Ellison, J.

Greer, I.A.

Thomson, A.J.

Walker, I.D.

English

PubMed

Enlighten: Publications

Drug Points: Apparent interaction between warfarin and levonorgestrel used for emergency contraception

Enlighten

measure, but this has not been supported.4 Despite this,half of patients with advanced cancer who lose 10 ormore points per week die within two weeks (95% confi›dence interval 8.6 days to 19.4 days), and three quartersare dead at three weeks. In contrast, 50% of patients inwhom the weekly score does not deteriorate survive fortwo months (35.2 days to 76.8 days).Although Barthel score at admission correlatedwith overall survival, no differences in scores onadmission were found among the three groups ineither sample (sample 1, P = 0.08, and sample 2,P = 0.74, Kruskal›Wallis; see table on website). Admis›sion score therefore cannot be used to determine pat›tern of subsequent change and hence to estimatesurvival more accurately.We thank Professor Anne Chamberlain, Dr Bippin Bhakta, andDr Jan Geddes for their comments.Contributors: MB had the original idea, designed the study,analysed the results, and drafted the paper. NR helped to collectand interpret the data and revise the paper. MB is guarantor forthe study.Funding: None.Competing interests: None declared.1 Evans C, McCarthy M. Prognostic uncertainty in terminal care: can theKarnofsky index help? Lancet 1985;i:1204›6.2 Yates JW, Chalmer B, McKegner FP. Evaluation of patients with advancedcancer using the Karnofsky performance status. Cancer 1980;45:2220›4.3 Shah S, Vanclay F, Cooper B. Improving the sensitivity of the Barthelindex for stroke rehabilitation. J Clinical Epidemiol 1989;42:703›9.4 Tennant A, Geddes JM, Chamberlain MA. The Barthel index: an ordinalscore or interval level measure? Clin Rehab 1996;10:301›8.(Accepted 7 February 2000)Drug pointsApparent interaction between warfarin andlevonorgestrel used for emergency contraceptionJ Ellison, A J Thomson, I A Greer, Department of Obstetrics andGynaecology and I D Walker, Department of Haematology, GlasgowRoyal Infirmary, Glasgow G31 2EREmergency contraception with progestogen only (twodoses of levonorgestrel 0.75 mg given 12 hours apart andwithin 72 hours of unprotected intercourse) is bettertolerated and more effective than the combinedoestrogen›progestogen (Yuzpe) regimen.1 Furthermore,treatment with progestogen only may be preferable to theYuzpe regimen in women with a known thrombophilicdefect or history of thromboembolic events. For womenreceiving warfarin, drug information cites either no inter›action between progestogens and warfarin2 or a reductionin anticoagulant effect.3 We describe an enhancedanticoagulant effect of warfarin after giving a womanlevonorgestrel for emergency contraception.A 35 year old woman with familial type 1 (quantitative)antithrombin deficiency and a history of extensive deepvenous thrombosis and pulmonary thromboembolism,attended the clinic after an episode of unprotectedintercourse. She was receiving warfarin 7 mg daily foranticoagulation but no other drugs. Her internationalnormalised ratio was 2.1, which was within the therapeuticrange (2.0›3.0). She requested emergency contraception.After counselling, she declined the insertion of an intra›uterine contraceptive device, preferring the progestogenonly regimen. Her international normalised ratio wasrechecked three days later and was reported as 8.1. Shewas advised to discontinue warfarin treatment for twodays, at which point her international normalised ratio was2.5, and then to restart it at a dose of 5 mg once daily. Nohaemorrhagic problem occurred.One possible explanation for this enhanced anti›coagulant effect is the displacement of warfarin bylevonorgestrel from the F1S binding site of human á1›acidglycoprotein, the main transport protein for drugs inplasma.4 The variant of the F1S binding site comprisespart of the F1S/A phenotype of á1›acid glycoprotein,which is encountered in 50% of the population.Thus women receiving warfarin treatment may be atrisk of an interaction between warfarin and levonorgestrel ifthey are prescribed the progestogen only regimen becauseof its apparent safety. The manufacturer of levonorgestrel(Wyeth) has not received any reports describing such aninteraction with warfarin. This potential interaction requiresprompt investigation, particularly in light of recommenda›tions that emergency contraception be made available overthe counter.5 If patients are fully anticoagulated with war›farin, the conventional Yuzpe regimen may be effectivewithout being associated with any increased risk of venousthromboembolism.Competing interests: None declared.1 Task Force on Postovulatory Methods of Fertility Regulation.Randomised controlled trial of levonorgestrel versus the Yuzpe regimenof combined oral contraceptives for emergency contraception. Lancet1998;352:428›33.2 Crowther NR, Holbrook AM, Kenwright R, Kenwright M. Druginteractions among commonly used medications. Can Fam Physician1997;43:1972›81.3 Appendix 1: interactions. British national formulary, No 39. Bath: BritishMedical Association and Royal Pharmaceutical Society of Great Britain,2000:614.4 Herve F, Duche J›C, d’Athis P, Marche C, Barre J, Tillement J›P. Binding ofdisopyramide, methadone, dipyridamole, chlorpromazine, lignocaineand progesterone to the two main genetic variants of human á1›acidglycoprotein: evidence for drug›binding differences between the variantsand for the presence of two separate drug›binding sites on á1›acid glyco›protein. Pharmacogenetics 1996;6:403›15.5 Royal College of Obstetricians and Gynaecologists and the Faculty ofFamily Planning and Reproductive Health Care. Joint statement onemergency hormonal contraception. London: RCOG, 1995.Barthel score, change in Barthel score, and survival time of patients in hospice with cancerSample 1(n=93)Sample 2(n=104)P value(Mann›WhitneyU test)Mean (range) Barthel score atadmission66 (3›100) 58 (2›100) 0.056Median (range) length of stay (days) 18 (5›104) 19 (3›86) 0.82Median (range) survival (days) 35 (5›473) 27 (3›349) 0.2Median (interquartile range) change in Barthel index:No loss of points 56 (23›137) (n=50) 68 (19›128) (n=41) 0.911›9 points lost 32 (17›56) (n=24) 31 (15›45) (n=39) 0.51>10 points lost 14 (11›20) (n=19) 15 (6›20) (n=24) 0.65P value (Kruskal›Wallis test) <0.001 <0.001 –Papers1382 BMJ VOLUME 321 2 DECEMBER 2000 bmj.com

J Ellison

A J Thomson

I A Greer

I D Walker

Crossref

Drug points: Apparent interaction between warfarin and levonorgestrel used for emergency contraception

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=27541

Drug Points: Apparent interaction between warfarin and levonorgestrel used for emergency contraception

Abstract

Similar works

Full text

Available Versions

Enlighten: Publications

Enlighten

Crossref