Usage
Cefalexin + Probenecid is a combination of a first-generation cephalosporin antibiotic (Cefalexin) and a uricosuric agent (Probenecid). It is primarily used to treat bacterial infections susceptible to Cefalexin. Probenecid is included in this combination specifically to enhance the effects of Cefalexin. This combination is indicated for respiratory tract infections (bronchitis, pneumonia, tonsillitis, pharyngitis), skin and soft tissue infections, bone and joint infections, urinary tract infections (cystitis and prostatitis), and dental infections.
Alternate Names
While “Cefalexin + Probenecid” is the generic name, Cefalexin is also known as Cephalexin. Brand names for Cefalexin include Keflex, Biocef, Daxbia, and Keftab. Brand names containing Probenecid may also exist regionally.
How It Works
Cefalexin:
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Pharmacodynamics: Cefalexin is bactericidal. It inhibits bacterial cell wall synthesis by binding to and inactivating penicillin-binding proteins (PBPs). This disruption leads to cell lysis and bacterial death.
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Pharmacokinetics: Cefalexin is well-absorbed orally. It is minimally metabolized and primarily excreted unchanged in the urine. Probenecid significantly impacts its pharmacokinetics by inhibiting its renal tubular secretion, resulting in higher and prolonged serum concentrations of Cefalexin.
Probenecid:
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Pharmacodynamics: Probenecid inhibits renal tubular secretion of certain organic anions, including Cefalexin and uric acid.
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Pharmacokinetics: Probenecid is well-absorbed after oral administration and undergoes hepatic metabolism, with metabolites and parent drug excreted in the urine.
Dosage
Standard Dosage
Adults:
The typical adult dosage of Cefalexin is 1-4 g daily in divided doses. The usual dose is 250 mg every 6 hours, or 500 mg every 8-12 hours. In severe infections, the dosage may be doubled. Probenecid dosage, when used as an adjunct, can vary depending on the specific clinical situation and is generally 500mg twice a day. It’s crucial to consult specific product information for guidance.
Children:
The usual pediatric dosage of Cefalexin is 25-50 mg/kg/day, divided into doses given every 6-8 hours. For skin infections, strep throat, or uncomplicated UTIs, the daily dose can be given every 12 hours. Children under 5 years: 125 mg every 8 hours. Children 5 years and over: 250 mg every 8 hours. In severe infections, the dosage may be doubled. Probenecid use in children requires careful assessment and specific dosing guidance beyond the scope of general recommendations.
Special Cases:
- Elderly Patients: Dose adjustments may be needed for patients with age-related renal impairment. Monitor renal function.
- Patients with Renal Impairment: Cefalexin dosage should be reduced based on creatinine clearance. Probenecid coadministration is generally not recommended in this population.
- Patients with Hepatic Dysfunction: Caution is advised, although specific adjustments may not always be required.
- Patients with Comorbid Conditions: Consider potential drug interactions, particularly with Metformin in diabetic patients and anticoagulants like Warfarin.
Clinical Use Cases
The dosage of Cefalexin + Probenecid doesn’t change dramatically in these settings. However, monitoring and potential dose adjustments based on renal function are essential, especially in critically ill patients. It’s important to note that Probenecid primarily serves to increase Cefalexin’s serum levels rather than directly addressing these clinical scenarios. Therefore, the focus is on managing the underlying condition and ensuring appropriate Cefalexin levels.
- Intubation: Standard dosage, adjusted for renal function.
- Surgical Procedures: Prophylactic use might be indicated; standard dosage adjusted for renal function.
- Mechanical Ventilation: Standard dosage, adjusted for renal function.
- Intensive Care Unit (ICU) Use: Standard dosage, adjusted for renal function. Close monitoring for adverse effects.
- Emergency Situations: Standard dosage, adjusted for renal function.
Dosage Adjustments
Dose adjustments are primarily based on renal function. Monitor serum creatinine and creatinine clearance, especially in elderly patients and those with pre-existing renal impairment.
Side Effects
Common Side Effects:
- Diarrhea
- Nausea
- Vomiting
- Rash
- Headache
Rare but Serious Side Effects:
- Clostridium difficile-associated diarrhea
- Allergic reactions (including anaphylaxis)
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Serum sickness
Long-Term Effects:
Long-term use may lead to C. difficile infection, vitamin K deficiency (rare), and secondary infections.
Adverse Drug Reactions (ADR):
Clinically significant ADRs include severe allergic reactions, C. difficile infection, and blood dyscrasias (rare).
Contraindications
- Hypersensitivity to cephalosporins or Probenecid
- Patients with a history of severe reactions to penicillins
Drug Interactions
- Probenecid: Increases Cefalexin levels, raising the risk of side effects.
- Metformin: Cefalexin may decrease metformin clearance, requiring metformin dose adjustments.
- Warfarin: Cefalexin may enhance warfarin’s anticoagulant effect. Monitor INR closely.
- Other antibiotics (aminoglycosides, tetracyclines): Monitor for potential nephrotoxicity.
- NSAIDS (ibuprofen, naproxen): Potential interaction, monitor renal function.
Pregnancy and Breastfeeding
- Pregnancy: Cefalexin is generally considered safe to use during pregnancy. However, benefits and risks should be carefully weighed.
- Breastfeeding: Both Cefalexin and Probenecid are excreted in breast milk in low concentrations. Monitor infants for diarrhea, candidiasis, and other potential side effects. Consider temporarily discontinuing breastfeeding or using an alternative antibiotic, if necessary.
Drug Profile Summary
- Mechanism of Action: Cefalexin: Inhibits bacterial cell wall synthesis. Probenecid: Inhibits renal tubular secretion.
- Side Effects: Diarrhea, nausea, vomiting, rash, headache (common); C. difficile infection, allergic reactions (serious).
- Contraindications: Hypersensitivity to cephalosporins or Probenecid.
- Drug Interactions: Probenecid, Metformin, Warfarin, aminoglycosides, NSAIDs.
- Pregnancy & Breastfeeding: Generally safe, monitor for side effects in infants.
- Dosage: Adults: 1-4g daily. Children: 25-50mg/kg/day. Adjust for renal impairment.
- Monitoring Parameters: Renal function, signs of infection, INR (if on Warfarin).
Popular Combinations (generally not advised)
The combination of Cefalexin and Probenecid is itself considered the “combination” of focus. Co-administration with other drugs should be done cautiously, considering potential interactions mentioned above.
Precautions
- General Precautions: Assess renal function before and during treatment, especially in elderly patients and those with pre-existing kidney disease. Monitor for signs of allergic reactions and C. difficile infection.
- Specific Populations: See Dosage - Special Cases.
- Lifestyle Considerations: Alcohol may exacerbate certain side effects (e.g., nausea, vomiting). No specific restrictions on driving or diet are typically necessary, unless other co-administered drugs require them.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cefalexin + Probenecid?
A: Cefalexin: Adults: 1-4g daily, Children: 25-50 mg/kg/day. Probenecid: Adult: 500 mg twice daily (as an adjunct to antibiotic treatment). Adjust for renal impairment.
Q2: What infections are commonly treated with Cefalexin + Probenecid?
A: Respiratory tract infections, skin and soft tissue infections, bone and joint infections, urinary tract infections, and dental infections.
Q3: What is the role of Probenecid in this combination?
A: Probenecid enhances Cefalexin’s effect by inhibiting its renal excretion, leading to higher and sustained serum levels.
Q4: What are the most common side effects?
A: Diarrhea, nausea, vomiting, rash, and headache.
Q5: Are there any serious side effects to be aware of?
A: Yes, rare but serious side effects include Clostridium difficile infection and allergic reactions, including anaphylaxis.
Q6: Can this combination be used in pregnant or breastfeeding women?
A: Cefalexin is generally considered safe during pregnancy. Both Cefalexin and Probenecid are present in breastmilk in low levels. Monitor infants for side effects and discuss risk/benefit with the patient.
Q7: What are the key drug interactions?
A: Probenecid, Metformin, Warfarin, aminoglycosides, and some NSAIDs.
Q8: Are there any contraindications to using Cefalexin + Probenecid?
A: Hypersensitivity to cephalosporins or Probenecid is a contraindication.
Q9: What monitoring is necessary during therapy?
A: Monitor renal function, signs of infection, and INR if the patient is on Warfarin. Observe for signs of allergic reactions and C. difficile infection.
