INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
‘RIDAURA’Tablets 3 mg.

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

‘RIDAURA’Tablets 3 mg.

COMPOSITION:
The chemical name of auranofin is: (2,3,4,6-Tetra-O-acetyl-1-thio-ß-D-glucopyranosato-S) (triethyl-phosphine) gold.
Each tablet contains 3 mg auranofin, which is approximately 29 % gold.

PHARMACOLOGICAL CLASSIFICATION:
A.3.1 Anti-Rheumatics (Anti-inflammatory agents).

PHARMACOLOGICAL ACTION:
‘Ridaura’reduces inflammation and lowers erythrocyte sedimentation rates. It also normalises rheumatoid factor levels and lowers elevated immunoglobulin levels.

In standard animal models, ‘Ridaura’has exhibited significant anti-inflammatory properties.

‘Ridaura’:

•        ·	enhances cell mediated immunity.
•        ·	inhibits antibody dependent cellular cytotoxicity.
•        ·	inhibits release of lysosomal enzymes.
•        ·	suppresses the generation of super oxide radicals.
•        ·	inhibits platelet aggregation in vitro.

‘Ridaura’ has also been shown to inhibit chemotaxis, phagocytosis, and the inflammatory effects of prostaglandins.

Pharmacokinetics:
Following oral administration in man of a single dose of 6,0 mg radiolabelled drug, a peak plasma radioactive gold concentration of 23 µg% occurs 102 minutes post administration. Almost 50 % of the gold is bound to blood cells. The principal route of excretion of ‘Ridaura’gold is via the faeces (84 - 92%), the urine accounting for 9 - 17%.

Ninety-five percent of an administered dose has been accounted for in ten days in one study, 76 % in the faeces (72 % in four days), 4 % in the urine and 15% was retained. Retained material is then slowly eliminated so that 100 days after dosing less than 5% of the dose remains in the body and after 6 months, only 1% remains. These data are in contrast with those for parenterally administered gold salts.

During long-term therapy with ‘Ridaura’, serum gold concentrations reach a plateau after 12 weeks treatment and then remain stable, provided the dose is unchanged. With ‘Ridaura’ at 6 mg per day, mean blood gold levels of 0,63 µg/mL (0,30 -1,20) have been observed. Serum concentrations are proportional to dose, but no correlation between gold blood levels and degree of efficacy or safety has been established.

INDICATIONS:
‘Ridaura’is indicated in the treatment of rheumatoid arthritis in adults. As a remittive drug, ‘Ridaura’may suppress the progress of the disease and so prevent or reduce subsequent damage to the joints. Because it cannot repair the damage already caused by chronic rheumatoid arthritis, the greatest benefit of ‘Ridaura’ is achieved when therapy is initiated before permanent destructive changes have occurred in joint structures. ‘Ridaura’is not indicated in non-rheumatoid arthropathies, such as osteoarthrosis.

It has been demonstrated by clinical, laboratory and radiological evaluation, that prolonged treatment with ‘Ridaura’may suppress the progress of active rheumatoid arthritis.

Clinically, therapeutic response has been observed in some patients as early as two months; while others have needed as long as six months to show response. This response includes improvements in parameters such as joint swelling, tenderness pain fatigue, morning stiffness and grip strength. Some patients have been maintained on ‘Ridaura’for over three years with sustained improvement. Radiologic assessments have demonstrated that ‘Ridaura’ may decrease the rate of new erosion formation.

CONTRA-INDICATIONS:
Previous significant toxicity to parenteral gold salts or to ‘Ridaura’, or to heavy metals other than gold.

Pregnant or lactating women.

‘Ridaura’should not be prescribed for patients with renal disease or severe active hepatic disease, or for patients with a past history of bone marrow toxicity, or ulcerative colitis.

DOSAGE AND DIRECTIONS FOR USE:
The usual adult starting dosage is 6 mg per day, taken as one 3 mg tablet with breakfast and with the evening meal or taken as one single daily administration (two 3 mg tablets with breakfast or the evening meal).

‘Ridaura’may be co-prescribed with anti-inflammatory drugs/analgesics as part of a comprehensive treatment program. Such concomitant therapy is beneficial during the first weeks of ‘Ridaura’ therapy, before full benefit of ‘Ridaura’is seen.

For patients who have not shown satisfactory response to ‘Ridaura’therapy with 6 mg/day after 4 - 6 months, the daily dosage may be increased to 9 mg/ day by giving one ‘Ridaura’ tablet three times a day with meals. Safety at doses exceeding 9,0 mg daily has not been studied.

Paediatric Use:
‘Ridaura’has not been evaluated in juvenile rheumatoid arthritis, and, therefore, its use in children cannot be recommended.

Side-Effects and Special Precautions:
Adverse reactions reported during clinical studies with ‘Ridaura’were largely gastro-intestinal and mucocutaneous in nature.

Loose stools or diarrhoea usually mild and transient, have been reported relatively frequently. If it becomes more severe or prolonged then symptomatic treatment may be of benefit. Discontinuation of ‘Ridaura’ therapy is rarely necessary. Abdominal pain, nausea and other gastro-intestinal symptoms may occur in association with loose stools and diarrhoea.

Skin rashes may occur during ‘Ridaura’therapy. They may necessitate discontinuation of ‘Ridaura’therapy. Cases of pruritus, stomatitis and conjunctivitis have also been reported.

Decreases in white blood cell count and platelet count and red cell count may occur during treatment with ‘Ridaura’, and these may necessitate discontinuation of therapy.

Proteinuria may develop during treatment with ‘Ridaura’. If proteinuria develops, treatment with ‘Ridaura’ should be promptly discontinued. Abnormalities in tests of liver function (transaminases and alkaline phosphatase) and of renal function (BUN, creatinine, uric acid) may develop during treatment with ‘Ridaura’.

Precautions:
‘Ridaura’contains a heavy metal. It is recommended that WBC, platelets and urinary protein be measured prior to ‘Ridaura’ therapy and monitored at monthly intervals thereafter. Patients should be advised to report promptly any unusual signs and symptoms occurring during treatment with ‘Ridaura’.

‘Ridaura’should not be used in patients with ulcerative colitis and should be used with caution in patients with inflammatory bowel disease because of the possibility of inducing diarrhoea and further bowel irritation.

‘Ridaura’should be used with caution in patients with a history of atopy because of the possibility of skin rashes occurring during treatment. In conditions such as SLE and Sjögren’s Syndrome, ‘Ridaura’cannot be recommended. ‘Ridaura’should not be co-administered with penicillamine, levamisole and chloroquine - nor with high doses of corticosteroids.

As with all heavy metals, including gold, karyomegaly of renal tubular epithelium has been observed in rats. This heavy metal nephropathy is specific for rodents and has no counterpart in humans.

Paediatric Use:
‘Ridaura’has not been evaluated in juvenile rheumatoid arthritis and, therefore, its use in children cannot be recommended.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
The absence of experience with acute overdosage with ‘Ridaura’ precludes characterisation of sequelae and assessment of antidotal efficacy at this time. However, in case of accidental overdosage, immediate induction of emesis or gastric lavage is recommended.

IDENTIFICATION:
Square, bevel-edged, pale yellow, film coated tablets having raised domes on both faces.

PRESENTATION:
‘Ridaura’is available as 3 mg tablets in packs of 60.

STORAGE INSTRUCTIONS:
Store at room temperature below 25°C.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
P/3.1/250

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
SmithKline Beecham Pharmaceuticals (Pty) Limited.
6 Carey Street,
Wynberg Ext. 6,
Johannesburg 2090

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
21.02.1983

P0257
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