POLYCILLIN-PRB
Clinical safety rating: caution
Comprehensive clinical and safety monograph for POLYCILLIN-PRB (POLYCILLIN-PRB).
POLYCILLIN-PRB combines ampicillin and probenecid. Ampicillin is a beta-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). Probenecid inhibits renal tubular secretion of ampicillin, increasing its plasma concentration.
| Metabolism | Ampicillin is partially metabolized by hydrolysis, but mainly excreted unchanged; probenecid is metabolized primarily via glucuronidation and oxidation. |
| Excretion | Renal: 60-80% unchanged via glomerular filtration and tubular secretion; Biliary/fecal: 20-40% as metabolites and unchanged drug. |
| Half-life | Terminal elimination half-life: 1-1.5 hours in patients with normal renal function; prolonged to 7-10 hours in anuria. |
| Protein binding | 55-60% bound primarily to serum albumin. |
| Volume of Distribution | 0.3-0.4 L/kg; indicates distribution into extracellular fluid. |
| Bioavailability | Oral: 30-50% (acid-labile, food reduces absorption); Intramuscular: 70-85% (procaine delays absorption). |
| Onset of Action | Oral: 30-60 minutes; Intramuscular: 15-30 minutes. |
| Duration of Action | Oral: 6-8 hours; Intramuscular: 12-24 hours due to procaine component. |
| Molecular Weight | Penicillin G: 334.4 Da; Probenecid: 285.4 Da; combination: average ~310 Da |
250-500 mg orally every 6 hours or 500 mg-1 g intramuscularly every 6-8 hours.
| Dosage form | FOR SUSPENSION |
| Renal impairment | CrCl 10-50 mL/min: every 8-12 hours; CrCl <10 mL/min: every 12-18 hours; hemodialysis: dose after dialysis. |
| Liver impairment | No adjustment required for mild to moderate hepatic impairment. Severe impairment: use with caution; no specific guidelines. |
| Pediatric use | Children >1 month: 12.5-25 mg/kg orally every 6 hours; 25-50 mg/kg/day IM in divided doses every 6-8 hours. Maximum 2 g/day. |
| Geriatric use | Initiate at lower end of dosing range; monitor renal function; adjust based on CrCl. |
| 1st trimester | Generally considered safe; no known teratogenic effects in humans. Crosses placenta but risk of fetal harm is low. Use only if clearly needed. |
| 2nd trimester | Safe for use; no evidence of fetal risk. Commonly used for syphilis in pregnancy. |
| 3rd trimester | Safe for use; may cause maternal diarrhea or allergic reactions but no fetal risks known. |
Clinical note
Comprehensive clinical and safety monograph for POLYCILLIN-PRB (POLYCILLIN-PRB).
| Placental transfer | Penicillin G crosses the placenta; achieves therapeutic concentrations in fetal serum. Probenecid component may reduce clearance but does not significantly alter placental transfer. |
| Breastfeeding | Penicillins are excreted into breast milk in small amounts, not expected to cause adverse effects in nursing infants. Risk of diarrhea or allergic sensitization is low. Use caution in infants with known penicillin allergy. |
■ FDA Black Box Warning
None identified.
| Serious Effects |
Hypersensitivity to penicillinsHypersensitivity to probenecidSevere renal impairment (creatinine clearance <50 mL/min) due to probenecid accumulationConcurrent use with methotrexate (increased toxicity due to probenecid inhibition of excretion)
| Precautions | Severe hypersensitivity reactions (anaphylaxis), Clostridioides difficile-associated diarrhea, Renal impairment (dose adjustment required), Prolonged use may lead to superinfection |
| Food/Dietary | Avoid grapefruit juice and high-fat meals as they may affect absorption. No specific food restrictions, but take on an empty stomach for optimal absorption. Avoid alcohol. |
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| Lactation Rating | L1 (Compatible) |
| Teratogenic Risk | FDA Pregnancy Category B. No evidence of teratogenicity in animal studies. Limited human data; fetal risk cannot be ruled out. Use only if clearly needed. |
| Fetal Monitoring | Monitor maternal renal function, hematologic parameters (CBC with differential) during prolonged therapy. Assess for signs of hypersensitivity or superinfection. Fetal monitoring as clinically indicated. |
| Fertility Effects | No known adverse effects on fertility in animal studies. No human data available; unlikely to impair fertility at therapeutic doses. |
| Clinical Pearls |
| POLYCILLIN-PRB (ampicillin/probenecid) is used for uncomplicated gonorrhea. Probenecid reduces renal excretion of ampicillin, increasing serum levels. Ensure patient is not allergic to penicillins or sulfa drugs (probenecid is sulfa-like). Administer as a single oral dose; follow-up test of cure is recommended due to resistant strains. |
| Patient Advice | Take this medication exactly as prescribed as a single dose. · Avoid alcohol for at least 24 hours after taking probenecid to prevent disulfiram-like reaction. · Do not take with aspirin or other salicylates as they may decrease probenecid's effect. · Inform your doctor if you have kidney disease, gout, or a history of penicillin allergy. · This medication treats gonorrhea but does not protect against future infections; use protection. · Report any rash, itching, or difficulty breathing immediately as it may indicate an allergic reaction. · If you miss the dose, contact your healthcare provider promptly. |