Dear Healthcare Professional Letter on the risk of thromboembolism associated with use of combined hormone contraceptives (Adexa, Belara, Cilest, Estal, Evra, Lindynette, Logest, Novynette, NuvaRing, Qlaira, Yasmin, Yaz)

28.01.2014

Bayer d.o.o., Farmal d.d., MSD d.o.o., Sandoz d.o.o. and Johnson&Johnson SE d.o.o., in agreement with the Agency for Medicinal Products and Medical Devices (HALMED) and European Medicines Agency (EMA), have sent a letter to healthcare professionals on the results of safety assessment of combined hormone contraceptives (CHC) carried out in Europe and the newest evidence on the risk of thromboembolism associated with certain CHC.

Summary

This review confirms the previous positions according to which the VTE (venous thromboembolism) risk is low for all low doses CHC (ethynylestradiol < 50 mg
There are valid evidence on the existence of differences in the risk of VTE between CHCs, depending on the progestogen type they contain. Currently available data indicate that progestogen-containing CHCs levonorgestrel, norethisterone or norgestimate have the lowest VTE risk among those medicines.
When prescribing those medications, the account should be taken of risk factors in each patient separately, especially the VTE risk, as well as the difference in VTE risk between medicines.
The patient who uses CHC without any difficulties, do not need stop using it.
There is no evidence on the differences between low doses CHC (ethynylestradiol < 50 mg) regarding the risk of arterial thromboembolism (ATE)
The benefits associated with the use of CHC in majority of patients largely outweigh the risk of serious adverse reactions. Attention should be paid to emphasize the importance of risk factors in each patient separately and regular risk re-assessment as well as awareness raising on signs and symptoms of VTE and ATE that should be described to patients when prescribing CHCs.
Account should be always taken of a thromboembolism possibility associated with use of CHC in women with thromboembolism symptoms.
In order to facilitate the consultation between doctors and patients, additional documents with instructions for prescribers will be prepared, including a list that prescribers need to go through with the patient to ensure the appropriateness of the CHC. Also, a patient card indicating important signs of VTE and ATE that the patient should be aware of, will be prepared.

Additional information on safety issues and recommendations

The VTE risk (deep venous thromboembolism, lung embolism) has been reviewed in many studies in patients using different CHCs. Based on these data, it was concluded that the VTE risk differs among medicines - medicines with lower risk are those containing progestogen levonorgestrel, norethysterone and norgestimate. For certain medicines, currently there is not enough data for comparison with lower risk medicines.

When deciding about the most appropriate contraceptive type for every patient, prescribers must be aware of the new information and clinical guidelines. The highest VTE risk is during the first year of use of every CHC and after re-use of CHC following a 4 or more weeks break. The VTE risk is also higher if intrinsic risk factors are present. VTE risk factors change over time and therefore the individual risk must be periodically re-assessed. In order to facilitate an early diagnose, all women with VTE signs and symptoms should be asked whether they use any medicines or combined hormone contraceptives. It is known that the ATE risk (myocardial infarction, cerebrovascular incident) also increase in the CHC use. However there is not enough available data indicating whether this risk differs between different medicines.

The decision which medicine should be may be taken only after an interview with the patient including a VTE risk assessment associated with various medicines, estimation how current risk factors contribute to a VTE and ATE risk and an interview about the predisposition of the patient itself.

The Summary of Product Characteristics and Package Leaflet will be updated to reflect the current understanding of available evidence and to explain this information as much as possible.

Here you may view the Dear Healthcare Professional Letter (in Croatian).

Here you may view the information for patients about the CHCs (in Croatian).

We remind healthcare professionals that they should report any adverse reaction to HALMED, as well as quality defect. Patients who have developed any adverse reaction to medicinal product may report it directly to HALMED via form or on-line application, with recommendation regarding any adverse reaction they discover to consult with their doctor or pharmacist about the continuation of their therapy.