Current Concepts In Managing Chronic Gout
First-line therapies for hyperuricemia include allopurinol or febuxostat (Uloric, Takeda Pharmaceuticals), which are both xanthine oxidase inhibitors. If the patient can tolerate neither of these medications or if these medications are contraindicated, probenecid could be a first-line alternative. As I discussed previously, one should use urate lowering medications to obtain a serum uric acid below 6 mg/dL. Targeting a serum uric acid level below 5 mg/dL is preferable so one can debulk the total body urate pool more quickly.8
Allopurinol is the most widely prescribed urate lowering medication. Allopurinol use should start at no greater than 100 mg per day and no more than 50 mg per day for patients who have stage IV or higher chronic kidney disease. Monitor serum uric acid levels and titrate the allopurinol dosing up every three to five weeks until the patient has met therapeutic goals or the maximum dosage of 800 mg. It is important to note that multiple studies have revealed that allopurinol given at 300 mg per day often fails to attain the target serum uric acid of less than 6 mg/dL.10,12 Also keep in mind that one can utilize allopurinol in patients with chronic kidney disease provided there is adequate monitoring and patient education.
The newest xanthine oxidase inhibitor on the market is febuxostat, which one can start at 40 or 80 mg per day. In the clinical trials for febuxostat, the percentage of patients who obtain a serum uric acid below 6 mg/dL was much higher for patients utilizing the 80 mg per day dose in comparison to those who had the 40 mg per day dosing regimen.12 The 40 mg per day dosing reduced the serum uric acid level to less than 6 mg/dL in 45 percent of patients while the 80 mg per day dose reduced the serum uric acid level to less than 6 mg/dL in 70 percent of patients.
If patients cannot tolerate allopurinol or febuxostat, or if the drugs are contraindicated or ineffective, probenecid becomes the first-line alternative medication. The dosing for probenecid starts at 250 mg PO b.i.d. times seven days. After a week, the dose increases to 500 mg PO b.i.d. One may also need to titrate up probenecid to obtain serum uric acid in a therapeutic range.
Probenecid is contraindicated in patients with urate nephropathy and renal stones. Do not use probenecid in patients with a creatinine clearance of less than 50 mL per minute. Obtain a urinary uric acid level prior to initiating probenecid. An elevated urinary uric acid level is indicative of uric acid overproduction and one should not use probenecid in these patients. Clinicians should also continue to monitor urinary uric acid levels while the patient is on probenecid.
What You Should Know About The Urate Lowering Therapy Paradox
It is important to educate patients that paradoxically, the initiation of urate lowering therapy can trigger acute gouty attacks. This is thought to be secondary to the rapid decrease in the serum uric acid that causes a large change in the concentration gradient. This concentration gradient causes mobilization of the urate, which is thought to increase so-called “mobilization flares.”
Therefore, one must utilize concomitant use of nonsteroidal anti-inflammatory medications when initiating urate lowering therapy. It is important to note colchicine (Colcrys, Takeda), given at 0.6 mg PO q.d. or b.i.d., is the only FDA approved medication for gout prophylaxis.