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Drug Interactions between Docefrez and zalcitabine

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

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Interactions between your drugs

Moderate

zalcitabine DOCEtaxel

Applies to: zalcitabine and Docefrez (docetaxel)

GENERALLY AVOID: Zalcitabine can cause peripheral neuropathy in up to one-third of patients with advanced HIV disease, and concurrent use of other agents that are also associated with this adverse effect can potentiate the risk and/or severity of nerve damage. Zalcitabine-related peripheral neuropathy is a sensorimotor neuropathy characterized initially by numbness and burning dysesthesia involving the distal extremities. These symptoms may be followed by sharp shooting pains or severe continuous burning pain if the drug is not withdrawn, and progress to severe pain requiring narcotic analgesics. The neuropathy is potentially irreversible. However, with prompt discontinuation of zalcitabine, it is usually slowly reversible, although symptoms may initially progress following discontinuation.

MANAGEMENT: Use of zalcitabine with other drugs that have the potential to cause peripheral neuropathy should be avoided whenever possible. Otherwise, careful monitoring is recommended for symptoms of neuropathy such as burning, tingling, pain, numbness, or weakness in the extremities, particularly in patients with a low CD4 cell count or diabetes. Since the development of peripheral neuropathy appears to be dose-related, the recommended dosage of zalcitabine should not be exceeded. Patients should be advised to promptly discontinue zalcitabine therapy and contact their physician if neuropathy develops. Therapy may be reinstituted following resolution of neuropathy symptoms, but dosage should be reduced to one-half the initially recommended dosage. Zalcitabine should be permanently discontinued in patients who develop severe peripheral neuropathy during treatment.

References

  1. (2001) "Product Information. HIVID (zalcitabine)." Roche Laboratories
  2. Argov Z, Mastaglia FL (1979) "Drug-induced peripheral neuropathies." Br Med J, 1, p. 663-6

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Drug and food interactions

Major

DOCEtaxel food

Applies to: Docefrez (docetaxel)

GENERALLY AVOID: Coadministration with inhibitors of CYP450 3A4, such as grapefruit juice, may significantly increase the plasma concentrations of docetaxel, 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. In a pharmacokinetic study consisting of 7 cancer patients, mean dose-normalized docetaxel systemic exposure (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. In addition, 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 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%.

MANAGEMENT: The use of docetaxel in combination with grapefruit and grapefruit juice should generally be avoided. If concomitant use is required, a reduced dosage of docetaxel should be considered, particularly if used with large amounts of grapefruit juice, and therapeutic drug monitoring of docetaxel considered per local treatment protocols. Patients should be closely monitored for the development of docetaxel toxicity such as myelosuppression, stomatitis, neurotoxicity (e.g., paraesthesia, dysesthesia, pain), myalgia, asthenia, fluid retention, nausea, vomiting, and diarrhea.

References

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

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Minor

zalcitabine food

Applies to: zalcitabine

Zalcitabine bioavailability may be decreased by 14% if taken with meals. The mechanism and clinical significance are unknown.

References

  1. (2001) "Product Information. HIVID (zalcitabine)." Roche Laboratories

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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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