Treatment of chronic or intermittent gouty arthritis and tophaceous gout.
Used in patients with frequent disabling attacks of gout.
Used when tophi are visible or serum urate concentrations are >8.5–9 mg/dL in patients with family history of tophi or low uric acid excretion.
Not recommended for management of asymptomatic hyperuricemia; however, some clinicians initiate therapy when serum urate concentrations are >9 mg/dL (by colorimetric method) because such concentrations often are associated with increased joint changes and renal complications.
Goal of therapy is to lower serum urate concentrations to about 6 mg/dL.
Alternative to probenecid, which generally is better tolerated. May be used with allopurinol for additive effect, especially in the presence of tophaceous deposits. May be used with probenecid if the uricosuric response to one drug is insufficient at maximum therapeutic dosage.
Not effective in patients with moderate to severe chronic renal insufficiency. (See Renal Impairment under Cautions.)
Of no value in the treatment of acute gout attacks. (See Actions and also see Acute Gout under Cautions.)
Hyperuricemia Secondary to Other Causes
Has been used effectively and is commonly employed to promote uric acid excretion in hyperuricemia secondary to administration of thiazide and related diuretics†, furosemide†, ethacrynic acid†, pyrazinamide†, or ethambutol†.
Do not use to treat hyperuricemia secondary to cancer chemotherapy, radiation, or myeloproliferative neoplastic diseases; may increase risk of uric acid nephropathy.
Platelet Aggregation Inhibition
Has been used to decrease platelet aggregation and increase platelet survival time in cardiovascular disorders†, including angina, MI, TIAs, amaurosis fugax, peripheral arterial atherosclerosis, DVT and recurrent venous thrombosis, and in patients with arteriovenous dialysis shunts and prosthetic mitral valves.
Not associated with benefit in patients with unstable angina or non-ST-segment elevation MI†; not recommended by ACC/AHA as antiplatelet therapy in such patients.
Has been used to maintain graft patency in patients undergoing CABG surgery†; however, not consistently effective and not recommended by the American College of Chest Physicians (ACCP) for this use.
Dosage and Administration
General
All patients should maintain daily urine output at ≥2–3 L; alkalinization of urine desirable.
Administration
Oral Administration
Take with meals, milk, or antacids to minimize adverse GI effects.
Dosage
Adjust dosage according to the response and tolerance of the patient.
Use low dosages initially to reduce possibility of acute gout attacks and prevent massive uricosuria.
Adults
Hyperuricemia Associated with Gout
Oral
Initially, 100–200 mg twice daily during the first week of therapy, then increase as needed to full maintenance dosage of 200–400 mg twice daily. Serum urate concentrations usually fall to minimum levels within a few days; once controlled, may attempt to reduce dosage to 200 mg daily in divided doses.
Patients previously controlled with other uricosuric therapy may begin sulfinpyrazone at full maintenance dosage.
Uricosuric therapy should be continued indefinitely and without interruption; irregular dosage schedules may result in increased serum urate concentrations.
Inhibition of Platelet Aggregation
Oral
600–800 mg daily has been used.†
Special Populations
Hepatic Impairment
No specific dosage recommendations at this time.
Renal Impairment
No specific dosage recommendations at this time. (See Renal Impairment under Cautions.)
Geriatric Patients
No specific dosage recommendations at this time.
Cautions
Contraindications
Active peptic ulcer or symptoms of GI inflammation or ulceration.
Known hypersensitivity to sulfinpyrazone or any ingredient in the formulation, or to other pyrazolone derivatives such as phenylbutazone.
Some formulations contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.
General Precautions
Hematologic Effects
Pyrazole compound; closely monitor patients and perform periodic blood counts.
Acute Gout
Of no value in treatment of acute gout attacks; will prolong and exacerbate inflammation during the acute phase. May increase frequency of acute attacks during the first 6–12 months of therapy despite maintenance of normal or subnormal serum urate concentrations. Therefore, administer prophylactic doses of colchicine concurrently during first 3–6 months of therapy.
Acute attacks usually become less severe and of briefer duration after several months; during acute attacks, continue sulfinpyrazone and give full therapeutic doses of colchicine or other anti-inflammatory agents.
Urolithiasis
May promote development of uric acid stones; may cause renal colic and hematuria, especially early in therapy. Advise patient to ingest large amounts of fluids to maintain large volumes of alkaline urine to reduce risk of stone formation. Allopurinol preferred in patients with urinary uric acid excretion >900 mg/day or with gouty nephropathy, urinary tract stones or obstruction, or azotemia.
GI Effects
May reactivate or aggravate peptic ulcers. May use with caution in patients with history of healed peptic ulcer.
Specific Populations
Pregnancy
No reports of congenital malformation. Use caution in pregnant women, weighing possible risks against potential benefits.
Pediatric Use
Safety and efficacy not established.
Renal Impairment
Use caution in patients with mild renal impairment; avoid when Clcr <50 mL/minute. Assess renal function periodically in patients with impaired renal function.
Common Adverse Effects
Nausea, dyspepsia, GI pain and blood loss, reactivation or aggravation of peptic ulcer, rash, dizziness, vertigo, tinnitus, edema.
Interactions
Weak Organic Acids
Competitively inhibits renal tubular secretion of many weak organic acids, possibly potentiating their effects by elevating plasma concentrations. Substantially increases plasma concentrations of acidic drugs eliminated principally by renal secretion, but increases plasma concentrations only slightly if the drug is eliminated mainly by glomerular filtration. Drugs for which high urinary concentrations are desired (i.e. nitrofurantoin) may be less effective due to blocked renal secretion.
Protein-bound Drugs
Because of high protein binding, could interact with other protein-bound drugs; observe for signs of toxicity if such drugs used concurrently.
Drugs that Increase Serum Uric Acid
Increase in sulfinpyrazone dosage may be necessary. Avoid uricosurics in patients receiving cancer chemotherapy due to risk of uric acid nephropathy.
Use with caution and close monitoring; consider different uricosuric agent
Pharmacokinetics
Absorption
Bioavailability
Rapidly and completely absorbed from GI tract. Peak plasma concentrations reached 1–2 hours after single oral dose.
Duration
Usually 4–6 hours (up to 10 hours).
Distribution
Plasma Protein Binding
Approximately 98% bound to plasma proteins.
Elimination
Metabolism
Rapidly metabolized in liver to glucuronide conjugate and three oxidation products: a sulfone, a 4-hydroxy, and a p-hydroxy compound, which possesses uricosuric activity.
Elimination Route
Small amounts of sulfinpyrazone filtered at glomeruli; most actively secreted at proximal tubule. Minimal amounts then reabsorbed by kidney tubule. After 2 days, approximately 45% of a single oral 200-mg dose is excreted in urine as unchanged drug, 25% as sulfinpyrazone glucuronide, and 10% as the other 3 metabolites. Approximately 5% of dose excreted in feces.
Half-life
3 hours (range 1–9 hours).
Stability
Storage
Oral
Capsules and Tablets
15–30°C in tight containers.
Actions
Pyrazolone-derivative renal tubular blocking agent; competitively inhibits active reabsorption of uric acid at proximal convoluted tubule, promoting urinary excretion of uric acid and resorption of tophi and reducing serum urate concentrations.
May reduce plasma protein binding of urate and, in subtherapeutic doses, may inhibit renal secretion of uric acid. Has no effect on glomerular filtration rate or tubular reabsorption of normal urinary constituents such as sodium, potassium, and water in healthy patients.
Exerts no clinically apparent analgesic or anti-inflammatory activity. (See Acute Gout under Cautions.)
Inhibits release of adenosine monophosphate, diphosphate, and triphosphate and 5-hydroxytryptamine (5-HT); inhibition of adenosine diphosphate and 5-HT results in decreased platelet adhesiveness and increases platelet survival time. No effect on plasma prothrombin or thromboplastin levels but may increase platelet count. Blood clotting time not altered.
A small but significant lowering of serum cholesterol has been demonstrated in gouty patients receiving sulfinpyrazone.
Advice to Patients
Importance of informing patient that sulfinpyrazone is not intended for relief of an acute gout attack.
Importance of taking with meals, milk, or antacids to minimize adverse GI effects.
Importance of informing patient that acute gout attacks may increase in frequency during the first 6–12 months of therapy, then diminish. Continue sulfinpyrazone during attacks; other drugs for acute gout attack may be prescribed by clinician.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Sulfinpyrazone
Routes
Dosage Forms
Strengths
Brand Names
Manufacturer
Oral
Capsules
200 mg*
Anturane® (with sodium bisulfite)
Novartis
Tablets
100 mg*
Anturane® (scored)
Novartis
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
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