auranofin
Brand names: RIDAURA, Auranofin
Boxed warning
Auranofin Capsules (auranofin) contains gold and, like other gold-containing drugs, can cause gold toxicity, signs of which 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. Therefore, the results of recommended laboratory work (See PRECAUTIONS ) should be reviewed before writing each Auranpfin Capsules prescription. Like other gold preparations, Auranofin Capsules is only indicated for use in selected patients with active rheumatoid arthritis. Physicians planning to use Auranofin Capsules should be experienced with chrysotherapy and should thoroughly familiarize themselves with the toxicity and benefits of Auranofin Capsules. In addition, the following precautions should be routinely employed: The possibility of adverse reactions should be explained to patients before starting therapy. Patients should be advised to report promptly any symptoms suggesting toxicity. (See PRECAUTIONS—Information for Patients .)
Warnings
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 ADVERSE REACTIONS ) treated with Auranofin Capsules (auranofin), some of whom developed bleeding. The thrombocytopenia usually appears to be peripheral in origin and is usually reversible upon withdrawal of Auranofin Capsules. Its onset bears no relationship to the duration of Auranofin Capsules therapy and its course may be rapid. While patients' platelet counts should normally be monitored at least monthly (See PRECAUTIONS— Laboratory Tests ), 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 Auranofin Capsules and other therapies with the potential to cause thrombocytopenia, and to obtain additional platelet counts. No additional Auranofin Capsules 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 ADVERSE REACTIONS ) treated with Auranofin Capsules. If clinically significant proteinuria or microscopic hematuria is found (See PRECAUTIONS— Laboratory Tests ), Auranofin Capsules and other therapies with the potential to cause proteinuria or microscopic hematuria should be stopped immediately.
Contraindications
CONTRAINDICATIONS Auranofin Capsules (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.
Overdose
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. Auranofin Capsules overdosage experience is limited. A 50-year-old female, previously on 6 mg Auranofin Capsules daily, took 27 mg (9 capsules) daily for 10 days and developed an encephalopathy and peripheral neuropathy. Auranofin Capules was discontinued and she eventually recovered. There has been no experience with treating Auranofin Capsules overdosage with modalities such as chelating agents. However, they have been used with injectable gold and may be considered for Auranofin Capsules overdosage.
Drug interactions
Drug Interactions: In a single patient-report, there is the suggestion that concurrent administration of Auranofin Capsules and phenytoin may have increased phenytoin blood levels.
Uses
INDICATIONS AND USAGE Auranofin Capsules (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. Auranofin Capsules should be added to a comprehensive baseline program, including non-drug therapies. Unlike anti-inflammatory drugs, Auranofin Capsules 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 Auranofin Capsules with injectable gold, Auranofin Capsules 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 Auranofin Capsules in patients who are candidates for chrysotherapy.
Dosage forms & strengths
DOSAGE AND ADMINISTRATION Usual Adult Dosage: The usual adult dosage of Auranofin Capsules (auranofin) is 6 mg daily, given either as 3 mg twice daily or 6 mg once daily. Initiation of therapy at dosages exceeding 6 mg daily is not recommended because it is associated with an increased incidence of diarrhea. If response is inadequate after six months, an increase to 9 mg (3 mg three times daily) may be tolerated. If response remains inadequate after a three-month trial of 9 mg daily, Auranofin therapy should be discontinued. Safety at dosages exceeding 9 mg daily has not been studied. Transferring from Injectable Gold: In controlled clinical studies, patients on injectable gold have been transferred to Auranofin Capsules (auranofin) by discontinuing the injectable agent and starting oral therapy with Auranofin Capsules, 6 mg daily. When patients are transferred to Auranofin Capsules, they should be informed of its adverse reaction profile, in particular the gastrointestinal reactions. (See PRECAUTIONS— Information for Patients .) At six months, control of disease activity of patients transferred to Auranofin Capsules and those maintained on the injectable agent was not different. Data beyond six months are not available.
All identified pills
Side effects
ADVERSE REACTIONS The adverse reactions incidences listed below are based on observations of 1) 4,784 Auranofin Capsules 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. Reactions occurring in more than 1% of Auranofin Capsules-treated patients Gastrointestinal: loose stools or diarrhea (47%); abdominal pain (14%); nausea with or without vomiting (10%); constipation; anorexia*; flatulence*; dyspepsia*; dysgeusia. Dermatological: rash (24%); pruritus (17%); hair loss; urticaria. Mucous Membrane: stomatitis (13%); conjunctivitis*; glossitis. Hematological: anemia; leukopenia; thrombocytopenia; eosinophilia. Renal: proteinuria*; hematuria. Hepatic: elevated liver enzymes. *Reactions marked with an asterisk occurred in 3-9% of the patients. The other reactions listed occurred in 1-3%. Reactions occurring in less than 1% of Auranofin Capsules-treated patients Gastrointestinal: dysphagia; gastrointestinal bleeding†; melena†; positive stool for occult blood†; ulcerative enterocolitis. Dermatological: angioedema. Mucous Membrane: gingivitis†. Hematological: aplastic anemia; neutropenia†; agranulocytosis; pure red cell aplasia; pancytopenia. Hepatic: jaundice. Respiratory: interstitial pneumonitis. Neurological: peripheral neuropathy. Ocular: gold deposits in the lens or cornea unassociated clinically with eye disorders or visual impairment. † Reactions marked with a dagger occurred in 0.1-1% of the patients. The other reactions listed occurred in less than 0.1%. Reactions reported with injectable gold preparations, but not with Auranofin Capsules (auranofin) (based on clinical trials and on postmarketing experience) Cutaneous Reactions: generalized exfoliative dermatitis Incidence of Adverse Reactions for Specific Categories – 18 Comparative Trials Ridaura (445 patients) Injectable Gold (445 patients) Proteinuria 0.9% 5.4% Rash 26% 39% Diarrhea 42.5% 13% Stomatitis 13% 18% Anemia 3.1% 2.7% Leukopenia 1.3% 2.2% Thromocytopenia 0.9% 2.2% Elevated liver function tests 1.9% 1.7% Pulmonary 0.2% 0.2%