Consumer medicine information

Ridaura

Auranofin

BRAND INFORMATION

Brand name

Ridaura

Active ingredient

Auranofin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ridaura.

What is in this leaflet

Please read this leaflet carefully before you start taking Ridaura.

This leaflet answers some of the common questions about Ridaura. It does not contain all the available information.

Reading this leaflet does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Ridaura against the benefits this medicine is expected to have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may want to read it again.

What Ridaura is used for

Ridaura contains auranofin, a synthetic gold compound. It is used together with other treatments, such as non-steroidal anti-inflammatory drugs (NSAIDs), for active rheumatoid arthritis.

It is thought to modify the progress of active rheumatoid arthritis. Ridaura may prevent or reduce further damage to the joints. Ridaura can also reduce the inflammation in the joints.

Rheumatoid arthritis can affect most joints, but the small joints of the hands and feet are frequently affected. The joints become swollen, warm and tender. This leads to pain and loss of joint movement. Deformity occurs with time. Morning stiffness in affected joints is a common symptom of rheumatoid arthritis.

Your doctor may have prescribed this medicine for another reason.

Ask your doctor if you have questions about why it has been prescribed for you.

Ridaura is only available with a doctor’s prescription.

There is no evidence that Ridaura is addictive.

Before you take Ridaura

When you must not take it

Do not take Ridaura if:

  • you have previously had a severe reaction to Ridaura, or to other products containing gold (e.g. Myocrisin, Gold-50) or other heavy metals, or you have had lung or gut problems caused by gold
  • you have or have had any of the following medical conditions:
    - severe liver problems
    - progressive kidney disease
    - severe blood disorder
    - bone marrow disorder, e.g. due to disease or other medicine, chemical or radiation
    - confirmed or suspected systemic lupus erythematosus (SLE)
    - severe chronic skin disease such as severe eczema, hives or dermatitis.

Do not take Ridaura if you are allergic to:

  • auranofin or any of the ingredients listed at the end of this leaflet
  • gold or any other heavy metal.

Do not take Ridaura if you are already taking:

  • any medicine that affects the bone marrow, including some medicines used to treat cancer
  • clozapine, used to treat schizophrenia
  • penicillamine, used to treat rheumatoid arthritis
  • leflunomide, high dose corticosteroids and other immunosuppressants (medicines which reduce the activity of your immune system)
  • medicines used to prevent or treat malaria, e.g. chloroquine, hydroxychloroquine, atovaquone, proguanil, mefloquine or quinine

Do not take it after the expiry date (‘Exp.’) printed on the pack. If the expiry date has passed, it may not work as well.

Do not take it if the packaging is torn or shows signs of tampering.

If you are not sure whether you should start taking this medicine, talk to your doctor or pharmacist.

Before you start to take it

Tell your doctor if:

  • you have or have had allergies to any other medicines, foods, preservatives or dyes
  • you are prone to allergies in general, including allergic skin reactions, hay fever or asthma
  • you have or have had:
    - any liver problems
    - any kidney problems
    - inflammatory bowel disease
    - Sjogren’s syndrome, an autoimmune disease
    - diabetes mellitus
    - heart failure or high blood pressure
    - systemic sclerosis
    - skin rashes
    - porphyria, a rare blood pigment disorder
    - inherited intolerance to sugar, including galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
    - recent or current treatment with radiotherapy.

Tell your doctor if you are pregnant or intend to become pregnant. Like most medicines of this kind, Ridaura should not be used during pregnancy.

Tell your doctor if you are breast-feeding, or planning to breast-feed. Ridaura passes into breast milk and may affect your baby.

If you have not told your doctor or pharmacist about any of the above, tell them before you start taking Ridaura.

Do not give Ridaura to a child or adolescent. There is no experience with its use in children or adolescents under 16 years old.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Tell any health professional who is prescribing a new medicine for you that you are taking Ridaura.

Some medicines and Ridaura may interfere with each other. These include:

  • medicines listed above under “When you must not take it”
  • clonidine, a medicine used to treat high blood pressure
  • corticosteroids, used in the treatment of many diseases including rheumatoid arthritis
  • medicines used to control pain, such as dextropropoxyphene
  • aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) including phenylbutazone and oxyphenbutazone
  • medicines known as ACE inhibitors, used to treat high blood pressure and heart failure
  • chelating agents, used to remove metals like copper, gold and mercury from the body
  • some antibiotics, including aminoglycosides, amphotericin B, penicillins and sulphonamides
  • aciclovir, used to treat viral infections
  • phenytoin, used to treat epilepsy
  • any medicine that affects gut motility including laxatives, e.g. senna, and treatments for diarrhoea, e.g. loperamide
  • theophylline, used to treat asthma
  • warfarin, used to prevent blood clots
  • levamisole, a treatment for worm infections
  • quinidine.

The above medicines may be affected by Ridaura, or may affect how well it works. You may need to use different amounts of Ridaura, or take it at different times, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or to avoid while taking this medicine.

How to take Ridaura

Read the label carefully and follow all directions given to you by your doctor and pharmacist. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist for help.

How much to take

The usual dose of Ridaura for rheumatoid arthritis is two 3 mg tablets per day.

Ask your doctor or pharmacist if you are unsure of the correct dose for you. They will tell you exactly how much to take. This depends on your condition and whether or not you are taking any other medicines.

If you take the wrong dose, Ridaura may not work as well and your problem may not improve.

Take Ridaura with a full glass of water.

When to take it

Ridaura may be taken as either a single daily dose (2 tablets once a day) or twice daily (one tablet twice a day).

Take Ridaura during or immediately after a meal, at about the same time(s) each day.

How long to take it

Continue taking the medicine for as long as your doctor tells you to. It may take 3 to 4 months (or more) before Ridaura has any effect. Your doctor may decide that you should continue to use Ridaura for some time, even when your symptoms subside.

Do not stop taking Ridaura even if you begin to feel better. For best effect Ridaura must be taken regularly.

If you are unsure whether you should stop taking Ridaura, talk to your doctor or pharmacist.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take the next dose when you are meant to.

Do not try to make up for missed doses by taking more than one dose at a time. This may increase the chance of getting an unwanted side effect.

If there is still a long time to go before your next dose, take it as soon as you remember, and then go back to taking it as you would normally.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for hints.

If you take too much (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (telephone 13 11 26 in Australia or 0800 764 766 in New Zealand), or go to Accident and Emergency at your nearest hospital, if you think you or anyone else may have taken too much Ridaura.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose may include dizziness, headache, flushing, fast or irregular heart beat or any of the side effects mentioned below.

While you are taking it

Things you must do

If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking Ridaura. Likewise, tell any other doctors, dentists and pharmacists who are treating you that you are taking this medicine.

Keep all of your doctor’s appointments so that your progress can be checked. Treatment with Ridaura requires careful monitoring. You will have regular blood, liver and urine tests and eye examinations.

Tell your doctor promptly if you start having any unusual symptoms such as:

  • itching, rash
  • metallic taste
  • mouth ulcer, sore throat or tongue
  • easy bruising, red-purple spots on the skin
  • nose bleed or bleeding gums
  • diarrhoea
  • abnormally heavy periods in women

These are some of the possible symptoms of gold toxicity. You may need immediate medical attention.

If you are a woman, you must take measures to avoid pregnancy during treatment and for at least 6 months after stopping treatment with Ridaura. Ridaura should not be used in pregnant women because of the possible risk of birth defects.

Pregnancy must be avoided after stopping treatment because it takes some time for gold to be removed from the body.

Tell your doctor immediately if you become pregnant during treatment or within 6 months of stopping treatment. Your doctor will discuss with you the risks and options if this occurs.

Things you must not do

Do not take Ridaura to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking Ridaura or lower the dosage without checking with your doctor.

For best effect Ridaura must be taken regularly.

Things to be careful of

Protect your skin when you are in the sun, especially between 10am and 3pm. If you are outdoors, wear protective clothing and use a 30+ sunscreen. Ridaura may cause your skin to be much more sensitive to sunlight than it is normally. This could cause a skin rash, itching, redness or severe sunburn.

Talk to your doctor or pharmacist and follow their advice about drinking alcohol while being treated with Ridaura Depending on your particular medical condition and other treatments, your doctor or pharmacist may recommend you limit or stop drinking alcohol while taking Ridaura.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Ridaura.

Like all medicines, Ridaura may occasionally cause side effects in some people. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • mild stomach pains or cramps
  • gas from the stomach or bowel
  • nausea or vomiting
  • indigestion
  • constipation
  • loss of appetite
  • increased sensitivity to sunlight
  • hair loss
  • diarrhoea.

The above list includes the more common side effects of your medicine. These side effects are usually mild.

Diarrhoea is a common side effect with Ridaura. The severity of the diarrhoea can be affected by the amount of Ridaura you take. It may be necessary for your doctor to change how much or how often you take Ridaura.

Tell your doctor immediately if you notice any of the following:

  • metallic taste
  • sore throat, tongue or mouth, or mouth ulcers
  • itching, rash, redness or peeling of the skin
  • easy bruising or bleeding, red-purple spots on the skin
  • abnormally heavy periods in women
  • sore eyes or eye changes
  • blood in the urine
  • yellowing of the skin or eyes (jaundice)
  • blood in vomit or stools, or black, tarry stools
  • stomach pains or cramps that are severe, persist or recur
  • unintended weight loss
  • shortness of breath or coughing, particularly if accompanied by fever, fatigue or loss of appetite.

These may be serious side effects. You may need urgent medical attention.

Stop taking Ridaura and tell your doctor immediately, or go to Accident and Emergency at your nearest hospital if you notice any of the following:

  • serious allergic reaction (swelling of the face, lips, mouth or throat which may cause difficulty swallowing or breathing).

This is a very serious side effect. You may need urgent medical attention or hospitalisation.

Some side effects may only be found when your doctor does laboratory tests to check your progress, e.g. low blood cell counts, changes in the urine, some effects on liver and kidney function.

Tell your doctor if you notice anything else that is making you feel unwell. Other side effects not listed above may also occur in some people.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After taking it

Storage

Keep your tablets in the original pack until it is time to take them. If you take the tablets out of the bottle they may not keep well.

Keep the medicine in a cool dry place where the temperature stays below 30°C.

Do not store it or any other medicine in the bathroom, near a sink, or on a window-sill. Do not leave it in the car. Heat and dampness can destroy some medicines.

Keep it and any other medicine where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

Return any unused medicine, and any medicine past its expiry date (as shown on the dispensing label or on the packaging) to your pharmacist.

Product description

What it looks like

Ridaura is available in bottles of 60 tablets. The tablets are square, bevel-edged, and pale yellow.

Ingredients

Active ingredient:

  • 3mg auranofin per tablet

Inactive ingredients:

  • lactose monohydrate
  • maize starch
  • microcrystalline cellulose
  • sodium starch glycollate
  • magnesium stearate
  • hypromellose
  • propylene glycol
  • titanium dioxide
  • iron oxide yellow (CI77492).

Ridaura tablets contain lactose monohydrate. They do not contain sucrose, tartrazine or any other azo dyes.

Sponsor details

Amdipharm Mercury (Australia) Pty Ltd
Level 9, 76 Berry Street
North Sydney NSW 2060

AUST R 13000

Date of preparation

This leaflet was revised on 1 May 2020.

Amdipharm Mercury (Australia) Pty Ltd is licensed to use the trademark Ridaura

Published by MIMS July 2021

BRAND INFORMATION

Brand name

Ridaura

Active ingredient

Auranofin

Schedule

S4

 

1 Name of Medicine

Auranofin.

2 Qualitative and Quantitative Composition

Each Ridaura tablet contains auranofin 3 mg.

Excipients with known effect.

Sugars (as lactose monohydrate).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Ridaura tablets are square, bevel-edged, pale yellow, film-coated tablets having raised domes on both faces.

4 Clinical Particulars

4.1 Therapeutic Indications

Adjunctive treatment of active classical or definite rheumatoid arthritis in adults who have an insufficient therapeutic response to, or are intolerant of, an adequate trial of a baseline therapeutic program, including among other measures, full doses of one or more nonsteroidal anti-inflammatory drugs. Ridaura is not indicated in non-rheumatoid arthropathies such as osteoarthrosis. Ridaura should be added to a comprehensive baseline therapeutic program.

4.2 Dose and Method of Administration

The usual adult dosage is 6 mg per day with food.
Ridaura may be co-prescribed with anti-inflammatory medicine/analgesics as part of a comprehensive treatment program. Such concomitant therapy may be necessary especially during the first weeks of Ridaura therapy, before full benefit of Ridaura is seen. Ridaura has also been used successfully with low dose (less than 10 mg) corticosteroid therapy.
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. Daily dosages above 9 mg are not recommended because of insufficient experience in human studies and increased risk of adverse effects.
Clinical studies have shown that patients may be safely transferred to Ridaura from injectable gold salt therapy without the need for overlap or a washout period.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients (see Section 6.1 List of Excipients).
Hypersensitivity to gold compounds or other heavy metals.
Previous serious toxicity to parenteral gold or to auranofin or to heavy metals other than gold.
Progressive renal disease.
Severe active hepatic disease.
Bone marrow aplasia, history of bone marrow suppression or combined use with myelotoxic or myelosuppressive medicines (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Severe haematological disorders.
Suspected systemic lupus erythematosus.
Severe chronic forms of dermatitis (severe urticaria or eczema, exfoliative dermatitis).
History of gold-induced necrotising enterocolitis.
History of gold-induced pulmonary fibrosis.
Concurrent administration with clozapine, antimalarial agents (e.g. chloroquine phosphate, hydroxychloroquine sulfate, atovaquone/proguanil hydrochloride, mefloquine and quinine), penicillamine or with immunosuppressive agents.

4.4 Special Warnings and Precautions for Use

The use of gold therapy should be introduced under specialist supervision. Physicians should familiarise themselves thoroughly with this Product Information and discuss the potential adverse effects that may occur with patients on this therapy. Patients should be alerted to report promptly any unusual signs or symptoms suggesting toxicity, such as pruritus, rash, metallic taste, sore throat or tongue, mouth ulceration, easy bruising, purpura, epistaxis, bleeding gums, menorrhagia or diarrhoea.

Other disease conditions.

In conditions such as systemic sclerosis and Sjogren's syndrome, Ridaura has not been evaluated and therefore its use cannot be recommended. Diabetes mellitus, congestive cardiac failure and hypertension should be under control before gold therapy is instituted.
Ridaura should be used with caution in patients with inflammatory bowel disease because of the possibility of inducing diarrhoea and further bowel irritation. Ulcerative enterocolitis is a rare serious gold reaction. Therefore, patients with gastrointestinal symptoms should be monitored for the appearance of gastrointestinal bleeding (see Section 4.4 Special Warnings and Precautions for Use, Gastrointestinal effects).
Ridaura has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.
Data suggest that gold may increase the effects of radiotherapy. Treatment should therefore be avoided in patients who have recently received or are undergoing radiotherapy.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Gastrointestinal effects.

The most common reaction to Ridaura is diarrhoea or loose stools (see Section 4.8 Adverse Effects (Undesirable Effects)). The incidence of diarrhoea appears to be related to the size of the dose, but not frequency of administration, and is apparently increased in patients of low body weight. The auranofin-induced diarrhoea may be controlled by a dose reduction, appropriate symptomatic treatment, use of variable dosage regimen or oral iron administration. If all the above fails, auranofin should be withdrawn.
Enterocolitis is a rare but potentially serious adverse effect. The development of diarrhoea with rectal bleeding or rectal bleeding alone, unless rapidly explained otherwise, mandates the immediate cessation of the therapy. Patients should be advised to seek medical advice as soon as possible if they develop these symptoms.

Haematological reactions.

Blood dyscrasias including leucopenia, granulocytopenia and thrombocytopenia have all been reported as reactions to parenteral gold and Ridaura. These reactions may occur separately or in combination and may occur anytime during treatment. Pure red cell aplasia has been reported (see Section 4.8 Adverse Effects (Undesirable Effects)). Because of the potentially serious consequences, regular monitoring for early diagnosis of blood dyscrasias is recommended.
It is recommended that whole blood count with differential cell count, haemoglobin, urinary protein, and renal and liver function tests be performed prior to Ridaura therapy to establish a baseline and to identify any pre-existing conditions.
Whole blood count with differential cell count, platelet count and urinary protein should then be monitored monthly; other parameters should be monitored as appropriate.
Danger signs of possible gold toxicity include: rapid fall in haemoglobin, leucopenia below 4000 WBC/mm3, granulocytes below 1,500/mm3, decrease in platelets below 150,000/mm3. Ridaura should be withdrawn if the thrombocyte count falls below 100,000/mm3 or if other symptoms indicating thrombocytopenia, leucopenia or aplastic anaemia occur.
Thrombocytopenia has occurred in up to 1-3% of patients treated with Ridaura, some of whom developed bleeding. The thrombocytopenia appears to be peripheral in origin and is usually reversible upon withdrawal of Ridaura. Its onset bears no relationship to the duration of Ridaura therapy. Its course may be rapid. While patients' platelet counts should normally be monitored monthly, the occurrence of signs and symptoms (e.g. purpura, ecchymoses or petechiae most commonly) suggestive of thrombocytopenia indicates a need to immediately withdraw Ridaura and all other therapies with the potential to cause thrombocytopenia and to obtain additional platelet counts. No additional Ridaura should be given unless further studies show the signs, symptoms or thrombocytopenia to be caused by conditions other than gold toxicity.

Mucocutaneous effects.

Patients should be cautioned to minimise exposure to ultraviolet light as gold induced dermatitis may be aggravated by exposure to sunlight. Phototoxic/photosensitivity reactions, including permanent slate-gray discoloration of the skin and sclera (chrysiasis), may develop. This has been reported mainly with long term use of parenteral gold.
Pruritus usually precedes dermatitis and early transient pruritus is considered a warning signal that the tolerance level has been exceeded. A metallic taste may precede oral mucous membrane reactions and may be considered as a warning signal of impending gold toxicity.
Patients with rash or pruritus (which may precede rash), or with stomatitis or a metallic taste in the mouth (which may precede stomatitis), should be closely monitored as such symptoms may indicate a need for modification of dosage or withdrawal. Treatment with Ridaura should be stopped in cases of persistent rash, especially if accompanied by pruritus.
Moderately severe skin mucous membrane reactions may be relieved by symptomatic treatment (e.g. topical steroids, oral antihistamines and/or soothing anaesthetic lotion). Severe or generalised gold compound induced stomatitis or dermatitis may require systemic steroid therapy.
Ridaura should be used with caution in patients with rash or a history of atopy because of the possibility of skin rashes occurring during treatment. Any eruption, especially if pruritic, that develops during treatment should be considered a gold reaction until proven otherwise.

Respiratory effects.

Pulmonary fibrosis may occur rarely and chest X-ray is recommended at least annually.

Ocular effects.

As gold preparations including auranofin cause ocular adverse effects, periodic ophthalmic examination is recommended in patients being treated with Ridaura.

Use in hepatic impairment.

Ridaura should be used with caution in patients with mild degree of hepatic dysfunction. Avoid use in moderate to severe liver impairment (see Section 4.3 Contraindications).
In view of known hepatotoxic effect of gold preparations (including auranofin) regular liver function monitoring is recommended.

Use in renal impairment.

Ridaura should be used with caution in patients with mild degree of renal impairment (see Section 4.3 Contraindications).
Gold compounds are well documented to be nephrotoxic. Complete urinalysis should be performed prior to therapy (treatment should not start if protein of ≥ 2+ as measured on dipstick, without haematuria, is detected in the urine sample) and at least monthly thereafter. If significant proteinuria (greater than 500 mg/day), or microscopic haematuria develops, treatment with auranofin and all other therapies with the potential to cause proteinuria or haematuria should be stopped. The renal function should be investigated and the medicinal product should not be given until the renal function is normal.

Use in the elderly.

Use with caution in elderly patients.

Paediatric use.

Ridaura has not been evaluated in juvenile rheumatoid arthritis and, consequently, its use in children below 16 years cannot be recommended.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Ridaura must not be combined with clozapine (myelotoxicity), antimalarial agents (e.g. chloroquine phosphate, hydroxychloroquine sulfate, atovaquone/proguanil hydrochloride, mefloquine and quinine), penicillamine or with myelosuppresssive, cytotoxic or immunosuppressive agents due to possible additive risk of haematological toxicity or renal adverse reactions (see Section 4.3 Contraindications).
The combined use of Ridaura and leflunomide (myelosuppressive) is contraindicated as the combined use of Ridaura with this medicinal product has not been adequately studied and the risk associated with combination therapy, in particular long-term treatment, is unknown. There is a risk of serious adverse reactions (hepato- or haematoxicity).
The safety of concomitant administration with phenylbutazone, oxyphenbutazone, levamisole, or high dose corticosteroids has not been established. In view of potential of these medicines to cause blood dyscrasias or other additive toxicity, concomitant use of Ridaura with these agents cannot be recommended.
Caution is advised when Ridaura is used with angiotensin-converting-enzyme (ACE) inhibitors due to increased risk of vasomotor reaction (nitritoid reactions) which may include vasodilatation, loss of consciousness, cardiovascular collapse (hypotension or syncope), facial flushing, nausea, vomiting, and cerebrovascular accident. In some patients, the reaction appeared soon after the ACE-inhibitor was started while in others a lag time of several months occurred. The reactions are most commonly associated with gold sodium aurothiomalate (myocrisin) but have been reported with oral gold (auranofin).
Concomitant administration with metal antagonists, and potentially nephrotoxic or haemotoxic medicines or alcohol, requires caution. Such medicines include aminoglycosides, amphotericin B, penicillins, phenytoin, sulfonamides, NSAIDs and aciclovir. Patients should be closely monitored and medicines stopped in case renal impairment or proteinuria of greater than 500 mg/day develop.
The concomitant administration of gold salts and phenytoin may result in increased plasma phenytoin levels. This may in turn lead to increased risk of associated adverse events including skin reactions. Therefore caution is required if the combination is prescribed. Other medicines like penicillins, aspirin and quinidine may cause delayed hypersensitivity reactions just like gold, as well as Henoch-Schönlein purpura. It is therefore advisable that caution is exercised when these medicines are combined as their use in combination may enhance development of skin reactions. Drug therapy should be stopped when skin reactions occur.
Medicines affecting gastrointestinal motility such as prokinetics, antidiarrhoeals e.g. loperamide, and laxatives e.g senna, may alter the absorption of auranofin and lead to increased toxicity. Caution is advised when Ridaura is prescribed at the same time as these medicines.
Periodic theophylline serum determinations are advised until further studies provide the necessary clarification about the kinetic profile of theophylline in patients taking concomitant steroids and gold salts. Caution is advised when Ridaura and theophylline combination is prescribed.
Animal toxicology studies demonstrated an increase in toxicity of Ridaura when it was administered with warfarin, dextropropoxyphene and clonidine. Although the clinical significance of this is not clear it should be borne in mind when these medicines are used concomitantly.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
Adequate human data on use during pregnancy are not available, and animal studies have shown adverse effects on pregnancy and embryo-foetal development.
Auranofin has been shown to be teratogenic in some animal species. Auranofin induced abortion, increased resorption, decreased litter size and foetal weight when given in a dosage of 0.5-7.8 mg/kg/day to pregnant rabbits. The most prominent and constant foetal abnormalities were abdominal defects such as gastroschisis and umbilical hernia. Anomalies of the brain, heart, lung and skeleton were seen less frequently. Oedema was the only major defect noted in foetal offspring from pregnant rats administered auranofin from 0.5 to 80.0 mg/kg/day. The incidence of resorption was significantly greater than that of the control at higher doses (10-80 mg/kg/day).
Ridaura should not be used in pregnant women or those likely to become pregnant. 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.
Women of childbearing potential should be made aware of the necessity to avoid pregnancy during treatment and for at least six months after because of the slow excretion of gold and its persistence in the body tissues after discontinuation of treatment (see Section 5.2 Pharmacokinetic Properties, Excretion). Patients should be fully informed of the teratogenic risk and termination of pregnancy occurring during treatment should be considered in the light of the risk of malformations in the foetus.
 Adequate human data on use during lactation are not available, and adequate animal reproduction studies are not available.
Auranofin is excreted into breast-milk in quantities sufficient for there to be a risk of effects on the child even at therapeutic doses. Trace amounts of the medicine appeared in the serum and red blood cells of the nursing offspring. It has been postulated that this may be the cause of unexplained rashes, nephritis, hepatitis and haematological aberrations in the nursing infants of mothers treated with parenteral gold.
Because of potential serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue medicine therapy, taking into account the importance of the medicine to the mother. The slow excretion of gold and its persistence in the mother after discontinuation of treatment should be kept in mind.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

The incidences of adverse reactions listed below are based on post-marketing experience and on observations of 4,784 patients. Of these, 2,729 were treated for more than one year and 573 for more than three years. The highest incidence is during the first 6 months of treatment, however, reactions can occur after many months of therapy. With rare exceptions all patients were on concomitant nonsteroidal anti-inflammatory therapy; some of them were also taking low doses of corticosteroids.
The most serious adverse events are blood dyscrasias like leucopenia and granulocytopenia which could lead to increased risk of infections.
The most common adverse reaction to Ridaura is diarrhoea or loose stools. Nausea may be present, and abdominal pain or other gastrointestinal symptoms have been reported alone or in association. These may resolve if dosage is temporarily reduced but it may be necessary to stop treatment or interrupt treatment and start again at a lower dosage (see Section 4.4 Special Warnings and Precautions for Use, Gastrointestinal effects). Some patients will be unable to tolerate Ridaura because of diarrhoea.
As with all gold-containing medicines, ulcerative enterocolitis has been reported (see below). Patients with gastrointestinal symptoms should be monitored carefully for the appearance of gastrointestinal bleeding and treatment stopped if this occurs (see Section 4.4 Special Warnings and Precautions for Use, Gastrointestinal effects).

More common (> 1%).

Gastrointestinal.

Loose stools or diarrhoea (47%), abdominal pain/cramps (14%), nausea with or without vomiting (10%), constipation (1-3%), anorexia (3-9%), flatulence (3-9%), dyspepsia (3-9%), dysgeusia (1-3%).

Dermatological.

Rash (24%), pruritus (17%), hair loss (1-3%), photosensitivity.

Mucous membrane.

Stomatitis (13%), conjunctivitis (3-9%), glossitis (1-3%).

Haematological.

Anaemia, leucopenia, granulocytopenia, eosinophilia, thrombocytopenia (1-3%).

Renal.

Proteinuria (3-9%), haematuria (1-3%), increase in blood urea and serum creatinine (1-3%), changes in renal function.

Hepatic.

Elevated liver enzymes (1-3%), changes in liver function.

Less common (< 1%).

Gastrointestinal.

Positive stool for occult blood, ulcerative enterocolitis (< 0.1%), peptic ulcer, metallic taste, dysphagia, (< 0.1%), gastrointestinal bleeding, melaena.

Dermatological.

Angioedema (< 0.1%).

Mucous membrane.

Dry mucous membrane, gingivitis.

Haematological.

Neutropenia, agranulocytosis (< 0.1%), aplastic anaemia and pancytopenia.

Renal.

Membranous glomerulonephritis (< 0.1%), nephrotic syndrome (< 0.1%).

Respiratory.

Interstitial pneumonitis (< 0.1%).

Hepatic.

Jaundice (< 0.1%).

Neurologic.

Peripheral neuropathy (< 0.1%), headache and dizziness.

Unknown frequency.

Haematological.

Decrease in haemoglobin, decrease in haematocrit, pure red cell aplasia.

Respiratory.

Pulmonary fibrosis.

Gastrointestinal.

Inflammatory bowel disease.

Dermatological.

Exfoliative dermatitis.
The following have been reported on occasion in clinical trials but no definite relationship to Ridaura therapy has been established.
Bell's palsy, ototoxicity, progression of pre-existing pulmonary disease, corneal lesion and chrysiasis.
There have been some reports of gold deposits in the lens or corneas of patients treated with Ridaura. These deposits have not led to any eye disorders or any degree of visual impairment, and have cleared within 3-6 months of cessation of therapy.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

Dizziness, headache, flushing, tachyarrhythmias, palpitations, thrombocytopenia, and effects on liver and kidneys may occur; other reported adverse effects may be intensified by overdose.
The absence of experience with acute overdosage with Ridaura precludes characterisation of sequelae and assessment of antidotal efficacy at this time. A 50 year old female, previously on Ridaura 6 mg daily, took 27 mg daily for 10 days and developed encephalopathy and peripheral neuropathy. Ridaura was discontinued and she eventually recovered.

Treatment.

In the case of accidental overdosage, immediate induction of emesis or gastric lavage is recommended.
There has been no experience with treating Ridaura overdosage with modalities such as chelating agents. However, they have been used with injectable gold and may be considered for Ridaura overdosage.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

In standard animal models, Ridaura has exhibited significant anti-inflammatory properties. In vitro test systems have demonstrated immunoregulatory activity that further distinguishes it from other agents capable of producing disease modifying activity in RA patients.
Ridaura enhances cell mediated immunity; inhibits antibody dependent cellular cytotoxicity; inhibits release of lysosomal enzymes; suppresses the generation of superoxide radicals; inhibits platelet aggregation.
In vitro, Ridaura has also been shown to inhibit chemotaxis, phagocytosis, and the inflammatory effects of prostaglandins.

Clinical trials.

It has been demonstrated by clinical and laboratory evaluations that prolonged treatment with Ridaura may modify the progress of active rheumatoid arthritis and so prevent or reduce subsequent damage to the joints.
Clinically, therapeutic response has been observed in three to four months; some patients require as long as six months to show a response. This response includes improvements in parameters such as joint swelling, tenderness, pain, morning stiffness and grip strength. Patients have been maintained on Ridaura for over 4 years with sustained improvement.
Ridaura reduces inflammation, lowers erythrocyte sedimentation rates, reduces rheumatoid factor levels and lowers elevated immunoglobulin levels. Radiographic evaluation of the joints after 12 months of therapy suggests that Ridaura may slow or suppress the progression of erosion. Ridaura's efficacy was comparable to or slightly less than that of parenteral gold salts.

5.2 Pharmacokinetic Properties

Absorption.

Following oral administration in man, approximately 25% of the auranofin gold is absorbed.

Distribution.

In blood, approximately 40% of the gold from auranofin is associated with erythrocytes and 60% is associated with serum proteins. During long-term therapy with Ridaura, serum gold concentrations reach a plateau after about 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 microgram/mL (0.30-1.20) have been observed. Serum concentrations are proportional to dose, but no correlation between blood gold levels and degree of efficacy or safety have been established.

Excretion.

The principal route of elimination of Ridaura gold is via the faeces (84-92%), with the urine accounting for 9-17% of the administered dose (equivalent to about 60% of the absorbed gold).
Studies with radio-labelled auranofin in patients with rheumatoid arthritis demonstrated a plasma elimination half-life of 16.8 (range 11.0-23.1) days and 25.5 (range 20.7-31.3) days before and after 6 months treatment with non-labelled auranofin 6 mg per day. In the same patients mean terminal body half-life was 57.6 (range 30.0-78.3) and 81 (range 42.3-128.0) days respectively.

5.3 Preclinical Safety Data

Genotoxicity.

Ridaura has shown weak mutagenic potential in the mouse lymphoma cell assay. Auranofin produced no mutation effects in the Ames Test (Salmonella), in the in vitro assay (Forward and Reverse Mutation Inducement Assay with Saccharomyces), in the in vitro transformation of BALB/T3 cell mouse assay or in the Dominant Lethal Assay.

Carcinogenicity.

As with other gold preparations, karyomegaly, cytomegaly and cystic development leading to development of adenoma and adenocarcinoma of the renal tubular epithelium has been observed in rats.

6 Pharmaceutical Particulars

6.1 List of Excipients

Ridaura contains the following excipients: microcrystalline cellulose, ethanol, hypromellose, iron oxide yellow CI77492, lactose monohydrate, magnesium stearate, propylene glycol, sodium starch glycollate, maize starch, titanium dioxide and purified water.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C. Protect from light.

6.5 Nature and Contents of Container

Ridaura is supplied in bottles of 60 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.


Molecular formula: C20H35AuO9PS+.
Molecular weight: 678.485 g/mol.
Chemical name: Gold(+1) cation; 3,4,5-triacetyloxy-6-(acetyloxymethyl)oxane-2-thiolate; triethylphosphanium.
Auranofin is a synthetic gold co-ordination complex in which the oxidation state of the central atom of gold is stabilised by electron binding with two side groups or ligands: a phosphine ligand (triethylphosphine) and a sulphur (thiolate) ligand (tetraacetylthioglucopyranose).
Auranofin exists as a comparatively small monomeric species both in solid state and in solution. This size factor may contribute to the absorption of auranofin following oral administration.

CAS number.

34031-32-8.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes