] Contra Sulfonylurea sensitivity Disp Tabs, inj SE Orthostatic -1- BP, HA, dizziness, photosens, electrolyte imbalance, blurred vision, renal impair Notes 20 mg torsemide = 40 mg furosemide Interactions t Risk of ototox W/ aminoglycosides, cisplatin t effects W/ thiazides t effects OF anticoagulants, antih5rpCTtensives, Li, salicylates X effects IT/barbiturates, carbamaz ine, cholestyramine, NSAIDs, phenytoin, phenobarbital, probenecid, dandehon EMS t Effects of anticoagulants monitor for S/Sxs tinnitus, monitor ECG for hypokalemia (flattened T waves) OD May cause HA, hypotension, hypovolemia, and hypokalemia give IV fluids symptomatic and supportive... 

Sodium thiosulfate protects against cisplatin-induced nephrotoxicity by reacting covalently with cisplatin in the renal tubules. Other protectors include probenecid, orgotein, fosfomycin (203), amifostine (2-[3-aminopropyl) amino] ethylphosphorothioic acid, WR-2721, ethyofos), and anthiol. Experimental study drugs that may be useful in renal protection include BNP7787 (dimesna), selenium, and silibinin (146,204-212). The beneficial role of furose-mide is uncertain. 

The nephrotoxicity of dsplatin is reduced in humans [132], mice [133] and dogs [134] by co-admin-istration of probenecid, suggesting that cisplatin is transported by the PAH transport system. It has been proposed that platinum, hke other nephrotoxic metal ions such as mercury and potassium dichromate, are taken up by tubular cells as sulphydryl conjugate through a probenecid-sensitive pathway [133]. However, cisplatin might also be transported by the organic cation transport system, since quinidine, cimetidine and ranitidine inhibited its net secretion flux in the dog kidney [134]. 

Jacobs C, Kaubisch S, Flalsey J, Lum BL, Gosland M, Coleman CN, Sikic Bl.The use of probenecid as a chemoprotector against cisplatin nephrotoxicity. Cancer 1991 67 1518-1524. 

Clinically important, potentially hazardous interactions with acitretin, aldesleukin, aminoglycosides, amiodarone, amoxicillin, ampicillin, aspirin, bacampicillin, bismuth, carbenicillin, chloroquine, cisplatin, cloxacillin, co-trimoxazole, dapsone, demeclocycline, dexamethasone, diclofenac, dicloxacillin, etodolac, etoricoxib, etretinate, fenoprofen, flurbiprofen, folic acid antagonists, haloperidol, hydrocortisone, ibuprofen, indomethacin, influenza vaccines, ketoprofen, ketorolac, lithium, magnesium trisalicylate, meclofenamate, mefenamic acid, methicillin, mezlocillin, minocycline, nabumetone, nafcillin, naproxen, NSAIDs, omeprazole, oxacillin, oxaprozin, oxytetracycline, paromomycin, penicillin G, penicillin V, penicillins, phenylbutazone, piperacillin, piroxicam, polypeptide antibiotics, prednisolone, prednisone, probenecid, procarbazine, rofecoxib, salicylates, salsalate, sapropterin, sulfadiazine, sulfamethoxazole, sulfapyridine, sulfasalazine, sulfisoxazole, sulindac, tazobactum, tenoxicam, tetracycline, ticarcillin, tolmetin, trimethoprim, vaccines... 

Clinically important, potentially hazardous interactions with ACE inhibitors, amikacin, aminoglycosides, aminophylline, anti-diabetics, antihypertensives, cephalosporinss, cisplatin, gentamicin, indomethacin, kanamycin, neomycin, probenecid, salicylates, streptomycin, tobramycin... 

Lamivudine inhibits the intracellular phosphorylation of zalcitabine and antagonizes zalcitabine s antiretroviral activity in vitro, although the clinical significance of this interaction is unknown. Probenecid increases the zalcitabine AUC by about 50%, probably through inhibition of tubular secretion cimetidine increases the AUC by 36% via an unknown mechanism. Zalcitabine should be avoided in patients with a history of pancreatitis or neuropathy because the risk and severity of both complications increase. Coadministration of other drugs that cause pancreatitis or neuropathy also will increase the risk and severity of these symptoms. Ethambutol, isoniazid, vincristine, cisplatin, and pentamidine, as well as the antiretroviral drugs didanosine and stavudine, therefore, should be avoided. 

Cefotetin, ceftriaxone, ceftizoxime, tobnetm, etodolac, chlorpropamide, carboplatin, cisplatin, ibuprofen, oxaliplatin, piperacillin, probenecid, quinine, quinidine... 

The available clinical data surest that the nephrotoxicity of cisplatin is reduced by probenecid, but uncertainty remains. 

Conversely, some researchers have suggested that the combination of probenecid and cisplatin is potentially more toxic than cisplatin alone. They found that probenecid increased the fractional clearance of free platinum from cisplatin in rats, and that pretreatment with probenecid increased nephrotoxicity, as assessed hy blood urea levels. Other authors similarly reported that probenecid increased cisplatin clearance in rats. ... 

It is unclear why some animal studies show that probenecid increases cisplatin-induced nephrotoxicity whereas others show a decrease. Although the available clinical data suggest that there is a decrease, some uncertainty remains. The combination should be used with caution. 

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