Aspects of EAC considerations – Rx-to-OTC switch of Levonorgestrel as Emergency Contraception

Aspects / Considerations
Primary Mode of Action / -Levonorgestrel’s (LNG) primary mode of action is blocking ovulation and / or delaying ovulation by suppressing LH peaks.
Approval status, efficacy, and dosing / -LNG is approved only to be taken within 72 hours of unprotected intercourse due to subsequent lack of efficacy beyond this time point.
-A study that has been designated "controversial" suggests that LNG may be less effective in women with greater body weight, which will be further investigated atthe European level. In light of the overall high level of safety of LNG, the so far insufficient evidencefora reduction in efficacy was not considered relevant to the question of an Rx-to-OTC switch (BfArM).
-A single dose now replaces the standard two step regimen (0.75 mg taken twice within 12 h) with comparable tolerability, efficacy and good compliance.
Contraindications / -The World Health Organization recommends LNG for emergency contraception and emphasises the absence of contraindications.
Toxicity / -A variety of prescription drugs currently available are considerably more toxic than levonorgestrel, for example, diclofenac triples the risk of mortality (EAC expert).
Adverse drug reactions / -LNG is only associated with mild adverse drug reactions of temporary nature.
-There have been no reports of levonorgestrel leading to serious adverse reactions.
-Single use of a low doseof LNG is not comparable with the long-term use of hormone preparations, which is associated with the well-known risk of thromboembolism (BfArM).
-According to what is currently known, the risk of an ectopic pregnancy is not increased at the onset of pregnancy due to the use of LNG.
-LNG does not terminate an existing pregnancy. There is no evidence that ingestion will harm the foetus in the case of an existing pregnancy.
Use (Rx) in Germany / -Age distribution of users nationally:
  • According to the German Drug Prescription Report, of approximately 400,000 prescriptions issued annually, only about 50,000 are issued to users under the age of 20(BfArM);
  • According to the figures provided by one Bundesland: The age group under 15 years accounted for about 2%, while the age group of 15-16 years for 20%, that of 17-18 years for 37%, and the age group of 19 -20 years for 27% of all prescriptions (EAC expert).
-Frequent use as a result of OTC availability is not expected due to menstrual cycle disorders and associated bleeding disorders resulting from frequent ingestion (BfArM).
-Comparison with approved products for the same indication:
  • An EAC expert expressed concerns that if LNG became available OTC but ulipristal remained Rx, patients would rather use LNG for emergency contraception because it is easier to obtain, while he finds that LNG has poor efficacy and is thereforeonly the second best option;
  • AcentralisedRx-to-OTC switch application for ulipristalemergency contraception is currently pending (BfArM);
  • For LNG, there are many years of experience available with large numbers of userswhich is not the case for ulipristal.

International OTC experience / -LNG is available OTC in about 80 countries (incl. the US and most European neighbouring countries).
-Its main usageis in the age group of 20-24 year olds (EAC expert)
-French and British publications do neither show an increase in unprotected intercourse, nor adecrease in the overall use of contraceptives/highly effective contraceptivesafter the Rx-to-OTC switch.
-In countries where emergency contraceptives are available OTC, the rate of abortions haveeither not declined or have hardly declined at all (BfArM).
Adequacy of product information / -The potential low risk of thromboembolism isreasonably reflected in the product information.
-The risk of an ectopic pregnancy issufficiently considered in the product information.
Benefits of OTC availability / -Time savings due toOTC availability. However, in the opinion of two experts,the argument of gaining time through faster (i.e. OTC) availability was not so significant. It would be possible for every woman, without an emergency having already occurred, to consult a doctor who could then write a prescription for an emergency contraception.
Advertisement and educational materials / -It was suggested to insert/distribute educational materials with the dispensation of LNG.
  • A BfArMrepresentative replied that this is theoretically possible, and implementation in this specific case is to be reviewed.
  • An advertising banwas discussed, but an EAC expert and a representative of the Ministry of Health explained thatpharmaceutical advertising is regulated at EU level and that national amendments to pharmaceutical advertising law is therefore not possible.

Internet sales / -It was feltunlikely that a woman concerned would order emergency contraception drugs on the Internet and would rely on order processing and postal delivery to her on the next working day instead of going to the nearest pharmacy (BfArM).

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