Brands of this drug
Drovelis
ssues for surgery
Risk of contraceptive failure and pregnancy (potentially leading to cancellation of surgery) if discontinued pre-operatively.
Risk of venous thromboembolism (VTE) if continued.
Advice in the perioperative period
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 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.
If it is deemed appropriate for the patient to discontinue their contraception, then they MUST be given advice on alternative contraception (see Further information) and pregnancy must be excluded on admission.
Emergency surgery
Ensure adequate thromboprophylaxis to reduce risk of VTE.
If prolonged immobilisation anticipated consider discontinuing on admission.
Perioperative considerations
If sugammadex is administered in theatre, see post-operative advice under Interactions with common anaesthetic agents.
Post-operative advice
If continued pre-operatively bear in mind that post-operative vomiting within 3 hours of a dose could result in reduced contraceptive efficacy – follow the missed dose advice in the package leaflet.
If stopped pre-operatively restart at the first menses occurring at least 2 weeks after full mobilisation (see Further information).
Patients undergoing major gynaecological surgery
Review appropriateness of restarting this preparation after major gynaecological surgery.
Patients undergoing small bowel resection or bariatric surgery
Review appropriateness of restarting this preparation after bariatric surgery or small bowel resection as absorption may be reduced which could lead to loss of contraceptive effect.
Interactions with common anaesthetic agents
Sugammadex
Administration of a single bolus dose of sugammadex is predicted to cause a 34% decrease in progestogen exposure; the effect on oestrogen will be lower. This predicted pharmacokinetic reaction has not been proven clinically however it is recommended that users of oral contraceptives follow the missed dose advice in the package leaflet and that users of non-oral hormonal contraceptives use an additional non-hormonal contraceptive method for the next 7 days.
Hyperkalaemia
Drospirenone is an aldosterone antagonist with potassium sparing properties. In most cases, no increase in potassium levels is expected; however, in patients with mild or moderate renal impairment, concomitant use of this preparation with suxamethonium may slightly, but not significantly, increase serum potassium levels.
Interactions with other common medicines used in the perioperative period
Hyperkalaemia
Drospirenone is an aldosterone antagonist with potassium sparing properties. In most cases, no increase in potassium levels is expected; however, in patients with mild or moderate renal impairment, concomitant use of this preparation with the following may slightly, but not significantly, increase serum potassium levels:
- non-steroidal anti-inflammatory drugs/NSAIDs (see also NSAIDs below)
- cyclooxygenase-2 (COX-2) inhibitors (see also etoricoxib below)
- low molecular weight heparin (LMWH)
- unfractionated heparin (UFH)
Whilst single doses should not pose a problem, consider monitoring serum potassium in patients with mild or moderate renal impairment where a course is required and this preparation has been continued pre-operatively.
Etoricoxib
Etoricoxib increases the exposure to combined hormonal contraceptives. If continued use beyond the immediate post-operative period is necessary, consideration should be given to switching to an alternative product containing a lower dose of oestrogen due to the potential for increased risk of side-effects, including VTE.
Non-steroidal anti-inflammatory drugs (NSAIDs)
There is potentially an increased risk of VTE in patients taking hormonal contraception concomitantly with non-aspirin NSAIDs (see Further information). Whilst short-term use should not pose a problem, bear the interaction in mind should a prolonged course be required and counsel the patient to mobilise as allowed, ensure adequate hydration, and report any signs of VTE.
Antimicrobials
Since oestrogen and progesterone metabolism can be affected by concomitant use of medicines that affect cytochrome P450 enzymes, specifically CYP3A4; the manufacturer’s note that concomitant use of medicines that inhibit CYP3A4, such as erythromycin/clarithromycin, may increase plasma concentrations of oestrogen or progestereone. The clinical relevance is not known, however increased exposure to drospirenone may increase the risk of hyperkalaemia (see above), consider monitoring serum potassium levels with concomitant use.
Whilst single surgical prophylactic doses should not pose a problem, bear the interaction in mind where a course is required, combined oral contraception has been continued pre-operatively and the patient experiences an increase in side-effects or an increase in serum potassium.
Further information
Risk of VTE
Patients taking combined hormonal contraceptives are at increased risk of venous thromboembolism (VTE) compared with non-users. The risk is thought to be greatest in the first year of treatment and also when restarting after a gap of more than four weeks. The incidence of VTE varies depending on both the oestrogen dose and the type of progesterone. Products that contain levonorgestrel, norgestimate or norethisterone are associated with the lowest risk of VTE whereas products containing third generation progestogens have a higher risk of VTE. Products with 20microgram oestrogen doses were associated with a lower incidence of VTE than products with 30-40microgram oestrogen doses in a population-based cohort study.
The estimated incidence of VTE in non-pregnant women, not using hormonal contraception, is 2 per 10,000 women per year of use. The incidence of VTE with other oestrogen containing contraceptives is between 6 – 12 per 10,000 women per year of use (i.e. additional 4 – 10 cases per 10,000 women per year of use); however, it is not yet known how the risk of VTE with contraceptives containing estetrol and drospirenone compares with the risk with other hormonal contraceptives. The incidence of VTE in users of oestrogen containing contraception remains considerably lower than in pregnant patients and postpartum patients.
Alternative contraception
Progesterone-only contraceptives are recommended as an alternative to combined hormonal contraceptives for patients before major elective surgery, before surgery to the lower limbs or before surgery that involves prolonged immobilisation of a lower limb. Consult the product literature for advice about switching.
NSAIDs and VTE risk
Results of a Danish study suggest the risk of VTE in users of hormonal contraception who also took non-aspirin NSAIDs was higher than those not taking non-aspirin NSAIDs. The study findings are limited by the observational nature of the study design and potential confounding factors, not least that the reason for prescription of the non-aspirin NSAID could increase the VTE risk. The FRSH advise that when hormonal contraception is prescribed according to their guidelines the risk of thrombotic events is minimised so the absolute risk from addition of non-aspirin NSAIDs is likely to remain very small.
References
Faculty of Sexual and Reproductive Healthcare. Clinical Guideline: Combined hormonal contraception. Clinical Effectiveness Unit. January 2019 (amended October 2023). https://www.fsrh.org [Accessed on 1st February 2024]
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 1st February 2024]
Summary of Product Characteristics – Drovelis (drospirenone, estetrol) 3 mg/14.2 mg film-coated tablets. Gedeon Richter (UK) Ltd. Accessed via www.medicines.org.uk 05/02/24 [date of revision of the text August 2023]
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 1st February 2024]
Summary of Product Characteristics – Sugammadex 100mg/ml solution for injection. Amarox Limited. Accessed via www.medicines.org.uk 01/02/24 [date of revision of the text September 2023]
Faculty of Sexual and Reproductive Healthcare. FSRH CEU Statement: Response to new study by Meaidi et al. Clinical Effectiveness Unit. September 2023. https://www.fsrh.org [Accessed on 1st February 2024]
Faculty of Sexual and Reproductive Healthcare. FSRH CEU Guidance: Drug Interactions with Hormonal Contraception. Clinical Effectiveness Unit. May 2022. https://www.fsrh.org [Accessed on 12th February 2024]