Norethisterone (Therapeutic doses i.e. >5mg)


 

[For norethisterone contraceptive see Progesterone Only Contraceptive monograph]


  Issues for Surgery


For treatment of endometriosis, menorrhagia or dysfunctional uterine bleeding – potential increase in symptoms if stopped.

Risk of venous thromboembolism (VTE) if therapeutic doses continued1 (see Further Information).


  Advice in the Perioperative period


Elective surgery

Consider stopping 4-6 weeks before surgery where prolonged immobilisation is likely (e.g. abdominal surgery or orthopaedic lower limb surgery)2.

EXCEPT:

  • Noriday® (see Progesterone Only Contraceptives monograph)

If continuing, ensure adequate thromboprophylaxis as risk of VTE comparable to combined oral contraceptive pill2.

Emergency surgery

Ensure adequate thromboprophylaxis as risk of VTE comparable to combined oral contraceptive pill2.

Consider stopping on admission if prolonged immobilisation is likely2

EXCEPT:

  • Noriday® (see Progesterone Only Contraceptives monograph)

Post-operative Advice

If discontinued pre-operatively, restart once mobile.


  Interaction(s) with Common Anaesthetic Agents


Sugammadex

Administration of a single bolus dose of sugammadex is predicted to cause a 34% decrease in progestogen exposure3, 4


  Interaction(s) with other Common Medicines used in the Perioperative Period


None1, 3.


  Further Information


Risk of VTE

Therapeutic doses of norethisterone and norethisterone acetate (used for endometriosis, menorrhagia, dysfunctional uterine bleeding or postponement of menstruation1) are thought to be associated with an increased risk of VTE.  Partial metabolism of norethisterone to ethinylestradiol has been noted at doses exceeding 5mg5.  A daily norethisterone dose of 10-20mg is likely to equate to a 20-30microgram dose of ethinylestradiol, and therefore carry the same VTE risk as the combined contraceptive pill6.

The conversion of norethisterone to ethinylestradiol has been attributed to a structural peculiarity of the norethisterone molecule and thus there are no implications for other progestogens regardless of dose6.

 

  References


  1. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. www.medicinescomplete.com [Accessed on 11th May 2019]
  2. Summary of Product Characteristics – Primolut® (norethisterone). Bayer plc. Accessed via www.medicines.org.uk 11/05/2019 [date of revision of the text December 2018]
  3. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. www.medicinescomplete.com/ [Accessed on 10th May 2019
  4. Summary of Product Characteristics - Bridion® (sugammadex). Merck Sharp & Dohme Limited.  Accessed via www.medicines.org.uk 10/05/2019 [date of revision of the text March 2019]
  5. Faculty of Sexual and Reproductive Healthcare. Clinical Guidance Progesterone-only pills. Clinical Effectiveness Unit. March 2015 (updated April 2019).  https://www.fsrh.org [Accessed on 11th May 2019]
  6. Mansour, D.  Safer prescribing of therapeutic norethisterone for women at risk of venous thromboembolism.  J Fam Plann Reprod Health Care. 2012; 38:148-149