Potential tamoxifen & methadone interaction

Drug Interactions

(as per Lexicomp Online accessed Jan 6/11)

Risk Rating D: Consider therapy modification


Summary: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the formation of highly potent active metabolites.

Severity: Major
Reliability Rating: Fair

Patient Management Moderate CYP2D6 inhibitors may reduce the clinical effectiveness of tamoxifen; consider alternative therapy with less of an effect on CYP2D6 activity when possible.

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Statins Do Not Interfere with Rituximab Treatment for Lymphomas, Mayo Clinic Study Finds

A medication review recently performed at our clinic identified a potential drug interaction with concurrent use of atorvastatin (Lipitor) and rituximab may result in decreased rituximab efficacy and impaired CD20 detection, according to Micromedex Online.

I had encountered the same interaction early last year and investigated further into this theoretically troublesome combination.

Micromedex Online (accessed June 2, 2010) states:

"Use caution when prescribing atorvastatin to patients who receive rituximab, as concomitant use of atorvastatin may cause interference with antilymphoma activity of rituximab. Atorvastatin may also interfere with the detection of CD20 binding to lymphocytes used to diagnose lymphomas (Winiarska et al, 2008)."

*However, upon further review of the reference Micromedex states in noting the theoretical major interaction between statins and rituximab, a further study has since been done by Grzegorz Nowakowski, M.D., Mayo Clinic hematologist, and others presented Dec 8/2008 at the 50th Annual Meeting of the American Society of Hematology in San Francisco. The results of this study "can provide reassurance to oncologists and their patients that statins will not reduce the effectiveness of rituximab and may in fact improve outcomes of some patients with lymphomas."

Conclusion: "This study shows we should not be concerned of the patient being on Lipitor (atorvastatin) while being treated with rituximab."

Please see the following link for more information:

http://www.mayoclinic.org/news2008-rst/5109.html

I will also be contacting the makers of Micromedex to inform them of this conflicting information.

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Drug Interaction: Cyclophosphamide and Allopurinol

*Interaction detected between allopurinol and cyclophosphamide, MAJOR increased toxicity (increase myelosuppression, nausea and vomiting) as per Micromedex Online
(Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically).

Onset: Delayed

Severity: Major

Documentation: Good

Summary: There may be an increase in cyclophosphamide levels and prolongation in half-life of cyclophosphamide (Anon, 1974; Stolbach et al, 1982).

Literature:


The Boston Collaborative Drug Surveillance Program examined the incidence of bone marrow depression in a series of 160 patients, 95 of whom were controls, during combined allopurinol use with either cyclophosphamide or other cytotoxic drugs (Anon, 1974). Their results indicated that the frequency of bone marrow depression in those patients who received allopurinol and cyclophosphamide was 57.7% as compared to 18.8% in those who did not receive allopurinol. In addition they noted that mortality may be somewhat higher in allopurinol recipient patients.

One study has reported that concomitant allopurinol and cyclophosphamide therapy results in significant elevations of cyclophosphamide cytotoxic metabolites, which may contribute to the increased bone marrow depression observed during concomitant therapy (Witten et al, 1980).

*At our centre and in this individual case, patient was on allopurinol 100 mg daily continuously for management of gout. The patient was to start FEC. After discussing with treating physician, there was insufficient time to temporarily discontinue allopurinol without delaying treatment. Therefore, it was decided to monitor CBCs carefully - that is, weekly (at least for the first cycle). It will then be decided if allopurinol will be held at all next cycle.

One possible recommendation would be to hold allopurinol for 5 days before and 2 days after chemotherapy treatment. This is based on half-life of active metabolite of allopurinol, oxypurinol, being 18-30 hours and cyclophosphamide's 3-12 hours.

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SSRIs and Tamoxifen: Does the Combination Increase Recurrence?

As recently reported by CTV: {excerpts from the article; data presented at ASCO May 31/09}

ORLANDO, Fla. — Breast cancer survivors risk having their disease come back if
they use certain antidepressants while also taking the cancer prevention drug
tamoxifen, worrisome new research shows...The new study, reported Saturday at a
cancer conference in Florida (ASCO), is the largest to look at the issue. It found that
using these interfering drugs -- including Prozac, Paxil or Zoloft -- can
virtually wipe out the benefit tamoxifen provides...Breast cancer recurred in
about seven per cent of women on tamoxifen alone, and in 14 per cent of women
also taking other drugs that could interfere -- mainly the antidepressants Paxil
and Prozac, and, to a lesser extent, Zoloft...No greater breast cancer risk was
seen in women taking the antidepressants Celexa, Lexapro or Luvox with
tamoxifen, and there are reasons to think that other antidepressants may be safe
as well, Epstein said..."This is a very controversial area," said Dr. Claudine
Isaacs, a breast specialist at Georgetown University's Lombardi Comprehensive
Cancer Center. "Until these data are absolutely clear, I would avoid drugs that
impact on tamoxifen metabolism."

From OncocologySTAT:

"SRIs, however, can also inhibit the 2D6 enzyme that converts tamoxifen to its
main active metabolite, endoxifen, thus possibly decreasing its efficacy."

Massachusetts General Hospital Centre For Women's Health posted an article in June '08 regarding interactions between tamoxifen and antidepressants. I discovered this post when searching for solutions after detecting the interaction via Micromedex/Lexicomp.
{Click here for link to article}.

The following table from the above mentioned article provides some guidance when faced with such a dilemma:

CPY2D6 Inhibitors

Strong Inhibitors (Should be avoided if
possible):
Paroxetine
Fluoxetine
Bupropion
Duloxetine

Moderate Inhibitors:
Sertraline
Citalopram/Escitalopram
Doxepin

Weak Inhibitors (Use not restricted by treatment with
tamoxifen):
Venlafaxine
Desvenlafaxine

If antidepressants are indicated in the treatment of a woman currently
taking tamoxifen, the following treatment recommendations have been made:
*If possible, avoid antidepressants, including fluoxetine and paroxetine, that are
strong inhibitors of the CPY2D6 enzyme (see the list of inhibitors above)
*If the antidepressant is being used solely for the management of hot
flushes, other agents, such as gabapentin, may be used instead
*If it is not possible to avoid these antidepressants, another option for postmenopausal women
only would be to switch from tamoxifen to an aromatase inhibitor, if medically
appropriate

Please post your comments below or email me at: chrisral@cancerboard.ab.ca

* Thanks to Scott Edwards, PharmD for the link to the CTV News article.

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