New Advice About Oral Contraceptives

21 March 2002

The Ministry of Health wants women taking the oral contraceptive pills Estelle 35/35ED and Diane 35/35ED, to visit their local doctor or nurse after studies showed women taking them have an increased risk of blood clots, Ministry spokesperson Dr Stewart Jessamine said today.

"Our advice to women taking these pills is to visit their health practitioner before they start their next pack of pills or pick up their next prescription. Women need to discuss the risks and benefits of the pill with their health practitioner before making any decision to stop or change their preferred method of contraception."

Dr Jessamine said this new information would clearly be distressing for the estimated 25,000 women currently taking Estelle or Diane and he encouraged women to talk about any concerns they have about the safety of their oral contraceptive with their health practitioner.

Dr Jessamine said the Medicines Adverse Reactions Committee asked Medsafe to issue the advice to women after reviewing a recently published United Kingdom study.

The study shows that the risk of blood clots (or venous thromboembolism) with contraceptive pills containing oestrogen and cyproterone acetate is at least as great as that with third generation oral contraceptives.

"Estelle and Diane are the only medicines containing oestrogen and cyproterone acetate currently available in New Zealand."

For every 100,000 women aged 15-44 years who are not taking an hormonal contraceptive; between five and ten will develop a blood clot in one year.

"The risk of blood clotting is three to four times higher for women taking a second generation pill, for example Monofeme, Levlen ED and Triquilar, and six to eight times higher for third generation pills such as Femodene, Marvelon, Melodene, Mercilon and Minulet."

"For women taking pills containing cyproterone acetate the risk is possibly eight times higher. That means the risk for Estelle and Diane is at least as high as that of third generation pills."

Dr Jessamine said Medsafe has provided GP and family planning clinics with updated patient information leaflets.

In addition, it has issued prescribing advice to doctors, midwives and pharmacists recommending that they confine the use of Estelle and Diane to women with conditions such as polycystic ovary syndrome, hirsutism (abnormal hair growth) and other androgen-dependant diseases such as pronounced acne.

ENDS

Background

How many women are estimated to be taking Estelle 35, Estelle 35ED, Diane 35 or Diane 35ED? Approximately 25,000 women are taking these medications, with the majority taking Estelle as it is subsidised.

Are there any figures on how many women in New Zealand have been on Estelle or Diane and suffered blood clots? Up until November 2001 The Centre of Adverse Reactions Monitoring had received 18 reports of blood clotting occurring in women taking oral contraceptives containing cyproterone acetate. Fifteen of those 18 women had developed a pulmonary embolism, however none were fatal.

Of these, 18 women 10 had been prescribed the medication for contraceptive purposes, five for the reduction of acne problems, and two for irregular menstruation. In one case the reason for prescribing is not recorded.

When are Estelle and Diane usually prescribed? Diane and Estelle are approved for the treatment of androgen-dependant diseases (such as pronounced acne and abnormal hair growth), polycystic ovary syndrome and for oral contraception in women with these conditions.

What will be the prescribing advice from now on? Prescribers have been advised to prescribe Estelle and Diane only to women with disorders such as polycystic ovary syndrome, abnormal hair grown, pronounced acne and as a contraception for women with these conditions. The Medicines Adverse Reactions Committee has recommended that women with mild acne should not commence on a cyproterone-containing oral contraceptive as first line contraception.

Prescribers have also been advised to review the appropriateness of Estelle and Diane for patients already taking them.

Prescribers should fully advise patients of the risks of blood clotting and take into account the personal and family history of the woman before prescribing Estelle or Diane, or any other contraceptive.

New Zealand is the first, and so far only, country to advise women about the risk of blood clots posed by pills containing cyproterone acetate.

What does the prescriber have to take into account? Before prescribing a contraceptive, or reviewing the current choice of contraceptive, a doctor should discuss the options and explain the risks and benefits of contraception with a patient. The doctor and patient can then make an informed choice on the best contraceptive option.

This latest information gives doctors and patients further information necessary to make informed decisions.

What is Medsafe doing to publicise the updated advice? Medsafe has provided the following material: a letter to doctors, midwives and pharmacists outlining the findings and updating the prescribing advice articles in health professional reading material updated its patient information leaflet on oral contraceptives and blood clots updated the Ministry of Health prescribing advice for oral contraceptives

All four items have been sent to family planning clinics, Family Planning Association offices, Women's Health Action, the Plunket Association, private maternity hospitals, gynaecology departments of public hospitals, general practitioners and specialists, registrars, midwives and hospital and retail pharmacies.

Copies of this material are available form the Medsafe website (www.medsafe.govt.nz/hot.htm)

Why weren't these brands of pills incorporated into the advice given to women about third generation pills in 1996? Previous advice issued in 1996 and 1999 on the safety of the oral contraceptive pill has successfully led to major changes in medical practice and prescribing behaviour in this country.

The advice issued back then to patients and doctors, that third generation pills carry a small increased risk of blood clots over other oral contraceptive pills, did carry information about pills containing cyproterone acetate. This advice asked doctors to inform women about the risks of oral contraceptives and consider prescribing second-generation pills for women seeking oral contraception. That advice did not specifically comment on the risk of clots with Diane and Estelle, as the data on risk published at that time was insufficient.

Information further defining the risk for pills such as Diane and Estelle began to accumulate in 1999 with the major study which conclusively demonstrated increased risk only being published in late 2001. The study was reviewed by the Medicines Adverse Reactions Committee in December 2001. The articles and leaflets were then written, consulted on, peer reviewed and released this week.

It is important to note use of third generation pills in New Zealand significantly decreased since the advice was first issued. It is now common practice in this country for doctors to advise women about the benefits and risks of taking oral contraceptive pills and to assess each woman carefully for risk factors.

What is a blood clot? The blood clots associated with using oral contraceptives occur in the veins of the legs. They cause a blockage in the vein. On rare occasions pieces of the clot dislodge and travel to the lungs. Clots in the legs or lungs are called venous thromboembolism or VTE. While most women recover completely from VTE, some have ongoing health problems. A small number of women have died.

These blood clots in the veins are not the same as the clots that you can see in menstrual blood when you have your period.

How often do blood clots occur with oral contraceptives? Blood clots only happen very occasionally in women using oral contraceptives, and deaths from blood clots are even more rare. The risk of having a blood clot depends on a number of factors. It increases with age and it also depends on what kind of oral contraceptive is being taken.

Most oral contraceptives contain both oestrogen and a progestogen. These are called combined oral contraceptives. Depending on the type of progestogen in the pill, they are known as either second or third generation contraceptive pills. There are also pills containing cyproterone, which are used to treat conditions caused by an excess of the hormone androgen like pronounced acne. These cyproterone-containing pills provide contraception as well. Another type of oral contraceptive is the progestogen-only pill, also known as the mini-pill.

Women can have blood clots when they are not using oral contraceptives. For every 100,000 women aged 15-44 who are not taking the pill, approximately 5-10 will develop a blood clot in one year.

Taking a combined oral contraceptive increases this very small risk of developing a clot by 3-4 times if you are on a second generation pill, 6-8 times if you are taking a third generation pill, and possibly over 8 times for those on pills containing cyproterone. Women using progestogen-only pills are at little or no increased risk of blood clots.

Which pills are which? Progestogen-only pills: Femulen, Microlut, Microval, Noriday, Cerazette Second generation pills: Brevinor, Brevinor-1, Levlen ED, Loette, Microgynon 20ED/30/30ED, Monofeme, Nordette, Norimin, Synphasic, Trifeme, Triphasil, Triquilar ED Third generation pills: Femodene, Marvelon, Mercilon, Minulet, Melodene Anti-androgen pills: Diane35/35ED, Estelle 35/35ED Pills containing 50mcg oestrogen and progestogen: Biphasil, Microgynon 50ED, Nordiol, Norinyl-1, Ovral.

How often are blood clots fatal? Of those women who get a blood clot, about 3% will die. As combined oral contraceptives are used by many women in New Zealand, two deaths a year from blood clots would be expected in this country.

During 1990 ? 2001, 20 women in New Zealand using combined oral contraceptives are known to have died of a blood clot in the lungs. Of those who died, 15 were using third generation pills and 2 were using pills containing cyproterone. There is a risk of death with second generation pills but it is lower

What increases the risk of blood clots? Some of the risk factors for blood clots are: · a previous blood clot · a close family member who has had a blood clot · being overweight · cancer · some blood disorders · being immobilised · bad varicose veins.

Your risk of having a blood clot can also be temporarily increased, for example by a long flight, childbirth, being immobilised by injury or illness, or by having surgery. Women who have had a previous blood clot should not take a combined oral contraceptive. You should tell your doctor if any of these risk factors apply to you.

What are the symptoms and what should I do about them? The symptoms of a blood clot in the leg are swelling, tenderness and pain, but a blood clot may occur without symptoms. Breathlessness and sharp chest pain can occur with a blood clot in the lungs. These symptoms can also occur for other reasons.

If you develop any of these symptoms, you should see a doctor immediately. You should be particularly alert to these symptoms if you have a risk factor for blood clots.

If you get a blood clot, your doctor may refer you to hospital for tests and treatment with blood-thinning medication. Treatment may last for several months and some women may have ongoing problems such as pain or swelling.

Who can I discuss this information with? You should discuss your risk of blood clots with your doctor. If together you decide your risk on a combined oral contraceptive is too high, there are a number of different types of contraceptives available, including the progestogen-only pill and non-hormonal barrier methods such as condoms. You should discuss with your doctor which type is likely to suit you best. You have a right to expect your doctor to explain this information in a way that you can understand.

Remember that blood clots are rare events in healthy women taking the contraceptive pill. Serious consequences are even less likely to occur. Your risk will be reduced even further if you see a doctor immediately if you get any symptom of a possible blood clot.

Where else can I get information? Consumer information including symptoms of a clot can be found on the Medsafe website at http://www.medsafe.govt.nz/Consumers/medicine/oralcontraceptives.htm Information for doctors can be found at http://www.medsafe.govt.nz/Profs/PUarticles/OCletter.html

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