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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Tamoxifen: To Crush Or Not To Crush?

1. From: http://www.gghbpharmacy.scot.nhs.uk/Hospitals/Southern/NIL_BY_MOUTH.pdf

*States tamoxifen should not be crushed, but tablets can be dispersed in water.


2. From: http://www.rosemontpharma.com/education/healthcare-professional/tablets-not-to-crush & http://www.guardian.co.uk/uk/2006/oct/26/health.healthandwellbeing

Hormonal cytoxic or steroidal medicines (i.e. tamoxifen, methotrexate)


Risk assessment form requires completion if drug is to be crushed prior to administration. If the tablet is crushed, the drug may go into the air and the dose inadvertently received by the administrating nurse or carer.


3. From BCCA: http://www.bccancer.bc.ca/RS/CommunitiesOncologyNetwork/Educators/faqs.htm#One

1. How can we administer an oral cancer medication to a cancer patient who has just had an NG tube inserted? For safety reasons, we were told not to crush tablets or open capsules.

Oral cancer medications that are considered hazardous or cytotoxic should not be manipulated outside of a containment cabinet (ie. Biological Safety Cabinet) due to the risk of generating Hazardous Drug (HD) powder residue causing possible HD contamination and exposure. You may try dissolving or suspending the tablet/capsule particles in an enclosed system (i.e. syringe plus water) and administering the liquid through the NG tube.



If line occlusion occurs and impedes cancer drug administration you could consider holding the drug for a few days. For example; tamoxifen has an elimination half-life of ~ 5-7 days and the half-life of its active metabolite is ~ 9-14 days, so it is possible to hold tamoxifen therapy for ~2 weeks.



If the oral cancer medication cannot be withheld, it may be possible to compound it into a liquid dosage form. All activities likely to result in particle or aerosol generation, such as crushing tablets/capsules or compounding/pouring of oral solutions should be performed in a Biological Safety Cabinet (BSC) or Isolator. Oral solutions for hospital inpatients should be prepared in the pharmacy and dispensed to the ward in unit dose syringes. The nurses should not measure doses from a bottle.

Reference:

BCCA Division of Pharmacy. BCCA Pharmacy Practice Standards for Hazardous Drugs. 2008.

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Any other thoughts out there on how to handle the situation where tamoxifen tablets cannot be swallowed?

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Long-term Tamoxifen Use Linked To Second Breast Cancer

{Tamoxifen 3D - photo left}

Long-term tamoxifen use linked to second breast cancer:
http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20090825/tamoxifen_risk_090825/20090825?hub=Health
From The Canadian Press, “A new study suggests long-term use of tamoxifen is linked to an increased risk of a second type of breast cancer…another rare subtype of the disease increased by more than 400 per cent.”

Adjuvant Hormonal Therapy for Breast Cancer and Risk of Hormone Receptor–Specific Subtypes of Contralateral Breast Cancer
http://cancerres.aacrjournals.org/cgi/content/abstract/0008-5472.CAN-09-1355v1
From Cancer Res 2009;69(17):6865–70, “Compared with the breast cancer risk women in the general population have, breast cancer survivors have a substantially higher risk of developing a second primary contralateral breast cancer. Adjuvant hormonal therapy reduces this risk, but preliminary data indicate that it may also increase risk of hormone receptor–negative contralateral tumors…Compared with women not treated with hormonal therapy, users of adjuvant tamoxifen for 5 years had a reduced risk of ER+ contralateral breast cancer [odds ratio, 0.4; 95% confidence interval (CI), 0.3–0.7], but a 4.4-fold (95% CI, 1.03–19.0) increased risk of ER- contralateral breast cancer. Tamoxifen use for <5>

From U.S. News (HealthBuzz):
http://health.usnews.com/articles/health/2009/08/26/health-buzz-rare-risk-of-cancer-after-taking-tamoxifen-and-other-health-news.html
“The study's lead author (Dr. Christopher Li ) told HealthDay News he does not think women should be afraid to take the drug, stating that its benefits outweigh its risks. Tamoxifen is customarily given only for five years because there's no evidence that longer-term use has additional benefits.”

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