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Drug Interactions between bioflavonoids / zinc glycinate and Depen Titratabs

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

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Interactions between your drugs

Moderate

penicillAMINE zinc glycinate

Applies to: Depen Titratabs (penicillamine) and bioflavonoids / zinc glycinate

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. These changes could result in diminished therapeutic effects of penicillamine.

When used concomitantly with copper-chelating agents for the treatment of Wilson's disease, zinc salts can compete with copper for chelation and renal excretion. The clinical significance is unknown, although reduced efficacy of one or both agents may theoretically occur. Zinc alone can reduce copper levels by blocking its absorption in the intestine and promoting fecal copper excretion. A small study found that adding penicillamine (1 gm/day) or trientine (1 gm/day) to zinc therapy reduced fecal copper excretion but increased urinary excretion, with the overall copper balance not appreciably changed compared to during zinc therapy alone. In the study, the chelating agent and zinc were given one hour apart. It is not known if simultaneous administration would result in more clinically significant alterations. Other studies have reported on the effectiveness of combination therapy in some patients. However, no data are available to demonstrate that zinc should be added to other drugs used for the treatment of Wilson's disease.

MANAGEMENT: Mineral supplements or other products containing polyvalent cations should be administered at least two hours before or two hours after the penicillamine dose if possible.

References

  1. Farinati F, Cardin R, Mestriner C, Sturniolo GC, Naccarato R "Mechanisms of pennicillamine and zinc in the treatment of Wilson's disease." Am J Gastroenterol 90 (1995): 2264-5
  2. Brewer GJ "Practical recommendations and new therapies for Wilson's disease." Drugs 50 (1995): 240-9
  3. Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V, Dick RD, Wang Y "Treatment of Wilson's disease with zinc: XI. Interaction with other anticopper agents." J Am Coll Nutr 12 (1993): 26-30
  4. "Product Information. Galzin (zinc acetate)." Teva Pharmaceuticals USA PROD (2001):
  5. Anderson LA. Hakojarvi SL, Boudreaux SK "Zinc acetate treatment in Wilson's disease." Ann Pharmacother 32 (1998): 78-87
View all 5 references

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Drug and food interactions

Moderate

penicillAMINE food

Applies to: Depen Titratabs (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: Depen Titratabs (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.

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