Brands of this drug
Premarin
Issues for surgery
Risk of menopausal symptoms, e.g. hot flushes, if discontinued preoperatively.
Reduced protection against osteoporosis if discontinued for prolonged period.
Risk of venous thromboembolism (VTE) if continued.
Advice in the perioperative period
Elective surgery
Minor surgery
Continue unless there is a risk of prolonged immobilisation – see Major surgery.
Ensure adequate VTE prophylaxis if continued.
Major surgery
Consider stopping 4-6 weeks before major elective surgery where prolonged immobilisation is likely, particularly vascular and orthopaedic lower limb surgery. See Further information
Consider other risk factors that the patient may have that further increase the risk of VTE, e.g. age, weight, previous history of VTE.
Please note, if doses are missed, it may result in breakthrough bleeding in women with a uterus.
Emergency surgery
Ensure adequate thromboprophylaxis to reduce risk of VTE.
If prolonged immobilisation anticipated, consider discontinuing on admission.
Please note, if doses are missed, it may result in breakthrough bleeding in women with a uterus.
Patients admitted with gallstones (cholelithiasis)
Use of conjugated oestrogens can aggravate gallstones in patients who have a previous history of this condition; bear this in mind for patients admitted with gallstones who are on this medication.
Post-operative advice
If stopped pre-operatively restart after full mobilisation.
Patients undergoing major gynaecological surgery
Review appropriateness of restarting this preparation after major gynaecological surgery.
Interactions with common anaesthetic agents
None.
Interactions with other common medicines used in the perioperative period
Dexamethasone
Since oestrogen metabolism can be affected by concomitant use of medicines that affect cytochrome P450 enzymes, specifically CYP3A4; the manufacturer notes that concomitant use of an inducer of CYP3A4, such as dexamethasone, may reduce plasma concentrations of oestrogen, with a possible reduction in therapeutic effect and/or changes in uterine bleeding. It is unlikely that use of dexamethasone perioperatively will have a significant effect, but bear the interaction in mind where there is concomitant use of both medications and there is a change in therapeutic effect.
Etoricoxib
Etoricoxib slightly increases the exposure to conjugated oestrogens from HRT. There appears to be no reason for avoiding the combination. Although, if continued use beyond the immediate post-operative period is necessary, consideration should be given to the potential for increased risk of side-effects.
Antimicrobials
Since oestrogen metabolism can be affected by concomitant use of medicines that affect cytochrome P450 enzymes, specifically CYP3A4; the manufacturer notes that concomitant use of inhibitors of CYP3A4, such as erythromycin/clarithromycin, may increase plasma concentrations of oestrogen, with a possible increase in side-effects. Whilst single surgical prophylactic doses should not pose a problem, bear the interaction in mind where a course is required, conjugated equine oestrogens have been continued pre-operatively, and the patient experiences an increase in side-effects.
Further information
Risk of VTE with oral HRT preparations containing oestrogen
During first pass metabolism in the liver oral HRT preparations containing oestrogen affect the clotting cascade by increasing resistance to protein S and protein C (natural anticoagulants) and increasing fibrinogen, thus increasing the risk of thrombosis. Patients taking oral HRT are at increased risk of VTE compared with non-users. The risk is thought to be greatest in the first year of treatment and also in women with an increased body mass index. The baseline risk of VTE also increases substantially with age.
The risk of VTE varies depending on the oestrogen (and progesterone) content of the preparation. Preparations with conjugated equine oestrogen are associated with higher VTE risk compared to those with estradiol. Higher doses of oestrogen are also associated with higher VTE risk. The highest risk is with preparations containing both conjugated equine oestrogen and medroxyprogesterone acetate and the lowest risk is with estradiol with dydrogesterone.
References
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 5th January 2024]
Summary of Product Characteristics – Premarin® (oestrogens, conjugated) 1.25 mg Coated Tablets. Pfizer Limited. Accessed via www.medicines.org.uk 05/01/24 [date of revision of the text October 2020]
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 5th January 2024]
National Institute of Health and Clinical Excellence (2019). NG23 Menopause: diagnosis and management. https://www.nice.org.uk/guidance/ng23 [Accessed on 5th January 2024]
Vinogradova, Y. Coupland, C & Hippisley-Cox, J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019; 364: k4810. DOI: 10.1136/bmj.k4810