UK Clinical Pharmacy Association

Tamoxifen

Issues for surgery

For breast cancer treatment – risk of breast cancer progression if omitted.

For breast cancer prevention – risk of breast cancer development if omitted.

Risk of venous thromboembolism (VTE) if continued (see Further information).

For patients undergoing breast reconstruction surgery – risk of microvascular flap complications if continued (see Further information).

Advice in the perioperative period

Elective surgery 

For patients with breast cancer

A risk:benefit decision should be made on continuing tamoxifen pre-operatively and a shared-decision making (SDM) approach taken with the patient.

Consideration should be given to risk factors for VTE that may also be present such as age > 60 years, BMI > 30 Kg/m2, significant co-morbidities, recent chemotherapy, type of surgery and anticipated prolonged immobility post-operatively. In addition, the stage of breast cancer (early stage vs. advanced) should be borne in mind (the risks of short-term cessation of SERM therapy is unknown).

Ideally, tamoxifen should be continued pre-operatively; however, if the risks of tamoxifen-induced thrombosis or microvascular flap complications (in breast surgery – see Further information) from continuing are deemed to outweigh the risks associated with interrupting treatment, tamoxifen may be stopped 2 – 3 weeks pre-operatively (minimum 7 days). A useful algorithm can be found in the here. Also see Further information.

Consideration should be given to discussing with the patient’s oncologist or surgeon if there is any doubt about the decision to discontinue or continue tamoxifen pre-operatively.

For patients with anovulatory infertility

Discontinue six weeks before surgery (if possible).

Emergency surgery 

Ensure adequate thromboprophylaxis to reduce risk of VTE.

If prolonged immobilisation anticipated, consider discontinuing on admission if risk of thrombosis outweighs risks of interrupting treatment – see Further information.

Post-operative advice

If continued pre-operatively restart when next dose due. Ensure adequate thromboprophylaxis to reduce risk of VTE.

If stopped pre-operatively restart once the patient is fully mobile, or 3 weeks post-operatively for those at high risk of VTE.

If a patient develops a VTE in the post-operative period, tamoxifen should be stopped immediately and appropriate treatment initiated. Advice should be sought from an oncology specialist.

Interactions with common anaesthetic agents

Neuromuscular blocking drugs (NMBDs)

There has been one case report of prolonged effects of atracurium which was attributed to tamoxifen. The significance of this interaction remains unclear but bear it in mind in the case of an unusual reaction.

Interactions with other common medicines used in the perioperative period

None.

Further information

Risk of VTE

A two to three-fold increase in VTE has been demonstrated in those taking tamoxifen. This risk is further increased in those undergoing surgical procedures, those who have had recent chemotherapy and where there may be prolonged periods of reduced mobility. In 2002, the Committee of Safety of Medicines (CSM) recommended continuation of tamoxifen therapy before surgery or following long-term immobility, unless the risk of tamoxifen-induced thrombosis outweighs the risk of interrupting the treatment in breast cancer patients. There has been evidence from several trials since the CSM recommendation linking pre-operative use of tamoxifen to an increased risk of VTE following surgery; with the risk remaining high up to 12 weeks following inpatient and up to 6 weeks after day surgery under general anaesthetic. A patient-centred approach must be used when deciding when, and if, to discontinue tamoxifen prior to surgery.

The multidisciplinary team may find the practical classification of the VTE risk and the recommended management options proposed by Hussain and Kneeshaw useful in facilitating their decision making.

Risk of cancer progression

There is currently no evidence with regards the impact of stopping tamoxifen pre-operatively on cancer progression.

Rationale for timeframe for stopping tamoxifen pre-operatively

Tamoxifen is metabolised to a similar biologically active metabolite and with a single 20mg daily dose, steady state plasma levels are achieved of both tamoxifen and the metabolite in 4 and 8 weeks. Plasma concentration declines in a biphasic manner with an elimination half-life of 7 – 14 days. Excretion of tamoxifen is via faeces with 65% of the administered dose being excreted over a 2-week period. Hence, approximately 98% of the drug would be fully eliminated from the plasma by 3 weeks.

Risk of microvascular flap complications

There is some evidence which suggests that continuing tamoxifen perioperatively may contribute to microvascular flap complications in those undergoing breast reconstruction surgery. For this reason, some sites suggest discontinuing tamoxifen prior to surgery. Results from these studies are however not conclusive and therefore recommendations made for discontinuing tamoxifen are based on theoretical risk.

References

Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 6th September 2022]

Hussain T, Kneeshaw P. Stopping tamoxifen peri-operatively for VTE risk reduction: A proposed management algorithm. International Journal of Surgery. 2012; 10:313–316

Mirzabeigi MN, Nelson JA, Fischer JP, et al. Tamoxifen (selective estrogen-receptor modulators) and aromatase inhibitors as potential perioperative thrombotic risk factors in free flap breast reconstruction. Plastic and Reconstructive Surgery. 2015; 135:670–679

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 6th September 2022]

Kelley BP, Valero V, Yi M, et al. Tamoxifen increases the risk of microvascular flap complications in patients undergoing microvascular breast reconstruction. Plastic and Reconstructive Surgery. 2012; 129:305–314

Selzer A, Mendez, Regan D et al. Preoperative Management of Endocrine, Hormonal, and Urologic Medication: Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement. Thematic Review on Perioperative Medicine, 2021; 96(6): 1655 – 1669. DOI: 10.1016/j.mayocp.2020.10.002

Summary of Product Characteristics – Tamoxifen 20mg Film-Coated Tablets. Wockhardt UK Ltd. Accessed via www.medicines.org.uk 06/09/2022 [date of revision of the text 06/08/2021]