(Aust Prescr 1998;21:5-8)
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, - I refer to the article `Drug distribution in human milk' (Aust Prescr 1997;20:35-40).I am impressed by the assessment and summary of the safety of breast feeding during maternal drug therapy. I am particularly interested to learn about the drug transfer into milk of anti-tuberculosis drugs, especially isoniazid.
Do infants born to lactating mothers with tuberculosis and who are taking isoniazid need isoniazid prophylaxis? Or do we have to readjust (decrease) the dose of isoniazid provided when they need isoniazid prophylaxis?
Surafel Kebede
General Practitioner
Police Forces Hospital
Addis Ababa, Ethiopia
K.F. Ilett, J.H. Kristensen, R.E. Wojnar-Horton and E.J. Begg, the authors of the article, comment:
Space constraints in this journal and a marked lack of data have precluded us from addressing a broad range of drugs. Thus, our article concentrated on drugs which are commonly prescribed in Australia. However, the references listed under `Further Reading', or a telephone call to the nearest Obstetric Drug Information Service can often provide useful information on other drugs.
Dr Kebede's request for information on the transfer of antitubercular drugs into human milk is an example of a group of drugs where there is limited information. Data for pyrazinamide and p-aminosalicylic acid come from a single patient study that found an estimated infant exposure of 0.3% and 0.1% respectively of the weight-adjusted maternal dose.1 Breast feeding was considered to be safe. Rifampicin and ethambutol have each been studied in only two patients, but milk concentrations were low and breast feeding was considered safe.2,3
Both isoniazid and its active metabolite N-acetylisoniazid are excreted in milk. In one patient, maximum infant exposure was calculated to be approximately 12% of the weight-adjusted maternal dose4, or 6% of a children's dose of isoniazid (10 mg/kg). Others have calculated that a breast-fed infant would receive 9-31% of a 10 mg/kg infant dose of isoniazid.5 The American Academy of Pediatrics regards maternal isoniazid therapy as being safe to use while breast feeding.6 Some individualised reduction in dose might be necessary for infants who are also being treated with the drug. In addition, since isoniazid has a significant adverse effect profile in adults, it would seem prudent to monitor the breast-fed infant for toxic adverse effects, some of which occur more frequently in the slow acetylator phenotype.
References
1. Holdiness MR. Antituberculosis drugs and breast-feeding. Arch Int Med 1984;144:1888.
2. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 4th ed. Baltimore: Williams & Wilkins, 1994:768-70.
3. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 4th ed. Baltimore: Williams & Wilkins, 1994:342.
4. Berlin CM, Lee C. Isoniazid and acetylisoniazid disposition in human milk, saliva and plasma. Fed Proc 1979;38:426.
5. Friedman JM, Polifka JE. The effects of drugs on the fetus and nursing infant. Baltimore: The John Hopkins University Press, 1996:331-3.
6. American Academy of Pediatrics Committee on Drugs. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137-50.
Concern about labelling of guarana preparations
Editor, - Preparations of guarana from the South American tree Paullinia cupana are sold over the counter in pharmacies in Australia in several forms. These include a powder form derived from ground seeds (Rio Amazon Guarana powder for drinks) and a spearmint flavoured gum containing guarana extract (Go Gum). Advertising information on the displays in pharmacies and the packaging includes: `Catch a buzz, naturally', `Great for divers, athletes, students, night staff, busy mums' and `the secret ingredient ... puts dynamite into juices, mixes and punch'. It also states that the powder may `be used in cakes or cookies'.Nowhere on the packaging does it list the chemical constituents of guarana. The main constituent in guarana that allows you to `Catch a buzz, naturally' is caffeine. In fact, guarana seeds contain between 3 and 5 times the caffeine in terms of dry weight than Arabica coffee beans, and ground guarana seeds have long been used to make a stimulating beverage by indigenous peoples. More recently, guarana has been used in Europe as a stimulant at all-night `techno-parties'.1 The release and absorption of caffeine from guarana preparations has been shown to be equivalent to that of preparations of caffeine alone in animal studies.2
Caffeine is contraindicated in conditions such as anxiety states and some cardiovascular disorders, and symptoms associated with the stimulant effect of caffeine or caffeine withdrawal may create diagnostic problems for clinicians that are unaware of the presence of caffeine in the marketed preparations of guarana. Aqueous extracts of guarana have also been shown to have antiplatelet activity3,4, so possibly guarana should be avoided during anticoagulant therapy.
This raises a couple of important issues. Firstly, well-known chemical constituents of herbal preparations such as caffeine should be documented on the packaging so consumers can make an informed choice about what they are buying. Secondly, in the context of increasing use of herbal remedies, perhaps medical practitioners should have easier access to information on the pharmacological activities, potential drug interactions and chemical constituents of these products. A reply from the Therapeutic Goods Administration clarifying these issues would be appreciated.
Mark Myerscough
General Practitioner
Tiwi, N.T.
References
1. Baumann TW, Schulthess BH, Hanni K. Guarana (Paullinia cupana) rewards seed dispersers without intoxicating them by caffeine. Phytochemistry 1995;39:1063-70.
2. Bempong DK, Houghton PJ. Dissolution and absorption of caffeine from guarana. J Pharm Pharmacol 1992;44:769-71.
3. Bydlowski SP, Yunker RL, Subbiah MT. A novel property of an aqueous guarana extract (Paullinia cupana): inhibition of platelet aggregation in vitro and in vivo. Braz J Med Biol Res 1988;21: 535-8.
4. Bydlowski SP, D'Amico EA, Chamone DA. An aqueous extract of guarana (Paullinia cupana) decreases platelet thromboxane synthesis. Braz J Med Biol Res 1991;24:421-4.
Laurayne Bowler, Acting Branch Head, Chemicals and Non-Prescription Drugs Branch, Therapeutic Goods Administration, comments:
The Therapeutic Goods Administration (TGA) has noted the concern raised with regard to products containing Paullinia cupana (guarana). Paullinia cupana may be included in both foods and therapeutic goods. When included in foods, the herb is regulated through the Australia New Zealand Food Authority (ANZFA). State and Territory health authorities monitor compliance of foods with the Food Standards Code. The TGA will seek expert advice on the need for a label warning statement, a declaration of caffeine content or other appropriate action in relation to products containing Paullinia cupana.
A drug such as alendronate may precipitate significant adverse effects in susceptible elderly individuals. The worrying thing is that these elderly patients frequently will not present with specific symptoms and signs, but rather a cycle of illness and failing function, with the underlying reason easily missed. The increasing recognition of osteoporosis and the widespread use of bone densitometry will place pressure on doctors to treat osteoporosis with these drugs. We may see a consequent increase in adverse events in susceptible patients.
Tuly Rosenfeld
Geriatrician
Prince of Wales Hospital
Randwick, N.S.W.
Zoloft tablets as currently sold are unscored (although a scored 50 mg tablet is in the process of registration to facilitate initial treatment at a lower dose for the indication of panic disorder which, we hope, will be approved soon). Breaking the present tablets to achieve intermediate doses is not endorsed in the product information and, accordingly, not recommended by the manufacturer even though no problems are likely to result. This is because the tablets are of a conventional formulation with no sustained release properties, and their coating is simple, and not `enteric'. If the advice is intended to apply generally, the implications are more serious, since splitting tablets that are formulated for sustained release or are dependent on the integrity of a special coating for their designed performance may have serious consequences for patients. As far as Zoloft is concerned, we would have no objections to the writing of two strengths on the same prescription. We would make no more out of it, although the pharmacist would presumably pick up an additional dispensing fee.
M.M. Lawrie
Director, Medical Affairs
Pfizer Pty Limited
West Ryde, N.S.W.
Ginsberg et al1 studied percutaneous absorption of lindane in infants and children. They showed that blood levels peaked at 6 hours. Therefore, washing of the skin 6 or 8 hours after application was not likely to significantly reduce transcutaneous absorption of lindane.
Toxicity from the use of lindane in infants and children has been documented.2,3
A text on paediatric dermatology 4 recommends against the use of lindane for the treatment of scabies in infants and children. The Australian text on paediatric dermatology5 makes the same recommendation.
I think therefore that instead of discouraging the use of lindane for the treatment of scabies in infants and children, we should avoid it.
On a separate issue, a textbook on dermatology6 recommends that the treatment of Norwegian (crusted) scabies is as for ordinary scabies, although several applications of a scabicide may be necessary.
James A. Keipert
Physician
East Melbourne, Vic.
References
1. Ginsberg CM, Lowry W, Reisch JS. Absorption of lindane (gamma benzene hexachloride) in infants and children. J Pediatr 1977;91:998-1000.
2. Pramanik AK, Hansen RC. Transcutaneous gamma benzene hexachloride absorption and toxicity in infants and children. Arch Dermatol 1979;115:1224-5.
3. Lee B, Groth P. Scabies: transcutaneous poisoning during treatment [letter]. Pediatrics 1977;59:643.
4. Schachner LA, Hansen RC, editors. Pediatric dermatology. 2nd ed. New York: Churchill Livingstone, 1995:1378-9.
5. Keipert JA. Essential pediatric dermatology. Chur, Switzerland: Harwood Academic Publishers, 1990:92.
6. Champion RH, Burton JL, Ebling FJ, editors. Textbook of dermatology. 5th ed. Oxford: Blackwell Scientific Publications, 1992:1306.
Editor, - The `New drugs' information on nefazodone (Aust Prescr 1997;20:77-8) was based on the material available in early 1997. As the views are `regarded as tentative', Bristol-Myers Squibb Pharmaceuticals appreciates the opportunity to update the information.Nefazodone's primary action is potent post-synaptic 5-HT2 antagonism, although it does have weak serotonin reuptake inhibition, hence its designation as a serotonin antagonist and reuptake inhibitor.1 Data available indicate that food does not alter nefazodone's bioavailability.2 Treatment doses may be started at less than 100 mg twice daily (50 mg twice daily) in most people, particularly the elderly. This tends to reduce the occurrence of adverse effects; although if they do occur, they usually tail off in the first 6 weeks of therapy. The gradual increase to the median long-term dose of 400 mg/day will also reduce or prevent emergence of adverse effects.3
The anxiolytic effect and restoration of sleep quality often commences in the first week of therapy, with depression lifting usually between 10-21 days, even if therapy has been initiated slowly. Clinical trial and pooled data comparing nefazodone to SSRIs, imipramine and placebo have indicated efficacy in depression and prevention of relapse up to 12 months.3,4
M.D. Anderson-Hunt
Medical Practitioner and
Medical Affairs Manager (Neurosciences)
Bristol-Myers Squibb Pharmaceuticals
Noble Park, Vic.
References
1. Taylor DP, Carter RB, Eison AS, Mullins UL, Smith HL, Torrente JR, et al. Pharmacology and neurochemistry of nefazodone, a novel antidepressant drug. J Clin Psychiatry 1995;56 (Suppl 6):
S3-S11.
2. Dockens RC, Greene DS, Barbhaiya RH. The lack of effect of food on the bioavailability of nefazodone tablets. Biopharm Drug Dispos 1996;17:135-43.
3. Robinson DS, Roberts DL, Smith JM, Stringfellow JC, Kaplita SB, Seminara JA, et al. The safety profile of nefazodone. J Clin Psychiatry 1996;57 (Suppl 2):S31-S38.
4. Montgomery SA. Efficacy in long-term treatment of depression. J Clin Psychiatry 1996;57 (Suppl 2):S24-S30.
The Editor comments:
Observant readers will notice that some of the new information provided is at variance with the approved product information (PI). For example, the PI informs us that food delays absorption and decreases systemic exposure by 20%. Reference 2 confirms this finding. The study found that food significantly reduces the area under the curve for nefazodone by 18%, although the rate of absorption was not significantly altered. In practice, these effects may not be clinically significant.
In the PI, the recommended starting dose for most patients is 100 mg twice daily and 50 mg twice daily for the elderly. Reference 3 suggests that some adverse effects will resolve with time. It does not say that adverse events are reduced by starting at a lower dose, although clinical practice suggests that this may be the case. Starting at a low dose and increasing too slowly may delay the response to treatment. (Consideration should be given to discontinuing nefazodone if no response occurs after 4-6 weeks of treatment).
Reference 4 is a review of long-term treatment with antidepressants, not specifically nefazodone. Part of the review discusses the 139 patients who continued to take nefazodone for a year after completing studies of acute efficacy. Their rate of relapse was 9% compared with 8% in patients taking imipramine and 25% in those given placebo. Approximately 11% of patients will discontinue long-term use of nefazodone because of adverse effects, compared with 16% for tricyclic antidepressants and 9% for placebo.
| Australian Prescriber supplement |
Australian Prescriber supplement |
| The findings of the Australian National Consensus Conference on the Prevention and Management of Osteoporosis were reviewed in the previous issue (Aust Prescr 1997;20:82-3). Readers who wish to see the evidence on which the consensus statement was based can now read the proceedings of the conference.
If you wish to obtain a copy, please contact: Ms Diana MacDonell Pharmaceutical Benefits Branch, MDP 83 Facsimile (02) 6289 8633 |
While there are reasonable data on the quantity of drugs prescribed in Australia, there is little information about what the drugs are used for. A seminar has been held to consider what sources of data are available and how these could be used in the creation of a national pharmacoepidemiological database. Copies of the Transcript and Proceedings of the Australian National Pharmacoepidemiological Database Seminar are available from:
Professor John Marley Department of General Practice Facsimile (08) 8303 3511 |
