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Drug Interactions between Centrum Singles-Vitamin E and Docefrez

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

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Moderate

vitamin E DOCEtaxel

Applies to: Centrum Singles-Vitamin E (vitamin e) and Docefrez (docetaxel)

GENERALLY AVOID: The potential effects of vitamin E on cancer chemotherapy and radiation have not been established. Because vitamin E is an antioxidant, pharmacologic doses could theoretically interfere with radiation therapy and chemotherapeutic agents whose cytotoxic mechanism depends on generation of reactive oxygen species (ROS) that damage DNA and proteins, including but not limited to alkylating agents (e.g., busulfan, cyclophosphamide, melphalan), anthracyclines (e.g., doxorubicin, epirubicin), platinum coordination complexes (e.g., cisplatin, carboplatin), DNA topoisomerase inhibitors (e.g., etoposide, teniposide, irinotecan, topotecan), and photodynamic agents (e.g., porfimer). On the other hand, vitamin E may help reduce oxidative stress associated with more aggressive cancers and protect non-cancer cells from oxidative damage generated by cancer treatments, which can enhance patient tolerance and lessen the need for reducing dosage or duration of treatment. Limited data from clinical studies suggest that vitamin E may attenuate cisplatin-induced neurotoxicity without compromising antineoplastic efficacy, whereas no effect on doxorubicin-induced cardiotoxicity has been reported. Animal studies have also reported an increase in the effectiveness of some antineoplastic agents against certain cancers in the presence of vitamin E (e.g., fluorouracil for colon cancer), although these results have not been replicated in human studies. Still other studies have found neither a beneficial nor adverse effect of vitamin E on cancer development or treatment, although slightly increased risks of heart failure and mortality in association with vitamin E have been observed. A review of published randomized clinical trials regarding concurrent antioxidant supplementation during cytotoxic therapy was conducted by a group of investigators at the Naval Medical Center San Diego and published in 2008. Based on their findings, the investigators recommended that use of supplemental antioxidants during chemotherapy and radiation therapy be discouraged due to the possibility of tumor protection and reduced survival. Additional and larger studies are clearly needed to determine the exact nature of the interaction between vitamin E and ROS-generating chemotherapies. Other antineoplastic agents such as the taxanes (e.g., docetaxel, paclitaxel), vinca alkaloids (e.g., vinblastine, vincristine), and antimetabolites (e.g., cytarabine, fluorouracil, methotrexate) are also known to generate a low level of oxidative stress in biological systems, but free radical damage is not considered their primary mechanism of action and it is not known if or how vitamin E may affect them.

MANAGEMENT: Until more information is available, vitamin E supplementation should preferably be avoided in patients undergoing cancer chemotherapy or radiation treatment. Clinicians should closely monitor antitumor response if vitamin E is used in these patients. No specific dosing of vitamin E has been established for uses other than to treat vitamin E deficiency. There has been evidence suggesting possible adverse health effects including increased risk of heart failure and mortality in association with long-term use of 400 IU/day or greater.

References

  1. Whittaker JA, Al-Ismail SA "Effect of digoxin and vitamin E in preventing cardiac damage caused by doxorubicin in acute myeloid leukaemia." Br Med J (Clin Res Ed) 288 (1984): 283-4
  2. Lonn E, Bosch J, Yusuf S, et al. "Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial." JAMA 293 (2005): 1338-47
  3. Labriola D, Livingston R "Possible interactions between dietary antioxidants and chemotherapy." Oncology (Williston Park) 13 (1999): 1003-8; discussion 1008, 1011-2
  4. Therapeutic Research Faculty "Natural Medicines Comprehensive Database. http://www.naturaldatabase.com" (2008):
  5. Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C "Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic review of the evidence from randomized controlled trials." Int J Cancer 123 (2008): 1227-39
  6. D'Andrea GM "Use of antioxidants during chemotherapy and radiotherapy should be avoided." CA Cancer J Clin 55 (2005): 319-21
  7. Prasad KN "Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy." J Nutr 134 (2004): 3182S-3S
  8. Conklin KA "Cancer chemotherapy and antioxidants." J Nutr 134 (2004): 3201S-4S
  9. Pace A, Savarese A, Picardo M, et al. "Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy." J Clin Oncol 21 (2003): 927-31
View all 9 references

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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. "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.


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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.