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Drug Interactions between D-Penamine and leflunomide

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

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Interactions between your drugs

Major

penicillAMINE leflunomide

Applies to: D-Penamine (penicillamine) and leflunomide

GENERALLY AVOID: Coadministration of leflunomide with other immuno- or myelosuppressive antirheumatic agents may potentiate the risk of infections. Serious infections including sepsis, as well as opportunistic infections like Pneumocystis jiroveci pneumonia, pulmonary and extrapulmonary tuberculosis, and aspergillosis have been reported with the use of leflunomide, particularly in patients on concomitant hematotoxic therapy. There have also been rare reports of pancytopenia, agranulocytosis, and thrombocytopenia in patients receiving leflunomide alone. However, these events occurred more frequently in patients who received concomitant treatment with methotrexate or other hematotoxic agents, or who had recently discontinued these agents.

MANAGEMENT: Concomitant use of leflunomide with other immuno- or myelosuppressive antirheumatic agents should generally be avoided. When switching from leflunomide to one of these agents, consideration should be given to administering a washout procedure with cholestyramine or activated charcoal to accelerate elimination of leflunomide's active metabolite from plasma, which otherwise may take up to two years. This will decrease the overlap of systemic exposure to both compounds and reduce the likelihood of additive hematologic toxicities. However, the washout procedure may also induce disease worsening if the patient had been responding to leflunomide treatment. Patients who do not receive the washout procedure prior to switching should be monitored closely for hematologic toxicity. All patients treated with leflunomide should be advised to contact their physician if they develop signs and symptoms of infection such as fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, and pain or burning during urination. If evidence of serious infection or bone marrow suppression occurs, treatment with leflunomide should be stopped and washout procedure administered.

References

  1. (2001) "Product Information. Arava (leflunomide)." Hoechst Marion Roussel
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."

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Drug and food interactions

Moderate

penicillAMINE food

Applies to: D-Penamine (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 (1983) "Reduction in oral penicillamine absorption by food, antacid and ferrous sulfate." Clin Pharmacol Ther, 33, p. 465-70
  2. (2001) "Product Information. Cuprimine (penicillamine)." Merck & Co., Inc

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Moderate

leflunomide food

Applies to: leflunomide

GENERALLY AVOID: The consumption of alcohol during therapy with leflunomide may potentiate the risk of liver injury. Leflunomide has been associated with hepatotoxicity, including elevated liver transaminases, hepatitis, jaundice/cholestasis, hepatic failure, and acute hepatic necrosis,

MANAGEMENT: Patients should be advised to avoid excessive alcohol use during leflunomide treatment.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  3. Cerner Multum, Inc. "Australian Product Information."

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Moderate

penicillAMINE food

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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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