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Drug Interactions between Ferriprox and penicillamine

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

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Interactions between your drugs

Major

penicillAMINE deferiprone

Applies to: penicillamine and Ferriprox (deferiprone)

GENERALLY AVOID: Coadministration of deferiprone and other drugs that can cause neutropenia or agranulocytosis may increase the risk and/or severity of hematologic toxicity. Serious infection and death have been reported. The mechanism by which deferiprone leads to neutropenia or agranulocytosis is unknown. In pooled clinical trials of 642 patients with thalassemia syndromes, neutropenia occurred in 6.2% and agranulocytosis in 1.7% of deferiprone-treated patients. Similarly, agranulocytosis occurred in 1.5% of deferiprone-treated patients in pooled clinical trials of 196 patients with sickle cell disease or other anemias. Pediatric patients experienced a higher rate of decreases in neutrophil count when compared to adults being treated with deferiprone for the same condition. Neutropenia and agranulocytosis generally resolve upon discontinuation of deferiprone.

MANAGEMENT: Concomitant use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis should generally be avoided. Some authorities consider this combination to be contraindicated. If coadministration is unavoidable, the patient's baseline absolute neutrophil count (ANC) should be measured and then closely monitored during deferiprone therapy according to the manufacturer's product labeling. If neutropenia or infection develops, deferiprone and any other concomitant therapy associated with neutropenia or agranulocytosis should be discontinued. A complete blood cell (CBC) count, including a white blood cell (WBC) count corrected for the presence of nucleated red blood cells, an ANC, and a platelet count should be obtained daily until recovery. Patients should be advised to seek immediate medical assistance if they develop symptoms of infection (e.g., fever, sore throat, flu-like symptoms). For patients who develop agranulocytosis (ANC less than 0.5 x 10^9/L), hospitalization should be considered, and deferiprone should not be resumed following recovery unless potential benefits outweigh the risks. Likewise, patients who develop neutropenia with deferiprone should not be rechallenged unless potential benefits outweigh the risks.

References

  1. (2023) "Product Information. Ferriprox (deferiprone)." Chiesi Ltd
  2. (2022) "Product Information. Ferriprox (deferiprone)." Apotex Pty Ltd, 2.0
  3. (2023) "Product Information. Ferriprox MR (deferiprone)." Chiesi Canada Corp
  4. (2023) "Product Information. Ferriprox (deferiprone)." Chiesi USA, Inc
View all 4 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 (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: 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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