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Drug Interactions between azathioprine and D-Penamine

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

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Interactions between your drugs

Moderate

azaTHIOprine penicillAMINE

Applies to: azathioprine and D-Penamine (penicillamine)

GENERALLY AVOID: The use of azathioprine with other immunosuppressive or myelosuppressive agents may result in additive hematologic toxicities and increased risk of infections, particularly in transplant patients. Azathioprine alone may cause dose-related and potentially life-threatening bone marrow suppression, although it is usually reversible when managed promptly. Leucopenia, anemia, thrombocytopenia, and rarely, agranulocytosis, pancytopenia, and aplastic anemia have been reported. Dose-related reductions in numbers of circulating total white cells, granulocytes, and lymphocytes may also occur. Treatment with azathioprine alone or in combination with other immunosuppressants, particularly corticosteroids, has been associated with increased susceptibility to infections including severe or atypical infection and reactivation with varicella zoster virus, hepatitis B, cytomegalovirus, and other infectious agents. Very rare cases of JC virus-associated progressive multifocal leukoencephalopathy (PML), a severely disabling and potentially fatal opportunistic viral infection of the brain, have also been reported. In addition, chronic use of azathioprine with other immunosuppressants may increase the risk of lymphoma, skin cancer, and other malignancies. Again, the risk is greatest in transplant patients, with the exception of hepatosplenic T-cell lymphoma (HSTCL), which has occurred primarily in patients with Crohn's disease or ulcerative colitis, especially adolescent and young adult males.

MANAGEMENT: Concomitant use of azathioprine with other immunosuppressive or myelosuppressive agents should be avoided whenever possible. Close clinical and laboratory monitoring for hematologic toxicity is advised if coadministration is required. Since azathioprine is considered a slow-acting drug, delayed myelosuppression may occur, and effects may persist even after the drug has been discontinued. Prompt reduction in dosage or temporary withdrawal of azathioprine may be necessary if a persistently low or rapid decline in leucocyte count occurs, or if there is other evidence of bone marrow depression.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."

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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

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

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