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Drug Interactions between Ferriprox and paclitaxel

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

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Interactions between your drugs

Major

PACLitaxel deferiprone

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

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Drug and food interactions

Moderate

PACLitaxel food

Applies to: paclitaxel

MONITOR: Coadministration with inhibitors of CYP450 3A4, such as grapefruit juice, may increase the plasma concentrations of paclitaxel, which is a substrate of the isoenzyme. Current data suggest that consumption of large quantities of grapefruit juice inhibit both intestinal and hepatic CYP450 3A4 due to certain compounds present in grapefruit. Specific data for paclitaxel are lacking; however, in a case report of a 52-year-old woman with esophageal squamous cell carcinoma receiving a twice weekly chemotherapy regimen including intravenous docetaxel (40 mg/m2) reported that docetaxel systemic exposure (AUC) increased by 65% compared with the AUC target of 1.96 mg*h/L and clearance decreased by 63%, with a 71% reduction in the patient's neutrophil count. In the absence of other CYP450 3A4 inhibitors, these effects were attributed to daily consumption of 250 mL of grapefruit juice, which the patient had been consuming for at least 3 months. Two weeks after the patient ceased the grapefruit juice, the docetaxel AUC was closer to the target value and the neutrophil count reduction was less than 35%. In addition, in a pharmacokinetic study consisting of 7 cancer patients, mean dose-normalized docetaxel AUC increased by 2.2-fold and clearance decreased by 49% when intravenous docetaxel was given at a reduced dosage of 10 mg/m2 in combination with the potent CYP450 3A4 inhibitor ketoconazole (200 mg orally once daily for 3 days) compared to docetaxel administered alone at 100 mg/m2.

MANAGEMENT: Caution is recommended if paclitaxel is to be used in combination with grapefruit and grapefruit juice. Patients should be closely monitored for the development of paclitaxel toxicity, including diarrhea, mucositis, myelosuppression, and peripheral neuropathy and dose adjustment considered per local treatment protocols.

References

  1. "Product Information. Taxotere (docetaxel)." Rhone Poulenc Rorer PROD (2001):
  2. Aronson JK, Grahame-Smith DG "Clinical pharmacology: adverse drug interactions." Br Med J 282 (1981): 288-91
  3. McInnes GT, Brodie MJ "Drug interactions that matter: a critical reappraisal." Drugs 36 (1988): 83-110
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  5. Yong WP, Wang LZ, Tham LS, et al. "A phase I study of docetaxel with ketoconazole modulation in patients with advanced cancers." Cancer Chemother Pharmacol 62 (2008): 243-51
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Engels FK, Mathot RA, Loos WJ, van Schaik RH, Verweij J "Influence of high-dose ketoconazole on the pharmacokinetics of docetaxel." Cancer Biol Ther 5 (2006): 833-9
  8. Valenzuela B, Rebollo J, Perez T, Brugarolas A, Perez-Ruixo JJ "Effect of grapefruit juice on the pharmacokinetics of docetaxel in cancer patients: a case report." Br J Clin Pharmacol (2011):
  9. Starr SP, Hammann F, Gotta V, et al. "Pharmacokinetic interaction between taxanes and amiodarone leading to severe toxicity." Br J Clin Pharmacol 450 (2016): 22-27
View all 9 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.

See also

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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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