Probenecid, penicillin interactions

Uses Infxns of resp tract, skin/soft tissue, scarlet fevCT, S5 philis Action Bactericidal -1- cell wall synth Dose Adults. 0.6-4.8 million Units/d in doses ql2-24h give probenecid at least 30 min prior to PCN to prolong action Feds. 25,000-50,000 Units/kg/d IM daily-bid Caution [B, M] Contra AU gy Disp Inj SE Pain at inj site, int stitial n hritis, anaphylaxis Interactions t Effects W/probenecid t penicillin 1/2-life Wf ASA, furosemide, indomethacin, sulfonamides, thiazide diuretics T risk of bleeding W/ anticoagulants -1- effects Wf chloramphenicol, macrolides, tetracyclines -1- effects OF OCPs EMS See Penicillin G, Aqueous OD See Penicillin G, Aqueous... 

Two main effects occur here. First, change in the pH of urine—weak bases, such as pethidine, are more easily excreted in an acid urine while alkalinisation promotes excretion of weak acids, such as salicylates and phenobarbital. Second, drugs that compete for an active excretion mechanism will reduce each other s elimination—probenecid was used in the early days of penicillin to conserve the drug, while less desirable interactions also occur, e.g. chlorpropamide and phenylbutazone interact to give increased levels of chlorpropamide and a danger of hypoglycaemia. 

Piperacillin-Tazobactam (Zesyn) [Anribioric/Extended Spectrum Penicillin, Beta Lactamase Inhibitor] Uses Infxns of skin, bone, resp urinary tract, abd, sepsis Action PCN plus 3-lactamase inhibitor bactericidal i cell wall synth Dose Adults. 3.375-4.5 g IV q6h i in renal insuff Caution [B, M] Contra PCN or 3-lactam sensitivity Disp Powder for inj frozen, premix inj 3.25, 3.375, 4.5 g SE D, HA, insomnia, GI upset, serum sickness-like Rxn, pseudomembranous colitis Interactions T Effects W/ probenecid T effects OF anticoagulants, MTX i effects W/ macrolides, tetracyclines i effects OF OCPs EMS T Effects of anticoagulants monitor for signs of electrolyte disturbances and hypovolemia d/t D such as X- K+ may cause allergic Rxn in pts sensitive to PCN OD May cause N/V/D, resp difficulty, and Szs symptomatic and supportive... 

Interference with active transport. Organic acids are passed from the blood into the urine by active transport across the renal tubular epithelium. Penicillin is mostly excreted in this way. Probenecid, an organic acid that competes successfully with penicillin for this transport system, may be used to prolong the action of penicillin when repeated administration is impracticable, e.g. in sexually transmitted diseases, where compliance is notoriously poor. Interference with renal excretion of methotrexate by aspirin, of zidovudine by probenecid and of digoxin by quinidine, contribute to the potentially harmful interactions with these combinations. 

Penicillins and Probenecid. A number of organic acids are actively transported from the blood into the tubular urine and vice versa. In some situations, these agents interfere with each other s excretion. Probenecid (e.g., Benemid) can increase the serum concentrations and increase and prolong the activity of penicillin derivatives by blocking their tubular secretion. This is an interaction that has been used to therapeutic advantage in the treatment of certain infections. 

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... 

Nafcillin and aminoglycosides are chemically inactivated and should not be mixed together. Probenecid blocks renal tubular secretion of penicillins however, this interaction has only a small effect on the excretion of nafcillin. 

Severe drug-drug interactions are known to occur between methotrexate and NSAIDs, probenecid, and penicillin G partially due to inhibition of renal... 

OAT-mediated secretion of methotrexate. By using mouse proximal tubule cells stably expressing human transporters, methotrexate has been demonstrated to be taken up via hOAT3 and hOATl at the basolateral side of the proximal tubule and effluxed or taken up at the apical side via hOAT4, where drug interactions occur between methotrexate and NSAIDs, probenecid, and penicillin G (Takeda et al., 2002). 

The increased levels and decreased renal excretion of clinafloxacin caused by probenecid are not considered large enough to warrant dosage adjustment," and most of the changes seen with the other quinolones were of a similar magnitude. However, caution has been advised in the presence of other drugs that may also compete for renal excretion (such as some penicillins or cephalosporins). " Grepafloxacin, moxifloxacin, sparfloxacin, and probably ofloxacin, appear not to interact. 

In 1950 (but not reported until 1975) a woman with subacute bacterial endocarditis was given probenecid orally and penicillin by intravenous drip, which was kept open with minimal doses of heparin. After a total of about 20 000 units of heparin had been given over a 3-week period, increasing epistaxes developed and the clotting time was found to be 24 minutes (normal 5 to 6 minutes). This was controlled with protamine. However, no reports of this interaction appear to have been made subsequently. This interaction seems unlikely to be of general significance. 

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