Web site: February 1999
Medsafe Editorial Team
Seven deaths and 1 case of pulmonary embolism and cardiac arrest leading to severe hypoxic brain damage with third generation oral contraceptives (OCs) have been reported in New Zealand. One of the deaths occurred in the absence of any known risk factors. Only one woman may have had a known contraindication - a previous pulmonary embolism which may have been undiagnosed. Several had temporary risk factors and/or early warning symptoms of deep vein thrombosis.
Prior to prescribing an OC, medical practitioners should assess women for risk factors for venous thromboembolism (VTE), and advise them of temporary risk factors. Discussion with women should also include the symptoms of deep vein thrombosis and action to be taken if symptoms occur. Because the risk of VTE with low dose second generation OCs is lower (by about a half) than that with third generation OCs, consideration should be given to prescribing a low dose second generation pill, particularly in the presence of risk factors for VTE.
A case-control study of deaths from pulmonary embolism in New Zealand women of child-bearing age has been initiated.
In recent weeks the media has given some attention to the issue of oral contraceptives (OCs) and venous thromboembolism (VTE) following the publication of a Prescriber Update article describing 6 deaths in women taking combined OCs containing desogestrel or gestodene.1 Since the article was written the Centre for Adverse Reactions Monitoring (CARM) has received a further report of death and a report of a case of pulmonary embolism and cardiac arrest leading to severe hypoxic brain damage. In both cases the woman was taking a third generation OC.
Some comment about the New Zealand deaths has implied that if contraindications are observed, there is no risk of VTE. However, for some of the women who died from pulmonary embolism, there was no known reason for not prescribing or for suspending OC use. Of the 7 women who died, only one women may have had a known contraindication for the use of a combined OC. At autopsy this woman was found to have evidence of an old pulmonary embolism. However, it was not clear whether this previous event had been identified. It may have been silent or undiagnosed. One woman had no known risk factors. The only known risk factor for two of the women was a recent injury (5 months previously in one), and another was immobilised due to injury. Two women were obese and one of these also had a family history of VTE.
It is important to emphasise that several of the women experienced symptoms of deep vein thrombosis prior to the development of the pulmonary embolism that caused their death. Women taking combined OCs need to be alert to the symptoms of VTE so that they seek medical attention immediately should these occur, particularly in the presence of risk factors.
To fulfil the requirements of the Code of Health and Disability Services Consumers’ Rights, medical practitioners should discuss with women requesting prescriptions of contraceptives the risks and benefits of the options. Prior to being given a prescription for a combined OC, women should be assessed for risk factors for VTE. They should be advised of the possible temporary risk factors and what precautions they should take if undergoing elective surgery, taking a long flight or being immobilised because of injury or illness (e.g. discontinue contraception or take aspirin 100-150mg daily). Discussion with women should also include the symptoms of deep vein thrombosis and action to be taken should they develop.
Medical practitioners are reminded that they should continue to observe the advice issued by the Ministry of Health in July 1996. Combined OCs are contraindicated in those with a personal history of VTE or hereditary thrombophilia. Prescribing a low dose combined OC containing ethinyloestradiol and a progestogen other than desogestrel or gestodene should be considered, where the woman has no contraindication and has indicated that she wishes to take a combined OC. In the presence of risk factors for VTE a woman should be advised against taking a preparation containing desogestrel or gestodene. A woman’s informed choice should be respected if she chooses to continue to take her current contraceptive.
The Medicines Adverse Reactions Committee (MARC) has carefully reviewed the literature on the issue of the relative risk of VTE with second and third generation OCs as it has been published. It is aware of contrary opinions being published, but it continues to hold the view that the balance of evidence points to there being approximately double the risk of VTE with third generation OCs (2 in 10,000 women every year) compared with second generation low dose OCs (1 in 10,000 women every year).
Since VTE with OCs was made an adverse reaction of current concern in February 1996, the MARC has been actively monitoring reports of these events. By June 1998 6 reports of death had been received and 4 of these deaths had occurred in the previous 18 months. At this time Professor David Skegg, a member of the MARC and Head of the Department of Preventive and Social Medicine, University of Otago, proposed a case-control study of deaths from pulmonary embolism in New Zealand women of child-bearing age during the period 1986 to 1997. Medsafe has undertaken to provide funding for the study which should be completed during 1999.
Medsafe has produced a new consumer leaflet, entitled Oral Contraceptives and Blood Clots, which has been widely distributed to GPs, GP practices, selected hospital doctors and specialists, pharmacies, Family Planning Centres, midwives, maternity hospitals and others.
For those who want to print copies of the leaflet, a 107KB PDF format is available for downloading by clicking this link.
Further copies of the leaflet can be ordered from Nadia Gate, Information Officer, Ministry of Health, e-mail firstname.lastname@example.org, phone (04) 496-2277, fax (04) 496-2010, P O Box 5013, Wellington.