INFORMATION FOR HEALTH PROFESSIONALS
Home | Consumers | Health Professionals | Regulatory | Other | Hot Topics | Search
Home | Consumers | Health Professionals | Regulatory | Other | Hot Topics | Search
Sulphinpyrazone as:
100mg tablets: Circular, white, flat, bevel-edged tablets with a score on one face and embossed N over the scoreline and 100 under the scoreline.
200mg tablets: Circular, white, sugar-coated tablets.
Sulphinpyrazone potentiates the urinary excretion of uric acid and so is useful for reducing blood urate levels in patients with chronic tophaceous gout and acute intermittent gout. It also promotes the resorption of tophi. Sulphinpyrazone has minimal anti-inflammatory effect and is not intended for the relief of an acute attack of gout.
In patients with large tophaceous deposits and marked joint destruction, sulphinpyrazone will often halt or even reverse the course of the disease.
By controlling the serum urate level, sulphinpyrazone materially reduces or eliminates the number and severity of acute attacks in both chronic tophaceous and acute intermittent gout, and theoretically may delay the onset of clinical disease in asymptomatic hyperuricaemia.
In most patients, it rapidly reduces the serum urate levels to normal. This not only prevents the formation of new tophaceous deposits, but mobilises and promotes the excretion of uric acid already present in the tissues. The reduction of tophi and periarticular crystals results in greater mobility of the joints, thus materially aiding in the rehabilitation of the patient.
Because of its high potency, sulphinpyrazone is often effective in patients refractory to other uricosuric agents. It may be used with caution in patients with diminished kidney function, whether secondary to gout or from co-existing renal disease. Patients can be maintained indefinitely on sulphinpyrazone without cumulative effects or development of tolerance.
Sulphinpyrazone is used in various stages of chronic gout, because of its potency and its continued effectiveness over a prolonged period of time. It may be effective in patients refractory to other uricosuric agents.
Sulphinpyrazone administered either intrperitoneally, subcutaneously or orally inhibits formalin-induced acute inflammation in rats. This effect is somewhat less pronounced after adrenalectomy, but tends to be more pronounced after hypophysectomy. In formalin-induced peritonitis and in dextran-induced oedema in the rat paw, the anti-inflammatory effect of sulphinpyrasone is similar to that of aminopyrine.
Sulphinpyrazone is less effective in other forms of experimental inflammation, such as serotonin oedema, ultraviolet (epithelial) necrosis or the Selye granuloma-pouche in the rat, ultraviolet erythema in the guinea pig, increased capillary permeability caused by dextran in rat skin, and histamine-contracture of the vessels of the Krawlow-Pissemski isolated rabbit ear.
The analgesic activity of the medicine is slight, but can be clearly demonstrated in mice by the hotplate and tail-flick methods and in rabbits by electrical stimulation of the dental pulp. Sulphinpyrazone does not affect the pyrexia produced by injection of yeast in the rat.
Sulphinpyrazone also diminishes platelet adhesiveness and aggregation and inhibits the platelet release reaction. In addition platelet prostaglandin synthesis is also inhibited. These effects enable the use of sulphinpyrazone in certain forms of vascular disease to prolong pathologically shortened platelet turnover. Sulphinpyrazone causes no significant retention of sodium chloride or water in humans.
Sulphinpyrazone is rapidly and virtually completely absorbed after oral administration, peak plasma concentrations of 12-15 mcg/mL being attained between 1-2 hours after a dose of 200mg. The elimination of sulphinpyrazone is relatively rapid, half-lives ranging from 2-4 hours.
Plasma protein binding accounts for approximately 98% of administered sulphinpyrazone. Elimination occurs by renal excretion, 85% of an administered dose appearing in the urine as unchanged sulphinpyrazone within 24 hours. Some metabolism also occurs in the liver to produce two active metabolites. The p-hydroxide metabolite has uricosuric activity while the sulphide has antiplatelet activity. Accumulation does not appear to occur and no significant alterations in sulphinpyrazone pharmacokinetics are seen in the elderly when compared to younger patients.
SPZ tablets are indicated for the treatment of: chronic gouty arthritis, and intermittent gouty arthritis.
SPZ tablets may also be used to: reduce the incidence of cardiac death following acute myocardial infarction, reduce the incidence of reinfarction, prevent thromboembolic complications of vascular prostheses or artificial heart valves, prevent thromboembolic complications in arteriovenous shunts in dialysis patients.
SPZ tablets may also be used in the treatment of: recurrent venous thrombosis and transient blindness due to cerebral ischaemia.
SPZ tablets are to be taken orally and it is recommended that they be given with meals and the total daily dose should be distributed evenly over a 24 hour period. An appropriate fluid intake should be maintained and, if necessary, an urine-alkalinising agent should be prescribed. In all cases an incremental dose schedule should be adopted when starting therapy.
If SPZ is to be used to reduce post-infarction mortality and incidence of reinfarction, at least two weeks should be allowed to pass after the acute event before treatment is started. A recommended treatment schedule is: 1st and 2nd day 200mg once daily; 3rd and 4th day 200mg twice daily; 5th and 6th day 200mg three times daily; from the 7th day onward 200mg two to four times daily.
In the management of gout, treatment should be continued indefinitely even during acute attacks, which are treated concomitantly with NSAI's or colchicine.
Active peptic ulcer, blood dyscrasias, known hypersensitivity to sulphinpyrazone and other pyrazolone derivatives, severe hepatic or renal disease, unless due to platelet aggregates.
The safe use of sulphinpyrazone in pregnancy has not been established. Studies on the teratogenicity of pyrazole compounds in animals have yielded inconclusive results. It should not be used during pregnancy unless, in the opinion of the treating physician, the expected benefits outweigh the potential risks. It is not known if sulphinpyrazone enters breast milk.
Avoid salicylate therapy, unless administered under careful supervision:
It should be administered with care to patients with a history of healed peptic ulcer.
As with all pyrazole compounds, patients receiving SPZ tablets should be kept under close medical supervision and periodic blood counts are recommended. Recent reports have indicated that sulphinpyrazone potentiates the action of sulphonamides, e.g. sulphadiazine, sulphisoxazole.
Other pyrazole compounds, e.g. phenylbutazone, potentiate the hypoglycaemic effects of sulphonylureas. There have also been reports that phenylbutazone enhances the effects of insulin in diabetics. Therefore, it is recommended that SPZ tablets be used with caution in conjunction with insulin, sulphonamides, sulphonylurea hypoglycaemic agents and, in general, with agents known to displace or to be displaced by other substances such as penicillin from serum albumin binding sites.
Because sulphinpyrazone is a potent uricosuric agent, it may precipitate urolithiasis and renal colic, especially in the initial stages of therapy, in hyperuricaemic patients. For this reason, an adequate fluid intake and alkalinisation of the urine are recommended. In cases with significant renal impairment, periodic assessment of renal function is indicated.
Since sulphinpyrazone modifies platelet behaviour and, therefore, interferes with one of the components of the blood-clotting system, it should be used with care in conjunction with certain vitamin K antagonists which inhibit clotting through a different mechanism. Regular estimations of bleeding time should be performed.
Sulphinpyrazone has minimal anti-inflammatory effect and is not intended for the relief of an acute attack of gout. In the initial stages of therapy, because of the marked ability of sulphinpyrazone to mobilise urates, acute attacks of gouty arthritis may be precipitated.
The most frequently reported adverse reactions to sulphinpyrazone have been upper gastrointestinal complaints or disturbances. In these patients it is advisable to administer the medicine with food, milk or antacids. Sulphinpyrazone may aggravate or reactivate peptic ulcer. Gastrointestinal bleeding has been reported.
Skin rashes have been reported in rare instances. When they occur, SPZ tablets should be withdrawn. Sulphinpyrazone has not been observed to change electrolyte balance, in contrast to certain other pyrazone derivatives.
Anaemia, leucopenia, agranulocytosis, thrombocytopenia have rarely been associated with the administration of sulphinpyrazone.
If aspirin or other NSAI's capable of interfering with haemostasis are prescribed for a patient on treatment with SPZ, any bleeding episode should be reported at once.
Sulphinpyrazone may potentiate the effects of concomitantly administered anticoagulants such that dosage adjustments of the anticoagulants should be carefully monitored by means of prothrombin time. Sulphinpyrazone may also potentiate the effects of oral hypoglycaemics, penicillins or sulphonamides.
No cases of sulphinpyrazone overdose are known, however, if it ever occurs the most likely symptoms are: nausea, vomiting, diarrhoea, epigastric pain, ataxia, laboured respiration, convulsion with subsequent coma, anaemia, jaundice, GI ulceration and haemorrhage, renal damage.
There is no specific antidote to sulphinpyrazone overdose.
The following measures may be tried: induce emesis or gastric lavage, give symptomatic supportive treatment, intravenous glucose infusion and analeptic therapy if respiration is affected. Alkalinise the urine or, if renal failure is present, perform haemodialysis. The effectiveness of measures to remove sulphinpyrazone or its metabolites are unknown.
Protect from light and moisture. Keep out of reach of children. Store below 30°C.
Prescription Medicine.
Bottles of 100 tablets
Sulphinpyrazone is 1,2-diphenyl-4-[2-(phenyl sulphinyl]ethyl)-3,5-pyrazolidinedione. Its molecular formula and weight are C23H20N2O3S and 404.48 respectively.
Douglas Pharmaceuticals Ltd
P O Box 45-027
AUCKLAND 8
Ph: (09) 835 0660
Fax: (09) 835 0665
3 September 1999