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Drug Interactions between D-Penamine and monomethyl fumarate

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

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Interactions between your drugs

Moderate

penicillAMINE monomethyl fumarate

Applies to: D-Penamine (penicillamine) and monomethyl fumarate

MONITOR: The use of fumaric acid esters in combination with medications that can cause nephrotoxicity (e.g., aminoglycosides, diuretics, nonsteroidal anti-inflammatory drugs, cyclosporine, lithium, methotrexate) may increase the potential for adverse renal reactions. In clinical trials in patients with multiple sclerosis treated with dimethyl fumarate, a fumaric acid ester that is converted to the active metabolite monomethyl fumarate, adverse events of proteinuria were reported at slightly higher frequencies than in patients receiving placebo. The clinical significance of these observations is unknown. Cases of Fanconi syndrome have been reported for a medicinal product containing dimethyl fumarate in combination with other fumaric acid esters. Renal toxicity, including tubular changes and/or interstitial fibrosis, has been observed in animal studies with dimethyl fumarate and diroximel fumarate.

MANAGEMENT: The use of fumaric acid esters in patients who receive concomitant treatment with potentially nephrotoxic agents, particularly for longer durations, has not been evaluated and should be approached with caution. Assessment of renal function (e.g., serum creatinine, blood urea nitrogen, urinalysis) is recommended prior to initiating treatment with fumaric acid esters and as clinically indicated during treatment.

References

  1. (2022) "Product Information. Vumerity (diroximel fumarate)." Biogen Australia Pty Ltd
  2. (2023) "Product Information. Tecfidera (dimethyl fumarate)." Biogen Idec Inc, SUPPL-29
  3. (2022) "Product Information. Tecfidera (dimethyl fumarate)." Biogen Idec Ltd
  4. (2022) "Product Information. Skilarence (dimethyl fumarate)." Almirall Ltd
  5. (2022) "Product Information. Vumerity (diroximel fumarate)." Biogen Idec Ltd
  6. (2023) "Product Information. Vumerity (diroximel fumarate)." Biogen Idec Inc, SUPPL-9
  7. (2022) "Product Information. Furatec (dimethyl fumarate)." Pharmacor Pty Ltd, 03
View all 7 references

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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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