Ridaura
(auranofin)Ridaura Prescribing Information
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 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.
Usual Adult Dosage: The usual adult dosage of RIDAURA (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, RIDAURA 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 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.
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.
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.
Reactions occurring in more than 1% of RIDAURA-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 RIDAURA-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 RIDAURA (auranofin) (based on clinical trials and on postmarketing experience)
Cutaneous Reactions: generalized exfoliative dermatitis
| 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% |
Drug Interactions: In a single patient-report, there is the suggestion that concurrent administration of RIDAURA and phenytoin may have increased phenytoin blood levels.
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.
Pharmacokinetics: Pharmacokinetic studies were performed in rheumatoid arthritis patients, not in normal volunteers. Auranofin is rapidly metabolized and intact auranofin has never been detected in the blood. Thus, studies of the pharmacokinetics of auranofin have involved measurement of gold concentrations. Approximately 25% of the gold in auranofin is absorbed.
The mean terminal plasma half-life of auranofin gold at steady state was 26 days (range 21 to 31 days; n=5). The mean terminal body half-life was 80 days (range 42 to 128; n=5). Approximately 60% of the absorbed gold (15% of the administered dose) from a single dose of auranofin is excreted in urine; the remainder is excreted in the feces.
In clinical studies, steady state blood-gold concentrations are achieved in about three months. In patients on 6 mg auranofin/day, mean steady state blood-gold concentrations were 0.68 ±0.45 mcg/mL (n=63 patients). In blood, approximately 40% of auranofin gold is associated with red cells, and 60% associated with serum proteins. In contrast, 99% of injectable gold is associated with serum proteins.
Mean blood-gold concentrations are proportional to dose; however, no correlation between blood-gold concentrations and safety or efficacy has been established.
Reactions reported with injectable gold preparations, but not with RIDAURA (auranofin) (based on clinical trials and on postmarketing experience)
Cutaneous Reactions: generalized exfoliative dermatitis
| 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% |
Capsules, containing 3 mg auranofin, in bottles of 60.
NDC 54766-093-06
STORAGE AND HANDLING
Store between 15° and 30°C (59° and 86°F). Dispense in a tight, light-resistant container.
©2018 Sebela Pharmaceuticals Inc.
All rights reserved.
RIDAURA is a registered trademark of Sebela International Limited
Distributed by:
Sebela Pharmaceuticals Inc.
645 Hembree Parkway, Suite I
Roswell, Georgia 30076
www.sebelapharma.com
Toll Free 1-844-732-3521
Revised October 2017
PI 09306001
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.