Pyrazone

Uses

Sulphinpyrazone helps to remove excess uric acid from the body. Too much uric acid can cause gout or gouty arthritis. Certain illness or medications can increase uric acid level. It can help to reduce the risk of complications (such as kidney stones) that can occur if uric acid levels in the blood are too high (hyperuricemia). It completely inhibits the reabsorption of uric acid at the proximal convoluted tubule, thereby facilitating urinary excretion of uric acid and decreasing plasma urate concentrations.

Sulphinpyrazone is used for the treatment of: Chronic gouty arthritis, Intermittent gouty arthritis

Pyrazone is also used to associated treatment for these conditions: Hyperuricemia, Platelet Aggregation

How Pyrazone works

Pyrazone is an oral uricosuric agent (pyrazolone derivative) used to treat chronic or intermittent gouty arthritis. Pyrazone competitively inhibits the reabsorption of uric acid at the proximal convoluted tubule, thereby facilitating urinary excretion of uric acid and decreasing plasma urate concentrations. This is likely done through inhibition of the urate anion transporter (hURAT1) as well as the human organic anion transporter 4 (hOAT4). Pyrazone is not intended for the treatment of acute attacks because it lacks therapeutically useful analgesic and anti-inflammatory effects. Pyrazone and its sulfide metabolite possess COX inhibitory effects. Pyrazone has also been shown to be a UDP-glucuronsyltransferase inhibitor and a very potent CYP2C9 inhibitor. Pyrazone is also known to be a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor as well as an inhibitor of several multridrug resistance proteins (MRPs).

Dosage

Pyrazone dosage

Initial dose: 200-400 mg daily in two divided doses, with meals or milk, gradually increasing when necessary to full maintenance dosage in one week.

Maintenance dose: 400 mg daily, given in two divided doses, as above. This dosage may be increased to 800 mg daily, if necessary, and may sometimes be reduced to as low as 200 mg daily after theblooduratelevel has been controlled. Treatment should be continued without interruption even in the presence ofacuteexacerbations, which can be concomitantly treated with phenylbutazone orcolchicine. Patients previously controlled with other uricosuric therapy may be transferred to Anturane (sulfinpyrazone) at full maintenance dosage.

Side Effects

The symptoms are upset stomach, vomiting, loss of appetite and joint pain. If you experience any of the following symptoms like difficulty in breathing, tightness in the chest, skin rash, unusual bleeding, fever, sore throat and mouth sores, call your doctor immediately.

Toxicity

Symptoms of overdose include nausea, vomiting, diarrhea, epigastric pain, ataxia, labored respiration, convulsions, coma. Possible symptoms, seen after overdosage with other pyrazolone derivatives: anemia, jaundice, and ulceration.

Precaution

Patients receiving Sulphinpyrazone should be kept under close medical supervision and periodic blood counts are recommended. It may be administered with care to patients with a history of healed peptic ulcer. It is suggested that Sulphinpyrazone should be used with caution in conjunction with sulfa drugs, the sulfonylurea hypoglycemic agents and insulin. Because Sulphinpyrazone is a potent uricosuric agent, it may precipitate urolithiasis and renal colic, especially in the initial stages of therapy. For this reason, an adequate fluid intake and alkalinization of the urine are recommended. Salicylates antagonize the uricosuric action of Sulphinpyrazone and for this reason, their concomitant uses are contraindicated in gouty arthritis.

Interaction

Decreased therapeutic effect when given with drugs that increase uric acid concentration (e.g. diuretics, pyrazinamide). May potentiate the action of coumarin anticoagulants (e.g. warfarin, acenocoumarol), hypoglycaemic agents and sulfonamides. May decrease plasma levels of theophylline. May increase plasma levels of penicillins and phenytoin. Increased risk of haemorrhage with substances affecting homeostasis (e.g. non-steroidal antirheumatic drugs). Probenecid may inhibit renal tubular secretion of sulfinpyrazone.

Food Interaction

• Take with food.

Pyrazone Drug Interaction

Moderate: acetaminophen, oxycodone, acetaminophen / tramadolMinor: niacinUnknown: ubiquinone, heparin, sodium iodide, carbonyl iron, ferrous sulfate, thiamine, cyanocobalamin, pyridoxine, ascorbic acid, cholecalciferol, phytonadione

Pyrazone Disease Interaction

Major: blood dyscrasias, upper GI irritationModerate: dehydration, renal dysfunction

Half Life

Approximately 4-6 hours

Pregnancy & Breastfeeding use

Pregnancy category C. This means that it is not known whether Sulphinpyrazone will harm an unborn baby. Don't take this without first talking to your doctor if you are pregnant.

It is also not known whether Sulphinpyrazone passess into breast milk. Do not take it without first talking to your doctor if you are breast-feeding a baby.

Contraindication

Patients with an active peptic or symptoms of gastro-intestinal inflammation or ulceration should not receive the drug. The drug is contraindicated in patients with a history or the presence of hypersensitivity to phenylbutazone or other pyrazoles.

Special Warning

Renal Impairment: Mild to moderate: Reduce dose.

Severe: Contraindicated.Hepatic Impairment: Severe: Avoid.

Acute Overdose

Symptoms: Nausea, vomiting, diarrhea, epigastric pain, laboured respiration, convulsions and coma.

Treatment: No specific antidote. Induce emesis, gastric lavage, supportive treatment (intravenous glucose infusions).

Storage Condition

Store between 15-30° C.

Innovators Monograph

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