Ridaura Information
Ridaura ()
Ridaura ()
Ridaura () Description
Ridaura () (auranofin) is available in oral form as capsules containing 3 mg auranofin.
Auranofin is (2,3,4,6-tetra-O-acetyl-1-thio-ß-D-glucopyranosato-S-) (triethyl–phosphine) gold.
Auranofin contains 29% gold and has the following chemical structure:
Each Ridaura () capsule, with opaque brown cap and opaque tan body, contains auranofin, 3 mg, and is imprinted with the product name Ridaura () . Inactive ingredients consist of benzyl alcohol, cellulose, cetylpyridinium chloride, D&C Red No. 33, FD&C Blue No. 1, FD&C Red No. 40, FD&C Yellow No. 6, gelatin, lactose, magnesium stearate, povidone, sodium lauryl sulfate, sodium starch glycolate, starch, titanium dioxide and trace amounts of other inactive ingredients.
Ridaura () Clinical Pharmacology
The mechanism of action of Ridaura () (auranofin) is not understood. In patients with adult rheumatoid arthritis, Ridaura () may modify disease activity as manifested by synovitis and associated symptoms, and reflected by laboratory parameters such as ESR. There is no substantial evidence, however, that gold-containing compounds induce remission of rheumatoid arthritis.
Ridaura () Indications And Usage
Ridaura () (auranofin) is indicated in the management of adults with active classical or definite rheumatoid arthritis (ARA criteria) who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of full doses of one or more nonsteroidal anti-inflammatory drugs. Ridaura () should be added to a comprehensive baseline program, including non-drug therapies.
Unlike anti-inflammatory drugs, Ridaura () does not produce an immediate response. Therapeutic effects may be seen after three to four months of treatment, although improvement has not been seen in some patients before six months.
When cartilage and bone damage has already occurred, gold cannot reverse structural damage to joints caused by previous disease. The greatest potential benefit occurs in patients with active synovitis, particularly in its early stage.
In controlled clinical trials comparing Ridaura () with injectable gold, Ridaura () was associated with fewer dropouts due to adverse reactions, while injectable gold was associated with fewer dropouts for inadequate or poor therapeutic effect. Physicians should consider these findings when deciding on the use of Ridaura () in patients who are candidates for chrysotherapy.
Ridaura () Contraindications
Ridaura () (auranofin) is contraindicated in patients with a history of any of the following gold-induced disorders: anaphylactic reactions, necrotizing enterocolitis, pulmonary fibrosis, exfoliative dermatitis, bone marrow aplasia or other severe hematologic disorders.
Ridaura () Warnings
Danger signs of possible gold toxicity include fall in hemoglobin, leukopenia below 4,000 WBC/cu mm, granulocytes below 1,500/cu mm, decrease in platelets below 150,000/cu mm, proteinuria, hematuria, pruritus, rash, stomatitis or persistent diarrhea.
Thrombocytopenia has occurred in 1–3% of patients (See ) treated with Ridaura () (auranofin), some of whom developed bleeding. The thrombocytopenia usually 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 and its course may be rapid. While patients' platelet counts should normally be monitored at least monthly (See ), the occurrence of a precipitous decline in platelets or a platelet count less than 100,000/cu mm or signs and symptoms (e.g., purpura, ecchymoses or petechiae) suggestive of thrombocytopenia indicates a need to immediately withdraw Ridaura () and other therapies with the potential to cause thrombocytopenia, and to obtain additional platelet counts. No additional Ridaura () should be given unless the thrombocytopenia resolves and further studies show it was not due to gold therapy.
Proteinuria has developed in 3-9% of patients (See ) treated with Ridaura () . If clinically significant proteinuria or microscopic hematuria is found (See ), Ridaura () and other therapies with the potential to cause proteinuria or microscopic hematuria should be stopped immediately.
Ridaura () Precautions
General:
Medical problems that might affect the signs or symptoms used to detect Ridaura () toxicity should be under control before starting Ridaura () (auranofin).
The potential benefits of using Ridaura () in patients with progressive renal disease, significant hepatocellular disease, inflammatory bowel disease, skin rash or history of bone marrow depression should be weighed against 1) the potential risks of gold toxicity on organ systems previously compromised or with decreased reserve, and 2) the difficulty in quickly detecting and correctly attributing the toxic effect.
The following adverse reactions have been reported with the use of gold preparations and require modification of Ridaura () treatment or additional monitoring. See for the approximate incidence of those reactions specifically reported with Ridaura () .
Information for Patients:
Women of childbearing potential should be warned of the potential risks of Ridaura () therapy during pregnancy (See ).
Laboratory Tests:
CBC with differential, platelet count and urinalysis should then be monitored at least monthly; other parameters should be monitored as appropriate.
Drug Interactions:
Carcinogenesis/Mutagenesis:
There was a significant increase in the frequency of renal tubular cell karyomegaly and cytomegaly and renal adenoma in the animals treated with 1.0 or 2.5 mg/kg/day of auranofin and 2 or 6 mg/kg twice weekly of gold sodium thiomalate. Malignant renal epithelial tumors were seen in the 1.0 mg/kg/day and the 2.5 mg/kg/day auranofin and in the 6 mg/kg twice weekly gold sodium thiomalate–treated animals.
In a 12-month study, rats treated with auranofin at 23 mg/kg/day (192 times the human dose) developed tumors of the renal tubular epithelium, whereas those treated with 3.6 mg/ kg/day (30 times the human dose) did not.
In an 18-month study in mice given oral auranofin at doses of 1, 3 and 9 mg/kg/day (8, 24 and 72 times the human dose), there was no statistically significant increase above controls in the instances of tumors.
In the mouse lymphoma forward mutation assay, auranofin at high concentrations (313 to 700 ng/mL) induced increases in the mutation frequencies in the presence of a rat liver microsomal preparation. Auranofin produced no mutation effects in the Ames test (Salmonella), in the assay (Forward and Reverse Mutation Inducement Assay with Saccharomyces), in the transformation of BALB/T3 cell mouse assay or in the Dominant Lethal Assay.
Pregnancy:
Pregnant rabbits given auranofin at doses of 0.5, 3 or 6 mg/kg/day (4.2 to 50 times the human dose) had impaired food intake, decreased maternal weights, decreased fetal weights and an increase above controls in the incidence of resorptions, abortions and congenital abnormalities, mainly abdominal defects such as gastroschisis and umbilical hernia. Pregnant rats given auranofin at a dose of 5 mg/kg/day (42 times the human dose) had an increase above controls in the incidence of resorptions and a decrease in litter size and weight linked to maternal toxicity. No such effects were found in rats given 2.5 mg/kg/day (21 times the human dose).
Pregnant mice given auranofin at a dose of 5 mg/kg/day (42 times the human dose) had no teratogenic effects.
There are no adequate and well-controlled Ridaura () studies in pregnant women.
Nursing Mothers:
Following auranofin administration to rats and mice, gold is excreted in milk. Following the administration of injectable gold, gold appears in the milk of nursing women; human data on auranofin are not available.
Pediatric Use:
Ridaura () Adverse Reactions
The adverse reactions incidences listed below are based on observations of 1) 4,784 Ridaura () treated patients in clinical trials (2,474 U.S., 2,310 foreign), of whom 2,729 were treated more than one year and 573 for more than three years; and 2) postmarketing experience. The highest incidence is during the first six 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 dosages of corticosteroids.
Gastrointestinal:
Dermatological:
Mucous Membrane:
Hematological:
Renal:
Hepatic:
*Reactions marked with an asterisk occurred in 3-9% of the patients. The other reactions listed occurred in 1-3%.
Gastrointestinal:
Dermatological:
Mucous Membrane:
Hematological:
Hepatic:
Respiratory:
Neurological:
Ocular:
† Reactions marked with a dagger occurred in 0.1-1% of the patients. The other reactions listed occurred in less than 0.1%.
Cutaneous Reactions:
Ridaura () Overdosage
The acute oral LD50 for auranofin is 310 mg/kg in adult mice and 265 mg/ kg in adult rats. The minimum lethal dose in rats is 30 mg/kg.
In case of acute overdosage, immediate induction of emesis or gastric lavage and appropriate supportive therapy are recommended.
Ridaura () overdosage experience is limited. A 50-year-old female, previously on 6 mg Ridaura () daily, took 27 mg (9 capsules) daily for 10 days and developed an encephalopathy and peripheral neuropathy. Ridaura () was discontinued and she eventually recovered.
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.
Ridaura () How Supplied
Capsules, containing 3 mg auranofin, in bottles of 60.
NDC 65483-093-06
Ridaura ()
