PRESCRIBING INFORMATION
RIDAURA.
Auranofin
Capsules

R_x Only

Ridaura (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 Ridaura prescription. Like other gold preparations, Ridaura is only indicated for use in selected patients with active rheumatoid arthritis. Physicians planning to use Ridaura should be experienced with chrysotherapy and should thoroughly familiarize themselves with the toxicity and benefits of Ridaura.

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.)

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.

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 (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 (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.

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 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 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 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 ADVERSE REACTIONS) treated with Ridaura. If clinically significant proteinuria or microscopic hematuria is found (See PRECAUTIONS— Laboratory Tests), Ridaura and other therapies with the potential to cause proteinuria or microscopic hematuria should be stopped immediately.

The adverse reactions incidences uled 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: 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 uled occurred in 1-3%.

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 uled occurred in less than 0.1%.

Cutaneous Reactions: generalized exfoliative dermatitis.

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.

In controlled clinical studies, patients on injectable gold have been transferred to Ridaura (auranofin) by discontinuing the injectable agent and starting oral therapy with Ridaura, 6 mg daily. When patients are transferred to Ridaura, 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 Ridaura and those maintained on the injectable agent was not different. Data beyond six months are not available.

Capsules, containing 3 mg auranofin, in bottles of 60.

NDC 65483-093-06

Store between 15° and 30°C (59° and 86°F). Dispense in a tight, light-resistant container.

REVISED AUGUST 2004

©Prometheus, 2004

Manufactured for:
Prometheus Laboratories Inc.
San Diego, CA 92121-4203
by Cardinal Health
Winchester, KY 40391
RI002C04