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Pulmonary embolism associated with combined oral contraceptives: reporting incidences and potential risk factors for a fatal outcome
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
2004 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, Vol. 83, no 6, 576-585 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: It is established that combined oral contraceptive (COC) treatment increases the risk of a pulmonary embolism (PE), but specific risk factors for a fatal outcome from a PE remain to be determined. This study aimed to identify such risk factors, and to calculate the reporting rates of fatal and non-fatal PE. METHODS: Cases of suspected PE during treatment with COCs reported to the Swedish Adverse Drug Reactions Advisory Committee (SADRAC) between 1965 and 2001 were included. Medical records were scrutinized for potential risk factors for a venous thromboembolism (VTE). Annual sales data were obtained from the National Corporation of Pharmacies. RESULTS: A total of 248 cases of a suspected PE were reported; 207 non-fatal and 41 fatal. A VTE was verified in all fatal, and in 83.5% of non-fatal cases. The presence of nausea or abdominal pain, an age >35 years, concomitant treatment with other drugs which may increase the VTE risk, vein or lymph vessel malformation, and a deep vein thrombosis above the knee level were positively associated with a fatal outcome. Chest pain and previous COC use were negatively associated with a fatal outcome. The reporting rate of a PE with a verified VTE was 1.72 (95% confidence interval 1.47-2.00) cases per 100 000 treatment years, and of a fatal PE 0.25 (95% confidence interval 0.16-0.37) cases per 100 000 treatment years. CONCLUSION: Several specific potential risk factors for a fatal outcome from a COC-induced PE were identified. Recognition of these in combination with a high suspicion of VTE in COC users may reduce the risk of a fatal outcome.

Place, publisher, year, edition, pages
2004. Vol. 83, no 6, 576-585 p.
Keyword [en]
combined oral contraceptives, pulmonary embolism, risk factors
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-93244DOI: 10.1111/j.0001-6349.2004.0533.xPubMedID: 15144341OAI: oai:DiVA.org:uu-93244DiVA: diva2:166669
Available from: 2005-06-02 Created: 2005-06-02 Last updated: 2010-03-04Bibliographically approved
In thesis
1. Hazards of Drug Therapy: On the Management of Adverse Drug Reactions: From Signal Detection and Evaluation to Risk Minimization
Open this publication in new window or tab >>Hazards of Drug Therapy: On the Management of Adverse Drug Reactions: From Signal Detection and Evaluation to Risk Minimization
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Spontaneous reporting systems (SRSs) for adverse drug reactions (ADRs) have been developed as a result of the thalidomide disaster, whereby thousands of children world-wide were born with birth defects. The Swedish Adverse Drug Reactions Advisory Committee was established in 1965. Since 1975, reporting has been compulsory for all suspected serious or new ADRs. International collaboration started in 1968 with countries contributing their ADR reports to an international database set up by the World Health Organization.

ADRs represent the negative side of the benefit-to-risk balance that in theory needs to be counteracted by perceived or established positive drug effects. All drugs are subject to preclinical and clinical testing prior to marketing authorization. However, these studies are insufficient to detect rare ADRs, ADRs that occur after long-term administration or with latency, ADRs that occur in special patient groups such as children, the elderly, patients with renal or hepatic insufficiency or patients on concomitant drug treatment, and ADRs that represent a modest increase in the risk of diseases (including mortality) that are prevalent in the study population. Postmarketing surveillance of drugs is therefore essential, and regulatory action may be needed on the basis of new ADR information.

SRSs are important sources of ADR information as exemplified here by the evaluation of peripheral sensory disturbances with fluoroquinolones, hyponatremia with antidepressants, blood dyscrasias with dipyrone, glucose intolerance with atypical antipsychotics, pulmonary embolism with combined oral contraceptives and extrapyramidal symptoms with selective serotonin reuptake inhibitors. SRSs can be used to study clinical manifestations of ADRs (that can give insights into potential ADR mechanisms), risk factors for the ADR or for specific outcomes of the ADR, and ADR reporting incidences when combined with sales data. Signals from SRSs may need to be studied further e.g., by use of large-scale epidemiologic studies based on record linkage between drug prescription databases and health databases. Owing to the rapid availability of information, however, SRSs are likely to remain of major importance for the post-marketing surveillance of drugs.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 86 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 54
Pharmacology, adverse drug reactions, spontaneous reporting systems, drug regulation, pharmacovigilance, incidence, Farmakologi
National Category
Pharmacology and Toxicology
urn:nbn:se:uu:diva-5866 (URN)91-554-6291-X (ISBN)
Public defence
2005-09-16, Enghoffsalen, Ingång 50, Akademiska sjukhuset, Uppsala, 09:15
Available from: 2005-06-02 Created: 2005-06-02Bibliographically approved

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