Auranofin is a disease-modifying antirheumatic drug (DMARD) used to treat early active cases of rheumatoid arthritis (RA) and is the only gold compound available for oral administration. Auranofin is less effective against advanced, chronic cases of RA, as it does not reverse prior structural deformities from the disease. Initiation of a DMARD within 3 months of RA diagnosis is recommended. Periodic assessment of disease activity is advised; auranofin usually requires 3-6 months to achieve full therapeutic response. If ongoing, active disease is present after 3 months of maximal therapy, addition of another DMARD or initiation of a different DMARD is recommended in methotrexate-naive patients. Addition of another DMARD, initiation of a different DMARD, or initiation of a biologic is recommended for patients with a suboptimal response to methotrexate. Similar efficacy of auranofin 3 mg twice daily, methotrexate 2.5 mg every 12 hours for 3 doses per week, or the combination was noted in a large, randomized, 48-week trial of patients with active RA; most patients (about 70%) had moderate disease and had been unsuccessfully treated with conventional doses of at least 2 nonsteroidal anti-inflammatory drugs. About a third of patients in each group had at least a 50% improvement in the number of painful/tender joints or swollen joints. However, in another study of 36 weeks duration that allowed a methotrexate dose of 15 mg weekly if a clinical response had not been achieved with 7.5 mg weekly, greater clinical efficacy (painful and swollen joint counts) and less radiographic progression (erosion score and joint space narrowing score) were noted among methotrexate recipients as compared with auranofin 6-9 mg daily recipients. Rheumatoid arthritis originally was believed to be caused by an infectious agent and because auranofin exhibited antimicrobial activity, attempts to treat RA with gold compounds were initiated in the late 1920s. Somewhat favorable results were obtained (although probably not due to the drug's antimicrobial properties), and the clinical efficacy of gold preparations in the treatment of rheumatoid arthritis was accepted in 1961. Auranofin was approved for clinical use by the FDA in May 1985.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Administer with meals to minimize gastric irritation.
Most adverse events occur within the first 6 months of auranofin receipt, although reactions can occur after many months of therapy. Chrysotherapy can produce severe toxic reactions, and care should be taken to ensure that patients receiving gold compounds are monitored closely for early signs of adverse reactions.
Overall, auranofin is better tolerated and requires discontinuance less often than do parenterally administered gold compounds. The most common adverse effects associated with auranofin therapy are gastrointestinal (GI) system effects. Such effects include changes in bowel habits (loose stools or diarrhea: 47%), which may be related to changes in intestinal water and electrolyte absorption. Diarrhea may be alleviated by dosage reduction, by concomitant administration of an antidiarrheal agent such as diphenoxylate hydrochloride, and by increasing the patient's dietary fiber. With dose reduction, only 6% of patients require permanent auranofin discontinuation due to diarrhea. Auranofin initiation with doses greater than 6 mg/day is not recommended because of an increased incidence of diarrhea. Because toxicity can be severe, monitor patients with GI symptoms. Inform patients about the risks associated with chrysotherapy, and tell patients to promptly report persistent diarrhea. Other common adverse GI effects associated with auranofin administration among 4,784 patients in clinical trials include nausea/vomiting (10%), abdominal pain (14%), anorexia (3% to 9%), dyspepsia (3% to 9%), dysphagia (less than 0.1%), flatulence (3% to 9%), constipation (1% to 3%). Rare effects included GI bleeding (0.1% to 1%), and melena (0.1% to 1%). Ulcerative enterocolitis is a rare, serious reaction to gold, occurring in less than 0.1% of patients. In 1 case, a man suddenly developed colitis with abdominal pain, tenesmus, and mucous and bloody diarrhea with 6 to 7 stools a day approximately 11 months after starting auranofin. Mucosal erosions, a dense inflammatory infiltration of the lamina propria, and numerous cryptal abscesses were revealed by analysis of a rectal biopsy specimen. Auranofin was stopped and sulfasalazine and prednisone were started; all symptoms disappeared after 14 days. Normal findings on a rectosigmoidoscopy were found 4 weeks after auranofin discontinuation, and the patient had no evidence of relapse after 1 year. Auranofin is contraindicated for use by a patient with a history of gold-induced necrotizing enterocolitis.
Several mucocutaneous reactions are associated with auranofin. Pruritus (17%), rash (unspecified) (24%) (including maculopapular rash, bullous rash, and exfoliative dermatitis), alopecia (1% to 3%), and urticaria (1% to 3%) have been reported during therapy. Skin discoloration of a gray to blue pigmentation has been seen and is due to gold deposition in the tissue. Angioedema is rare, reported in less than 0.1% of patients. Mucous membrane reactions among 4,784 patients in clinical trials include stomatitis (13%), conjunctivitis (3% to 9%), gingivitis (0.1% to 1%), and glossitis (1% to 3%). Stomatitis may manifest as shallow oral ulceration on the buccal membranes, on the tongue borders, on the palate, or in the pharynx. Diffuse glossitis or gingivitis may occur. Consider any skin eruption, especially if pruritic, that develops during auranofin treatment as a gold reaction until otherwise proven. Pruritus often occurs before dermatitis becomes apparent, so consider pruritus a warning signal of a cutaneous reaction. Also, dysgeusia (metallic taste) may precede oral mucous membrane reactions; dysgeusia occurred in 1% to 3% of 4,784 patients in clinical trials. Tell patients to promptly report rash, pruritus, dysgeusia, stomatitis or other symptoms that may suggest toxicity. Patients should avoid sun exposure or artificial ultraviolet light, as gold dermatitis may be aggravated by sunlight exposure; an actinic rash may develop. Auranofin is contraindicated for use by a patient with a history of gold-induced anaphylactic reactions or exfoliative dermatitis.
Auranofin can cause nephrotoxicity, causing glomerulonephritis with hematuria, azotemia, interstitial nephritis, proteinuria, or nephrotic syndrome. Among 4,784 patients in clinical trials, proteinuria occurred in 3% to 9%, and hematuria occurred in 1% to 3% of patients. Renal reactions are usually mild if noted early and completely resolve if auranofin is discontinued. If auranofin is continued, renal reactions may become severe and chronic. Obtain a urinalysis and renal function tests before auranofin initiation. During therapy, obtain a urinalysis at least monthly. Immediately stop auranofin if clinically significant proteinuria or microscopic hematuria occurs.
Hematologic signs of gold toxicity due to auranofin include a reduction in hemoglobin (anemia), leukopenia (4000 WBC/mm3 or less), neutropenia (1500/mm3 or less), thrombocytopenia (150,000/mm3 or less). Other signs of gold toxicity that may accompany these changes include proteinuria, hematuria, pruritus, rash, stomatitis, or persistent diarrhea. Hematologic toxicity of auranofin, including rare severe blood dyscrasias, can be fatal. Obtain a complete blood count with differential and platelet count before auranofin initiation. During therapy, obtain a complete blood count with differential and platelet count at least monthly. Inform patients about the risks associated with chrysotherapy, and tell patients to promptly report possible signs of gold toxicity including unusual bleeding or bruising. Among 4,784 patients in clinical trials, anemia, leukopenia, thrombocytopenia, and eosinophilia occurred in 1% to 3% of patients, neutropenia occurred in 0.1% to 1%, and aplastic anemia, agranulocytosis (severe neutropenia), pure red cell aplasia, and pancytopenia occurred in 0.1% or less of patients. Thrombocytopenia usually appears to be peripheral in origin and is usually reversible upon auranofin withdrawal. Onset of thrombocytopenia bears no relationship to auranofin therapy duration, and the thrombocytopenia course may be rapid. Immediately withdraw auranofin if a precipitous platelet decline, a platelet count less than 100,000/mm3, or signs and symptoms suggestive of thrombocytopenia such as purpura, ecchymosis, or petechiae exist. Do not readminister auranofin unless resolution of thrombocytopenia occurs, and the cause was not gold therapy. Auranofin is contraindicated for use by a patient with a history of gold-induced bone marrow aplasia or other severe hematologic disorders.
Obtain liver function tests before auranofin initiation. Among 4,784 patients who received auranofin in clinical trials, elevated hepatic enzymes occurred in 1% to 3%. Rarely, jaundice with cholestasis has been attributed to gold therapy.
Nitritoid or vasomotor reactions have been rarely reported with oral gold therapy (auranofin). One case report documented multiple episodes of vasomotor reactions in a patient receiving auranofin therapy during different time periods which included faintness (pre-syncope), nausea, flushing, and/or palpitations; hypotension was not documented. Nitritoid reactions are more common following gold sodium thiomalate injection (5%) and may include facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, sinus tachycardia, and/or syncope. Nitritoid reactions may present as anaphylactic type reactions; some reactions may be life-threatening. If signs of nitritoid reactions occur, it is prudent to discontinue the gold compound and re-evaluate treatment options, weighing the risks and benefits for the individual patient.
Peripheral neuropathy and fever are rare adverse reactions associated with auranofin use; peripheral neuropathy occurred in less than 0.1% of auranofin-treated patients during clinical trials.
Monitor patients who are receiving auranofin closely for any signs/symptoms of a pulmonary complication such as dyspnea, wheezing, and nonproductive cough. Interstitial pneumonitis, gold bronchitis, and pulmonary fibrosis are rare reactions attributed to gold therapy. Among 4,784 patients who received auranofin in clinical trials, less than 0.1% had interstitial pneumonitis. A 65 year-old woman developed skin rash, dry cough, oppressive chest pain (unspecified), dyspnea on exertion, fever, and weakness about 3 weeks after starting sodium aurothiomalate and prednisone for rheumatoid arthritis (RA). She also had a diffuse, bilateral alveolar and interstitial infiltrate. Gold was continued despite progressive dyspnea, and she developed dyspnea at rest approximately 3 weeks later. She had decreased pulmonary volume with bilateral, diffuse alveolar and interstitial pulmonary infiltrates. Despite gold discontinuation and supportive therapy initiation, she died of respiratory failure. Both lungs had proliferative and exudative diffuse alveolar damage with hyperplasia of alveolar lining cells, hyaline membranes, and some degree of alveolar septal fibrosis. No evidence of an infectious or rheumatoid etiology was noted. The mechanism of gold-induced lung injury is unknown but may be due to a cell-mediated immune reaction. In a review of 140 cases of gold-induced pulmonary toxicity, gold discontinuation and corticosteroid receipt led to a complete remission of pulmonary symptoms in most cases. Diagnostic criteria for gold-induced interstitial lung disease have been developed. The presence of at least 9 factors suggest probable disease whereas the presence of at least 7 factors suggest possible disease: acute dyspnea onset, recent dry cough onset, fever more than 38 degrees C, skin rash, absence of finger clubbing, crackles on chest examination, peripheral blood eosinophilia, positive lymphocyte stimulation testing to gold salts, bronchoalveolar lavage lymphocytosis (at least 25% with a CD4+/CD8+ lymphocyte ratio less than 1, restrictive pattern or decreased diffusion on pulmonary function tests, interstitial or alveolar opacities on chest radiogram, alveolar opacities along bronchovascular bundles on chest CT, and histopathologic evaluation that excludes other pulmonary disease. Determination of major histocompatibility complex (MHC) markers may be of benefit in patients with RA, as an association has been found between specific MHC human leukocyte antigens (HLA) and gold-induced pneumonitis. Of 17 patients with RA and gold-induced pneumonitis, 8 had the alleles HLA-A3 B35 Dwl BfF C4A3,2 (BO), and 8 had HLA-B40 with a C4 null allele. Fifteen of the 17 patients had at least 1 of the two high-risk markers. A strong association between gold-induced pneumonitis and these MHC combinations was found; the relative risk of having either of the two markers was 16 as compared with patients with RA but with no gold-induced side effects and was 33 as compared with healthy individuals. No relationship between the total dose of gold received by the patient and pulmonary toxicity appears to exist. Auranofin is contraindicated for use by a patient with a history of gold-induced pulmonary fibrosis.
Auranofin is generally avoided for use in patients who have recently undergone radiation therapy.
Auranofin products may contain benzyl alcohol and may be inappropriate for patients with benzyl alcohol hypersensitivity.
Auranofin products may contain lactose; patients with lactase deficiency should take appropriate precautions with use.
Auranofin is only recommended for use in selected patients with active rheumatoid arthritis. Auranofin therapy requires an experienced clinician knowledgeable with chrysotherapy and the toxicity and benefits of gold therapy with auranofin. Auranofin is contraindicated in patients with a history of gold-induced disorders including anaphylaxis, serious rash or exfoliative dermatitis, pulmonary fibrosis, necrotizing enterocolitis, bone marrow aplasia, or other severe hematological disease. Auranofin may cause serious gold toxicity. Signs of gold toxicity include a reduction in hemoglobin (anemia), leukopenia (less than 4000 WBC/mm3), neutropenia (less than 1500/mm3), thrombocytopenia (less than 150,000/mm3), and may be accompanied by other signs or symptoms such as proteinuria, hematuria, pruritus, rash, stomatitis, or persistent diarrhea. Because they have potentially serious consequences, blood dyscrasias should be constantly watched for through regular monitoring (at least monthly) of the formed elements of the blood throughout treatment. Review the recommended laboratory results before writing each auranofin prescription. Auranofin should be used cautiously in patients with a history of blood dyscrasias or bone marrow suppression such as agranulocytosis (severe neutropenia), granulocytopenia, aplastic anemia, or bleeding. The potential risks of auranofin therapy should be weighed against the potential benefits in patients with preexisting renal disease (e.g., renal impairment, renal failure) inflammatory bowel disease, hepatic disease, bone marrow suppression, or skin rash. These conditions indicate compromised organ systems, which could increase the risk of gold toxicity and could cause difficulty in rapidly detecting gold toxicity. Explain the possible adverse effects of auranofin before therapy initiation, and instruct patients to promptly report any potential toxicity symptoms.
Auranofin may distribute in breast milk and is, therefore, not recommended for use in women who are breast-feeding by the manufacturer. Although human data are unavailable, gold is excreted in the milk of rats and mice given auranofin. Furthermore, gold does appear in milk of women who receive injectable gold. Consider alternative agents. Assess indication and patient-specific factors before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Auranofin use by pregnant women is not recommended. Although no adequate and well-controlled studies in pregnant women exist, animal reproduction studies have shown adverse fetal effects. Chrysotherapy is usually avoided during pregnancy, given the potential toxicities of the drug. If auranofin will be used by a pregnant woman, discuss the potential risks of auranofin therapy with her.
The safety and efficacy of auranofin have not been established in pediatric patients. At this time, use in children cannot be recommended. There is no indication for chrysotherapy in infants. Receipt of auranofin 0.15 to 0.20 mg/kg/day for 6 months by children with juvenile rheumatoid arthritis did not lead to statistically significant improvements in efficacy as compared with data from placebo recipients.
Tell patients to avoid sunlight (UV) exposure or artificial ultraviolet light while taking auranofin. Gold dermatitis may be aggravated by sunlight exposure; an actinic rash may develop.
For the treatment of active rheumatoid arthritis in patients who have had an insufficient therapeutic response to or are intolerant of an adequate trial of full doses of at least one nonsteroidal anti-inflammatory drug:
NOTE: Add auranofin to a comprehensive baseline program that includes non-drug therapies.
NOTE: Improvement may not be observed before 6 months of use. Gold cannot reverse existing structural damage; best efficacy may occur in patients with active synovitis.
NOTE: Discontinuation of injectable gold and initiation of auranofin 6 mg PO daily led to similar disease control 6 months after the switch from injectable to oral gold receipt as compared with patients who remained on injectable gold.
NOTE: Obtain a complete blood count (CBC) with differential and platelet count, urinalysis, and renal and hepatic function tests before auranofin initiation. During therapy, obtain a CBC with differential and platelet count and urinalysis at least monthly.
Oral dosage:
Adults: Initially, 6 mg/day PO, administered either as 3 mg PO twice daily or 6 mg PO once daily. To reduce the incidence of adverse effects, a lower initial dose of 3 mg PO once daily may be used. This dose is increased to 6 mg PO daily after several weeks if the lower dose is tolerated. If inadequate response after 6 months, may increase dosage to 3 mg PO 3 times daily. If inadequate response after 3 months at 9 mg/day, discontinue auranofin. Safety at a dosage higher than 9 mg/day has not been established.
Maximum Dosage Limits:
-Adults
9 mg/day PO.
-Elderly
9 mg/day PO.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Use with caution in patients with preexisting hepatic impairment. Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Use with caution in patients with preexisting renal impairment. Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Acetaminophen; Ibuprofen: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Amikacin: (Minor) Both aminoglycosides and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Aminoglycosides: (Minor) Both aminoglycosides and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Amlodipine; Benazepril: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Amlodipine; Celecoxib: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Amphotericin B lipid complex (ABLC): (Minor) Both amphotericin and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Amphotericin B liposomal (LAmB): (Minor) Both amphotericin and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Amphotericin B: (Minor) Both amphotericin and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Angiotensin-converting enzyme inhibitors: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Benazepril: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Benazepril; Hydrochlorothiazide, HCTZ: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Bupivacaine; Meloxicam: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Captopril: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Captopril; Hydrochlorothiazide, HCTZ: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Carbamazepine: (Minor) Auranofin should be used cautiously in patients receiving carbamazepine, due to the potential for additive bone marrow/hematologic effects.
Celecoxib: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Celecoxib; Tramadol: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Diclofenac: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Diclofenac; Misoprostol: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Diflunisal: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Dimercaprol: (Major) Avoid concomitant use of therapeutic gold and dimercaprol. Concomitant use reduces the concentrations of both compounds and diminishes efficacy.
Diphenhydramine; Ibuprofen: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Diphenhydramine; Naproxen: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Enalapril, Enalaprilat: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Enalapril; Hydrochlorothiazide, HCTZ: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Etodolac: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Fenoprofen: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Flurbiprofen: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Foscarnet: (Moderate) The risk of renal toxicity may be increased if foscarnet is used in conjunction with other nephrotoxic agents, including gold compounds.
Fosinopril: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Fosinopril; Hydrochlorothiazide, HCTZ: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Gentamicin: (Minor) Both aminoglycosides and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Hydrochlorothiazide, HCTZ; Moexipril: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Hydrocodone; Ibuprofen: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Ibuprofen: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Ibuprofen; Famotidine: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Ibuprofen; Oxycodone: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Ibuprofen; Pseudoephedrine: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Indomethacin: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Ketoprofen: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Ketorolac: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Lisinopril: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Lisinopril; Hydrochlorothiazide, HCTZ: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Meclofenamate Sodium: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Mefenamic Acid: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Meloxicam: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Moexipril: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Nabumetone: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Naproxen: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Naproxen; Esomeprazole: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Naproxen; Pseudoephedrine: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Nonsteroidal antiinflammatory drugs: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Oxaprozin: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Paromomycin: (Minor) Both aminoglycosides and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Penicillamine: (Contraindicated) Gold compounds have adverse reactions similar to those of penicillamine. Concomitant use of these agents is contraindicated because of the increased risk of developing severe hematologic and renal toxicity.
Perindopril: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Perindopril; Amlodipine: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with auranofin. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Phenytoin: (Minor) One patient receiving concomitant phenytoin and auranofin therapy developed an increased blood concentration of phenytoin. Further studies of this potential interaction are warranted.
Piroxicam: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Plazomicin: (Minor) Both aminoglycosides and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Pretomanid: (Major) Avoid coadministration of pretomanid with auranofin, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Quinapril: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Quinapril; Hydrochlorothiazide, HCTZ: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Ramipril: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and auranofin. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Rituximab: (Moderate) The concomitant use of rituximab with other disease modifying anti-rheumatic drugs (DMARDs), including gold compounds, may result in additive immunosuppression and an increased risk of infection. According to treatment guidelines, thare no data that adequately address the safety and efficacy of gold compounds in combination with biologic therapies. Monitor patients closely for signs or symptoms of infection.
Rituximab; Hyaluronidase: (Moderate) The concomitant use of rituximab with other disease modifying anti-rheumatic drugs (DMARDs), including gold compounds, may result in additive immunosuppression and an increased risk of infection. According to treatment guidelines, thare no data that adequately address the safety and efficacy of gold compounds in combination with biologic therapies. Monitor patients closely for signs or symptoms of infection.
Streptomycin: (Minor) Both aminoglycosides and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Sulindac: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Sumatriptan; Naproxen: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Tobramycin: (Minor) Both aminoglycosides and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Tolmetin: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy.
Trandolapril: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Trandolapril; Verapamil: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Vancomycin: (Minor) Both vancomycin and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Auranofin contains 29% gold. Like other gold compounds, auranofin exhibits antiarthritic, anti-inflammatory, and immunomodulating properties. Gold compounds are known as disease-modifying drugs. Auranofin may modify disease activity; reduced synovitis and ESR may occur. No substantial evidence, however, exists to support induction of rheumatoid arthritis (RA) remission by gold-containing compounds. Gold cannot reverse existing structural damage; best efficacy may occur in patients with active synovitis.
The mechanism of the antiarthritic effects of auranofin is unknown. Auranofin appears to induce heme oxygenase 1 (HO-1) mRNA. Heme oxygenase 1 is an inducible heme-degrading enzyme with anti-inflammatory properties. Induction of HO-1 appears to suppress inflammatory responses in patients with RA. Auranofin incubation of synovial cells from patients with RA led to HO-1 expression induction in a concentration-dependent manner. Further, cells incubated with auranofin had significantly suppressed TNFalpha mRNA expression and COX-2 expression in a dose-dependent manner. Expression levels of TNFalpha mRNA and COX-2 protein were negatively correlated with the level of HO-1 protein. The impact of HO-1 induction inhibition by use of a HO-1 small interfering RNA was examined. Incubation of the cell lines with auranofin and HO-1 small interfering RNA reduced the induction of HO-1 mRNA as compared with incubation of the cells with only auranofin. Further, the TNF alpha mRNA concentration in the presence of HO-1 small interfering RNA was similar to the control value. Thus, auranofin appears to induce HO-1 mRNA, which reduces TNF alpha mRNA expression.
Auranofin is administered orally.
Following multiple dosing, steady state is achieved within 8-12 weeks, although 13-16 weeks of therapy may be required in some patients. The mean steady-state gold concentrations in the blood of patients taking auranofin 6 mg daily was 0.68 +/- 0.45 mcg/mL. The mean blood-gold concentrations are proportional to dose, but no correlation between concentrations and either safety or efficacy has been established. Blood gold concentrations are generally higher than serum or plasma gold concentrations because the gold is sequestered with circulating cells. Gold distributes widely throughout the body and is found in the lymph nodes, bone marrow, spleen, adrenals, liver, and kidneys. Auranofin is approximately 60% plasma protein-bound, and gold appears to cross the placenta and to be distributed in breast milk in animals.
Approximately 60% of an auranofin dose is excreted in the urine, and the remainder is excreted in the feces. The elimination half-life of auranofin following cumulative dosing is 26 days (blood) and 80 days (tissues).
-Route-Specific Pharmacokinetics
Oral Route
Twenty-five percent of the gold in an orally administered dose of auranofin is absorbed from the GI tract. The drug is metabolized rapidly; unchanged auranofin does not appear in the blood following oral administration. Auranofin may undergo rapid deacetylation within the GI mucosa before absorption.
Peak blood gold concentrations of 0.025 mcg/ml are usually obtained within 2 hours following oral administration.
-Special Populations
Hepatic Impairment
No data are available on the effect of hepatic impairment on the pharmacokinetics of auranofin.
Renal Impairment
No data are available on the effect of renal impairment on the pharmacokinetics of auranofin. A patient with bilateral nephrectomy on hemodialysis received auranofin 3 mg PO daily for 5 months. The serum gold concentration was 585 ng/ml after 2 months and 850 ng/ml after 5 months of gold receipt. Gold could not be detected in the dialysate fluid; the assay sensitivity was 50 ng/ml.