What is Probenecid?
Probenecid is a uricosuric agent, meaning it works by helping the kidneys remove uric acid from the body [1.7.5]. It's primarily used to treat gout and gouty arthritis by preventing the buildup of uric acid crystals in the joints [1.7.1]. By blocking the reabsorption of uric acid in the kidneys, it increases its excretion in the urine [1.7.5]. This medication is not an analgesic and is not effective for treating acute gout attacks; rather, it's a long-term therapy initiated after an acute attack has subsided [1.2.2, 1.3.2]. Additionally, probenecid is sometimes used to increase the concentration and prolong the effect of certain antibiotics, like penicillin and other beta-lactams [1.2.1, 1.3.2].
Absolute Contraindications: Who Should Not Take Probenecid?
There are several groups of people for whom probenecid is strictly not recommended. Taking the drug despite these contraindications can lead to serious health risks.
Individuals with a History of Uric Acid Kidney Stones
Because probenecid works by increasing the amount of uric acid in the urine, it is contraindicated in people with a known history of uric acid kidney stones [1.2.2, 1.2.6]. The increased concentration of uric acid can promote the formation of new stones, potentially causing renal colic, hematuria (blood in the urine), or other kidney complications [1.2.2, 1.2.4].
Patients with Known Blood Dyscrasias
Individuals with pre-existing blood disorders, known as blood dyscrasias, should not use probenecid [1.2.2, 1.3.3]. The medication has been associated with rare but serious hematologic adverse reactions, including aplastic anemia, hemolytic anemia, and leukopenia (low white blood cell count) [1.2.2, 1.2.4]. People with a G6PD deficiency may be at a higher risk for some of these blood-related side effects [1.3.2].
During an Acute Gout Attack
Therapy with probenecid should not be started during a sudden, severe gout attack [1.2.2, 1.2.3]. In fact, initiating the medication can sometimes exacerbate or prolong the inflammation of an acute attack, and it may increase the frequency of attacks during the first 6 to 12 months of therapy [1.2.1, 1.2.7]. For this reason, doctors often prescribe a prophylactic dose of colchicine or an NSAID for the first few months of probenecid treatment [1.2.1].
Children Under 2 Years of Age
Probenecid is contraindicated in children younger than two years old [1.2.2, 1.5.2, 1.5.5]. The safety and efficacy in this very young pediatric population have not been established.
Known Hypersensitivity or Allergy
Anyone with a known allergy or hypersensitivity to probenecid or any of its ingredients should not take the medication [1.2.2, 1.3.1]. Allergic reactions can be severe, ranging from a rash and hives to anaphylaxis, which is a life-threatening condition [1.2.2, 1.2.4].
Cautions and Special Considerations
Beyond absolute contraindications, there are situations where probenecid should be used with caution and under close medical supervision.
- Kidney Impairment: The drug's effectiveness diminishes in patients with chronic renal insufficiency. It may not be effective if the glomerular filtration rate (GFR) is 30 mL/minute or less [1.2.2, 1.2.7].
- History of Peptic Ulcers: Caution is advised for patients with a history of peptic ulcer disease, as GI side effects like nausea can occur [1.2.2, 1.3.5].
- Pregnancy and Breastfeeding: Probenecid crosses the placental barrier. While studies have not documented adverse fetal outcomes, it should be used in pregnancy only if the potential benefit outweighs the possible risks [1.5.2, 1.5.3, 1.8.1]. It is also excreted in breast milk in low levels, and caution is recommended [1.5.3].
Significant Drug Interactions
Probenecid can significantly alter the levels of other drugs in the body, which is a critical consideration for patient safety.
- Salicylates (Aspirin): Taking aspirin or other salicylates, even in small doses, is contraindicated as it antagonizes the uricosuric effect of probenecid [1.2.2, 1.3.2]. Acetaminophen is a preferred alternative for mild pain relief [1.2.2].
- Methotrexate: Probenecid increases plasma concentrations of methotrexate, a drug used for cancer and autoimmune diseases, which can heighten the risk of toxicity [1.2.2, 1.3.6]. If used together, the methotrexate dosage may need to be reduced and monitored [1.2.2].
- Antibiotics: While sometimes used intentionally to boost levels of penicillins and cephalosporins, this interaction requires close monitoring [1.2.1].
- Other Medications: It can also increase blood levels of NSAIDs (like naproxen and indomethacin), certain benzodiazepines (like lorazepam), and zidovudine, an HIV medication [1.2.1, 1.4.2].
Probenecid vs. Allopurinol: A Quick Comparison
| Feature | Probenecid | Allopurinol |
|---|---|---|
| Mechanism of Action | A uricosuric agent; increases the excretion of uric acid via the kidneys [1.7.5, 1.8.1]. | A xanthine oxidase inhibitor; blocks the body from producing uric acid [1.8.1]. |
| Primary Use | Chronic gout in patients who are "underexcreters" of uric acid [1.8.1]. | Chronic gout, especially in patients who are "overproducers" of uric acid, and for hyperuricemia from chemotherapy [1.8.1]. |
| Key Contraindication | History of uric acid kidney stones, blood dyscrasias, children <2 years [1.2.2, 1.8.1]. | Hypersensitivity to the drug [1.8.1]. Caution in liver and renal disease [1.4.5]. |
| Aspirin Interaction | Aspirin counteracts its effect and should be avoided [1.2.2, 1.3.6]. | No major interaction with low-dose aspirin. |
Conclusion
Probenecid is an effective medication for managing chronic gout, but it is not suitable for everyone. A thorough understanding of who should not take probenecid is essential for its safe use. Absolute contraindications include a history of uric acid kidney stones, specific blood disorders, being under two years of age, and use during an acute gout attack. Furthermore, its potential for serious drug interactions, especially with common medications like aspirin and methotrexate, requires careful management by a healthcare provider. Patients should always disclose their full medical history and a complete list of their current medications to their doctor to ensure probenecid is a safe and appropriate choice for them.
