GOUT MEDICATIONS





Acronyms



Open all
Allopurinol
Zyloprim®

Dosage forms

Tablet
  • 100 mg
  • 300 mg

Dosing

Hyperuricemia in gout
  • Starting:
    • Package insert: 100 mg once daily
    • ACR: starting with a dose of ≤ 100 mg/day lowers the risk of gout flares and allopurinol hypersensitivity syndrome. For patients with CrCl < 60 ml/min, a starting dose of ≤ 50 mg/day should be considered. [3]
  • Maintenance:
    • Mild gout: 200 - 300 mg/day
    • Moderate-severe: 400 - 600 mg/day
  • Maximum: 800 mg/day
  • Increase dose by 100 mg/day at weekly intervals
  • Doses > 300 mg/day should be given in divided doses
  • Target uric acid level is < 6 mg/dl
  • When initiating therapy, patients should receive prophylaxis against acute attacks - see ACR recommendations
  • Test high-risk individuals for the HLA-B*5801 haplotype before initiating therapy. See precautions for more.
  • Check uric acid level every 2 - 5 weeks during titration
Hyperuricosuria in patients with calcium oxalate stones
  • Dosing: 200 - 300 mg/day
  • Adjust dose up or down until desired effect
  • Dose may be given in one or two divided doses
  • Normal uric acid excretion is < 800 mg/day in men, and < 750 mg/day in women
  • See kidney stones for more
Kidney disease
  • CrCL < 60 ml/min: the ACR recommends a starting dose of ≤ 50 mg/day to lower the risk of gout flare and allopurinol hypersensitivity syndrome. Dose titrations to ≥ 300 mg/day may still be required and have been shown to be safe in this population. [3]
  • CrCl 10 - 20 ml/min: the prescribing information states that 200 mg/day is a suitable maintenance dose
  • CrCl < 10 ml/min: the prescribing information states that doses should not exceed 100 mg/day, and increasing the dosing interval should be considered
Liver disease
  • In patients with liver disease, periodic liver function tests are recommended during the early stages of therapy

Efficacy

Gout Coronary artery disease (CAD) Kidney disease

Generic / Price

  • YES/$

Other

  • Take after meals to minimize stomach upset
  • It is not necessary to discontinue allopurinol during an acute gout flare
  • Maintain good fluid intake

Mechanism of action

  • Xanthine oxidase is a key enzyme involved in the metabolism of purines. Allopurinol inhibits xanthine oxidase and prevents the production of uric acid.
  • See uric acid homeostasis for more

FDA-approved indications

  • Hyperuricemia in gout
  • Hyperuricosuria in patients with calcium oxalate stones
  • Hyperuricemia associated with cancer treatment

Side effects

The incidence of allopurinol side effects is not well defined
  • Acute gout attack - up to 6%
  • Rash - up to 3%
  • Diarrhea
  • Nausea
  • Elevated liver enzymes
  • Drowsiness

Drug interactions

  • Azathioprine - allopurinol inhibits one pathway of azathioprine metabolism and may lead to toxicity if given concomitantly. Reduce azathioprine dose to a fourth or a third of the usual dose when given with allopurinol. If patients have low TPMT activity, allopurinol should not be given with azathioprine.
  • Mercaptopurine - allopurinol inhibits one pathway of mercaptopurine metabolism and may lead to toxicity if given concomitantly. Reduce mercaptopurine dose to a fourth or a third of the usual dose when given with allopurinol. If patients have low TPMT activity, allopurinol should not be given with azathioprine.
  • Uricosuric agents - uricosuric agents may increase the excretion of oxipurinol, the major active metabolite of allopurinol. This may decrease the effectiveness of allopurinol.
  • Thiazide diuretics - there have been case reports of renal toxicity in patients receiving allopurinol with thiazide diuretics. It's unclear if the toxicity was related to a drug interaction.
  • Cytotoxic agents (e.g. cyclophosphamide) - cases of enhanced bone marrow suppression have been reported in patients receiving allopurinol with cytotoxic agents
  • Chlorpropamide - allopurinol may increase the half-life of chlorpropamide and increase the risk of hypoglycemia
  • Cyclosporine - allopurinol may increase levels of cyclosporine. Monitor levels closely when co-administered
  • Ampicillin and amoxicillin - there have been reports of an increase in the frequency of skin rashes in patients receiving ampicillin/amoxicillin with allopurinol
  • Dicumarol - allopurinol may prolong the half-life of the anticoagulant, dicumarol

Contraindications / Precautions

  • Acute gout attack - when initiating allopurinol, the risk of an acute gout attack is increased. This may be due to the mobilization of uric acid from tissue deposits which causes fluctuations in uric acid levels. The ACR recommends prophylactic therapy when initiating allopurinol - see gout flare prophylaxis for more.
  • Skin rash - allopurinol may cause a skin rash in some patients. The most common rash is a pruritic, maculopapular rash that may become scaly or exfoliative. Severe skin reactions including Stevens-Johnson syndrome and/or vasculitis may occur. Patients should stop allopurinol immediately at the first signs of a skin rash.
  • Allopurinol hypersensitivity syndrome (AHS) - AHS is marked by Stevens-Johnson syndrome, toxic epidermal necrolysis, eosinophilia, vasculitis, rash, and end-organ damage. AHS incidence in the U.S. is estimated to be 1 in 1000, with morbidity and mortality of up to 25%. Patients with the HLA-B*5801 haplotype are at greater risk, and the ACR recommends testing for the allele prior to treating patients of Southeast Asian descent (e.g. Han Chinese, Korean, Thai) and African Americans. [3]
  • Liver toxicity - cases of reversible liver toxicity including asymptomatic liver enzyme elevations have been reported in some patients. If signs of liver toxicity develop (e.g. weight loss, jaundice, anorexia), liver functions should be evaluated. In patients with pre-existing liver disease, liver function tests should be monitored periodically when beginning therapy.
  • Renal toxicity - cases of renal toxicity have been observed in patients receiving allopurinol. Patients with kidney disease should be monitored closely when receiving allopurinol.
  • Bone marrow suppression - cases of bone marrow suppression have been reported in patients receiving allopurinol. In most cases, patients were receiving other medications that are potentially myelosuppressive.
  • Liver disease - in patients with liver disease, periodic liver function tests are recommended during the early stages of therapy. Manufacturer makes no dosage recommendations.
  • Kidney disease
    • CrCL < 60 ml/min: the ACR recommends a starting dose of ≤ 50 mg/day to lower the risk of gout flare and allopurinol hypersensitivity syndrome. Dose titrations to ≥ 300 mg/day may still be required and have been shown to be safe in this population. [3]
    • CrCl 10 - 20 ml/min: the prescribing information states that 200 mg/day is a suitable maintenance dose
    • CrCl < 10 ml/min: the prescribing information states that doses should not exceed 100 mg/day, and increasing the dosing interval should be considered

Open all
Febuxostat
Uloric®

Dosage forms

Tablet
  • 40 mg
  • 80 mg

Dosing

Hyperuricemia in gout
  • Starting: 40 mg once daily
  • If patients do not achieve uric acid < 6 mg/dl after 2 weeks then increase dose to 80 mg once daily
  • The ACR states that the dose may be raised to 120 mg once daily (a dose approved in many countries outside the U.S.)
  • When initiating therapy, patients should receive prophylaxis against acute attacks - see ACR recommendations for more

Efficacy

Gout

Generic / Price

  • YES/$

Other

  • May take without regard to food or antacids
  • It is not necessary to discontinue febuxostat during an acute gout flare
  • Maintain good fluid intake

Mechanism of action

  • Xanthine oxidase is a key enzyme involved in the metabolism of purines. Febuxostat inhibits xanthine oxidase and prevents the production of uric acid.
  • See uric acid homeostasis for more

FDA-approved indications

  • Hyperuricemia in gout

Side effects

Side effect Febuxostat 40 mg
(N=757)		 Febuxostat 80 mg
(N=1279)		 Placebo
(N=134)
Liver function abnormalities 6.6% 4.6% 0.7%
Nausea 1.1% 1.3% 0.7%
Arthralgia 1.1% 0.7% 0%
Rash 0.5% 1.6% 0.7%

Drug interactions

  • Azathioprine - DO NOT COMBINE. Febuxostat may inhibit azathioprine metabolism and lead to toxicity.
  • Mercaptopurine - DO NOT COMBINE. Febuxostat may inhibit mercaptopurine metabolism and lead to toxicity.
  • Theophylline - febuxostat inhibits theophylline metabolism. In studies, febuxostat caused a 400-fold increase in the major theophylline metabolite, 1-methylxanthine. Use caution if given concomitantly.
  • Xanthine oxidase substrates - febuxostat inhibits xanthine oxidase, increasing exposure of xanthine oxidase substrates. Use caution when combining.
  • Cytotoxic chemotherapy - febuxostat has not been studied with cytotoxic chemotherapy. Use caution when combining.
  • Rosuvastatin (Crestor®) - febuxostat increases rosuvastatin exposure more than 1.9-fold. Rosuvastatin dosing should not exceed 20 mg/day when combining.
  • In vivo drug interaction studies have shown that febuxostat does not significantly interact with colchicine, naproxen, indomethacin, hydrochlorothiazide, warfarin, or desipramine
  • Febuxostat is metabolized by UGT1A1, UGT1A3, UGT1A9, and UGT2B7. It also undergoes oxidation via CYP1A2, CYP2C8, and CYP2C9. Febuxostat is a CYP2D6 weak inhibitor.

Contraindications / Precautions

  • Acute gout attack - when initiating febuxostat, the risk of an acute gout attack is increased. This may be due to the mobilization of uric acid from tissue deposits which causes fluctuations in uric acid levels. The ACR recommends prophylactic therapy when initiating febuxostat - see gout flare prophylaxis for more.
  • Cardiovascular events - in long-term pre-market studies, there was a slightly higher risk of cardiovascular events in febuxostat-treated patients (0.74 events/100 patients-years) when compared to allopurinol-treated patients (0.60 events/100 patient-years). A follow-up trial published in 2018 that was designed to look specifically at the cardiovascular safety of febuxostat found that among patients with gout and established CVD, febuxostat-treated patients had a significantly higher risk of cardiovascular death (4.3% vs 3.2%) and overall mortality (7.8% vs 6.4%) when compared to allopurinol-treated patients. [PMID 29527974] This study caused the FDA to place a boxed warning on febuxostat about the possibility of an increased risk of cardiovascular death among patients with CVD. Contrarily, a study published in 2020 that was designed to evaluate cardiovascular endpoints among patients with gout and CVD risk factors did not find an increased risk with febuxostat when compared to allopurinol. [PMID 33181081] The ACR recommends that patients with a history of CVD avoid febuxostat if possible.
  • Liver toxicity - there have been case reports of liver toxicity in patients receiving febuxostat. In trials, 3% of febuxostat-treated patients had ALT elevations ≥ 3 X ULN. The manufacturer recommends checking liver enzymes at baseline and in patients who develop signs of liver disease (e.g. fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice). Febuxostat should be discontinued in patients who have ALT levels > 3 X the reference range with serum total bilirubin > 2 X the reference range.
  • Serious skin reactions - serious skin reactions including Stevens-Johnson Syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS) and toxic epidermal necrolysis (TEN) have been reported in patients taking febuxostat. Many of these patients reported previous similar skin reactions to allopurinol.
  • Liver disease
    • Mild to moderate (Child-Pugh A/B): no dose adjustment necessary
    • Severe (Child-Pugh C): has not been studied. Use caution.
  • Kidney disease
    • CrCl ≥ 30 ml/min: no dose adjustment necessary
    • CrCl 15 - 29 ml/min: do not exceed 40 mg once daily

Open all
Probenecid
Probalan®

Dosage forms

Tablet
  • 500 mg

Dosing

Hyperuricemia in gout
  • Starting: 250 mg twice a day for 1 week
  • Maintenance: 500 mg twice a day
  • Maximum: 2000 mg/day
  • Increase daily dose by 500 mg every 4 weeks if necessary
  • If urinary uric acid excretion exceeds 700 mg/day, the risk of kidney stones increases and the dose should be reduced
  • Patients should maintain good fluid intake to help prevent kidney stones
  • Urinary alkalinization with potassium citrate is recommended until serum urate levels return to normal and tophi disappear
  • When initiating therapy, patients should receive prophylaxis against acute gout attacks - see ACR recommendations for more
  • After uric acid levels normalize, dose should be reduced by 500 mg every 6 months to lowest effective dose
Facilitate increase in beta-lactam antibiotic levels
  • 2000 mg/day given in divided doses
  • Beta-lactams include penicillins, cephalosporins, and carbapenems

Generic / Price

  • YES/$

Other

  • It is not necessary to discontinue probenecid during a gout flare
  • Maintain good fluid intake

Mechanism of action

  • Probenecid inhibits renal tubular reabsorption of urate. This causes urate to be lost in the urine. See uric acid homeostasis for more.
  • Probenecid inhibits renal secretion of beta-lactam antibiotics. This causes a 2 - 4 fold increase in beta-lactam plasma levels. Beta-lactams include penicillins, cephalosporins, and carbapenems.

FDA-approved indications

  • Hyperuricemia in gout
  • Facilitate increase in beta-lactam antibiotic levels

Side effects

The incidence of probenecid side effects is not well defined
  • Acute gout attack
  • Kidney stones
  • Urinary frequency
  • Headache
  • Dizziness
  • Vomiting/Nausea/Anorexia
  • Hepatic necrosis
  • Nephrotic syndrome
  • Hypersensitivity reactions
  • Aplastic anemia
  • Leukopenia
  • Hemolytic anemia
  • Dermatitis
  • Alopecia
  • Flushing
  • Sore gums

Drug interactions

  • Acetaminophen - probenecid may increase the half-life of acetaminophen. Lower doses of acetaminophen may be necessary.
  • Baricitinib (Olumiant®) - probenecid increases exposure to baricitinib through OAT3 inhibition. Baricitinib dose should be reduced to 1 mg once daily when taken with probenecid.
  • Beta-lactam antibiotics - probenecid blocks the secretion of beta-lactam antibiotics and raises their plasma levels. This effect can be used therapeutically in some cases, but may lead to adverse drug reactions in other cases. Beta-lactams include penicillins, cephalosporins, and carbapenems.
  • Indomethacin - probenecid may increase the half-life of indomethacin. Lower doses of indomethacin may be necessary.
  • Ketamine - probenecid may increase the effects of ketamine
  • Ketoprofen - probenecid may increase the half-life of ketoprofen. Lower doses of ketoprofen may be necessary.
  • Lorazepam - probenecid may increase the half-life of lorazepam. Lorazepam dose should be decreased by 50% when taken with probenecid.
  • Meclofenamate - probenecid may increase the half-life of meclofenamate. Lower doses of meclofenamate may be necessary.
  • Methotrexate - probenecid may increase plasma concentrations of methotrexate. If given concomitantly, reduce methotrexate dose and monitor blood levels.
  • OAT3 substrates - probenecid is a strong OAT3 inhibitor and it may increase exposure to OAT3 substrates [2]
  • Naproxen - probenecid may increase the half-life of naproxen. Lower doses of naproxen may be necessary.
  • Pyrazinamide - pyrazinamide reduces the uricosuric effects of probenecid
  • Rifampin - probenecid may increase the half-life of rifampin. Lower doses of rifampin may be necessary.
  • Salicylates (aspirin, etc.) - salicylates reduce the uricosuric effects of probenecid. Low-dose aspirin does not appear to have this effect. [12,14]
  • Sulfonamides (e.g. antibiotics, diuretics, sulfonylureas) - probenecid increases sulfonamide levels. The effect is generally mild, but may become significant with prolonged coadministration. Patients taking sulfonylureas should monitor blood glucose levels closely while taking probenecid.
  • Sulindac - probenecid may increase levels of sulindac. Sulindac may cause a modest reduction in the uricosuric effect of probenecid.
  • Thiopental - probenecid may increase the effects of thiopental

Lab interactions

  • Theophylline - probenecid may cause falsely elevated theophylline levels when measured with the Schack and Waxler technique
  • Urine glucose - probenecid may cause a false-positive urine glucose test

Contraindications / Precautions

  • Uric acid kidney stones - DO NOT USE. Probenecid should not be given to patients with a history of uric acid kidney stones.
  • Blood dyscrasias - DO NOT USE
  • Calcium kidney stones - probenecid increases the risk of both uric acid and calcium kidney stones. Probenecid should not be used as a first-line agent in patients with a history of calcium stones. Urinary alkalinization with potassium citrate may be necessary to prevent kidney stones in some patients. See kidney stones for more.
  • Uricosuria - urinary uric acid levels should be measured before and during therapy as appropriate. If levels are elevated, probenecid is contraindicated. If urinary uric acid rises above 700 mg/day during therapy, the risk of kidney stones is increased and the dosage should be reduced.
  • Acute gout attack - when initiating probenecid, the risk of an acute gout attack is increased. This may be due to the mobilization of uric acid from tissue deposits which causes fluctuations in uric acid levels. The ACR recommends prophylactic therapy when initiating probenecid - see gout flare prophylaxis for more.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported with probenecid
  • Peptic ulcers - use caution
  • Liver disease - manufacturer makes no specific recommendation
  • Kidney disease - probenecid may be less effective in patients with kidney disease, particularly when the CrCl is less than 30 ml/min. Probenecid should not be used as a first-line agent when the CrCl is less than 50 ml/min. Probenecid should not be used to increase beta-lactam levels in patients with kidney disease.

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Colchicine
Colcrys®, Mitigare®, Gloperba®

Dosage forms

Tablet (Colcrys®)
  • 0.6 mg
Capsule (Mitigare®)
  • 0.6 mg
Solution (Gloperba®)
  • 0.6 mg/5 ml
  • Comes in 150 ml bottle

Dosing - Colcrys®

Treatment of acute gout flare (adults)
  • 1.2 mg at the first sign of a flare followed by 0.6 mg one hour later
  • The maximum dose for an acute flare is 1.8 mg over one hour
  • If taking during a prophylactic regimen, wait 12 hours before resuming the regimen
  • May take without regard to food
Gout flare prophylaxis (≥ 16 years old)
  • 0.6 mg once or twice daily
  • Maximum recommended dose is 1.2 mg/day
  • May take without regard to food
Familial Mediterranean Fever (adults)
  • 1.2 - 2.4 mg/day given in one or two divided doses
  • Increase dose in increments of 0.3 mg/day as tolerated
  • May take without regard to food
Familial Mediterranean Fever (children ≥ 4 years)
  • 4 - 6 years: 0.3 - 1.8 mg/day given in one or two divided doses
  • 6 - 12 years: 0.9 - 1.8 mg/day given in one or two divided doses
  • > 12 years: 1.2 - 2.4 mg/day given in one or two divided doses
  • May take without regard to food
Dosing with CYP3A4 and/or P-glycoprotein inhibitors
  • Colchicine is a CYP3A4 and P-glycoprotein sensitive substrate
  • The Colcrys PI [sec 2.4] gives specific dosing recommendations for concomitant therapy with certain CYP3A4 and P-glycoprotein inhibitors

Dosing - Mitigare® | Gloperba®

Gout flare prophylaxis (adults)
  • 0.6 mg once or twice daily
  • Maximum recommended dose is 1.2 mg/day
  • May take without regard to food

Efficacy

Acute gout flare Gout flare prophylaxis Cardiovascular disease

Generic / Price

  • Colcrys® (30 tablets) - YES/$
  • Mitigare® (30 capsules) - YES/$$

Mechanism of action

  • The mechanism of colchicine is not completely understood. Evidence suggests it may interfere with the intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates activation of interleukin-1β. Additionally, colchicine disrupts cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules, and consequently prevents the activation, degranulation, and migration of neutrophils thought to mediate some gout symptoms.

FDA-approved indications

Colcrys
  • Treatment of acute gout attacks
  • Gout flare prophylaxis
  • Familial Mediterranean fever
Mitigare
  • Gout flare prophylaxis

Side effects

Acute gout flare trial
Side effect Colcrys 1.8 mg over 1 hr
(N=74)		 Placebo
(N=59)
Diarrhea 23% 14%
Gout 4% 2%
Throat pain 3% 0%

Drug interactions

  • Colcrys PI [sec 2.4] - the Colcrys PI gives specific dosing recommendations for Colcrys when it is given with certain CYP3A4 and P-glycoprotein inhibitors
  • Dual inhibitors of CYP3A4 and P-glycoprotein in renal or hepatic impairment - DO NOT COMBINE colchicine with dual inhibitors of CYP3A4 and P-glycoprotein (e.g. clarithromycin) in patients with renal or hepatic impairment
  • CYP3A4 inhibitors - colchicine is a sensitive CYP3A4 substrate, and CYP3A4 inhibitors may increase its exposure. The combination of colchicine with CYP3A4 inhibitors is not recommended. If co-administration cannot be avoided, the colchicine dose or frequency should be reduced, and the patient should be monitored for signs of toxicity, including abdominal pain, nausea, vomiting, and diarrhea.
  • Fibrates - the risk of myopathy may be increased when colchicine is taken with fibrates. Consider alternative therapy and check CK levels in patients who report muscle pain.
  • P-glycoprotein inhibitors - colchicine is a sensitive P-glycoprotein substrate, and P-glycoprotein inhibitors may increase its exposure. The combination of colchicine with P-glycoprotein inhibitors is not recommended. If co-administration cannot be avoided, the colchicine dose or frequency should be reduced, and the patient should be monitored for signs of toxicity, including abdominal pain, nausea, vomiting, and diarrhea.
  • Statins - the risk of myopathy may be increased when colchicine is taken with statins. Consider alternative therapy and check CK levels in patients who report muscle pain.

Contraindications / Precautions

  • Blood dyscrasias - blood dyscrasias, including leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia, have been reported in patients receiving colchicine. The risk is greater in patients with conditions that increase colchicine exposure, including kidney disease, liver disease, and concomitant CYP3A4 and/or P-glycoprotein inhibitors. Use caution in at-risk patients and monitor for gastrointestinal symptoms, which are often the first signs of toxicity.
  • Neuromuscular toxicity - Neuromuscular toxicity, including rhabdomyolysis, has been reported in patients receiving colchicine. The risk is greater in patients with conditions that increase colchicine exposure, including kidney disease, liver disease, and concomitant CYP3A4 and/or P-glycoprotein inhibitors. Combined use with other myopathy-inducing drugs (e.g. statins, fibrates) may also increase the risk. Use caution in at-risk patients and monitor for gastrointestinal symptoms, which are often the first signs of toxicity.
  • Liver disease
    • Gout flare prophylaxis
      • Mild to moderate (Child-Pugh A/B): no dose adjustment necessary
      • Severe (Child-Pugh C): consider dose adjustment. Manufacturer makes no specific recommendation.
    • Treatment of acute attack
      • Mild to moderate (Child-Pugh A/B): no dose adjustment necessary
      • Severe (Child-Pugh C): no dose adjustment necessary. Do not repeat treatment course more than once every 2 weeks.
      • Patients receiving colchicine prophylaxis with any degree liver disease: do not use colchicine for acute attack
  • Kidney disease
    • Gout flare prophylaxis
      • CrCl ≥ 30 ml/min: no dose adjustment necessary
      • CrCl < 30 ml/min: starting dose is 0.3 mg once daily. Increase dose with caution.
    • Treatment of acute attack
      • CrCl ≥ 30 ml/min: no dose adjustment necessary
      • CrCl < 30 ml/min: no dose adjustment necessary. Do not repeat treatment course more than once every 2 weeks.
      • Patients receiving colchicine prophylaxis with any degree kidney disease: do not use colchicine for acute attack

Open all
Pegloticase
Krystexxa®

Dosage forms

Vial
  • 8 mg single use vial

Dosing

Hyperuricemia in gout
  • Dosing: 8 mg via IV infusion every 2 weeks co-administered with weekly oral methotrexate 15 mg and folic acid or folinic acid supplementation. Pegloticase alone may be used in patients for whom methotrexate is contraindicated or not clinically appropriate. See methotrexate for more.
  • If co-administering with methotrexate, start weekly methotrexate and folic acid at least 4 weeks prior to pegloticase and continue throughout treatment
  • Pegloticase should only be used in patients who cannot tolerate or did not respond to other urate-lowering therapies
  • There is no consensus on the appropriate duration of therapy
  • Pegloticase should not be given concurrently with other urate-lowering therapies to avoid masking the loss of a pegloticase serum urate-lowering effect. Loss of effectiveness is associated with an increased risk of anaphylaxis and infusion reactions.
  • Consider discontinuing if uric acid levels rise above 6 mg/dl, particularly on 2 consecutive levels
  • Prophylactic gout attack therapy should be initiated 1 week before starting pegloticase and continue for at least 6 months. See ACR recommendations for more.

Efficacy

Generic / Price

  • NO/$$$$

Other

  • Unopened vials should be refrigerated
  • Infuse over no less than 2 hours
  • Patients should be premedicated before infusions. In trials, the following was given: fexofenadine 60 mg the evening before and again before infusion; acetaminophen 1000 mg + hydrocortisone 200 mg IV immediately before infusion. [15]
  • Infusions should be done in a healthcare setting. Patients should be observed for one hour after infusion.
  • It is not necessary to stop pegloticase during a gout flare

Mechanism of action

  • The uricase enzyme is found in many animals but not in humans. Uricase converts uric acid to allantoin, a highly soluble, easily eliminated purine metabolite. Pegloticase is a recombinant version of uricase.
  • See uric acid homeostasis for more

FDA-approved indications

  • Treatment of chronic gout in adult patients refractory to conventional therapy

Side effects

Side effect Pegloticase
(N=85)		 Placebo
(N=43)
Gout flare 77% 81%
Infusion reactions 26% 5%
Nausea 12% 2%
Bruising 11% 5%
Nasopharyngitis 7% 2%
Constipation 6% 5%
Chest pain 6% 2%
Anaphylaxis 5% 0%
Vomiting 5% 2%

Drug interactions

  • Methotrexate - methotrexate may increase pegloticase levels. It is recommended that pegloticase be taken with methotrexate when possible.
  • PEGylated products - because anti-pegloticase antibodies appear to bind to the PEG portion of the drug, there may be potential for binding with other PEGylated products. The impact of anti-PEG antibodies on patient responses to other PEG-containing therapeutics is unknown.

Contraindications / Precautions

  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency - DO NOT USE. Patients with G6PD deficiency are at increased risk of pegloticase-induced hemolysis and methemoglobinemia. Patients at high risk for G6PD deficiency (e.g. African or Mediterranean ancestry) should be screened for G6PD deficiency before initiating pegloticase.
  • Anaphylaxis - in pre-marketing trials, anaphylaxis occurred in 6.5% of patients receiving pegloticase every 2 weeks and 4.8% receiving it every 4 weeks. No cases occurred in placebo-treated patients. Treatment in these trials was not discontinued following 2 consecutive serum uric acid levels above 6 mg/dL, a precaution that lowers the risk of anaphylaxis. In a 52-week trial that compared pegloticase + methotrexate (peg/mtx) to pegloticase, pegloticase was discontinued following 2 consecutive serum uric acid levels above 6 mg/dL, and the incidence of anaphylaxis was 1% in peg/mtx-treated patients and 0% in pegloticase-treated patients. Anaphylaxis may occur with any infusion and generally manifests within 2 hours. Patients should be premedicated to help prevent reactions. In trials, the following regimen was given: fexofenadine 60 mg the evening before and again before infusion; acetaminophen 1000 mg + hydrocortisone 200 mg IV immediately before infusion. [15]
  • Infusion reactions - in trials, infusion reactions occurred in up to 31% of patients treated with pegloticase alone and 4% of patients who received pegloticase with methotrexate. Common reactions included urticaria (10.6%), dyspnea (7.1%), chest discomfort (9.5%), chest pain (9.5%), erythema (9.5%), and pruritus (9.5%). 91% of reactions occurred at the time of infusion. Some reactions were abated by slowing the infusion and/or stopping the infusion and restarting at a slower rate.
  • Loss of pegloticase efficacy - patients who lose their response to pegloticase are at higher risk for anaphylaxis and infusion reactions. This is due to the development of anti-pegloticase antibodies. If uric acid levels rise above 6 mg/dl, particularly on 2 consecutive readings, pegloticase should be discontinued. Other uric acid-lowering therapies should not be given with pegloticase because they may mask a loss of efficacy.
  • Anti-pegloticase antibodies - in pre-marketing trials, 92% of pegloticase-treated patients developed anti-pegloticase antibodies compared to 28% of placebo-treated patients. In a 52-week postmarket trial, 26% of patients had antibodies to pegloticase at baseline. An increase in antibody titers or development of antibodies was seen in 30% of pegloticase + methotrexate-treated patients and 51% of pegloticase-treated patients. Higher antibody titers are associated with a loss of efficacy and an increase in anaphylaxis and infusion reactions.
  • Anti-PEG antibodies - in trials, 42% of pegloticase-treated patients developed antibodies to the PEG portion of the drug. The impact of anti-PEG antibodies on patient responses to other PEG-containing therapeutics is unknown.
  • Acute gout attack - when initiating pegloticase, the risk of an acute gout attack increases. In trials, flares occurred in 74% of patients during the first 3 months of therapy despite receiving prophylaxis. Flares decreased after 3 months but still were seen in 41% of patients. Worsening of gout during therapy initiation is thought to be secondary to the mobilization of uric acid from tissue deposits which causes fluctuations in uric acid levels. Prophylactic gout attack therapy should be initiated 1 week before starting pegloticase and continue for at least 6 months. See ACR recommendations for more.
  • Heart failure - in trials, heart failure exacerbations occurred in a small number of pegloticase-treated patients. Use caution in susceptible patients.
  • Retreatment with pegloticase - the safety of retreating patients with pegloticase after stopping therapy for ≥ 4 weeks is unknown. Because of the high incidence of anti-pegloticase antibodies in treated patients, the risk of hypersensitivity reactions may be increased in patients who are retreated. Use caution in these patients.
  • Liver disease - has not been studied
  • Kidney disease - no dose adjustment necessary

Col-Probenecid®
Probenecid + colchicine

Dosage forms

Tablet
  • Probenecid : Colchicine
    • 500 mg : 0.5 mg

Dosing

Hyperuricemia in gout complicated by frequent attacks
  • Starting: One tablet once daily for a week
  • Maintenance: One tablet twice a day
  • Maximum: 4 tablets a day
  • Increase dose by 1 tablet every 4 weeks if symptoms are not controlled
  • If urinary uric acid excretion exceeds 700 mg/day, the risk of kidney stones increases and the dose should be reduced
  • Liberal fluid intake should be encouraged while taking
  • Sodium bicarbonate (3 to 7.5 g daily) or potassium citrate (7.5 g daily) supplementation may be necessary to maintain an alkaline urine

Generic / Price

  • YES/$

PRICE ($) INFO

  • $ = 0 - $50
  • $$ = $51 - $100
  • $$$ = $101 - $150
  • $$$$ = > $151
  • Pricing based on one month of therapy at standard dosing in an adult
  • Pricing based on information from GoodRX.com®
  • Pricing may vary by region and availability

BIBLIOGRAPHY