GOUT MEDICATIONS

PRICING INFO


PEGLOTICASE STUDIES



Drug Dosage form Dosage Generic / Price Other Mechanism of Action / FDA-approved indications Side Effects Drug Interactions Precautions / Contraindications
Colchicine

Colcrys®
Mitigare®
Tablet - Colcrys®
  • 0.6 mg

Capsule - Mitigare®
  • 0.6 mg
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
    Gout flare prophylaxis (≥ 16 years old)
    • 0.6 mg once or twice daily
    • Maximum recommended dose is 1.2 mg/day
    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
    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

Mitigare®

    Gout flare prophylaxis - Adults
    • 0.6 mg once or twice daily
    • Maximum recommended dose is 1.2 mg/day

Dosing with CYP3A4 and/or P-glycoprotein inhibitors
Colcrys®
YES/$ (3 tablets)

Mitigare®
YES/$$-$$$
(30 capsules)

  • May take without regard to food
Mechanism of action
  • Mechanism not completely understood
  • Evidence suggests that colchicine 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
NOTE: P = % of patients on placebo who reported side effect. Only side effects that occurred at an overall incidence of ≥ 2% and at an incidence greater than placebo are listed. Data is from Colcrys PI.

  • Diarrhea - 23%, P - 14%
  • Gout - 4%, P - 2%
  • Throat pain - 3%, P - 0%
  • Colchicine is a CYP3A4 and P-glycoprotein sensitive substrate. Colchicine has an extensive list of potential drug interactions. See the Colcrys PI [sec 2.4 and 7] for a list of interactions and recommendations.
  • Colchicine should not be given with P-glycoprotein inhibitors or strong CYP3A4 inhibitors in patients with renal or hepatic disease. Patients with normal renal and hepatic function may require dose adjustments.
  • Drug interactions - colchicine should not be given with P-glycoprotein inhibitors or strong CYP3A4 inhibitors in patients with renal or hepatic disease. Patients with normal renal and hepatic function may require dose adjustments. See the Colcrys PI [sec 2.4 and 7] for recommendations.
  • Blood dyscrasias - blood dyscrasias including leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia have been reported in patients taking colchicine
  • Muscle toxicity - neuromuscular toxicity including rhabdomyolysis has been reported in patients receiving colchicine. Elderly patients and patients with kidney disease may be at increased risk. Concomitant statins, fibrates, or cyclosporine may also increase the risk.
  • 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
Drug Dosage form Dosage Generic / Price Other Mechanism of Action / FDA-approved indications Side Effects Drug Interactions Precautions / Contraindications
Allopurinol

Zyloprim®
Tablet
  • 100 mg
  • 300 mg
Hyperuricemia in gout
  • Starting: 100 mg once daily
  • 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 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
Allopurinol
YES/$

  • 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
NOTE: Incidence of side effects is not well-defined

  • Acute gout attack - up to 6%
  • Rash - up to 3%
  • Diarrhea
  • Nausea
  • Elevated liver enzymes
  • Drowsiness
  • 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
  • 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 - allopurinol may cause a hypersensitivity syndrome marked by Stevens-Johnson syndrome, toxic epidermal necrolysis, eosinophilia, vasculitis, rash, and major end-organ disease. The incidence of the syndrome is estimated to be ∼ 1:1000 in the U.S.. The syndrome has a morbidity and mortality rate of up to 25%. The HLA-B*5801 haplotype has been associated with an increased risk. The ACR recommends testing high-risk individuals for the HLA-B*5801 haplotype before initiating allopurinol therapy. High-risk individuals include Han Chinese and Thai regardless of kidney function, and Koreans with CrCl ≤ 59 ml/min.
  • 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 10 - 20 ml/min: recommended dose is 200 mg/day
    • CrCl < 10 ml/min: do not exceed 100 mg/day. Consider increasing dosing interval.

Drug Dosage form Dosage Generic / Price Other Mechanism of Action / FDA-approved indications Side Effects Drug Interactions Precautions / Contraindications
Febuxostat

Uloric®
Tablet
  • 40 mg
  • 80 mg
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
Febuxostat
NO/$$$$

  • 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
NOTE: P = % of patients on placebo who reported side effect. Only side effects that were seen in ≥ 1% of febuxostat patients and at an incidence ≥ 0.5% more than placebo are listed. Data is for febuxostat 80 mg.

  • Elevated liver enzymes - 4.6%, P - 0.7%
  • Nausea - 1.3%, P - 0.7%
  • Arthralgia - 0.7%, P - 0%
  • Rash - 1.6%, P - 0.7%
  • 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.
  • Febuxostat is metabolized by UGT1A1, UGT1A3, UGT1A9, and UGT2B7. It also undergoes oxidation via CYP1A2, CYP2C8, and CYP2C9. Febuxostat is a CYP2D6 weak inhibitor.
  • 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 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). In 2017, the FDA issued a warning that preliminary results from an ongoing study showed a higher risk of heart-related death in febuxostat-treated patients when compared to allopurinol-treated patients. When final results from the trial are available, the FDA will issue another alert.
  • 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.
  • 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
Drug Dosage form Dosage Generic / Price Other Mechanism of Action / FDA-approved indications Side Effects Drug / Lab Interactions Precautions / Contraindications
Probenecid

Probalan®
Tablet - Probenecid
  • 500 mg

Col-Probenecid®
  • Colchicine : Probenecid
    • 0.5 mg : 500 mg
Probenecid
    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

Col-Probenecid®

    Treatment of gout
    • 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
    • See colchicine for more
Probenecid
YES/$ (60 tablets)

Col-Probenecid®
YES/$ (60 tablets)
  • 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
Probenecid
  • Hyperuricemia in gout
  • Facilitate increase in beta-lactam antibiotic levels
Col-Probenecid
  • Hyperuricemia in gout complicated by frequent attacks
NOTE: Incidence of side effects and strength of association are 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
  • Salicylates (aspirin, etc.) - salicylates reduce the uricosuric effects of probenecid. Low-dose aspirin does not appear to have this effect. [12,14]
  • 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.
  • Pyrazinamide - pyrazinamide reduces the uricosuric effects of probenecid
  • 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.
  • Indomethacin - probenecid may increase the half-life of indomethacin. Lower doses of indomethacin may be necessary.
  • Acetaminophen - probenecid may increase the half-life of acetaminophen. Lower doses of acetaminophen may be necessary.
  • Naproxen - probenecid may increase the half-life of naproxen. Lower doses of naproxen may be necessary.
  • Ketoprofen - probenecid may increase the half-life of ketoprofen. Lower doses of ketoprofen may be necessary.
  • Meclofenamate - probenecid may increase the half-life of meclofenamate. Lower doses of meclofenamate may be necessary.
  • Sulindac - probenecid may increase levels of sulindac. Sulindac may cause a modest reduction in the uricosuric effect of probenecid.
  • Lorazepam - probenecid may increase the half-life of lorazepam. Lorazepam dose should be decreased by 50% when taken with probenecid.
  • Methotrexate - probenecid may increase plasma concentrations of methotrexate. If given concomitantly, reduce methotrexate dose and monitor blood levels.
  • Rifampin - probenecid may increase the half-life of rifampin. Lower doses of rifampin may be necessary.
  • Thiopental - probenecid may increase the effects of thiopental
  • Ketamine - probenecid may increase the effects of ketamine

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
  • 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.
Drug Dosage form Dosage Generic / Price Other Mechanism of Action / FDA-approved indications Side Effects Drug interactions Precautions / Contraindications
Lesinurad

Zurampic®
Tablet - lesinurad
  • 200 mg
Hyperuricemia in gout
  • Dosing: 200 mg once daily
  • Maximum: 200 mg once daily
  • Lesinurad should be taken with a xanthine oxidase inhibitor (allopurinol or febuxostat). It should not be used as monotherapy.
  • Lesinurad is not recommended in patients taking < 300 mg of allopurinol (or < 200 mg in patients with CrCl < 60 ml/min)
  • If xanthine oxidase inhibitor therapy is interrupted, lesinurad should also be interrupted. Failure to do so may increase risk of renal events.
  • When initiating therapy, patients should receive prophylaxis for acute gout attacks - see ACR recommendations for more
Lesinurad
NO/$$$$
  • Take in the morning with food or water

  • Take at the same time as xanthine oxidase inhibitor

  • Maintain good fluid intake of at least 2 liters/day

  • It is not necessary to stop lesinurad therapy during an acute gout flare
Mechanism of action
  • Lesinurad inhibits renal tubular reabsorption of uric acid. Lesinurad has been shown to inhibit uric acid transporter 1 (URAT1) and organic anion transporter 4 (OAT4). URAT1 is responsible for the majority of the reabsorption of filtered uric acid from the renal tubular lumen.
  • See uric acid homeostasis for more

FDA-approved indications
  • Hyperuricemia in gout - should only be used in combination with a xanthine oxidase inhibitor in patients who have not achieved target uric acid levels on a xanthine oxidase inhibitor alone
NOTE: P = % of patients on placebo who reported side effect. Only side effects that occurred at an overall incidence of ≥ 2% and ≥ 1% more than placebo are listed

  • Headache - 5.3%, P - 4.1%
  • Influenza - 5.1%, P - 2.7%
  • Increased serum creatinine - 4.3%, P - 2.3%
  • GERD - 2.7%, P - 0.8%
  • Valproic acid - DO NOT COMBINE. Valproic acid is an epoxide hydrolase inhibitor. Epoxide hydrolase inhibitors may block the metabolism of lesinurad.
  • Epoxide hydrolase inhibitors - DO NOT COMBINE. Epoxide hydrolase inhibitors may block the metabolism of lesinurad. Lesinurad should not be given with epoxide hydrolase inhibitors.
  • CYP2C9 inhibitors and inducers - lesinurad is a sensitive CYP2C9 substrate. CYP2C9 inhibitors may increase blood levels of lesinurad and CYP2C9 inducers may decrease blood levels. Use caution when combining.
  • CYP3A4 substrates - lesinurad is weak inducer of CYP3A4. Blood levels of CYP3A4 sensitive substrates may be reduced when taken with lesinurad.
  • Hormone contraceptives - hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable when taken with lesinurad. Backup forms of contraception should be used.
  • Aspirin - Aspirin at doses > 325 mg/day may decrease the effectiveness of lesinurad. Doses ≤ 325 mg/day do not decrease the efficacy of lesinurad.
  • Sildenafil - in studies, lesinurad reduced plasma concentrations of sildenafil, a CYP3A4 substrate
  • Amlodipine - in studies, lesinurad reduced plasma concentrations of amlodipine, a CYP3A4 substrate
  • CYP2C9 poor metabolizers - lesinurad is a CYP2C9 sensitive substrate. Poor CYP2C9 metabolizers may have increased exposure to lesinurad. Use caution in these patients.
  • Tumor lysis syndrome - DO NOT USE
  • Lesch-Nyhan syndrome - DO NOT USE
  • Renal events - in trials, more patients on lesinurad had increases in serum creatinine than patients on placebo. Creatinine elevations 1.5 to < 2 X baseline occurred in 3.9% of lesinurad-treated patients and 2.3% of placebo-treated patients. Creatinine elevations ≥ 2 X baseline occurred in 1.8% of lesinurad-treated patients and 0% of placebo-treated patients. In 90% of patients, the elevations resolved with continued treatment. Renal function should be evaluated before treatment and periodically thereafter. Patients with CrCl < 60 ml/min, and those with increases in serum creatinine after starting therapy should be monitored more frequently. Treatment should be held if serum creatinine rises above 2 X the baseline value.
  • Kidney stones - lesinurad increases the urinary excretion of uric acid which can increase the risk of both uric acid stones and calcium stones. Use caution in susceptible patients.
  • Acute gout attack - when initiating lesinurad, 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 uric acid-lowering therapy - see gout flare prophylaxis for more.
  • Liver disease
    • Mild to moderate (Child-Pugh A/B): no dose adjustment necessary
    • Severe (Child-Pugh C): has not been studied. Not recommended.
  • Kidney disease
    • CrCl ≥ 45 ml/min - no dose adjustment necessary
    • CrCl < 45 ml/min - DO NOT USE
Drug Dosage form Dosage / Studies Generic / Price Other Mechanism of Action / FDA-approved indications Side Effects Drug interactions Precautions / Contraindications
Pegloticase

Krystexxa®
Vial
  • 8 mg single use vial
Dosing

    Hyperuricemia in gout
    • Dosing: 8 mg via IV infusion every 2 weeks
    • 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.

Studies
Pegloticase
NO/$$$$
  • 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
  • Hyperuricemia in gout - for use in patients who are refractory to other treatments
NOTE: P = % of patients on placebo who reported side effect. Only side effects that occurred at an incidence of ≥ 5% are listed

  • Gout flare - 77%, P - 81%
  • Infusion reactions - 26%, P - 5%
  • Nausea - 12%, P - 2%
  • Bruising - 11%, P - 5%
  • Nasopharyngitis - 7%, P - 2%
  • Constipation - 6%, P - 5%
  • Chest pain - 6%, P - 2%
  • Anaphylaxis - 5%, P - 0%
  • Vomiting - 5%, P - 2%
  • No known reactions
  • 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 patients’ responses to other PEG-containing therapeutics is unknown.
  • 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 trials, anaphylaxis occurred in 6.5% of patients treated with pegloticase. All patients were premedicated before infusions so the actual incidence may be higher. Anaphylaxis may occur with any infusion and generally manifests within 2 hours of an infusion. Patients should be premedicated before infusions. 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 26% of patients. 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, consideration should be given to stopping pegloticase. Other uric acid-lowering therapies should not be given with pegloticase because they may mask a loss of efficacy.
  • Anti-pegloticase antibodies - in trials, 92% of pegloticase-treated patients developed anti-pegloticase antibodies compared to 28% of placebo-treated patients. High antibody titers were 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 patients’ responses to other PEG-containing therapeutics is unknown.
  • Acute gout attack - when initiating pegloticase, 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. 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
Drug Dosage form Dosage Generic / Price FDA-approved indications
Col-Probenecid®

probenecid + colchicine
Tablet
  • Probenecid / Colchicine
    • 500 mg / 0.5 mg
    Treatment of gout
    • 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

YES/$ (60 tablets)
  • Hyperuricemia in gout complicated by frequent attacks
Drug Dosage form Dosage Generic / Price FDA-approved indications
Duzallo®

lesinurad + allopurinol
Tablet
  • Lesinurad / Allopurinol
    • 200 mg / 200 mg
    • 200 mg / 300 mg
    Hyperuricemia associated with gout
    • Dosing: One tablet once daily in the morning with food and water
    • Maximum: One tablet once daily
    • Dosage strength should be based on current dose of allopurinol
    • Patients should stay well hydrated (≥ 2 liters of liquid/day)
    • Do not initiate therapy in patients with CrCl < 45 ml/min
    • Gout flare prophylaxis should be used when initiating Duzallo. See ACR recommendations for more.

NO/$$$$
  • Treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a medically appropriate daily dose of allopurinol alone