Usage
This combination of amoxicillin, cloxacillin, and probenecid is primarily prescribed for the treatment of bacterial infections, particularly those caused by beta-lactamase-producing organisms. It is especially useful in infections where higher and sustained blood levels of amoxicillin are desired, such as in gonorrhea.
Pharmacological Classification: Antibiotic combination with a uricosuric agent.
Mechanism of Action: Amoxicillin and cloxacillin are beta-lactam antibiotics that inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). Cloxacillin is penicillinase-resistant, expanding its spectrum of activity. Probenecid inhibits renal tubular secretion of amoxicillin, increasing its serum concentration and prolonging its half-life.
Alternate Names
No widely recognized alternate names exist for this specific three-drug combination. However, amoxicillin/cloxacillin combinations are sometimes marketed under various brand names. Probenecid is available generically and under various brand names as well. Brand names can vary regionally and internationally.
How It Works
Pharmacodynamics: Amoxicillin and cloxacillin disrupt bacterial cell wall synthesis, leading to bacterial cell death. Probenecid increases serum uric acid excretion by inhibiting its reabsorption in the renal tubules. This action also inhibits the renal tubular secretion of amoxicillin, thereby increasing amoxicillin levels in the body.
Pharmacokinetics: Amoxicillin and cloxacillin are well-absorbed orally. Probenecid affects the pharmacokinetics of amoxicillin by reducing its renal clearance. The combination is primarily excreted renally.
Mode of Action: Amoxicillin and cloxacillin bind to PBPs on bacteria, inhibiting transpeptidation and peptidoglycan synthesis, crucial steps in cell wall formation. Cloxacillin is resistant to breakdown by bacterial beta-lactamases. Probenecid inhibits the organic anion transporters (OATs) in the kidneys, responsible for the secretion of various organic anions, including amoxicillin and uric acid.
Elimination Pathways: Primarily renal excretion for all three drugs.
Dosage
Standard Dosage
Children: Dosage is weight-based for children and requires careful calculation. Pediatric dosing guidance should be obtained from reputable resources.
Special Cases:
- Elderly Patients: Dose adjustments may be necessary based on renal function.
- Patients with Renal Impairment: Significant dose reductions are needed based on the degree of impairment.
- Patients with Hepatic Dysfunction: Cloxacillin is primarily metabolized hepatically, so caution is advised. Dosage adjustments may be needed.
- Patients with Comorbid Conditions: Consider potential drug interactions and adjust accordingly.
Clinical Use Cases
Dosing for clinical use cases like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations should be guided by established institutional protocols and tailored to the individual patient’s condition and infection.
Dosage Adjustments
Dose modifications based on renal function, hepatic function, and other factors are crucial to optimize efficacy and minimize toxicity.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, rash, and hypersensitivity reactions.
Rare but Serious Side Effects:
Severe allergic reactions (anaphylaxis), Stevens-Johnson syndrome, Clostridium difficile-associated diarrhea, and interstitial nephritis.
Long-Term Effects: With prolonged use, potential for antibiotic resistance development, and effects on gut microbiota.
Adverse Drug Reactions (ADR):
Severe skin reactions, hematological abnormalities, seizures (rare).
Contraindications
Hypersensitivity to penicillins, cephalosporins, or probenecid; history of severe penicillin allergy; uric acid kidney stones (probenecid); active gout attacks (probenecid); blood dyscrasias (probenecid).
Drug Interactions
Probenecid interacts with many drugs by inhibiting their renal tubular secretion. Clinically significant interactions can occur with allopurinol, methotrexate, oral anticoagulants, and other antibiotics. Amoxicillin may reduce the efficacy of oral contraceptives. Refer to comprehensive drug interaction resources before prescribing.
Pregnancy and Breastfeeding
Amoxicillin is generally considered safe during pregnancy. Cloxacillin and probenecid data are limited; use with caution only if clearly needed. Consult specialized resources. Amoxicillin is excreted in breast milk; cloxacillin and probenecid excretion is not well-established. Monitor infants for side effects if these medications are used during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Inhibition of bacterial cell wall synthesis (amoxicillin/cloxacillin); inhibition of renal tubular secretion of uric acid and amoxicillin (probenecid).
- Side Effects: Nausea, vomiting, diarrhea, rash, hypersensitivity reactions.
- Contraindications: Penicillin/cephalosporin allergy, uric acid kidney stones, blood dyscrasias.
- Drug Interactions: Numerous, including allopurinol, methotrexate, anticoagulants.
- Pregnancy & Breastfeeding: Amoxicillin generally safe in pregnancy; cloxacillin/probenecid data limited. Excretion in breast milk varies.
- Dosage: Highly variable; adjust for age, weight, renal function, and infection severity.
- Monitoring Parameters: Renal function, liver function, signs of hypersensitivity, complete blood count.
Popular Combinations
This combination itself is not a “popular” combination. Amoxicillin/cloxacillin is used. Probenecid is used with beta-lactam antibiotics other than amoxicillin/cloxacillin for specific indications like gonorrhea.
Precautions
- General Precautions: Assess for allergies, renal/hepatic function, and other medical conditions.
- Pregnant Women: Use cautiously if clearly needed.
- Breastfeeding Mothers: Monitor infant for potential side effects.
- Children & Elderly: Dosage adjustments required.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amoxycillin + Cloxacillin + Probenecid?
A: There is no standard combined regimen. Dosing is typically based on the individual component drugs and is tailored to the specific infection and patient factors.
Q2: What are the common side effects?
A: Common side effects include nausea, vomiting, diarrhea, and skin rashes.
Q3: What are the serious adverse effects?
A: Serious adverse effects include allergic reactions, C. difficile infection, and interstitial nephritis.
Q4: Can this combination be used in pregnant patients?
A: Amoxicillin is generally considered safe. The safety of cloxacillin and probenecid during pregnancy has not been fully established. Use cautiously if clearly needed and consult resources for up-to-date guidelines.
Q5: What are the key drug interactions to consider?
A: Probenecid significantly interacts with many drugs. Important interactions include allopurinol, methotrexate, oral anticoagulants, and other antibiotics. Amoxicillin can decrease the efficacy of oral contraceptives.
Q6: What infections are typically treated with this combination?
A: Bacterial infections, especially those caused by beta-lactamase producing bacteria, when higher and sustained levels of amoxicillin are beneficial.
Q7: How does probenecid work in this combination?
A: Probenecid inhibits the renal excretion of amoxicillin, increasing its serum concentration and half-life.
Q8: How does this combination affect patients with renal impairment?
A: Dose adjustments are essential in patients with renal impairment as all three drugs are primarily eliminated renally.
Q9: Are there alternative antibiotic choices?
A: Yes, many other antibiotics exist. The best choice depends on the specific infection and patient factors.
Q10: Is there a need for therapeutic drug monitoring with this combination?
A: It is not routinely required but may be beneficial in certain cases, especially in patients with renal impairment or severe infections.
