(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 (Aust Prescr 1998;21:100-3) states that anorexia nervosa 'occurs world wide'. Is there any evidence that these disorders also occur in under-privileged populations such as those in Africa, for example, or in those cultures where the body weight of 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 world wide, but they are much more prevalent in Western cultures. Elegant studies in the U.K. and Pakistan1, as well as other empirical research, attest to this.
Reference
1. Mumford DM, Whitehouse AM, Choudry IY. Survey of eating disorders 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 recent article by Professor C.I. Johnston, 'Angiotensin receptor antagonists for the treatment of hypertension' (Aust Prescr 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 marketing are small, with highly selected groups of patients, and with highly structured protocols. They are limited in their power to detect rare adverse drug reactions, such as angioedema, and to identify 'at risk' individuals or sub-groups not represented in the trials. It is only when the general population is exposed to drugs that many effects become apparent. The effective monitoring of drug safety is also reliant on spontaneous reports of adverse drug reactions submitted to the literature and national pharmacovigilance bodies such as the Adverse Drug Reactions Advisory Committee (ADRAC). The true incidence of adverse effects is probably higher than ADRAC reports suggest.
In the literature, there are at least 4 case reports of angioedema in association with angiotensin receptor antagonists1,2,3,4,as well as a report from the Netherlands Pharmacovigilance Foundation which describes 13 cases of angioedema involving losartan.5 In the most recent issue of the Australian Adverse Drug Reactions Bulletin, ADRAC reported on adverse reactions in association with the two angiotensin II receptor antagonists marketed in Australia, losartan and irbesartan.6 There have been 37 reports of cough associated with these two drugs and 24 reports of angioedema. Three reports of cough were particularly convincing as the adverse reaction recurred on rechallenge. Studies in the U.K. using prescription-event monitoring have demonstrated that, although rates of cough are significantly less with losartan than ACE inhibitors, coughing is associated with losartan use 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 angiotensin II blocker losartan [letter]. N Engl J Med 1995;333:1572.
2. Boxer M. Accupril- and Cozaar-induced angioedema in the same patient [letter]. J Allergy Clin Immunol 1996;98:471.
3. Sharma PK, Yium JJ. Angioedema associated with angiotensin II receptor antagonist losartan. South Med J 1997;90:552-3.
4. Frye CB, Pettigrew TJ. Angioedema and photosensitive rash induced 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 II receptor 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 cough associated with angiotensin receptor antagonists have now appeared in the literature and by two pharmacovigilance bodies. Perhaps I would have been wiser if I had used the phrase 'have not yet been' when I first wrote the article. I concur totally with him that clinical trials conducted prior to marketing are a very poor way of determining the scope and incidence of adverse effects of new drugs. I have long advocated that drug authorities should require less premarketing information and demand more postmarketing surveillance.
Angioedema can be a life-threatening adverse effect and, although it occurs with a very low frequency in the general population, it is prudent that patients who have a history of angioedema or have had angioedema or rash with ACE inhibitors not be given AT1 receptor antagonists.
Cough is a more contentious issue. Cough is a common symptom in the community and, 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 and telmisartan4 in which the AT1 receptor antagonists were given to patients with a known history of ACE inhibitor cough. In all of these studies, the incidence of cough was considerably less than in those patients rechallenged with the ACE inhibitor and the same frequency as in the placebo arm. Furthermore, a recent review5 of the published results of all the placebo-controlled and comparative trials of AT1 blockers demonstrated that the incidence of cough was similar to that of placebo. These challenge studies contribute stronger direct evidence, than reports to pharmacovigilance bodies, that cough is not a characteristic of AT1 receptor antagonists.
Furthermore, the recent Australian Adverse Drug Reactions Bulletin6 recorded only 37 reports of cough out of a total population of >150 000 patients who have been prescribed angiotensin receptor antagonists. The Adverse Drug Reactions Advisory Committee has a responsibility to put the report into some perspective, which leads to the suggestion that, with a common symptom, the Committee should at least give some idea of the denominator, i.e. the number of patients who have been treated with a particular drug.
References
1. Lacourciere Y, Brunner H, Irwin R, Karlberg BE, Ramsay LE, Snavely DB, et al. Effects of modulators of the renin-angiotensin-aldosterone system 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 with cough in patients with enalapril-induced cough [poster]. J Hypertens 1998;16Suppl 2:120.
3. Oparil S. Comparison of eprosartan and enalapril on incidence of cough in patients with essential hypertension [poster]. J Hypertens 1998;16Suppl 2:237.
4. Ramsay LE, Kirwan BA. A comparison of cough in hypertensive patients receiving telmisartan, enalapril or hydrochlorothiazide [poster].J Hypertens 1998;16 Suppl 2:241.
5. Pylypchuk GB. ACE inhibitor- versus angiotensin II blocker-induced cough 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 regarding the information available about the passage of budesonide into breast milk, your readers may be interested to learn of some tangentially related data that have recently become available. Good asthma control in pregnancy is vital for both mother and child as the known risks of uncontrolled asthma are far greater than the known risks to both from asthma medications.2 It is known from previous studies that mother and baby may both do badly if the mother's asthma is poorly controlled.3,4
A new study5 from the University of Lund, Sweden, reviews 2014 infants whose mothers stated they had used inhaled budesonide during early pregnancy. The infants were identified through the Swedish birth registry, which covers nearly all of the 100 000 births a year that take place in Sweden and contains computerised records of the paediatric examination of the new born. Since 1 July 1994, it has stored information on self-reported drug use by women in early pregnancy. The information is obtained by asking the woman at her first antenatal visit (usually about week 10 after the last menstrual period) if she has used any drugs during pregnancy and, if so, the name 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 indicates that 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 in Sweden in 1995-1997. There was no increase in the expected number of infants with congenital cardiac defects (17 vs. 17-18 expected), and the majority of the defects were mild.
The investigators concluded that `Even though a specific teratogenic effect of use of budesonide in early pregnancy cannot be ruled out, it is unlikely that 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]. Aust Prescr 1998;21:31-2.
2. National Institutes of Health. National Heart, Lung and 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 pregnancy in women with bronchial asthma. Acta Allergol 1972;27:397-406.
4. Schatz M. Asthma during pregnancy: inter relationships and management. Ann Allergy 1992;68:123-33.
5. Kallen B, Rydhstroem H, Aberg A. Congenital malformations after the use of inhaled budesonide in early pregnancy. Obstet Gynecol 1999;93:392-5.
Editor, – In his letter regarding antidepressant wash-out periods ('Letters' Aust Prescr 1999;22:3-4), Dr D. Grounds correctly notes that the approved product information for sertraline (Zoloft) explicitly includes reversible MAOIs in the contraindication against use concurrently or within two weeks, and that the product information for the other SSRIs available in Australia are not so explicit.
The subsequent comment from Professor Tiller errs in fact in referring to the 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 unchanged since then.
Although we acknowledge that, in many cases, failure to observe this rule has been free of adverse consequences, individual cases have been reported which 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.
