(Aust Prescr 1999;22:53-4)
The Editorial Executive Committee welcomes letters, which should be less than 250 words. Before a decision to publish is made, letters which refer to a published article may be sent to the author for a response. Any letter may be sent to an expert for comment. Letters are usually published together with their responses or comments in the same issue. The Editorial Executive Committee screens out discourteous, inaccurate or libellous statements and sub-edits letters before publication. The Committee's decision on publication is final.
Editor, – Dr Phillipa Hay's excellent article on eating disorders (AustPrescr 1998;21:100-3) states that anorexia nervosa `occurs worldwide'.Is there any evidence that these disorders also occur in under-privileged populationssuch as those in Africa, for example, or in those cultures where the body weightof women and dieting are not a big issue.Mannasseh Phiri
General Practitioner
Kitwe, Zambia
Dr P. Hay, the author of the article, comments:
Dr Phiri has raised an important issue. Eating disorders do occur worldwide,but they are much more prevalent in Western cultures. Elegant studies in theU.K. and Pakistan1, as well as other empiricalresearch, attest to this.
Reference
1. Mumford DM, Whitehouse AM, Choudry IY. Survey of eatingdisorders in English-Medium schools in Lahore, Pakistan. Int J Eat Disord 1992;11:173-84.
Angiotensin receptor antagonists
Editor, – It was with a good deal of scepticism that I read the recentarticle by Professor C.I. Johnston, `Angiotensin receptor antagonists for thetreatment of hypertension' (AustPrescr 1998;21:95-7). His statement that `unlike ACE inhibitors,angiotensin receptor antagonists have not been associated with cough or angioedema'appears to be based solely on clinical trials and ignores the recent literature.As I am sure your readers would be aware, trials conducted prior to marketingare small, with highly selected groups of patients, and with highly structuredprotocols. They are limited in their power to detect rare adverse drug reactions,such as angioedema, and to identify `at risk' individuals or sub-groups notrepresented in the trials. It is only when the general population is exposedto drugs that many effects become apparent. The effective monitoring of drugsafety is also reliant on spontaneous reports of adverse drug reactions submittedto the literature and national pharmacovigilance bodies such as the AdverseDrug Reactions Advisory Committee (ADRAC). The true incidence of adverse effectsis probably higher than ADRAC reports suggest.In the literature, there are at least 4 case reports of angioedema in associationwith angiotensin receptor antagonists1,2,3,4,as well as a report from the Netherlands Pharmacovigilance Foundation whichdescribes 13 cases of angioedema involving losartan.5 Inthe most recent issue of the Australian Adverse Drug Reactions Bulletin, ADRACreported on adverse reactions in association with the two angiotensin II receptorantagonists marketed in Australia, losartan and irbesartan.6 Therehave been 37 reports of cough associated with these two drugs and 24 reportsof angioedema. Three reports of cough were particularly convincing as the adversereaction recurred on rechallenge. Studies in the U.K. using prescription-eventmonitoring have demonstrated that, although rates of cough are significantlyless with losartan than ACE inhibitors, coughing is associated with losartanuse at a rate of 3.1 per 1000 patient months.7
Ian W. Boyd
Executive Secretary
Adverse Drug Reactions Advisory Committee
Canberra, A.C.T.
References
1. Acker CG, Greenberg A. Angioedema induced by the angiotensinII blocker losartan [letter]. N Engl J Med 1995;333:1572.
2. Boxer M. Accupril- and Cozaar-induced angioedema in thesame patient [letter]. J Allergy Clin Immunol 1996;98:471.
3. Sharma PK, Yium JJ. Angioedema associated with angiotensinII receptor antagonist losartan. South Med J 1997;90:552-3.
4. Frye CB, Pettigrew TJ. Angioedema and photosensitive rashinduced by valsartan. Pharmacotherapy 1998;18:866-8.
5. Van Rijnsoever EW, Kwee-Zuiderwijk WJ, Feenstra J. Angioneuroticedema attributed to the use of losartan. Arch Intern Med 1998;158:2063-5.
6. ADRAC. Angiotensin II receptor antagonists - new drugs... with some old problems ... and some new problems. Aust Adv Drug React Bull1999;18:2.
7. Mackay FJ, Pearce GL, Mann RD. Cough and angiotensin IIreceptor antagonists: cause or confounding? Br J Clin Pharmacol 1999;47:111-4.
Professor C.I. Johnston, the author of the article, comments:
Dr Ian Boyd is right to point out that reports of angioedema and coughassociated with angiotensin receptor antagonists have now appeared in the literatureand by two pharmacovigilance bodies. Perhaps I would have been wiser if I hadused the phrase `have not yet been' when I first wrote the article. I concurtotally with him that clinical trials conducted prior to marketing are a verypoor way of determining the scope and incidence of adverse effects of new drugs.I have long advocated that drug authorities should require less premarketinginformation and demand more postmarketing surveillance.
Angioedema can be a life-threatening adverse effect and, although it occurswith a very low frequency in the general population, it is prudent that patientswho have a history of angioedema or have had angioedema or rash with ACE inhibitorsnot be given AT1 receptor antagonists.
Cough is a more contentious issue. Cough is a common symptom in the communityand, indeed, in the placebo-controlled trials of AT1 receptor antagonists,the incidence of cough in the placebo arm was up to 5% in some of the studies.Dr Boyd has selectively quoted the literature as there have now been reported4 trials of AT1 receptor antagonists including losartan1,candesartan2, eprosartan3 andtelmisartan4 in which the AT1 receptorantagonists were given to patients with a known history of ACE inhibitor cough.In all of these studies, the incidence of cough was considerably less thanin those patients rechallenged with the ACE inhibitor and the same frequencyas in the placebo arm. Furthermore, a recent review5 ofthe published results of all the placebo-controlled and comparative trialsof AT1 blockers demonstrated that the incidence of cough was similarto that of placebo. These challenge studies contribute stronger direct evidence,than reports to pharmacovigilance bodies, that cough is not a characteristicof AT1 receptor antagonists.
Furthermore, the recent Australian Adverse Drug Reactions Bulletin6 recordedonly 37 reports of cough out of a total population of >150 000 patientswho have been prescribed angiotensin receptor antagonists. The Adverse DrugReactions Advisory Committee has a responsibility to put the report into someperspective, which leads to the suggestion that, with a common symptom, theCommittee should at least give some idea of the denominator, i.e. the numberof patients who have been treated with a particular drug.
References
1. Lacourciere Y, Brunner H, Irwin R, Karlberg BE, RamsayLE, Snavely DB, et al. Effects of modulators of the renin-angiotensin-aldosteronesystem on cough. Losartan Cough Study Group. J Hypertens 1994;12:1387-93.
2. Campbell LM, Kirkintilloch GB, Carranza J, Karrasch J,Tanser P, Toutouzas P, Watts R. Candesartan cilexetil is not associated withcough in patients with enalapril-induced cough [poster]. J Hypertens 1998;16Suppl 2:120.
3. Oparil S. Comparison of eprosartan and enalapril on incidenceof cough in patients with essential hypertension [poster]. J Hypertens 1998;16Suppl 2:237.
4. Ramsay LE, Kirwan BA. A comparison of cough in hypertensivepatients receiving telmisartan, enalapril or hydrochlorothiazide [poster].J Hypertens 1998;16 Suppl 2:241.
5. Pylypchuk GB. ACE inhibitor- versus angiotensin II blocker-inducedcough and angioedema. Ann Pharmacotherapy 1998;32:1060-6.
6. ADRAC. Angiotensin II receptor antagonists - new drugs... with some old problems ... and some new problems. Aust Adv Drug React Bull1999;18:2.
Editor, – Following concerns expressed in Australian Prescriber1 regardingthe information available about the passage of budesonide into breast milk,your readers may be interested to learn of some tangentially related data thathave recently become available. Good asthma control in pregnancy is vital forboth mother and child as the known risks of uncontrolled asthma are far greaterthan the known risks to both from asthma medications.2 Itis known from previous studies that mother and baby may both do badly if themother's asthma is poorly controlled.3,4A new study5 from the University of Lund, Sweden,reviews 2014 infants whose mothers stated they had used inhaled budesonideduring early pregnancy. The infants were identified through the Swedish birthregistry, which covers nearly all of the 100 000 births a year that take placein Sweden and contains computerised records of the paediatric examination ofthe new born. Since 1 July 1994, it has stored information on self-reporteddrug use by women in early pregnancy. The information is obtained by askingthe woman at her first antenatal visit (usually about week 10 after the lastmenstrual period) if she has used any drugs during pregnancy and, if so, thename of the drug. If possible, the dose and week of use are also recorded.The study does not provide any dosage information.
Although a few children in the study (3.7%, 95% confidence interval 2.9-4.6)were born with minor congenital abnormalities, analysis of the results indicatesthat their mother's use of inhaled budesonide was not related to this outcome.A very similar rate of abnormalities (3.5%) occurred in all children born inSweden in 1995-1997. There was no increase in the expected number of infantswith congenital cardiac defects (17 vs. 17-18 expected), and the majority ofthe defects were mild.
The investigators concluded that `Even though a specific teratogenic effectof use of budesonide in early pregnancy cannot be ruled out, it is unlikelythat a clinically significant teratogenic effect exists'.
Susan Parker
Manager, Customer Service and Information
Astra Pharmaceuticals Pty Ltd
North Ryde, N.S.W.
References
1. Drug distribution in human milk [letter]. AustPrescr 1998;21:31-2.
2. National Institutes of Health. National Heart, Lungand Blood Institute. Report of the Working Group on Asthma and Pregnancy.
http://rover.nhlbi.nih.gov/nhlbi/lung/asthma/prof/astpreg.txt
3. Bahna SL, Bjerkedal T. The course and outcome of pregnancyin women with bronchial asthma. Acta Allergol 1972;27:397-406.
4. Schatz M. Asthma during pregnancy: interrelationshipsand management. Ann Allergy 1992;68:123-33.
5. Kallen B, Rydhstroem H, Aberg A. Congenital malformationsafter the use of inhaled budesonide in early pregnancy. Obstet Gynecol 1999;93:392-5.
Editor, – In his letter regarding antidepressant wash-out periods (`Letters' AustPrescr 1999;22:3-4), Dr D. Grounds correctly notes that the approved productinformation for sertraline (Zoloft) explicitly includes reversible MAOIs inthe contraindication against use concurrently or within two weeks, and thatthe product information for the other SSRIs available in Australia are notso explicit.The subsequent comment from Professor Tiller errs in fact in referring tothe product information for Zoloft. The present wording of the contraindication(i.e. explicitly including moclobemide as well as the type-B selective MAOI,selegiline) was adopted in the latter part of 1995 and has remained unchangedsince then.
Although we acknowledge that, in many cases, failure to observe this rulehas been free of adverse consequences, individual cases have been reportedwhich support Professor Tiller's subsequent comment about `prior good luck',and we stand by the terms of the contraindication.
M.M. Lawrie
Director, Medical Affairs
Pfizer Australia
West Ryde, N.S.W.
