Usage
Amoxycillin + Probenecid is primarily prescribed for the treatment of uncomplicated urogenital gonorrhea. Amoxicillin is a beta-lactam antibiotic, while probenecid is a uricosuric agent. The combination is used to enhance the effectiveness of amoxicillin against gonorrhea.
Pharmacological Classification:
- Amoxicillin: Beta-lactam antibiotic
- Probenecid: Uricosuric agent
Mechanism of Action:
Amoxicillin inhibits bacterial cell wall synthesis, leading to bacterial cell death. Probenecid inhibits the renal tubular secretion of amoxicillin, thereby increasing and prolonging amoxicillin’s plasma concentration, which enhances its effectiveness in treating gonorrhea.
Alternate Names
There are no formally recognized alternate names for the combination of Amoxicillin + Probenecid. However, the individual components have various synonyms:
- Amoxicillin: Amoxycillin (British spelling), Amoxil, Trimox (brand names)
- Probenecid: Benemid (brand name)
How It Works
Pharmacodynamics:
Amoxicillin exerts its bactericidal action by binding to and inhibiting penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. This inhibition disrupts cell wall synthesis, leading to cell lysis and bacterial death. Probenecid inhibits the organic anion transporter (OAT) in the renal tubules, reducing the excretion of amoxicillin. This leads to higher and more sustained plasma concentrations of amoxicillin, making it more effective against gonorrhea.
Pharmacokinetics:
- Absorption: Amoxicillin is well-absorbed orally, and its absorption is not significantly affected by food. Probenecid is also well-absorbed orally.
- Metabolism: Amoxicillin is minimally metabolized. Probenecid undergoes metabolism, primarily through glucuronidation.
- Elimination: Amoxicillin is primarily excreted renally as unchanged drug. Probenecid is mainly eliminated via hepatic metabolism, with a smaller portion excreted unchanged in the urine.
Mode of Action:
Amoxicillin acts by inhibiting bacterial cell wall synthesis by interfering with PBPs. Probenecid, by blocking OATs in the kidney, reduces the excretion of amoxicillin.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation:
Amoxicillin: Inhibits PBPs.
Probenecid: Inhibits OATs, thus reducing amoxicillin excretion.
Elimination Pathways:
Amoxicillin: Primarily renal excretion.
Probenecid: Primarily hepatic metabolism, some renal excretion.
Dosage
Standard Dosage
Adults:
For uncomplicated urogenital gonorrhea: 3 grams of amoxicillin administered orally as a single dose, along with 1 gram of probenecid administered orally concomitantly.
Children:
For uncomplicated urogenital gonorrhea in prepubertal children (less than 88 pounds or 40 kg): 50 mg/kg of amoxicillin combined with 25 mg/kg of probenecid as a single oral dose. Children weighing more than 88 pounds should be dosed according to adult recommendations. This combination is contraindicated in children younger than 2 years of age for the treatment of gonorrhea.
Special Cases:
- Elderly Patients: Dose adjustment may be necessary based on renal function.
- Patients with Renal Impairment: Dose adjustment is required.
- Patients with Hepatic Dysfunction: Caution is advised as probenecid is metabolized in the liver.
- Patients with Comorbid Conditions: Consider individual patient factors and adjust the dose accordingly.
Clinical Use Cases
The primary clinical use case for Amoxicillin + Probenecid is uncomplicated urogenital gonorrhea. It is not typically used in settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations.
Dosage Adjustments
Dosage adjustments are based on patient-specific factors, particularly renal function, and should be determined based on individual patient needs.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, rash, vaginal yeast infection.
Rare but Serious Side Effects:
Allergic reactions (anaphylaxis, Stevens-Johnson syndrome), severe skin reactions, seizures (with high doses).
Long-Term Effects:
Data regarding chronic complications from prolonged use is limited as the drug is usually administered as a single dose.
Adverse Drug Reactions (ADR):
Anaphylaxis, Stevens-Johnson Syndrome.
Contraindications
Hypersensitivity to penicillins or cephalosporins, history of blood dyscrasias, uric acid kidney stones (for probenecid), children under 2 years of age for gonorrhea treatment.
Drug Interactions
Allopurinol, oral anticoagulants (warfarin), methotrexate, other antibiotics (tetracyclines).
Pregnancy and Breastfeeding
Amoxicillin is generally considered safe during pregnancy. Consult with a physician before using probenecid during pregnancy.
Amoxicillin and probenecid are present in breast milk in small quantities. Monitor for potential side effects in the infant.
Drug Profile Summary
- Mechanism of Action: Amoxicillin inhibits bacterial cell wall synthesis. Probenecid prolongs amoxicillin’s half-life by inhibiting its renal excretion.
- Side Effects: Nausea, vomiting, diarrhea, rash, allergic reactions.
- Contraindications: Penicillin hypersensitivity, blood dyscrasias, uric acid kidney stones.
- Drug Interactions: Allopurinol, warfarin, methotrexate, tetracyclines.
- Pregnancy & Breastfeeding: Amoxicillin generally safe; probenecid use with caution.
- Dosage: Adults: 3g amoxicillin + 1g probenecid single dose for gonorrhea. Pediatric: 50 mg/kg amoxicillin + 25 mg/kg probenecid single dose for gonorrhea (for children under 40kg and above 2 years old).
- Monitoring Parameters: Observe for allergic reactions, monitor renal and hepatic function in special populations.
Popular Combinations
The combination of amoxicillin and probenecid is itself a popular combination specifically used for gonorrhea treatment. There are no widely used additional drug combinations with this particular pairing.
Precautions
Screen for penicillin allergy, assess renal and hepatic function, especially in elderly patients and those with comorbidities. Caution in pregnant and breastfeeding women. Adequate hydration to minimize the risk of kidney stones.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amoxycillin + Probenecid for adults with gonorrhea?
A: 3 grams of amoxicillin + 1 gram of probenecid as a single oral dose.
Q2: What is the pediatric dosage of Amoxicillin + Probenecid for gonorrhea?
A: 50 mg/kg amoxicillin + 25 mg/kg probenecid orally as a single dose, for children under 40 kg and above 2 years old. Children weighing 40 kg or more should receive the adult dose.
Q3: Can Amoxicillin + Probenecid be used in pregnant women?
A: Amoxicillin is generally considered safe during pregnancy. Probenecid should be used with caution, and only if potential benefits outweigh the risks. Consult with a physician.
Q4: Is it safe to use Amoxicillin + Probenecid during breastfeeding?
A: Both drugs can be excreted in breastmilk in small amounts. Monitor the infant for potential side effects such as diarrhea, rash, or thrush.
Q5: What are the key drug interactions to be aware of with Amoxicillin + Probenecid?
A: Significant interactions can occur with allopurinol, oral anticoagulants (e.g., warfarin), methotrexate, and tetracyclines.
Q6: What are the most common side effects of this combination?
A: Nausea, vomiting, diarrhea, and rash are common side effects.
Q7: Are there any contraindications to using Amoxicillin + Probenecid?
A: Yes. Contraindications include a known hypersensitivity to penicillins or cephalosporins, blood dyscrasias, uric acid kidney stones (for probenecid), and children under 2 years of age for gonorrhea treatment.
Q8: What is the mechanism of action of Probenecid in this combination?
A: Probenecid inhibits the renal tubular secretion of amoxicillin, which leads to higher and more sustained plasma levels of the antibiotic, improving its efficacy against gonorrhea.
Q9: Why is this combination prescribed for gonorrhea?
A: The combination of amoxicillin and probenecid is used to treat gonorrhea because probenecid enhances the effectiveness of amoxicillin by increasing its concentration and duration of action in the body.
