Drug Interactions between calcium carbonate / melatonin / valerian / vitamin e and vinblastine

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.

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.