(Aust Prescr 1997;20:83-6)
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.
Editor, - I refer to the previous correspondence regarding the confusion over the use of Coumadin and Marevan (`Letters' Aust Prescr 1997;20:33).If no immediate solution exists, all new patients should be commenced on one dominant brand, and the other used only for continuation of treatment. This should progressively eliminate confusion, so that in 5 years, remaining patients could be converted, at smaller risk and inconvenience.
John D. Egan
General Practitioner
Harbord, N.S.W.
New drug comment - Fexofenadine
Editor, - We are contacting you out of concern for your comments regarding fexofenadine hydrochloride (`New drugs' Aust Prescr 1997;20:48) and, in particular, the sentence advising health professionals that `its approval was based on studies of two weeks' duration'.
This statement is incomplete and thus misleading. The approval of fexofenadine, the active metabolite of terfenadine, with no restriction to its duration of use, was based on the two-week efficacy studies to which you refer, as well as on the extensive data available from experience with terfenadine. Every patient who has taken terfenadine has been exposed to fexofenadine and thus the duration of exposure of the public to this molecule is actually far greater than two weeks.
Further addition to your article is required:
• Fexofenadine is the active metabolite of terfenadine; it requires no metabolic activation.
• Increases in fexofenadine levels in the presence of ketoconazole and erythromycin are associated with absorption interference rather than hepatic metabolism interference. In any case, fexofenadine has no inherent cardiac toxicity.
Michael Smith
Regulatory Project Manager
Hoechst Marion Roussel
Lane Cove, N.S.W.
Editor, - The editorial `Prescribing budgets: economic, clinical and ethical perspectives' (Aust Prescr 1997;20:28-9) by S.B. Soumerai and D. Ross-Degnan recommended that `we need to know how to educate physicians'. As a first year medical student, may I suggest you target medical students and their educators.
As well as using drug names, brand names have been used in our problem-based learning cases, with brand names also being used in some lectures. This seems pointless in a teaching environment, especially as we will initially be employed in hospitals which generally do not allow prescribing of brands.
Student concerns about the appropriateness of learning brand names at this stage have been ignored and I feel we have no influence in these matters. To give you an example of the extent of this problem, at our Medical Ball, a staff member gave a short speech during which it was suggested that we support brand names because they sponsor events like the Medical Ball!
Julian Fidge
Graduate medical student
University of Queensland
Herston, Qld
Drug distribution in human milk
Editor, - The Adverse Drug Reactions Advisory Committee (ADRAC) was most interested in the article `Drug distribution in human milk' (Aust Prescr 1997;20:35-40). In particular, the authors indicated that selective serotonin reuptake inhibitors (SSRIs) were probably safe in breast-feeding women, but that more data were needed. In this context, the ADRAC wishes to provide some relevant data from 4 reports which are strongly suggestive of breast milk transfer of maternal SSRIs to the neonate.
In one report, a 5-month-old breast-fed baby of a mother taking fluoxetine was found to have hyperglycaemia and glycosuria, which resolved after weaning. A second case describes a mother taking paroxetine whose breast-fed baby became agitated, unsettled and had difficulty feeding; the outcome is unknown. The third report is of a 5-month-old baby who initially became agitated for a few days whilst her mother took sertraline, but this settled spontaneously. In the final case, a breast-feeding mother began sertraline therapy at 10 days postpartum and took it for about 3 months. During the mother's drug therapy, the baby remained somnolent, with low muscle tone, hearing problems and suspected developmental difficulties, all of which improved markedly when the mother discontinued the drug.
Alain Rohan
Secretary
Adverse Drug Reactions Advisory Committee
Symonston, A.C.T.
Editor, - I refer to the article `Drug distribution in human milk'. I found it very interesting and useful, and will of course keep it for future reference as the previous articles covering this subject are rather dated.
However, there is one major omission which is not only germane to my practice, but I am sure is more important than some of the individual areas that were covered. This is the appearance of antihypertensive drugs in breast milk, particularly with respect to the ACE inhibitors. Although some authorities regard these as being completely innocuous, there are some drug inserts that seem to indicate otherwise.
I would be very interested if a supplementary table could be provided, covering not only the ACE inhibitors, but the calcium channel antagonists, beta blockers and the other more minor drugs used in the treatment of hypertension.
Michael Laver
Consultant Physician
Mildura, Vic.
K.F. Ilett, J.H. Kristensen, R.E. Wojnar-Horton and E.J. Begg, the authors of the article, comment:
We are grateful to Dr M. Laver for his enquiry on the distribution and likely infant dose of antihypertensive drugs in breast feeding. In our article, we set out to discuss those drugs/groups that, in our experience, are commonly used during lactation. However, we appreciate that different practitioners may see specialised groups of patients and have a need for information on drugs other than those that we covered. We hope that the Table below will provide a succinct summary of the available data for a range of different antihypertensives. We reiterate that the `Further Reading' texts listed in our article provide a comprehensive data summary of distribution and safety data for a broad range of individual drugs, and that this information is also available from Obstetric Drug Information Services in all States.
| Distribution of antihypertensive drugs into human milk, calculated infant dose and interpretation of data | ||||
| Infant dose3(%) | ||||
| Drug/Group1 | M/P ratio2 | Average | Maximum | Comments and recommendations for breast feeding |
| Ace inhibitors | ||||
| Captopril | 0.012-0.03 | 0.009 | 0.014 | Low exposure. Considered safe. |
| Enalapril (enaloprilat) | 0-0.14 | 0.27 | ND | Low exposure. Considered safe. |
| Calcium channel blockers | ||||
| Diltiazem | 1 | ND | 0.9 | Low exposure. Single case report. Considered safe. |
| Nifedipine | 1 | ND | 1.5 (including metabolite) |
Low exposure. Considered safe. |
| Verapamil | 0.23-0.94 | ND | 0.4-1.1 | Low exposure. Considered safe. |
| Beta blockers | ||||
| Atenolol | 1.1-6.8 | 8.4 | 19.2 | Significant quantities in milk. One report of bradycardia in an infant. Consider an alternative where possible. If used, observe infant for signs of beta blockade. |
| Labetalol | 0.22-1.51 | 0.06 | 0.33 | Low exposure. Considered safe. |
| Metoprolol | 2-3.6 | 0.7 | 3.2 | Moderate exposure. Considered safe, but observe infant for signs of beta blockade. |
| Propanolol | 0.5-0.85 | 0.3 | 0.4 | Low exposure. Considered safe, but observe infant for signs of beta blockade. |
| Sotalol | 2.2-8.8 | 21.8 | 42 | Significant exposure. No adverse effects seen in infants, but advisable to use an alternative. |
| Other antihypertensives | ||||
| Clonidine | 1.5-3.6 | 6.4 | 7.9 | Moderate exposure. No adverse effects reported in infants. May inhibit prolactin and reduce milk secretion. Advisable to use an alternative. |
| Hydralazine | 0.49-1.36 | ND | 0.8 | Low exposure. Considered safe. |
| Methyldopa | 0.17-0.46 | 1.6 | 3.2 | Moderate exposure. Considered safe. |
| 1 active metabolites in parenthesis 2 individual value, means or range from selected studies 3 infant dose in mg/kg as % maternal dose in mg/kg. Data from selected studies ND no data available |
||||
Editor, - I refer to the article `Current concepts in the management of cardiac arrest' by John L. Holmes (Aust Prescr 1997;20:41-5).
Dr Holmes appears to have taken official recommendations for cardiopulmonary resuscitation and mixed them with personal preferences.
The algorithm given for advanced cardiac life support (ACLS) does not concur with the Australian Resuscitation Council ACLS guidelines or the American Heart Association ACLS guidelines. Deviation occurs on a number of points, but of particular concern is the recommended list of drugs for ventricular fibrillation.
Fig. 1 (the resuscitation algorithm) should be kept simple. Blind defibrillation is usually reserved for cases where monitoring is difficult. Fig. 1 implies 3 x defibrillation then another 3 x defibrillation in the case of ventricular fibrillation.
The Australian Resuscitation Council has produced an ACLS flowchart which has removed many of the drugs referred to in Fig. 1. What level of evidence supports their retention here? Sotalol, procainamide and potassium cannot be routinely recommended and are potentially detrimental; bicarbonate should be given earlier than 20 minutes when hyperkalaemia is suspected.
Basic life support, defibrillation and intubation/hyperventilation are the only 3 manoeuvres supported as effective steps in the ALS algorithm. Adrenaline is still the main drug of ACLS (in addition to oxygen!).
Theresa Jacques
Director
Intensive Care Unit
St George Hospital
Kogarah, N.S.W.
Dr J.L. Holmes, the author of the article, comments:
Far from being my personal preferences, this article reflects the views of several experts who regularly treat cardiac arrest, as well as drawing on current resuscitation literature.
As in any medical emergency, the management of cardiac arrest requires judgement and expertise, and doctors should not be restricted to inflexible algorithms. The flowchart in my article proposes a simple, logical approach to cardiac arrest, emphasising the important core management (namely, ongoing CPR, intubation, hyperventilation, fluid loading and adrenaline) and outlining additional interventions which may be considered for asystole, ventricular fibrillation (VF) and electromechanical dissociation.
I agree with Dr Jacques that bicarbonate may be used early in resuscitation if there is pre-existing hyperkalaemia. It is important, however, to interpret the flowchart in the context of the article which already addresses most of the other issues she raises.
The drugs listed for the management of VF are not `routinely recommended'. The article clearly states that drug therapy in VF is of secondary importance to electrical defibrillation. Lignocaine is often used routinely, but the other drugs listed should only be considered in refractory VF which has not responded to repeated DC shocks. In such circumstances, most experienced practitioners will try any additional intervention which may help. It is specious to suggest that drugs such as sotalol should not be tried because they are `potentially detrimental' when the patient is virtually already dead!
Even though positive outcomes arising from the use of such interventions must remain anecdotal, positive outcomes are at least occasionally reported.
