Usage
Cefadroxil is a first-generation cephalosporin antibiotic prescribed for bacterial infections susceptible to this class of antibiotics. These infections commonly include skin and soft tissue infections (e.g., abscesses, cellulitis, impetigo), pharyngitis, tonsillitis, and urinary tract infections (e.g., cystitis, pyelonephritis). Probenecid is a uricosuric agent primarily used to treat gout and hyperuricemia. It increases uric acid excretion in urine. The combination of cefadroxil and probenecid increases cefadroxil’s serum levels by reducing its renal excretion. This can be advantageous in certain infections where higher cefadroxil concentrations are needed.
Pharmacological Classification:
- Cefadroxil: Antibiotic (first-generation cephalosporin)
- Probenecid: Uricosuric agent
Mechanism of Action:
Cefadroxil exerts its antibacterial effect by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs), disrupting the final transpeptidation step of peptidoglycan synthesis, leading to bacterial cell death. Probenecid inhibits the renal tubular secretion of various organic anions, including cefadroxil. This results in increased serum concentrations and prolonged half-life of cefadroxil.
Alternate Names
Cefadroxil: Duricef, Ultracef (brand names no longer available in the US. This information is subject to change)
Probenecid: Benemid
How It Works
Pharmacodynamics: Cefadroxil is bactericidal, meaning it kills bacteria. It is most effective against gram-positive bacteria. Probenecid inhibits the reabsorption of uric acid in the proximal tubules of the kidneys, resulting in increased uric acid excretion and lowered serum uric acid levels. When combined, probenecid increases and prolongs cefadroxil’s serum concentration by competing for renal excretion.
Pharmacokinetics:
- Cefadroxil: Rapidly absorbed after oral administration; peak plasma concentrations achieved in 1-2 hours. Approximately 20% protein-bound. Excreted primarily unchanged in the urine via glomerular filtration and tubular secretion. Half-life of 1-2 hours, prolonged in renal impairment.
- Probenecid: Well absorbed after oral administration. Highly protein-bound (85-95%). Metabolized by oxidation and glucuronide conjugation. Half-life of 6-12 hours. Excreted in the urine.
Mode of Action (Cefadroxil): Inhibits cell wall synthesis by binding to PBPs, specifically transpeptidases, which are essential enzymes for peptidoglycan cross-linking. This leads to cell wall instability and bacterial lysis.
Elimination Pathways:
- Cefadroxil: Primarily renal excretion (glomerular filtration and tubular secretion)
- Probenecid: Renal excretion.
Dosage
Standard Dosage
Adults:
- Cefadroxil: 1-2 g daily in single or divided doses.
- Probenecid (for gout): Initial dose of 250 mg twice daily for one week, then increased to 500 mg twice daily, up to a maximum of 2 g/day in divided doses. Dose adjustments are based on serum uric acid levels and gout control. When used with cefadroxil to enhance antibiotic effects, the dosage needs to be determined based on the specific clinical situation.
Children:
- Cefadroxil: Children ≥6 years: <40 kg: 30-50 mg/kg/day in single or two divided doses (maximum 100 mg/kg/day). >40 kg: Same as adult dose.
- Probenecid: Generally not indicated for use in children in combination with antibiotics.
Special Cases:
- Elderly Patients: Dose adjustments may be necessary in elderly patients with reduced renal function.
- Patients with Renal Impairment: Cefadroxil dosage should be adjusted based on creatinine clearance. Probenecid should be used cautiously and may not be effective in severe renal impairment.
- Patients with Hepatic Dysfunction: No dosage adjustment is necessary for cefadroxil. Probenecid should be used with caution.
- Patients with Comorbid Conditions: Patients with gout receiving probenecid may require dose adjustments depending on the severity of their gout and the presence of other medical conditions.
Clinical Use Cases
The Cefadroxil + Probenecid combination isn’t typically used in the specific clinical scenarios listed (intubation, surgical procedures, mechanical ventilation, ICU, emergency situations). These settings often require intravenous antibiotics with different pharmacokinetic properties.
Dosage Adjustments
Dose modifications are essential for patients with renal impairment. Refer to the standard dosage section for specific adjustments based on creatinine clearance (CrCl). Concomitant medications should be reviewed for potential drug interactions and necessary dose adjustments.
Side Effects
Common Side Effects:
- Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain, dyspepsia.
- Dermatological: Rash, urticaria, pruritus.
- Hypersensitivity: Allergic reactions.
Rare but Serious Side Effects:
- Clostridium difficile-associated diarrhea (pseudomembranous colitis).
- Stevens-Johnson syndrome.
- Toxic epidermal necrolysis.
- Serum sickness.
- Hematological abnormalities (neutropenia, eosinophilia, thrombocytopenia).
- Anaphylaxis (rare).
- Seizures (rare, usually with high doses or renal impairment).
Long-Term Effects: With prolonged use, the potential for C. difficile infection increases.
Adverse Drug Reactions (ADR): Anaphylaxis, severe skin reactions, C. difficile infection require urgent medical attention.
Contraindications
- Known hypersensitivity to cephalosporins or penicillins.
- Patients with a history of severe allergic reactions to beta-lactam antibiotics.
Drug Interactions
- Probenecid: Increases serum levels of cefadroxil and other beta-lactam antibiotics by inhibiting renal tubular secretion.
- Anticoagulants: Cephalosporins may enhance the anticoagulant effects of warfarin.
- Oral contraceptives: Cefadroxil can decrease the effectiveness of oral contraceptives.
Pregnancy and Breastfeeding
- Cefadroxil: Pregnancy Category B. Considered safe for use during pregnancy.
- Probenecid: Use with caution during pregnancy. Weigh risks and benefits.
- Breastfeeding: Cefadroxil is excreted in breast milk in low concentrations. Monitor infants for diarrhea or thrush. Probenecid’s presence in breast milk and its effects on nursing infants are not well established. Exercise caution.
Drug Profile Summary
- Mechanism of Action: Cefadroxil inhibits bacterial cell wall synthesis. Probenecid inhibits renal tubular secretion of cefadroxil, increasing its serum level.
- Side Effects: Nausea, vomiting, diarrhea, rash, allergic reactions (rarely severe).
- Contraindications: Hypersensitivity to cephalosporins or penicillins.
- Drug Interactions: Probenecid, anticoagulants, oral contraceptives.
- Pregnancy & Breastfeeding: Cefadroxil is generally considered safe in pregnancy and breastfeeding. Probenecid should be used cautiously.
- Dosage: Cefadroxil: 1-2 g/day, adjusted for renal impairment. Probenecid dosage varies depending on the indication.
- Monitoring Parameters: Renal function (creatinine clearance) in patients with renal impairment. Observe for signs of allergic reaction.
Popular Combinations
The combination of cefadroxil and probenecid is itself used to achieve higher serum concentrations of cefadroxil. There are no other routinely prescribed combination therapies involving both these drugs.
Precautions
- Assess renal function before and during treatment in patients with renal impairment.
- Monitor for signs and symptoms of hypersensitivity reactions.
- Caution is advised in patients with a history of gastrointestinal disorders, particularly colitis.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cefadroxil + Probenecid?
A: Cefadroxil dosage: 1-2 g daily in adults, adjusted for children and patients with renal impairment. Probenecid dosage varies depending on the indication (250 mg to 2 g/day for gout). When used with cefadroxil to enhance antibiotic effects, the dosage needs to be determined based on the specific clinical situation.
Q2: What are the primary uses of Cefadroxil + Probenecid?
A: This combination is primarily used to achieve higher serum levels of cefadroxil in treating bacterial infections, particularly when renal excretion would otherwise limit efficacy.
Q3: What are the most common side effects of Cefadroxil?
A: Common side effects of cefadroxil include nausea, vomiting, diarrhea, abdominal discomfort, and skin rashes.
Q4: Are there any serious side effects I should be aware of with Cefadroxil?
A: Although rare, serious side effects such as C. difficile infection, severe allergic reactions (including anaphylaxis), and Stevens-Johnson syndrome can occur.
Q5: Can Cefadroxil be used during pregnancy?
A: Cefadroxil is generally considered safe to use during pregnancy (Pregnancy Category B). However, consult with an obstetrician before prescribing.
Q6: Does Cefadroxil interact with other medications?
A: Yes, cefadroxil can interact with medications such as probenecid, anticoagulants (e.g., warfarin), and oral contraceptives.
Q7: How does Probenecid affect Cefadroxil’s action?
A: Probenecid inhibits the renal excretion of cefadroxil, leading to higher and more prolonged serum concentrations of the antibiotic.
Q8: Can Cefadroxil be used in patients with renal impairment?
A: Yes, but dosage adjustments are necessary based on the degree of renal impairment (creatinine clearance).
Q9: Is there a risk of cross-reactivity between Cefadroxil and Penicillin?
A: Yes, a small percentage of patients allergic to penicillin may also be allergic to cephalosporins like cefadroxil. Caution is advised.
Q10: What infections is Cefadroxil commonly used to treat?
A: Cefadroxil is typically used for bacterial infections of the skin and soft tissues, throat (pharyngitis, tonsillitis), and urinary tract.
