RIDAURA TILTAB TABLETS 3 MG

Tablet

Ridaura is an orally active gold preparation. It is indicated in the management of adults with active progressive rheumatoid arthritis only when non-steroidal anti-inflammatory drugs have been found to be inadequate alone to control the disease, i.e. when second-line therapy is required. In patients with adult rheumatoid arthritis Ridaura has been shown to reduce disease activity reflected by synovitis, associated symptoms, and appropriate laboratory parameters. Gold cannot reverse structural damage to joints caused by previous disease. Ridaura does not produce an immediate response and therapeutic effects may be seen after three to six months of treatment.

For Adults and the Elderly only:

For Adults:

The usual starting dose is 6 mg daily as one 3 mg tablet twice a day, in the morning and the evening with meals. If this is well tolerated a single daily dose may be given as two 3 mg tablets with breakfast or with the evening meal.

Treatment should be continued for a minimum of three to six months to assess response, as Ridaura is a slow-acting drug. If the response is inadequate after six months an increase to 9 mg (one tablet three times a day) may be tolerated. If response remains inadequate after a three month trial of 9 mg daily, Ridaura therapy should be discontinued. Safety at dosages exceeding 9 mg daily has not been studied.

Absorption of gold from Ridaura tablets is rapid but incomplete. Although mean blood gold levels are proportional to dose, no correlation between blood gold levels and safety or efficacy has been established. Dosage adjustments should therefore depend on monitoring clinical response and adverse events rather than on monitoring blood gold concentrations.

Anti-inflammatory drugs and analgesics may be prescribed as necessary with Ridaura.

The Elderly:

Dosage as for adults. As with all drugs extra caution should be exercised in administration to the elderly.

Contraindicated in pregnancy.

Contraindicated where hypersensitivity to gold compounds or other heavy metals exists.

Although not necessarily reported in association with Ridaura, do not use in patients with a history of any of the following gold-induced disorders: enterocolitis, pulmonary fibrosis, exfoliate dermatitis, bone marrow aplasia, or other severe blood dyscrasias or toxicity to other heavy metals. Use should also be avoided in progressive renal disease or severe active hepatic disease and in systemic lupus erythromatosus.

Use with caution in patients with any degree of renal impairment or hepatic dysfunction, inflammatory bowel disease, rash, or history of bone marrow depression.

Close monitoring is essential. Full blood count with differential and platelet counts (which should be plotted) and tests for urinary protein must be performed prior to Ridaura therapy and at least monthly thereafter, see also section 4.8. Ridaura should be withdrawn if the platelet count falls below 100,000 per ml or if signs and symptoms suggestive of thrombocytopenia, leucopenia and aplastic anaemia occur. The occurrence of purpura, ecchymoses or petechia would suggest the presence of thrombocytopenia and may indicate a need for additional platelet count determinations. Patients with gastrointestinal symptoms, with rash, with pruritus (which may precede rash), with stomatitis, or a metallic taste in the mouth (which might precede stomatitis), should also be closely monitored as such symptoms may indicate a need for modification of dosage or withdrawal, see also section 4.8. Pulmonary fibrosis may rarely occur and chest X-ray is recommended at least annually.

Prior to initiating treatment patients must be advised of the potential side effects associated with Ridaura. They should be warned to report promptly any unusual signs or symptoms during treatment such as pruritus, rash, metallic taste, sore throat or tongue, mouth ulceration, easy bruising, purpura, epistaxis, bleeding gums, menorrhagia, or diarrhoea.

Gold has been shown to be carcinogenic in rodents although there was no evidence of carcinogenicity in a 7-year dog study.

Patients should be cautioned to minimise exposure to ultraviolet light.

Auranofin has not been co-administered with other disease modifying agents such as penicillamine, levamisole and chloroquine/hydrochloroquine and, therefore, concomitant use cannot be recommended.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Enterocolitis is a rare but potentially serious side effect, the development of diarrhoea with rectal bleeding or rectal bleeding alone unless rapidly explained otherwise mandates the immediate cessation of therapy. Patients should be warned to seek medical advice as soon as possible if they develop these symptoms.

Specific experience of interactions with auranofin is lacking. However, the theoretical potential for interaction with gold therapy, both oral and parenteral, should be considered.

Concomitant therapy with metal antagonists and potentially nephrotoxic or haemotoxic drugs should be administered with caution. Such drugs include penicillamine, aminoglycosides, amphotericin B, penicillins, phenylbutazone, phenytoin, sulfonamides, NSAIDs, acyclovir and alcohol.

Drugs affecting GI motility and those which are highly protein-bound may alter the absorption and binding, respectively, of auranofin.

Gold is teratogenic in some animal species. Ridaura should not be used in pregnancy. Women of child-bearing potential should not be treated with Ridaura without full consideration of the benefits of treatment against the potential risk of teratogenicity; they should practise effective contraception during treatment and for at least six months after. Patients should be fully informed of the teratogenic risk, and termination of any pregnancy occurring during treatment should be considered in view of the possibility of foetal malformation. If women are to be treated post-partum with Ridaura, breast-feeding should be avoided.

None stated.

Adverse reactions can occur throughout treatment with Ridaura, although the highest incidence can be expected during the first six months of treatment. The most common reaction to Ridaura is diarrhoea or loose stools, occurring in about 30% of patients according to the literature. Up to about one patient in twenty will be unable to tolerate Ridaura because of diarrhoea.

* Please see section 4.4 for monitoring requirements and cessation of therapy

The frequencies are taken from adverse events reported in controlled studies and post-marketing experience.

Treatment with Ridaura should be stopped in cases of persistent rash, especially if accompanied by pruritus. In cases of clinically significant proteinuria treatment with Ridaura should be stopped promptly. Treatment may be restarted after the proteinuria has cleared, however, under close supervision in patients who have experienced only minimal proteinuria.

Transient decreases in haemoglobin or haematocrit early in treatment have been reported. Occasional decreases in white blood counts have been reported during auranofin treatment.

There have been some reports of gold deposits in the lens or corneas of patients treated with auranofin. These deposits have not led to any eye disorders or any degree of visual impairment.

Ridaura overdosage experience is limited. One patient who took 27 mg daily for 10 days developed an encephalopathy and peripheral neuropathy. Ridaura was discontinued and the patient eventually recovered.

In case of acute overdosage, immediate induction of vomiting or gastric lavage and appropriate supportive therapy are recommended. Chelating agents such as BAL have been used in injectable gold overdosage, and may be considered, although there has been no specific experience with Ridaura.

Auranofin is a disease-modifying slow-acting immunomodulating agent.

About 20% to 30% of the gold in a dose of Ridaura is absorbed and, although there is considerable variation in absorption, this is less than that seen with parenteral gold. Steady state blood concentrations are achieved 8 to 12 weeks after starting and are on average 5 to 10 times less than those following parenteral gold, with no correlation with clinical response or adverse events. About 70% of the gold administered in Ridaura appears in the faeces during the first week following a single dose, and at six months after dosing, less than 1% of the gold administered remains in the body, in contrast to around 30% of gold given parenterally. In contrast to parenteral gold, which does not become cell-associated, 40% of the gold in the blood of Ridaura-treated patients is associated with blood cells.

The metabolism of Ridaura is not fully understood, although it is clear from both animal and in-vitro studies with human blood that both the sulphur and the phosphorus ligands of Ridaura are rapidly dissociated from the gold.

No relevant pre-clinical safety data has been generated.

Lactose

Microcrystalline cellulose

Maize starch

Sodium starch glycollate

Magnesium stearate

Hydroxypropylmethylcellulose

Propylene glycol

Opaspray M-1-6054

None

Five years

None

Standard SKand F polypropylene securitainers or HDPE containers with wadless polypropylene screw caps containing 60 tablets.

None

Astellas Pharma Ltd

Lovett House

Lovett Road

Staines

TW18 3AZ

United Kingdom

PL0166/0176

31/10/97

28 January 2008

POM