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Drug Interactions between auranofin and penicillamine

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

penicillAMINE auranofin

Applies to: penicillamine and auranofin

GENERALLY AVOID: The concomitant use of penicillamine and gold salts may potentiate the risk of serious hematologic, dermatologic and renal adverse reactions due to overlapping toxicity profiles of these drugs. With respect to sequential use, prior development of toxicity with gold salts may be associated with increased risk of toxicity, though not necessarily of the same type, during subsequent therapy with penicillamine. Some studies have reported a higher frequency of penicillamine adverse reactions in patients who had previously experienced major toxic reactions with gold compounds, particularly proteinuria and bone marrow depression. One group of investigators found that to be true when penicillamine was prescribed less than 6 months after an adverse reaction to gold, and a shorter time interval between treatments was associated with more similar toxic effects to both drugs. Based on these findings, they suggested that the mechanism might involve mobilization of gold stores from various tissues via chelation with penicillamine. Another investigator suggested a genetic predisposition, while others have not found a predictable pattern of penicillamine toxicity based on previous gold use or intolerance or interval between treatments.

MANAGEMENT: Penicillamine and gold therapy should not be administered concurrently. Penicillamine may be prescribed following discontinuation of gold therapy, although some have suggested waiting a period of at least six months between treatments. Patients should be monitored closely and advised to notify their physician if they experience signs and symptoms of penicillamine toxicity such as fever, chills, sore throat, unusual bruising or bleeding, hematuria, coughing, wheezing, unexplained shortness of breath, muscle weakness, or double vision.

References

  1. Davis P, Barraclough D "Interaction of D-penicillamine with gold salts: in vivo studies on gold chelation and in vitro studies on protein binding." Arthritis Rheum 20 (1977): 1413-8
  2. Halla JT, Cassady J, Hardin JG "Sequential gold and penicillamine therapy in rheumatoid arthritis." Am J Med 72 (1982): 423-6
  3. Kean WF, Dwosh IL, Anastassiades TP, Ford PM, Kelly HG "The toxicity pattern of D-penicillamine therapy. A guide to its use in rheumatoid arthritis." Arthritis Rheum 23 (1980): 158-64
  4. Goldberg IJ, Lawton K, Redding JR, Francois PE, Phull J "Influence of previous gold toxicity on subsequent development of penicillamine toxicity." Br Med J (Clin Res Ed) 285 (1982): 1659
  5. Netter P, Bannwarth B, Pere P, Nicolas A "Clinical pharmacokinetics of D-penicillamine." Clin Pharmacokinet 13 (1987): 317-33
  6. "Product Information. Cuprimine (penicillamine)." Merck & Co., Inc PROD (2001):
  7. Day RO, Graham GG, Champion GD, Lee E "Anti-rheumatic drug interactions." Clin Rheum Dis 10 (1984): 251-75
  8. Haagsma CJ "Clinically important drug interactions with disease-modifying antirheumatic drugs." Drugs Aging 13 (1998): 281-9
  9. Billingsley LM, Stevens MB "The relationship between D-penicillamine--induced proteinuria and prior gold nephropathy." Johns Hopkins Med J 148 (1981): 64-7
  10. Calin A "Adverse reactionsto D-penicillamine after gold toxicity." Br Med J 281 (1980): 454
  11. Dodd MJ, Griffiths, Thompson M "Adverse reactions to D-penicillamine after gold toxicity." Br Med J 280 (1980): 1498-9
  12. Kean WF, Lock CJ, Howard-Lock HE, Buchanan WW "Prior gold therapy does not influence the adverse effects of D-penicillamine in rheumatoid arthritis." Arthritis Rheum 25 (1982): 917-22
  13. Smith PJ, Swinburn WR, Swinson DR, Stewart IM "Influence of previous gold toxicity on subsequent development of penicillamine toxicity." Br Med J 285 (1982): 595
  14. Webley M, Coomes EN "An assessment of penicillamine therapy in rheumatoid arthritis and the influence of previous gold therapy." J Rheumatol 6 (1979): 20-4
View all 14 references

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Drug and food interactions

Moderate

penicillAMINE food

Applies to: penicillamine

ADJUST DOSING INTERVAL: Food may interfere with the gastrointestinal absorption of penicillamine. In a study of six healthy volunteers, administration of penicillamine (500 mg) following a standard breakfast reduced the mean peak plasma concentrations of penicillamine by 48% compared to administration in the fasting state.

MANAGEMENT: Penicillamine should be administered on an empty stomach, at least one hour before or two hours after meals, and at least one hour apart from any other drug, food, or milk. This permits maximum absorption and reduces the likelihood of inactivation by metal binding in the gastrointestinal tract.

References

  1. Osman MA, Patel RB, Schuna A, Sundstrom WR, Welling PG "Reduction in oral penicillamine absorption by food, antacid and ferrous sulfate." Clin Pharmacol Ther 33 (1983): 465-70
  2. "Product Information. Cuprimine (penicillamine)." Merck & Co., Inc PROD (2001):

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Moderate

penicillAMINE food

Applies to: penicillamine

ADJUST DOSING INTERVAL: Oral administration of aluminum, copper, iron, zinc, magnesium, and possibly other minerals such as calcium may decrease the gastrointestinal absorption of penicillamine, and vice versa. The proposed mechanism involves chelation of penicillamine to polyvalent cations, which leads to formation of a nonabsorbable complex. In a study of six healthy volunteers, administration of penicillamine (500 mg) following a single dose of ferrous sulfate (300 mg) or antacid (Maalox Plus 30 mL) reduced the mean peak plasma concentration of penicillamine by 65% and 34%, respectively, compared to administration in the fasting state. In addition to chelation, some investigators suggest that antacids may also reduce penicillamine bioavailability by increasing gastric pH, which favors the oxidation of penicillamine to its poorly absorbed disulfide form. These changes could result in diminished therapeutic effects of penicillamine.

MANAGEMENT: Mineral supplements or other products containing polyvalent cations (e.g., antacids or preparations containing antacids such as didanosine buffered tablets or pediatric oral solution) should be administered at least two hours before or two hours after the penicillamine dose. In addition, pharmacologic response to penicillamine should be monitored more closely whenever these products are added to or withdrawn from therapy, and the penicillamine dosage adjusted as necessary. When penicillamine is coadministered with Suprep Bowel Prep (magnesium/potassium/sodium sulfates), the manufacturer recommends administering penicillamine at least 2 hours before and not less than 6 hours after Suprep Bowel Prep to avoid chelation with magnesium.

References

  1. Osman MA, Patel RB, Schuna A, Sundstrom WR, Welling PG "Reduction in oral penicillamine absorption by food, antacid and ferrous sulfate." Clin Pharmacol Ther 33 (1983): 465-70
  2. Harkness JA, Blake DR "Penicillamine nephropathy and iron." Lancet 2 (1982): 1368-9
  3. Netter P, Bannwarth B, Pere P, Nicolas A "Clinical pharmacokinetics of D-penicillamine." Clin Pharmacokinet 13 (1987): 317-33
  4. Joyce DA "D-penicillamine pharmacokinetics and pharmacodynamics in man." Pharmacol Ther 42 (1989): 405-27
  5. "Product Information. Cuprimine (penicillamine)." Merck & Co., Inc PROD (2001):
  6. Haagsma CJ "Clinically important drug interactions with disease-modifying antirheumatic drugs." Drugs Aging 13 (1998): 281-9
  7. Lyle WH "Penicillamine and iron." Lancet 2 (1976): 420
  8. "Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates)." Braintree Laboratories (2010):
View all 8 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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