Auranofin

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 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.

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%

<table border="0" width="100%"><caption>Incidence of Adverse Reactions for Specific Categories &#x2013; 18 Comparative Trials</caption><tbody><tr><td/><td>Ridaura (445 patients)</td><td>Injectable Gold (445 patients)</td></tr><tr><td>Proteinuria</td><td>0.9%</td><td>5.4%</td></tr><tr><td>Rash</td><td>26%</td><td>39%</td></tr><tr><td>Diarrhea</td><td>42.5%</td><td>13%</td></tr><tr><td>Stomatitis</td><td>13%</td><td>18%</td></tr><tr><td>Anemia</td><td>3.1%</td><td>2.7%</td></tr><tr><td>Leukopenia</td><td>1.3%</td><td>2.2%</td></tr><tr><td>Thromocytopenia</td><td>0.9%</td><td>2.2%</td></tr><tr><td>Elevated liver function tests</td><td>1.9%</td><td>1.7%</td></tr><tr><td>Pulmonary</td><td>0.2%</td><td>0.2%</td></tr></tbody></table>