Letters to the Editor

(Aust Prescr 1998;21:31-4)

Letters, which may not necessarily be published in full, should be restricted to not more than 250 words. When relevant, comment on the letter is sought from the author. Due to production schedules, it is normally not possible to publish letters received in response to material appearing in a particular issue earlier than the second or third subsequent issue.

Drug distribution in human milk

Editor, - It was disappointing to find that the informative article `Drug distribution in human milk' (Aust Prescr 1997;20:35-40) did not contain information regarding either oral or inhaled corticosteroids. For many lactating women with asthma, it is essential to maintain inhaled steroid medication and to treat acute exacerbations of asthma with increased doses. These drugs currently carry a B3 listing in the `Medicines in Pregnancy' publication.

The prescribing information for budesonide states that `there is no information available on the passage of budesonide into breast milk. It is recommended therefore that breast feeding be discontinued in women receiving budesonide'. This wording has the potential to alarm mothers and their doctors and to result in inappropriate advice to breast-feeding mothers. In view of the evidence suggesting that breast feeding may protect against the development of asthma, this is a double jeopardy.

Is it possible that this wording could be altered in keeping with clinical experience, which suggests that these medications do not pose a risk to the babies of breast-feeding mothers with asthma who are taking inhaled corticosteroids? Can the authors provide any information which informs us of the risk of breast feeding in women taking oral corticosteroids? The current prescribing information for most of the oral steroids suggests that administration to breast-feeding mothers is not recommended. Clinical experience tells us that it is not recommended to withhold oral steroids in asthma exacerbations.

Christine Jenkins
Thoracic Physician
North Sydney, N.S.W.

Susan Parker, Medical Information Manager, Astra Pharmaceuticals, comments:
Thank you for the opportunity to respond to Dr Christine Jenkins' letter regarding the wording of the information about breast feeding in the product information for budesonide.

Drug treatment during pregnancy and lactation continues to be an area of limited data, based on experiential rather than experimental science. Unfortunately, because there are no clinical data available on the passage of budesonide into breast milk, we have no data on which to base a request to the Therapeutic Goods Administration (TGA) to amend the product information.

Astra Pharmaceuticals would be happy to work with respiratory physicians to obtain data regarding the passage of budesonide into breast milk so that the statement may be amended to be more practical.

Alternatively, we would be happy to approach the TGA in an attempt to include a statement similar to that for fluticasone such as: In view of the pharmacokinetic profile, transfer into breast milk is unlikely.

It is interesting to note that the product information for products containing beclomethasone dipropionate do not include any lactation statement.

The Editor comments:
Based on information supplied by the New South Wales Medicines Information Centre, it would appear that inhaled corticosteroids can probably be used safely by women who are breast feeding. While the milk:plasma ratios are unknown, the concentrations secreted into milk following normal inhaled doses are probably small.

Prednisolone is secreted into breast milk, but, following a single 5 mg dose, only 0.2% appears in the milk. The milk:plasma ratio may increase with increasing serum concentrations, but exposure is probably minimal for daily doses of 20 mg. As prednisone requires conversion into prednisolone, the latter is probably preferred during lactation.

The lack of data on the safety of inhaled and oral steroids taken during breast feeding should be discussed with asthmatic mothers. They can then decide if the known benefits of breast feeding and good asthma control outweigh the probably small risk of adverse effects.

Fluoxetine and breast feeding

Editor, - We refer to the article `Drug distribution in human milk' (Aust Prescr 1997;20:35-40) where breast milk transfer of maternal selective serotonin reuptake inhibitors (SSRIs) to the neonate is calculated for paroxetine, sertraline and fluoxetine (norfluoxetine). Infant doses are found to be 1.4%, 0.67% and 6.3-13.9% of the mother's dose respectively. Under recommendations for breast feeding, paroxetine is considered `probably safe', sertraline `probably safe, but more data needed' and fluoxetine `possibly safe, but more data needed'. It is the latter recommendation on which we wish to comment.

The Australian Adverse Drug Reactions Advisory Committee¹ commented that breast milk transfer of maternal SSRIs to the breast-fed infant may be significant since 4 breast-fed infants experienced adverse reactions: one hyperglycaemia and glycosuria, two agitation, one somnolence. In two cases the mothers had been using sertraline, in one case fluoxetine and in one case paroxetine, but the doses or durations were not described.

The amount of fluoxetine ingested from breast milk is fairly high and the risk of accumulation in the breast-fed infant is important due to long half-lives of fluoxetine and active norfluoxetine. This is shown in the newly issued review from our department.² Therapeutic concentrations of fluoxetine and norfluoxetine have only been demonstrated in one breast-fed infant with colic. The colic disappeared after discontinuation of fluoxetine treatment.³ A review by Wisner⁴ concludes that fluoxetine is not a first-line antidepressant because of adverse effects observed in infants with mothers using fluoxetine while lactating. Prescription of an antidepressant for a breast-feeding woman is a case-specific risk-benefit decision, and observation of the infant should be conducted. We are presently monitoring the situation in our ongoing study of SSRIs in pregnant and lactating mothers.

An interesting study was done on 84 women with postpartum depression where no difference in efficacy between fluoxetine and counselling therapy was seen.⁵ Maybe, on the whole, would a non-drug treatment be a better alternative for the infant?

Hedvig Nordeng and
Ingrid Matheson
Department of Pharmacotherapeutics
University of Oslo
Oslo, Norway

R E F E R E N C E S
1. Rohan A. Drug distribution in human milk [letter]. Aust Prescr 1997;20:84.

2. Haberg M, Matheson I. The use of antidepressants when breast-feeding. Tidsskr Nor Lægeforen 1997;117:3952-5.

3. Hatzopoulos FK, Albrecht LM. Antidepressant use during breastfeeding. J Hum Lact 1996;12:139-41.

4. Wisner KL, Perel JM, Findling RL. Antidepressant treatment during breast-feeding. Am J Psychiatry 1996;153:1132-7.

5. Appleby L, Warner R, Whitton A, Faragher B. A controlled study of fluoxetine and cognitive-behavioural counselling in the treatment of postnatal depression. Br Med J 1997;314:932-6.

Treatment of migraine

Editor, - Accompanying Associate Professor Andrew Somogyi's article `Pethidine is inappropriate for migraine' (Aust Prescr 1997;20:71) is an insert recommending the treatment of acute migraine based on `Therapeutic Guidelines: Neurology' by Therapeutic Guidelines Ltd. In it, patients are advised to rest, etc., but no mention is made of what posture they should adopt while resting. It is important that they rest sitting up, or at least propped up as high as possible on pillows, as migraine is commonly aggravated by lying flat.

R.J. O'Bryan
General Practitioner
St. Kilda, Vic.

Benafsha Khariwala, the Managing Editor of Therapeutic Guidelines Ltd, comments:
The treatment of the acute attack of migraine is complex and subject to considerable variability between patients. One could argue theoretically for different positions to try to alter cerebral blood flow; however, in the acute phase of an attack, patients are photophobic and nauseated and patient comfort is an important factor in management. As many patients are also dizzy at this time, lying down is usually their preferred position. Other patients may find different positions to be more comfortable. We do not believe any one position is appropriate for all patients.

Antibiotic prophylaxis

ditor, - Recommended prophylaxis of endocarditis was clarified by the letter from Dr I. Hewson and response by B. Khariwala (`Letters' Aust Prescr 1997;20:57-8).

Antibiotic guidelines' 9th Edition 1996 makes no reference to prophylaxis for in situ implants other than cardiac valves. Prophylaxis is recommended at the time of insertions on pages 161 (orthopaedic), 162 (neurosurgery) and 164 (head, neck, thoracic). The dire results of established infection are briefly mentioned on pages 33 (intravascular) and 148 (orthopaedic).

Recent enquiry, precipitated by my wife's knee replacement, revealed my dentist uses amoxycillin 3 g, but an orthopaedic surgeon uses cephalosporin or flucloxacillin because the organism is more likely to be staphylococcus than a streptococcus.

Discussion with the physician associated with my wife's orthopaedic surgeon suggests amoxycillin may still be appropriate for oral procedures, but for urinary and colonic manipulations, gram negative organisms demand gentamicin.

L.K. Morgan
General Practitioner
Bendigo, Vic.

Benafsha Khariwala, the Managing Editor of Therapeutic Guidelines Ltd, comments:
Any patient with a joint prosthesis is at a small risk of infection of the prosthesis by the haematogenous route. Early recognition and treatment of infection at any site is important to prevent seeding of the prosthesis. The value of antibiotic prophylaxis has not been established for procedures in which bacteraemia is likely to occur e.g. dental surgery, cystoscopy and surgical procedures on infected tissues.

However, antibiotic prophylaxis may be considered for patients at potentially increased risk of haematogenous infection of joint prostheses, such as the immunocompromised and patients with insulin-dependent diabetes, when undergoing procedures with a high incidence of bacteraemia e.g. dental extractions or surgical procedures involving incisions of the oral or gingival mucosa.

Helicobacter pylori

Editor, - The opening remarks in `Testing for Helicobacter pylori' (Aust Prescr 1997;20:96-8) are cause for concern in a profession which must essentially be guided by scientific fact.

Drs Lambert and Badov state that `Helicobacter pylori commonly infects Australians and can cause gastritis, peptic ulcer disease and gastric cancer'.

To the best of my knowledge, there has been no published work which has indicated that H. pylori has actually caused peptic ulcer disease or gastric cancer in humans. Several attempts have been made in experimental animals to induce peptic ulcer by exposing the animals to H. pylori. Thus far, such attempts have failed in all animals except the Mongolian gerbil, and even in this animal it was not possible to induce duodenal ulcer.

There can be no doubting that H. pylori is often found to be present in the upper gastrointestinal tract of patients suffering from peptic ulcer, gastric ulcer, gastric MALT lymphoma or any one of a vast array of other pathologies.

The association with H. pylori does not give scientific basis for authorities, as yet, to state that H. pylori causes peptic ulcer or gastric cancer.

Until proof is available, authorities would be better advised to use more cautious terminology.

John R. Graham
Consultant Physician & Gastroenterologist
Sydney, N.S.W.

Dr David Badov, one of the authors of the article, comments:
The article deals with the diagnostic tests for H. pylori. The opening statement simply reflects a widely accepted view of the causal relationship between H. pylori and peptic ulcer disease and gastric carcinoma. This view is also supported by the Australian Gastroenterology Institute which, in its recent publication `Helicobacter pylori - Guidelines for healthcare providers' states on page 6:

`H. pylori is now accepted as a cause of: histological gastritis, duodenal ulcer, gastric ulcer and gastric malignancy' (Oct 1995).
This view is based upon the strong and consistent relationship between H. pylori infection and peptic ulcer disease. Infection can be diagnosed worldwide in virtually all patients with duodenal ulcers and in the vast majority of patients with gastric ulcers. There is a definite biological gradient: the risk of peptic ulceration correlates with bacterial load and a known biological mechanism. A final and strong argument in support of the causative role of H. pylori infection in both duodenal and gastric ulcer disease is the effect of bacterial eradication intervention. The risk of recurrent duodenal and gastric ulceration is reduced virtually to zero after eradication therapy.

In regard to gastric carcinogenesis, the World Health Organization has recently classed H. pylori as a definite carcinogen.

Use of brand names

Editor, - Julian Fidge's letter (`Letters' Aust Prescr 1997;20:84) suggests that medical students should not have to learn brand names of drugs as they are `pointless' in a teaching environment. To a certain extent, this is true as he will certainly be expected to prescribe by generic names when he graduates. However, the patients that he admits or sees in the Emergency Service and Outpatients Department will almost certainly refer to their drugs by brand names. Ignorance of the more common brand names will make life difficult for all concerned. I submit that the proper approach is to refer to the drugs by their generic names, but also to ensure that the more common brand names are also mentioned. In this way, all possible bases are covered.

Simon Vanlint
General Practitioner
Barmera, S.A.

Outcomes of the Australian Osteoporosis Consensus Conference

Editor, - I recently read an editorial written by Associate Professor R. Prince (Aust Prescr 1997;20:82-3) entitled `Outcomes of the Australian Osteoporosis Consensus Conference'. In it the Professor stated that `hip fracture kills as many women as breast cancer'.

Could you please provide me with the evidence for this statement?

Larry Light
General Practitioner
Middle Park, Vic.

Associate Professor R. Prince, the author of the editorial, comments:
Dr Light highlights an important issue, poorly understood by many medical practitioners in Australia and indeed worldwide. The issue relates to the relative likelihood of death from various diseases amongst their ageing patients. With this concept in mind, Elizabeth Geelhoed and myself set out to evaluate these issues in the Australian population and then calculate the effect of oestrogen replacement therapy on instance rates and mortality.

To do this, Ms Geelhoed obtained a data set from the Australian Institute of Health and Welfare comprising mortality events for coronary heart disease, stroke, breast cancer and endometrial cancer. Hip fracture mortality was calculated from Western Australian data. Using population sizes, rates for mortality in 1993 were calculated. These data were used in a conditional probability analysis based on a cohort of 50 year old women whose mortality was modelled for 50 years. On the basis of this analysis, it is clear that 2.7% of the subjects will die from a hip fracture and 2.8% will die from breast cancer. I should also add that the mortality from breast cancer occurs at an earlier age than for hip fracture. These data have been published in part in the Proceedings of the International Menopause Society Symposium in Sydney.¹

R E F E R E N C E
1. Prince RL. The health economics of osteoporosis and estrogen replacement therapy. In: Wren BG, editor. Progress in the management of the menopause: the proceedings of the 8th International Congress on the Menopause, Sydney, Australia, November 1996. New York: Parthenon Publishing Group, 1997:170-4.

Editor, - The editorial `Outcomes of the Australian Osteoporosis Consensus Conference' (Aust Prescr 1997;20:82-3) outlined that the prophylaxis and treatment of osteoporosis is aimed at reducing bone fractures, in particular hip fracture. The paragraph headed `Prevention' listed all those measures taken in a multiple factorial approach to falls prevention. In a practice of vascular surgery, we constantly see elderly people for assessment of peripheral vascular disease because of various symptoms, often due entirely to musculoskeletal problems such as osteoarthritis, and often associated with musculoskeletal problems. It is not uncommon to see postmenopausal women tottering into the consulting room on narrow-based, poorly structured footwear, often even with high heels! Many of these have already had hips and knees replaced and they are still on their high heels!

Neither your editorial nor the recent consensus statement on osteoporosis addressed the issue of inappropriate footwear in postmenopausal women. I wonder if some of the money spent on prophylactic medication would be better spent on simple footwear education. The very make-up of the shoe can reduce the potential risk of slips and trips in and outside the home. By encouraging wider- based supportive footwear, not only would the issue of prevention and reduction of hip fractures be addressed, but also the potential judicious spin-off in the prevention of ulcerations and infections in the diabetic foot.

M.M. Lawrence-Brown
F.J. Prendergast
M.A. Goodman
K. Sieunarine
Vascular Surgery Department

and

J.Cornwell
Podiatry Department
Royal Perth Hospital
Perth, W.A.