Auranofin

Auranofin comes as a capsule to take by mouth. It usually is taken once or twice a day. It must be taken on a regular schedule, as prescribed by your doctor, to be effective. The full effect of this drug usually is not felt for 3-4 months; in some people, it may take up to 6 months. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take auranofin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

There are no adequate studies in pregnant women. Use of auranofin in pregnant women is not recommended.

Auranofin has been found in the breast milk of nursing mothers. Nursing during auranofin therapy is not recommended.

Black Box Warnings

Prescribing physicians should understand severe and fatal toxicities of chrysotherapy

Thorough patient discussion explaining adverse reactions is essential; encourage patients to report any adverse reactions

Monitor for signs of gold toxicity (ie, decreased hemoglobin, leukopenia <4,000/cu.mm, granulocytes <1,500/cu.mm, platelets <150,000/cu.mm, proteinuria, hematuria, pruritus, rash, stomatitis, persistent diarrhea) and establish baseline measurements before prescribing

Should be reserved for use in certain patients with active rheumatoid arthritis

Contraindications

Pts who have had previous gold-induced disorders (anaphylaxis, necrotizing enterocolitis, pulmonary fibrosis, dermatitis, bone marrow suppression, or other hematologic disorder)

Cautions

Not to be used as the sole agent in Tx of RA

No evidence that gold compounds induce remission of RA

Gold toxicity

• Hemoglobin (decr)
• Leukopenia (WBC <4000/cu.mm) [4 x10^9/L]
• Granulocytes (<1500/cu.mm) [1.5 x10^9/L]
• Platelets (<150 x 10^3/cu.mm) [150 x10^9/L]
• Proteinuria, hematuria, pruritus, rash, stomatitis, chronic diarrhea

Half-Life: 21-31 d

Onset of effects: 3-6 mth

Peak Plasma (6 mg dose)

Time: 2 hr

Concentration: 0.025 mcg/ml

Other Information

Protein binding: 60%

Excretion: urine (60%), feces

Mechanism of Action

Unknown

Gold compound, has anti-inflammatory, antiarthritic, and immunomodulating effects

Auranofin is part of the drug class:

• Gold preparations

Take auranofin exactly as prescribed.

Auranofin comes in capsule form and is taken once or twice a day.

Take shortly after a meal or snack to decrease stomach upset.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of auranofin at the same time.

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 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:

1. The possibility of adverse reactions should be explained to patients before starting therapy.
2. Patients should be advised to report promptly any symptoms suggesting toxicity.

Seek emergency medical attention if you think you have used too much of this medicine.

Symptoms of an auranofin overdose are not known.

Tell your doctor about all other medications you use, especially:

• gold injections;

• hydroxychloroquine (Plaquenil);

• penicillamine (Cuprimine, Depen);

• phenytoin (Dilantin);

• high doses of steroid medication (prednisone and others); or

• drugs that weaken your immune system, such as cyclophosphamide (Cytoxan, Neosar), azathioprine, methotrexate (Rheumatrex, Trexall), and others.

This list is not complete and there may be other drugs that can interact with auranofin. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

• It is used to treat rheumatoid arthritis.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• It may take several months to see full effect.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
• You may get sunburned more easily. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.
• If you are taking phenytoin, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with auranofin.
• If you are pregnant or you get pregnant while taking this medicine, call your doctor right away.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Belly pain.
• Loose stools (diarrhea).
• Not hungry.
• Upset stomach or throwing up.
• Stomach cramps.
• Gas.
• Mouth irritation or mouth sores.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Delayed; therapeutic response may not be seen for 3-4 months after start of therapy, as long as 6 months in some patients

Time to Peak

Serum: ~2 hours (Blocka 1986)

Refer to adult dosing.

There are no known significant interactions.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Belly pain.
• Loose stools (diarrhea).
• Not hungry.
• Upset stomach or throwing up.
• Stomach cramps.
• Gas.
• Mouth irritation or mouth sores.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

CrCl < 50 mL/min: auranofin is contraindicated for use in these patients.

CrCl 50 to 80 mL/min: the dose should be reduced by 50%.

Summary of Use during Lactation

Excretion of gold into milk after auranofen has not been studied. Case reports with other gold salts indicate that gold appears in milk in small quantities and at least a little of it is absorbed because it is detectable in the infant's urine. No convincing cases of toxicity have been reported. Opinions of authors of review articles vary from recommending avoidance to allowing use.[1][2][3][4][5] Monitoring for possible adverse effects in the breastfed infant would seem prudent.

Drug Levels

Maternal Levels. Relevant published information was not found as of the revision date.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Four infants reportedly have been breastfed during maternal gold therapy (including gold sodium thiomalate and gold aurothioglucose).[6][7][8][9] Transient facial edema occurred in an 18-month-old infant, 3 months after the mother's treatment stopped.[6] The reaction was possibly due to gold in the mother's milk ingested by the infant.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

(Rheumatoid Arthritis) Etanercept, Gold Sodium Thiomalate, Hydroxychloroquine, Infliximab, Methotrexate, Penicillamine, Sulfasalazine

References

1. Ostensen M. Treatment with immunosuppressive and disease modifying drugs during pregnancy and lactation. Am J Reprod Immunol. 1992;28:148-52. PMID: 1285866

2. Rayburn WF. Connective tissue disorders and pregnancy. Recommendations for prescribing. J Reprod Med. 1998;43:341-9. PMID: 9583066

3. Janssen NM and Genta MS. The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy and lactation. Arch Intern Med. 2000;160:610-9. PMID: 10724046

4. Ramsey-Goldman R, Schilling E. Optimum use of disease-modifying and immunosuppressive antirheumatic agents during pregnancy and lactation. Clin Immunother. 1996;5:40-58. DOI: doi:10.1007/BF03259314

5. Brooks PM, Needs CJ. Antirheumatic drugs in pregnancy and lactation. Baillieres Clin Rheumatol. 1990;4:157-71. PMID: 2282661

6. Bell RA, Dale IM. Gold secretion in maternal milk. Arthritis Rheum. 1976;19:1374. Letter. PMID: 826260

7. Sorensen SS. [Pharmacodynamic examination of patients treated with gold preparations] Nord Med. 1970;84:1508. Letter. PMID: 5494985

8. Bennett PN, Humphries SJ, Osborne JP et al. Use of sodium aurothiomalate during lactation. Br J Clin Pharmacol. 1990;29:777-9. PMID: 2116162

9. Blau SP. Metabolism of gold during lactation. Arthritis Rheum. 1973;16:777-8. Letter. PMID: 4757877