Usage
Ampicillin + Probenecid is primarily prescribed for the treatment of uncomplicated urogenital gonorrhea caused by Neisseria gonorrhoeae. It combines a beta-lactam antibiotic (ampicillin) with a uricosuric agent (probenecid). Ampicillin is classified as a broad-spectrum antibiotic and probenecid is a uricosuric agent. The combination enhances ampicillin’s effectiveness by increasing and prolonging its presence in the bloodstream. Probenecid achieves this by inhibiting the renal tubular secretion of ampicillin.
Alternate Names
While “Ampicillin + Probenecid” is the standard generic name, no widely recognized international or regional variations exist. Ampicillin is marketed under various brand names, such as Principen or Omnipen. Probenecid is often marketed as Benemid or Probalan. However, fixed-dose combination products are less common, with prescriptions typically written separately for ampicillin and probenecid.
How It Works
Ampicillin exerts its bactericidal action by inhibiting bacterial cell wall synthesis. It targets penicillin-binding proteins (PBPs), crucial enzymes for cross-linking peptidoglycans, which are essential components of bacterial cell walls. This disruption weakens the cell wall, leading to bacterial cell lysis and death. Ampicillin is well-absorbed orally and parenterally, achieving therapeutic concentrations in various tissues and fluids. It undergoes minimal metabolism and is primarily eliminated by renal excretion.
Probenecid inhibits the active renal tubular secretion of various organic anions, including ampicillin. This inhibition decreases the rate at which ampicillin is cleared from the body, thereby increasing and prolonging ampicillin plasma concentrations. Probenecid also affects uric acid handling by inhibiting its reabsorption, promoting its excretion, and lowering serum uric acid levels. It is primarily metabolized in the liver and excreted renally.
Dosage
Standard Dosage
Adults:
For uncomplicated urogenital gonorrhea, a single oral dose of 3.5 grams of ampicillin is administered concurrently with 1 gram of probenecid.
Children:
For children weighing more than 20 kg, the dosage of ampicillin for genitourinary infections (excluding gonorrhea) is typically 500 mg four times per day. For children weighing 20 kg or less, the dosage is 100 mg/kg per day, divided into four equally spaced doses.
Special Cases:
- Elderly Patients: Due to age-related decline in renal function, dose adjustments may be necessary.
- Patients with Renal Impairment: Dose reduction or extended dosing intervals should be considered based on creatinine clearance.
- Patients with Hepatic Dysfunction: Close monitoring is advised, although specific dosage adjustments might not always be required.
- Patients with Comorbid Conditions: Individualized dosing based on the specific comorbid conditions is necessary.
Clinical Use Cases
Ampicillin + Probenecid is primarily indicated for gonorrhea. Its use in other clinical settings listed below would typically involve ampicillin alone at different dosages.
- Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations: Ampicillin dosage in these situations varies depending on the indication and patient’s specific condition. Consultation with local treatment guidelines is necessary.
Dosage Adjustments
Dosage adjustments should be made based on patient-specific factors such as renal or hepatic dysfunction and any potential drug interactions.
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Diarrhea
- Rash
Rare but Serious Side Effects:
- Clostridioides difficile colitis
- Anaphylaxis
- Seizures
- Severe skin reactions (e.g., Stevens-Johnson syndrome)
- Blood dyscrasias
Long-Term Effects:
Long-term use might increase the risk of fungal or bacterial superinfection.
Adverse Drug Reactions (ADR):
Any signs of hypersensitivity, severe gastrointestinal issues, or neurological symptoms should prompt immediate intervention.
Contraindications
- Known hypersensitivity to penicillins or probenecid.
- Blood dyscrasias
- Uric acid kidney stones
Drug Interactions
Ampicillin can interact with allopurinol, increasing the risk of skin rash. It can also interact with oral contraceptives, potentially reducing their effectiveness. Probenecid can interact with various medications, including nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin, and other antibiotics, influencing their efficacy. Consult a comprehensive drug interaction database for detailed information.
Pregnancy and Breastfeeding
Ampicillin is considered generally safe during pregnancy and breastfeeding. Probenecid use requires careful risk-benefit assessment during pregnancy and breastfeeding.
Drug Profile Summary
- Mechanism of Action: Ampicillin: Inhibits bacterial cell wall synthesis. Probenecid: Blocks renal tubular secretion of ampicillin.
- Side Effects: Range from mild gastrointestinal upset to severe hypersensitivity reactions.
- Contraindications: Penicillin or probenecid allergy, blood dyscrasias, uric acid stones.
- Drug Interactions: Numerous drug interactions can occur, especially with other antibiotics and NSAIDs.
- Pregnancy & Breastfeeding: Ampicillin generally safe. Probenecid: Use with caution.
- Dosage: Gonorrhea: 3.5g ampicillin + 1g probenecid single dose. Other infections: Ampicillin dosing varies.
- Monitoring Parameters: Renal function, liver function, complete blood count, signs of hypersensitivity.
Popular Combinations
The concurrent administration of ampicillin and probenecid is a well-established combination for treating gonorrhea. It isn’t routinely used with other medications.
Precautions
Standard precautions include screening for allergies, and assessing renal and hepatic function. Careful consideration is needed when prescribing to pregnant or breastfeeding women, children, and the elderly.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ampicillin + Probenecid for gonorrhea?
A: A single oral dose of 3.5 grams of ampicillin with 1 gram of probenecid.
Q2: What is the mechanism of action of Ampicillin + Probenecid?
A: Ampicillin inhibits bacterial cell wall synthesis. Probenecid enhances ampicillin’s effectiveness by reducing its renal excretion, thus increasing its serum concentration and duration of action.
Q3: What are the common side effects of this drug combination?
A: Common side effects include nausea, vomiting, diarrhea, and rash.
Q4: Are there any contraindications to using Ampicillin + Probenecid?
A: Yes. Contraindications include known hypersensitivity to penicillins or probenecid, blood dyscrasias, and uric acid kidney stones.
Q5: Can Ampicillin + Probenecid be used in pregnant or breastfeeding women?
A: Ampicillin is generally considered safe during pregnancy and breastfeeding. Probenecid should be used with caution and only if the benefits outweigh the risks.
Q6: What are the signs of an allergic reaction to ampicillin?
A: Allergic reactions can range from mild skin rashes and hives to severe anaphylaxis. Difficulty breathing or swallowing, wheezing, and swelling of the face, lips, or tongue are signs of a serious reaction requiring immediate medical attention.
Q7: What other medications can interact with Ampicillin + Probenecid?
A: Both ampicillin and probenecid can interact with other drugs. Ampicillin can notably interact with allopurinol and oral contraceptives. Probenecid can interact with NSAIDs and other antibiotics. A comprehensive drug interaction database should be consulted.
Q8: What is the role of probenecid in this combination?
A: Probenecid inhibits the renal excretion of ampicillin, leading to higher and more sustained blood levels of the antibiotic, thereby increasing its effectiveness against gonorrhea.
Q9: What should patients be advised about taking Ampicillin + Probenecid?
A: Patients should be advised to take the medication with food to minimize gastrointestinal upset and to maintain adequate hydration to prevent kidney stones. They should also be educated about the signs and symptoms of allergic reactions and instructed to seek immediate medical attention if they occur.
Q10: What is the difference between a common side effect and an adverse drug reaction?
A: A common side effect is an anticipated and frequently observed effect of a medication, typically mild and self-limiting. An adverse drug reaction is an unintended and potentially harmful reaction, ranging from moderate to severe and requiring medical intervention.
