AUSTRALIAN PRODUCT INFORMATION MYOCRISIN (SODIUM AUROTHIOMALATE) SOLUTION FOR INJECTION 2 QUALITATIVE AND QUANTITATIVE COMPOSITION

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1 AUSTRALIAN PRODUCT INFORMATION MYOCRISIN (SODIUM AUROTHIOMALATE) SOLUTION FOR INJECTION 1 NAME OF THE MEDICINE Sodium aurothiomalate 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each ampoule of MYOCRISIN solution for injection contains 10mg, 20mg or 50mg of sodium aurothiomalate and phenylmercuric nitrate and water for injections. 3 PHARMACEUTICAL FORM Solution for injection 4 CLINICAL PARTICULARS 4.1 THERAPEUTIC INDICATIONS Adjunctive treatment of rheumatoid arthritis that is not adequately controlled by other antiinflammatory agents and conservative measures. In chronic, advanced cases of rheumatoid arthritis, gold therapy is less valuable. Still's disease. 4.2 DOSE AND METHOD OF ADMINISTRATION MYOCRISIN should be administered only by intramuscular injection. Because of the possibility of an anaphylactic reaction, it is recommended that patients be kept under medical observation for a period of 30 minutes after the administration of the drug. Do not use a darkened solution (more than pale yellow). Rheumatoid arthritis Dosage should be adjusted according to the response of the patient. Recommended initial dosage schedules: injection, at weekly intervals, of 1, 5 and 10mg to test the patient's tolerance, followed by a 50mg/week to a total of 1g, or twenty weekly injections of 50mg to a total of 1g. Whatever initial dosage regimen is adopted it is essential to continue therapy on a maintenance basis, usually at the rate of 50mg/month until a total of about 3g has been given; alternatively, the treatment is continued indefinitely or maintained for at least two years after remission has been achieved. myocrisin-ccsiv1-piv5-06aug18 Page 1 of 8

2 Still's disease Dosage is proportionate to the body weight of the patient. MYOCRISIN is given at weekly intervals, initiating treatment with the smallest doses and increasing to the following maxima: under 25kg bodyweight: 10mg; 25 to 50kg bodyweight: 20mg; over 50kg bodyweight: 50mg. Therapy should be continued for about six months. If at this time there is no improvement the gold is stopped, but in cases showing improvement, maintenance therapy with fortnightly or monthly injections of the previous dosage should be given for one to five years. 4.3 CONTRAINDICATIONS Hypersensitivity to sodium aurothiomalate or to any of the excipients. Patients with severe renal or hepatic disease, diabetes, marked toxaemia, a history of blood dyscrasias or exfoliative dermatitis, a history of systemic lupus erythematosus. Use in Pregnancy is contraindicated (See Section 4.4 Special warnings and precautions for use). 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE MYOCRISIN should be administered with extra caution: in patients with a history of enterocolitis or pulmonary fibrosis in patients with a history of urticaria in patients with a history of eczema Every candidate for gold therapy should be investigated fully to prevent the administration of gold to those with gross renal or hepatic defects, diabetes, marked toxaemia, a history of blood dyscrasias or dermatitis. Before starting treatment, and again before each injection, the urine should be tested for protein, the skin inspected for rashes, and a full blood count performed, with a numerical platelet count (not an estimation) and the readings plotted. The availability, whenever possible, of the results of blood counts before the next injection is a useful aid in minimising toxic reactions. Minimum values below which gold should not be given until the count has been repeated and there is return to normal values are: total white cells 4,000/mm 3, neutrophils 2,000/mm 3, platelets 150,000/mm 3. It is unwise to continue with gold injections when there is a persistent or otherwise unexplained eosinophilia exceeding 1,000/mm 3, as this may indicate an impending toxic reaction. Particular vigilance should be maintained during the period when between 300 to 500mg of gold has been given because it is at this time that a blood dyscrasia is most likely to occur. If the full blood count is normal after the cumulative gold dose reaches 500mg, and provided the full blood count remains normal, full blood counts can be done before every second injection. The presence of proteinuria (including albuminuria), pruritus, or rash, or an eosinophilia are indications of developing toxicity; the dose of MYOCRISIN should be withheld for one to two weeks until all signs have disappeared, when the treatment may be restarted on a smaller dosage (test dose) followed by a decreased frequency of gold injections. myocrisin-ccsiv1-piv5-06aug18 Page 2 of 8

3 MYOCRISIN may be given in the presence of a trace of protein, but if there is 30mg/100mL or more, in the absence of urinary infection or other cause it may indicate a developing gold nephropathy and the treatment should be stopped. Generally, this induces a complete reversal although in some instances the proteinuria may persist for many months. The complaint of metallic taste, sore throat, glossitis, buccal ulceration and or easy bruising or bleeding demands an immediate blood count, followed, if indicated, by appropriate treatment for agranulocytosis, aplastic anaemia and or thrombocytopenia. All patients receiving the drug should be warned both verbally and in writing to report immediately the appearance of pruritus, metallic taste, sore throat, mouth or tongue, stomatitis, buccal ulceration or the development of bruising or unusual bleeding, purpura, epistaxis, bleeding gums, menorrhagia or diarrhoea. As gold preparations cause ocular adverse effects, ophthalmological examination is recommended if ocular symptoms occur. MYOCRISIN should be used with care in patients with marked hypertension or compromised cerebral or cardiovascular circulation. As with other gold preparations, reactions which resemble anaphylactoid effects have been reported. These effects and anaphylactoid reactions may occur after any course of therapy within the first 10 minutes following drug administration (see Section 4.2 Dose and method of administration). If anaphylactoid effects are observed, treatment with MYOCRISIN should be discontinued. Use in the elderly MYOCRISIN should be administered with extra caution in the elderly. Paediatric use Effects on laboratory tests 4.5 INTERACTIONS WITH OTHER MEDICINES AND OTHER FORMS OF INTERACTIONS Gold salts should not be used concomitantly with penicillamine. Extra caution should be exercised if phenylbutazone or oxyphenbutazone are administered concurrently. Gold administration may exacerbate aspirin induced hepatic dysfunction. Caution is needed in patients treated concomitantly with sodium aurothiomalate and angiotensin-converting enzyme inhibitors due to an increased risk of severe anaphylactoid reactions in these patients. myocrisin-ccsiv1-piv5-06aug18 Page 3 of 8

4 4.6 FERTILITY, PREGNANCY AND LACTATION Effects on fertility Use in pregnancy Category B2 Female patients receiving MYOCRISIN should be instructed to avoid pregnancy. Like other heavy metals, gold may pass the placental barrier and may cause foetal damage; therefore, pregnant patients should not be treated with MYOCRISIN, but as rheumatoid arthritis usually shows an improvement at this time, the withdrawal of gold is more than justifiable. Use in lactation The presence of gold has been demonstrated in the milk of lactating mothers and in the serum and red blood cells. Lactating mothers should not breast feed their infants. 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) These appear to be associated with individual tolerance, and may be largely avoided by careful titration of dosage. Skin rashes are frequent and commonly benign, but as such reactions may be the forerunners of severe gold toxicity, they must never be treated lightly. Skin complications include pruritus, erythema and transient eczema. Proteinuria is less common and indicates caution, but heavy proteinuria (including albuminuria) is a sign of more serious nephritis such as nephrotic syndrome or glomerulonephritis. There have been some reports of gold deposits in the lens or cornea of patients treated with gold. 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. Haematuria may also develop. The most severe reactions due to gold are agranulocytosis, thrombocytopenia or aplastic anaemia; these occur usually in sensitive patients when a total of about 300mg has been given. Blood disorders including pancytopenia, leucopenia, neutropenia and eosinophilia have also been reported. Stomatitis and oral mucous membrane reactions (such as ulcers) have been observed. Reactions of the "vasomotor (nitritoid) type" which may resemble anaphylactoid effects have been reported. Flushing, fainting, dizziness and sweating are most frequently reported. Anaphylactic/Anaphylactoid reactions have also been reported. Neurological manifestations of gold toxicity including very rare cases of peripheral neuropathy, Guillain-Barré syndrome and encephalopathy have been observed. myocrisin-ccsiv1-piv5-06aug18 Page 4 of 8

5 Hepatotoxicity with cholestatic jaundice is a complication which may occur early in the course of treatment. Severe skin reactions including exfoliative dermatitis and dermatitis bullous have been reported. Irreversible skin pigmentation (chrysiasis) can occur in sun-exposed areas after prolonged treatment with MYOCRISIN. Other Reactions Include Gastrointestinal reactions such as nausea, vomiting, anorexia, abdominal cramps, diarrhoea, ulcerative enterocolitis; reactions involving the eye such as iritis, corneal ulcers, gold deposits in ocular tissues; peripheral neuropathy, elevated spinal fluid protein; CNS complications including confusion, hallucinations and seizures; hepatitis; jaundice; gold bronchitis; pulmonary injury manifested by interstitial pneumonitis and fibrosis; alopecia; fever; arthralgia. Treatment with MYOCRISIN should be discontinued immediately when toxic reactions occur. MYOCRISIN should not be reinstated after severe or idiosyncratic reactions. 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 (Australia) or (New Zealand). 4.9 OVERDOSE The appearance of side effects indicates that the individual is receiving more gold than the system can assimilate. Subsequent dose should be withheld or reduced until the reactions have disappeared and the blood count is normal. Symptomatic treatment should be initiated in case of overdose. Major skin lesions and serious blood disorders demand hospital admission. Skin reactions should be treated with systemic and topical antihistamines and corticosteroids. In case of overdose, chelation of gold by antidote treatments may be used. If agranulocytosis, thrombocytopenia or aplastic anaemia is diagnosed, immediate injection of dimercaprol, with corticosteroids, androgens and penicillamine orally, must be given. Fresh blood and/or platelet transfusions should be given with reversed barrier nursing pending recovery of the bone marrow. For general advice on overdose management, contact the Poisons Information Centre, telephone number (Australia) or the National Poisons Centre, 0800 POISON or (New Zealand). 5 PHARMACOLOGICAL PROPERTIES 5.1 PHARMACODYNAMIC PROPERTIES Pharmacotherapeutic group: Gold preparations, ATC code: M01CB01 myocrisin-ccsiv1-piv5-06aug18 Page 5 of 8

6 Mechanism of action In rheumatoid arthritis, MYOCRISIN appears to suppress the disease processes in two ways. Firstly it penetrates into the joint cavity and affects the lysosomal membranes. Secondly, it binds to plasma proteins, including IgG, the rheumatoid factor and the immune complex so that when the lysosomes ingest immune complex the gold is absorbed with it and inactivates lysosomal enzymes within the cell. Clinical trials 5.2 PHARMACOKINETIC PROPERTIES. 5.3 PRECLINICAL SAFETY DATA Genotoxicity Carcinogenicity 6 PHARMACEUTICAL PARTICULARS 6.1 LIST OF EXCIPIENTS Refer to Section 2 Qualitative and quantitative composition 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 Protect from light. Store below 25 C. Solutions which have darkened in colour must not be used. myocrisin-ccsiv1-piv5-06aug18 Page 6 of 8

7 6.5 NATURE AND CONTENTS OF CONTAINER MYOCRISIN 10mg/0.5mL, 20mg/0.5mL, 50mg/0.5mL glass ampoules are available in packs of 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 Clean bright, almost colourless solution Chemical Structure CAS Number MEDICINE SCHEDULE (POISONS STANDARD) Schedule 4 8 SPONSOR sanofi-aventis australia pty ltd Talavera Road Macquarie Park NSW 2113 Tel: medinfo.australia@sanofi.com myocrisin-ccsiv1-piv5-06aug18 Page 7 of 8

8 9 DATE OF FIRST APPROVAL Myocrisin PI was Grandfathered and has not been evaluated by the TGA. 21 October DATE OF REVISION 6 August 2018 SUMMARY TABLE OF CHANGES Section Changed All Summary of new information Reformatted including addition of standard text 3 Pharmaceutical form added Contraindications re-worded and history of systemic lupus erythematosus added Additional precautions added throughout section Addition of extra caution in the elderly population Additional warning statement about avoiding pregnancy added. Lactation section re-worded Additional Adverse Effects added throughout section. Statement added for reporting of suspected adverse effects Additional statements added about symptomatic treatment, hospital admission and chelation of gold. 5.1 Pharmacotherapeutic group and ATC code added 6.5 Nature of the container added 6.7 Chemical structure and CAS number added 8 Telephone and address added 9 Date of first approval added myocrisin-ccsiv1-piv5-06aug18 Page 8 of 8