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Anturane

Generic Name: Sulfinpyrazone
Class: Uricosuric Agents
VA Class: MS400
CAS Number: 57-96-5

Introduction

Uricosuric agent,a b platelet aggregation inhibitor. a

Uses for Anturane

Hyperuricemia Associated with Gout

Treatment of chronic or intermittent gouty arthritis and tophaceous gout.a b

Used in patients with frequent disabling attacks of gout.a b

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.a

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.a b

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Goal of therapy is to lower serum urate concentrations to about 6 mg/dL. a

Alternative to probenecid, which generally is better tolerated.a May be used with allopurinol for additive effect, especially in the presence of tophaceous deposits.a May be used with probenecid if the uricosuric response to one drug is insufficient at maximum therapeutic dosage.a

Not effective in patients with moderate to severe chronic renal insufficiency.a (See Renal Impairment under Cautions.)

Of no value in the treatment of acute gout attacks.a b (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.a

Do not use to treat hyperuricemia secondary to cancer chemotherapy, radiation, or myeloproliferative neoplastic diseases; may increase risk of uric acid nephropathy.a

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. a

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.201

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.200

Anturane Dosage and Administration

General

  • All patients should maintain daily urine output at ≥2–3 L; alkalinization of urine desirable.a

Administration

Oral Administration

Take with meals, milk, or antacids to minimize adverse GI effects.a b

Dosage

Adjust dosage according to the response and tolerance of the patient.a

Use low dosages initially to reduce possibility of acute gout attacks and prevent massive uricosuria.a

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.a b 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.a b

Patients previously controlled with other uricosuric therapy may begin sulfinpyrazone at full maintenance dosage.a b

Uricosuric therapy should be continued indefinitely and without interruption; irregular dosage schedules may result in increased serum urate concentrations.a b

Inhibition of Platelet Aggregation
Oral

600–800 mg daily has been used.a

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.a

Renal Impairment

No specific dosage recommendations at this time.a (See Renal Impairment under Cautions.)

Geriatric Patients

No specific dosage recommendations at this time.a

Cautions for Anturane

Contraindications

  • Active peptic ulcer or symptoms of GI inflammation or ulceration.b

  • Known hypersensitivity to sulfinpyrazone or any ingredient in the formulation, or to other pyrazolone derivatives such as phenylbutazone.a b

  • Past or present blood dyscrasias.b (See Hematologic Effects.)

Warnings/Precautions

Sensitivity Reactions

Sulfite Sensitivity

Some formulations contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.a

General Precautions

Hematologic Effects

Pyrazole compound; closely monitor patients and perform periodic blood counts.a b

Acute Gout

Of no value in treatment of acute gout attacks; will prolong and exacerbate inflammation during the acute phase.a b May increase frequency of acute attacks during the first 6–12 months of therapy despite maintenance of normal or subnormal serum urate concentrations.a b Therefore, administer prophylactic doses of colchicine concurrently during first 3–6 months of therapy.a

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.a

Urolithiasis

May promote development of uric acid stones; may cause renal colic and hematuria, especially early in therapy.a Advise patient to ingest large amounts of fluids to maintain large volumes of alkaline urine to reduce risk of stone formation.a Allopurinol preferred in patients with urinary uric acid excretion >900 mg/day or with gouty nephropathy, urinary tract stones or obstruction, or azotemia.a

GI Effects

May reactivate or aggravate peptic ulcers.a b May use with caution in patients with history of healed peptic ulcer.a b

Specific Populations

Pregnancy

No reports of congenital malformation.a Use caution in pregnant women, weighing possible risks against potential benefits.a

Pediatric Use

Safety and efficacy not established.b

Renal Impairment

Use caution in patients with mild renal impairment; avoid when Clcr <50 mL/minute.a Assess renal function periodically in patients with impaired renal function.a

Common Adverse Effects

Nausea,a dyspepsia,a GI pain and blood loss,a reactivation or aggravation of peptic ulcer,a b rash,a b dizziness,a vertigo,a tinnitus,a edema.a

Interactions for Anturane

Weak Organic Acids

Competitively inhibits renal tubular secretion of many weak organic acids, possibly potentiating their effects by elevating plasma concentrations.a 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.a Drugs for which high urinary concentrations are desired (i.e. nitrofurantoin) may be less effective due to blocked renal secretion.a

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.a c

Drugs that Increase Serum Uric Acid

Increase in sulfinpyrazone dosage may be necessary.a Avoid uricosurics in patients receiving cancer chemotherapy due to risk of uric acid nephropathy.a

Specific Drugs and Laboratory Testsa b c

Drug

Interaction

Comments

Alcohol

Increased serum urate concentration

Higher sulfinpyrazone dose may be required

Allopurinol

Additive uricosuric effects

Used to therapeutic advantage

Aminohippuric acid test

Sulfinpyrazone decreases urinary excretion

Evaluate test results accordingly

Aminosalicylic acid

Increased plasma aminosalicylic acid concentration

Importance unknown

Antineoplastic agents

Increased serum urate concentration, risk of uric acid nephropathy

Avoid concurrent use

Cholestyramine

Binds and delays absorption of sulfinpyrazone

Give sulfinpyrazone >1 hour before or 4–6 hours after cholestyramine

Colchicine

Risk of acute myeloblastic leukemia and multiple myeloma

Careful hematologic examinations recommended if used concurrently

Diazoxide

Increased serum urate concentration

Higher sulfinpyrazone dose may be required

Diuretics

Increased serum urate concentration

Higher sulfinpyrazone dose may be required

Insulin

Increased plasma insulin concentration

Use with caution

Mecamylamine

Increased serum urate concentration

Higher sulfinpyrazone dose may be required

Nitrofurantoin

Reduced nitrofurantoin efficacy and possible toxicity

Avoid concurrent use

Penicillins

Increased plasma penicillin concentration

Not clinically important or useful

Phenolsulfonphthalein test

Sulfinpyrazone decreases urinary excretion

Evaluate test results accordingly

Probenecid

Inhibits secretion of sulfinpyrazone and active metabolite

No clinically important interaction; may be used concurrently

Pyrazinamide

Increased serum urate concentration

Higher sulfinpyrazone dose may be required

Salicylates

Antagonize uricosuric action of sulfinpyrazone

Concurrent use contraindicated; acetaminophen may be used

Sulfonamides

Increased plasma sulfonamide concentration

Not clinically important or useful

Sulfonylureas

Increased plasma sulfonylurea concentration

Theoretical risk of hypoglycemia; use with caution

Thrombolytics

GI bleeding, decreased platelet aggregation

Avoid concurrent use

Warfarin

Enhanced hypoprothrombinemic effect

Use with caution and close monitoring; consider different uricosuric agent

Anturane Pharmacokinetics

Absorption

Bioavailability

Rapidly and completely absorbed from GI tract.a Peak plasma concentrations reached 1–2 hours after single oral dose.a

Duration

Usually 4–6 hours (up to 10 hours).a

Distribution

Plasma Protein Binding

Approximately 98% bound to plasma proteins.a

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. a

Elimination Route

Small amounts of sulfinpyrazone filtered at glomeruli; most actively secreted at proximal tubule.a Minimal amounts then reabsorbed by kidney tubule.a 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.a Approximately 5% of dose excreted in feces.a

Half-life

3 hours (range 1–9 hours). a

Stability

Storage

Oral

Capsules and Tablets

15–30°C in tight containers.a b

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.a b

    May reduce plasma protein binding of urate and, in subtherapeutic doses, may inhibit renal secretion of uric acid.a Has no effect on glomerular filtration rate or tubular reabsorption of normal urinary constituents such as sodium, potassium, and water in healthy patients.a

  • Exerts no clinically apparent analgesic or anti-inflammatory activity.a b (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.a No effect on plasma prothrombin or thromboplastin levels but may increase platelet count.a Blood clotting time not altered.a

  • A small but significant lowering of serum cholesterol has been demonstrated in gouty patients receiving sulfinpyrazone.a

Advice to Patients

  • Importance of informing patient that sulfinpyrazone is not intended for relief of an acute gout attack. a b

  • Importance of drinking plenty of fluids and maintaining alkaline urine.a

  • Importance of taking with meals, milk, or antacids to minimize adverse GI effects.a b

  • Importance of informing patient that acute gout attacks may increase in frequency during the first 6–12 months of therapy, then diminish.a b Continue sulfinpyrazone during attacks; other drugs for acute gout attack may be prescribed by clinician.a b

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.b

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.b

  • Importance of informing patients of other important precautionary information.b (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Sulfinpyrazone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

200 mg*

Anturane (with sodium bisulfite)

Novartis

Tablets

100 mg*

Anturane (scored)

Novartis

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

200. Stein PD, Schunemann HJ, Dalen JE et al. Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts. The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004; 126:600S–608S.

201. Braunwald E, Antman E, Beasley JW et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Unstable Angina). 2002. Available from website.

a. AHFS Drug Information 2008. McEvoy GK, ed. Sulfinpyrazone. Bethesda, MD: American Society of Health-System Pharmacists; 2008:[page 2795-6].

b. Ciba-Geigy. Anturane (sulfinpyrazone) tablets and capsules prescribing information. Summit, NJ; 2006. (). Dated 1996 Apr. Accessed 9/21/07.

c. Jack Ansell J, Hirsh J, Poller L et al. The pharmacology and management of the vitamin K antagonists. The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004; 204S-33S.

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