Summary for UKPID


    Kathryn Pughe, BSc (Hons) MRPharmS

    National Poisons Information Service (Newcastle Centre)
    Regional Drug & Therapeutics Centre
    Wolfson Building
    Claremont Place
    Newcastle upon Tyne
    NE1 4LP

    This monograph has been produced by staff of a National Poisons
    Information Service Centre in the United Kingdom.  The work was
    commissioned and funded by the UK Departments of Health, and was
    designed as a source of detailed information for use by poisons
    information centres.

    Peer review group: Directors of the UK National Poisons Information



         Generic             Auranofin
         Proprietary         Ridaura

         Generic             Sodium aurothiomalate
         Proprietary         Myocrisin
         Synonyms            Gold sodium thiomalate,
                             Sodium aurothiosuccinate

    Chemical Group/Family

         Drugs suppressing rheumatic disease
         BNF 10.1.3

    Reference Number

         Na aurothiomalate
         CAS 12244-57-4 (xNa, anhydrous)
         CAS 39377-38-3 (2Na monohydrate)

         CAS 34031-32-8

         Product licence numbers:
         Myocrisin:     10 mg inj 0012/5114
                        20 mg inj 0012/5113
                        50 mg inj 0012/5006
         Ridaura:       0002/0082


         Myocrisin:     Rhone-Poulenc Rorer Ltd
                        RPR House
                        52 St Leonards Road
                        East Sussex
                        BN21 3YG

                        Tel: 01323 417125
                        Fax: 01323 534086

         Ridaura:       Bencard
                        Welwyn Garden City
                        AL7 1EY

                        Tel: 0800 616482
                        Fax: 0181 913 4560


         Myocrisin      Pale yellow solution
                        0.5ml amps in boxes of 10 x 10 mg
                        0.5ml amps in boxes of 10 x 20 mg
                        0.5ml amps in boxes of 10 x 50 mg

         Ridaura        Pale yellow, film coated square tablets
                        3 mg tabs in containers of 60

    Physico-Chemical Properties

    Chemical structure
         Myocrisin      C4H3AuNa2O4S
                        Disodium salt of (aurothio)succinic acid

         Auranofin      C20H34AuO9PS
                        S-tri-ethylphosphine gold

    Physical state at room temperature
         Aurothiomalate      Fine, pale yellow powder with a slight odour
         Auranofin           Fine white powder

    Molecular weight
         (Hexomer)           2500 in 0.5M NaCl
         (Monomer)           390.1
         Auranofin           678.5

         thiomalate          3.2
         carboxyl            4.2
         Auranofin           -

         Aurothiomalate      in alcohol     insoluble
                             in water       very soluble
         Auranofin           in alcohol     1 in 27
                             in water       1 in 5900



         Sodium aurothiomalate - active progressive rheumatoid arthritis,
         and progressive juvenile chronic arthritis.

         Auranofin - active progressive rheumatoid arthritis when NSAIDs
         inadequate alone.

    Therapeutic Dosage

          Sodium aurothiomalate

         By deep im injection only.
         Adults: Initial test dose of 10 mg in first week followed by
         weekly doses of 50 mg until signs of remission occur. With full
         remission, the interval between injections should be
         progressively increased to 3, 4 and then, after 18-24 months, to
         6 weeks. If after reaching a total dose of 1g, excluding the test
         dose, no major improvement has occurred and the patient has not
         shown any signs of gold toxicity, six 100 mg injections may be
         administered at weekly intervals. If no signs of remission occur
         after this time, consider alternative treatments.

         Children: Weekly doses of 1mg/kg up to maximum weekly dose of 50
         mg. This dose may be preceded by a smaller test dose of 1/10th or
         1/5th of the full dose for 2-3 weeks. Continue weekly doses until
         signs of remission appear then increase intervals to 2 weeks.
         With full remission increase interval to 3 then 4 weeks. I f no
         signs of remission after 20 weeks, consider alternative
         treatments. Treatment should be continued for 6 months. Expect
         response at 300-500 mg level. If patients respond, maintenance
         therapy should be continued with the dosage administered over the
         previous 2-4 weeks for 1-5 years.


         Adults: Starting dose 3 mg twice daily, then 6 mg as single daily
         dose if well tolerated. Continue for minimum of 3-6 months to
         assess response. Increase to 3 mg three times a day if response
         inadequate after 6 months, if still inadequate after a further 3
         months, then discontinue

         Child: Not recommended


          Sodium aurothiomalate

         Severe renal and hepatic disease; history of blood disorders or
         bone marrow aplasia; exfoliative dermatitis; systemic lupus
         erythematosus; necrotising enterocolitis; pulmonary fibrosis;
         pregnancy and breastfeeding; porphyria.


         Not for use in patients with a history of gold-induced disorders
         as for sodium aurothiomalate.







         Aurothiomalate      Intramuscular absorption 100%, not orally
         Auranofin           Oral absorption 13-33%


         Aurothiomalate      Volume of distribution - 0.1Lkg-1
         Auranofin           Volume of distribution - NIF


         Aurothiomalate      No presystemic metabolism, 95% plasma protein
         Auranofin           No presystemic metabolism, 60% plasma protein


         Aurothiomalate      70% excreted in urine, 30% in faeces
         Auranofin           85% excreted in faeces, 15% in urine

         Aurothiomalate      Initial 5.5 days; terminal 250 days
         Auranofin           17-25 days (plasma); total body 70 days

    Special Populations


    The safety of gold salts in pregnancy has not been established. Gold
    salts should not be used in women of child-bearing potential, unless
    the benefits outweigh the possible risks, as clinical experience is

    Gold is teratogenic in rats and rabbits at high doses which produce
    maternal toxicity, increased frequencies of skeletal, CNS and other
    malformations were seen.

    There are no controlled studies of gold administration     during
    human pregnancy. Placental passage of gold salts has been documented
    in clinical reports.

    The frequency of malformations was not increased in a study of 119
    children born to women who had been treated with gold compounds during
    the first trimester of pregnancy. 26 patients in this series received
    gold treatment throughout pregnancy, 2 minor anomalies were seen but a
    causal association with gold has not been established.

    Hepatic disease

    Use with caution in patients with any degree of hepatic dysfunction.
    Intrahepatic cholestasis with eosinophilia may be seen after gold
    injections. The condition is self-limiting, and liver function tests
    return to normal within about 3 months.

    Renal disease

    Use with caution in patients with any degree of renal impairment.


    Monitor with extra caution due to decreased renal function


    Avoid if breastfeeding as significant amounts of gold excreted.



    Acute overdose is usually the result of administration errors with IM
    injections, and until 1984 therapeutic gold drugs were only available
    parenterally. Most toxic data are based on therapeutic toxicity.


    There is a high incidence of adverse reactions when gold salts are
    used for rheumatoid arthritis, incidence is between 5-50% (Eyring &
    Engleman, 1963; Davis & Hughes, 1974). The rate of serious reactions
    is approximately 3-5%. Anaphylactoid effects may occur after any
    course of therapy, usually within the first 10 minutes of

    Problems with therapeutic use include mouth ulcers, skin reactions,,
    proteinuria, blood disorders (sometimes sudden onset and fatal).
    Rarely colitis, peripheral neuritis, pulmonary fibrosis,
    hepatotoxicity with cholestatic jaundice and alopecia can also occur.
    Diarrhoea and other gastrointestinal symptoms are associated with
    auranofin use.

    Proteinuria occurs in 2-20% of patients treated with injected gold and
    may be sufficiently severe to cause nephrotic syndrome in 10-30% of
    those affected. Proteinuria usually resolves on stopping treatment.

    Gold lung is a rare toxic side effect of gold therapy that may begin
    after administration of 300-1000 mg total gold dose. Dyspnoea appears
    suddenly over a period of 2-10 days. Chest x-rays show diffuse
    bilateral pulmonary shading (Gortenuti et al 1985), and a moderate
    eosinophilia may be present. The prognosis is good after withdrawal of
    treatment (McFadden et al 1989), although impairment of lung function
    may be permanent (Cohen 1988).

    Patients treated with gold salts should be asked to report immediately
    the appearance of pruritis, metallic taste, sore throat or tongue,
    buccal ulceration or easy bruising, purpura, epistaxis, bleeding gums,
    menorrhagia or diarrhoea.


    Increased risk of toxicity with other nephrotoxic and myelosuppressive



    No deaths have been recorded. Adults have been given up to 500 mg (10
    times the therapeutic dose ) in a single dose with variable
    consequences. One patient took 27 mg auranofin daily for 10 days and
    developed an encephalopathy and peripheral neuropathy. The patient
    made a gradual recovery after auranofin was discontinued


    Effects would be expected to be extensions of toxic therapeutic


    Most of the reported cases of overdose have not developed  features.
    Early features of acute overdose have included a generalized skin
    rash, which settled within a few hours, and oedema of the eyelids in
    one case, and ventricular tachycardia in another. Acute renal failure
    is a potential problem but has not been reported. Abnormal LFTs with
    elevation of ALT and alkaline phosphatase were reported 3 weeks post-
    overdose in one case.


    Observation and supportive measures are probably all that are
    required. There is some doubt as to whether toxic reactions seen are
    due to direct effects of gold, or an indirect effect through the
    immune system.


    Overdose with oral gold salts is not commonly seen and it is not known
    if activated charcoal is effective in minimizing drug absorption in
    such cases. Metallic gold is poorly adsorbed by activated charcoal.

    Supportive care

    D-Penicillamine has been used to treat skin reactions (Davis 1969)
    and thrombocytopenia (Bluhm et al 1962) in   cases where BAL and
    corticosteroids showed initial but not sustained results. It should be
    avoided in penicillin-allergic patients. Monitoring for proteinuria
    should be performed.

    Adults: 15-40mg/kg/day orally; max 250-500 mg four times a day before

    Children: 20-30mg/kg/day orally once or twice daily before meals.

    Immunosuppressives such as cyclophosphamide have also been used to
    control toxic reactions. A dose of 100 mg daily for 6 months was used
    until platelets stabilised at 100,000 per cubic mm, and then the dose
    was reduced to 75mg daily (Kozloff et al 1979).


    Haematology, liver and renal functions should be monitored.

    Gold urine levels during treatment vary      considerably. There seems
    to be no correlation between blood gold levels and toxicity or
    therapeutic effect. In a summary of 20 cases of toxicity, the
    cumulative toxic dose was from 230 mg to 10g of gold salt.


    Some patients have been given dimercaprol (BAL) to chelate the
    gold but there is no evidence that it is of value.

    The dose of BAL is individualized. A common dosage schedule is 3-5
    mg/kg/dose every 4 hours by deep IM injection for the first 2 days,
    then 2.5-3/mg/kg/dose IM every 6 hours for 2 days, then 2.5-3 mg/kg IM
    every 12 hours for 7 days.



    N-acetylcysteine (NAC) has been used to remove / redistribute gold and
    reduce haematological reactions (Godfrey et al 1982). Lorber et al
    (1973) demonstrated in vitro and in vivo chelation of gold by NAC,
    with up to a 54% increase over normal excretion in subjects tested.

    Dose: 2-9g in 100ml dextrose 5% or 0.45% sodium chloride iv over 2-6
    hours. Total dose per therapy ranged from 13 to 153g.

    D-Penicillamine was shown to enhance the urinary excretion of gold
    when tested in 9 patients (Erying & Engleman 1963).


    Haematology, liver and renal functions should be monitored.

    Management controversies 

    Use of dimercaprol: Patients with high gold levels not given
    dimercaprol do not appear to have had an adverse outcome, but there is
    insufficient data to make categoric statements. Chelation reduces the
    amount of circulating gold, but it is nearly impossible to remove all
    the gold from the system.



    1. Auranofin overdose (27 mg/day for 10 days) has resulted in
    peripheral neuropathy and encephalopathy, which resolved upon drug
    withdrawal (Ridaura Prod Info, 1985).


    1. Pik et al (1985) reported two acute overdose cases in which
    patients received 1000 mg and 500 mg of intramuscular aurothioglucose,
    respectively. Both patients were asymptomatic and recovered
    uneventfully without treatment. One patient, however, developed
    microhaematuria and granular casts without proteinuria which resolved
    spontaneously within four weeks.

    2. A 53 year old male was accidentally injected with an im dose of 450
    mg sodium aurothiomalate. Palpebral oedema and a cutaneous generalized
    rash were observed within 30 minutes. The gold blood levels reached
    29.7mg/L without significant toxicity. The patient was treated with
    BAL and recovered (Barelli et al 1987).

    3. A 32 year old patient developed ventricular tachycardia 3 hours
    after im injection of 500 mg of aurothiomalate (Sharf et al 1976).


    Kathryn Pughe, BSc (Hons) MRPharmS

    National Poisons Information Service (Newcastle Centre)
    Regional Drug & Therapeutics Centre
    Wolfson Building
    Claremont Place
    Newcastle upon Tyne
    NE1 4LP

    This monograph was produced by the staff of the Newcastle Centre of
    the National Poisons Information Service in the United Kingdom. The
    work was commissioned and funded by the UK Departments of Health, and
    was designed as a source of detailed information for use by poisons
    information centres.

    Peer review was undertaken by the Directors of the UK National Poisons
    Information Service.

    Last updated March 1997



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    2.   Bluhm GB, Sigler JW, Ensign DC et al. D-penicillamine therapy of
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         treatment of hematologic reactions to chrysotherpay. J Rheum
         1982; 9: 519-526.

    8.   Gortenuti G, Parrinello A, Vicentini D. Diffuse pulmonary changes
         caused by gold salt therapy. Report of a case. Diagn Imag Clin
         Med 1985; 54: 298-303.

    9.   Kozloff M, Votaw M & Penner JA. Gold-induced thrombocytopenia
         responsive to cyclophosphamide. South Med J 1979; 72: 1490-1491.

    10.  Lorber A, Baumgartner WA, Bovy RA et al. Clinical application for
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    11.  McFadden RG, Traher LJ, Thompson JM. Gold-naproxen pneumonitis. A
         toxic drug reaction? Chest 1989; 96: 216-218.

    12.  Pik A, Cohen N, Yona E et al. Should gold overdose be invariably
         treated? J Rheumatol 1985; 12: 1174-1175.

    13.  Rubinstein I et al. Aurothioglucose overdosage in five patients
         with rheumatoid arthritis. Clin Rheumatol 1987; 6: 583-587.

    14.  Sharf J, Nahir M, Nirenberg L. Ventricular tachycardia caused by
         gold overdose. Arthritis Rheum 1976; 19: 137-138.

    Computer databases:

    1.   Poisindex System(R), Micromedex inc., Denver Colorado, Edition
         Expires 31/3/97.

    2.   Reprotox System(R), Micromedex inc., Denver Colorado, Edition
         Expires 31/3/97.

    3.   TOXBASE, National Poisons Information Service, 1997.

    See Also:
       Toxicological Abbreviations