What are the potential interactions between Tamoxifen and antipsychotic or anxiolytic medications, such as Olanzapine (Zyprexa), Haloperidol (Haldol), or Lorazepam (Ativan)?

From the Guidelines

Tamoxifen should be used with caution when combined with Zyprexa (olanzapine), Haldol (haloperidol), or Ativan (lorazepam) due to potential interactions, with the most significant concern being the impact on tamoxifen's efficacy in treating or preventing breast cancer. The primary concern is the potential for altered blood levels of either medication, as tamoxifen and certain antipsychotics, such as Zyprexa and Haldol, are metabolized by the CYP2D6 enzyme system in the liver 1. This could lead to reduced effectiveness of tamoxifen or increased side effects from either medication. In contrast, Ativan has less potential for interaction with tamoxifen, as it uses different metabolic pathways.

Key Considerations

• Patients taking tamoxifen alongside any of these medications should have their medication levels monitored regularly and watch for changes in side effects or therapeutic response.
• Common side effects to monitor include increased sedation, dizziness, or changes in mental status.
• Never adjust or stop these medications without consulting a healthcare provider, as all serve important therapeutic purposes.
• If taking tamoxifen for breast cancer treatment while also requiring psychiatric medication, the oncologist and psychiatrist should coordinate care to optimize both treatment regimens.

Mechanism of Interaction

The interaction between tamoxifen and certain antipsychotics or anxiolytics is primarily related to the inhibition of the CYP2D6 enzyme, which is involved in the metabolism of tamoxifen to its active metabolite, endoxifen 1. Some medications, such as fluoxetine and paroxetine, are potent inhibitors of CYP2D6, while others, like sertraline, citalopram, and venlafaxine, have weaker or no effects on this enzyme.

Clinical Implications

Given the potential for interactions, it is essential to carefully select and monitor medications when combining tamoxifen with antipsychotics or anxiolytics. The most recent and highest quality study suggests that the use of mild CYP2D6 inhibitors, such as sertraline or citalopram, may be preferred over moderate-to-potent inhibitors when concomitant use with tamoxifen is necessary 1. Regular monitoring of medication levels and side effects, as well as coordination of care between healthcare providers, can help minimize the risks associated with these interactions.

From the Research

Potential Interactions between Tamoxifen and Antipsychotic or Anxiolytic Medications

• The potential interactions between Tamoxifen and antipsychotic or anxiolytic medications, such as Olanzapine (Zyprexa), Haloperidol (Haldol), or Lorazepam (Ativan), are not directly addressed in the provided studies.
• However, it is known that Tamoxifen is a prodrug that requires conversion to its active metabolite, endoxifen, through the cytochrome P450 enzyme system, specifically CYP2D6 2.
• Drugs that inhibit CYP2D6, such as certain antipsychotics and anxiolytics, may reduce the efficacy of Tamoxifen by decreasing the formation of endoxifen 2.
• Enzyme inducers, on the other hand, may increase the activity of various pathways involved in Tamoxifen disposition, potentially reducing its efficacy 2.
• The studies suggest that drug-drug interactions can lead to reduced efficacy of medical treatment, and that the combined use of certain medications with Tamoxifen should be avoided 3, 2.
• It is also noted that many drugs, including antipsychotics and anxiolytics, can act as precipitants or objects in drug interactions, and that regularly updated manuals of drug interactions and automated drug interaction alerts can help identify potential interactions 4, 5.