Australian Drug Evaluation Committee Research Articles

Fetal Exposure to Risky Drugs: Analysis of Antenatal Clinic Prescriptions in a Nigerian Tertiary Care Hospital

Objective: To assess fetal outcomes after in-utero exposure to unsafe drugs.Methods: This was a retrospective cohort study using data from medical records of pregnant women who received antenatal care over a two-year period (2019/2020). Inclusion was based on identification of prescription of potentially risky medications during pregnancy. Medication records, as well as delivery data, were extracted for analysis. The Australian drug evaluation committee classification system of risky medications was used for analysis.Results: Results showed that 44 – 65% of medicines prescribed in pregnancy carry significant risks to fetal wellbeing. Fetal outcomes showed high levels of low birth weight, still birth, and early neonatal death. The common medicines prescribed irrationally in pregnancy were, among others, antibiotics, ACEIs, NSAIDs, Biguanides, and opiates, all of which are associated with adverse fetal outcomes.Conclusion: There is a high level of fetal exposure to risky medications and adverse delivery outcomes. There is a need to improve prescription through prescriber training and awareness raising on existing guidelines on good prescribing practice for pregnant women.

Unexpected in utero exposure to psychotropic medications

Introduction Pregnancies in the world each year involve women who have or who will develop psychiatric illness during the pregnancy. Psychotropics in gestation could produce adverse perinatal and postnatal outcomes, however counseling these women to discontinue medication presents new risks associated with untreated or inadequately treated mental illness, such as poor prenatal care, inadequate nutrition, and increased alcohol and tobacco use. The single administration at a higher dosage over multiple medications, active pharmaceutical compounds with fewer metabolites and higher protein binding are preferred. Nevertheless all psychotropic medications cross the placenta, are present in amniotic fluid, and can enter breast milk. Case description The FDA, the Australian Drug Evaluation Committee and Micromedex have categorized medications according to risk during pregnancy. Based on these classifications Benzodiazepines, have been demonstrated possibly teratogenic however they are still used for treating anxiety, panic, seizures and insomnia. International Pharmacopoeia reported an increased risk of intrauterine growth retardation, hypotonia, bradycardia, respiratory depression, low Apgar and preterm delivery for fetal plasma drug concentrations equivalent to the therapeutic range of maternal prescription. Very few data are published on sudden intrauterine death (SIUD) for intrauterine exposure to psychotropic medication. We describe a SIUD correlated with unexpected toxic plasmatic fetal concentration of Lorazepam. Results and conclusions The pregnant manifested anxiety, panic attack and deficiency of emotional transport for the fetus. She was treated with Lorazepam evening dose of 2mg from 24 to 40 gestational weeks, according to therapeutic range prescription, when suddenly and unexpectedly fetus died in utero just before the delivery. We evaluated the maternal and fetal pharmacological plasmatic concentration and observed a fetal plasmatic level of Lorazepam of 330mcg/l greater the toxic cutoff of 45mcg/l, suggested by Micromedex to cause floppy infant syndrome. By autoptic diagnosis we hypothesized neuropathological signs of sudden cardiac arrest in health fetus. Take-home message We propose that the monitoring of the maternal plasma levels of benzodiazepines during pregnancy and assessment of the concentration umbilical cord at birth, have to be correlated with the fetal vital signs. Nevertheless, it is difficult to define the metabolic fate of drugs in utero. Each of the major metabolic pathways can be promoted by placental and/or fetal enzymes and the metabolite concentration in the fetus does not ineludibly reflect the ability of the fetus to metabolize drugs. For this reason it has to be strictly evaluated the toxicological etiopathogenesis of some cases of SIUD and still birth.

Delays in access to affordable medicines: putting policy into perspective

We raise some issues with the study by Pearce et al. that examined the timelines of submissions for medicines to the Pharmaceutical Benefits Advisory Committee (PBAC) following recommendation by the Australian Drug Evaluation Committee (ADEC), now known as the Advisory Committee on Prescription Medicines (ACPM).

Delays in access to affordable medicines: putting policy into perspective

To save costs, the Australian Government recently deferred approval of seven new medicines recommended by the Pharmaceutical Benefits Advisory Committee (PBAC) for up to 7 months. The aim of this research is to examine the timelines of PBAC applications following approval by the Therapeutic Goods Administration (TGA), allowing the recent Cabinet delays to be considered in the context of the overall medicines approval process. All new chemical entities and products for new indications approved in 2004 by the Australian Drug Evaluation Committee (ADEC) were identified. Outcomes of PBAC meetings from 2004 to 2010 were then searched to identify if and when these products were reviewed by PBAC. ADEC recommended 63 eligible products for registration in 2004. Of the 113 submissions made to PBAC for these products, 66 were successful. Only 43% of the products were submitted to PBAC within 2 years, with an average 17-month delay from TGA approval of a product to consideration by the PBAC. Cabinet decisions to defer listing of new medicines delays access to new treatments. This occurred in addition to other longer delays, earlier in the approval process for medicines, resulting in a significant impact on the overall timeliness of listing.

Farklı Risk Kategorilerine Göre Gebelikte İlaca Maruz Kalımın Değerlendirilmesi: FDA Esaslı Kararlar Daha Fazla Küretaja Neden mi Oluyor?

Objective: The aims of the study were to compare the risk levels of exposed drugs during pregnancy with regard to United States Food and Drug Administration (FDA), Australian Drug Evaluation Committee (ADEC) and Teratogen Information System (TERIS) risk categories, and to determine the outcomes of FDA risk category based decisions on the course of pregnancy in pregnant women who applied to Dokuz Eylul University (DEU) Teratogenity Information Service (TIS). Material and Methods: In this cross-sectional study, 220 pregnant women were enrolled who referred to DEU TIS for a teratogenity risk evaluation due to drug exposure during their pregnancies. Demographics, medical history, time and duration of the exposed drugs were recorded. Drugs exposed during pregnancy were divided into two categories as high or low risk. A drug that was exposed during pregnancy of the highest risk according to FDA was taken into consideration for the evaluation of the outcomes of the pregnancy. Additionally, FDA, TERIS and ADEC risk categories which were classified as

The Australian Drug Evaluation Committee (ADEC) has recommended approval for lenalidomide

The Australian Drug Evaluation Committee (ADEC) has recommended approval for lenalidomide

Case studies of three pregnant smokers and their use of nicotine replacement therapy

To examine the barriers encountered by pregnant women who attempt to stop smoking by highlighting three women who used nicotine patches. A randomised-controlled trial of nicotine-replacement therapy (NRT) in the form of patches to test its acceptability for pregnant women. Ethics approval was granted despite NRT being contraindicated in Australia for pregnant women and having a low safety rating (category D) (Australian Drug Evaluation Committee, 1999). Salivary cotinine levels were used to assess nicotine exposure and provide some indicator of NRT safety. All participants were given pregnancy-specific cessation counselling, and the 20 women in the treatment arm were offered nicotine patches (15 mg/16 hr), with the option of weaning to lower strength patches if desired. The Women's and Children's Hospital, Adelaide, a public tertiary teaching hospital in South Australia, with almost 4000 births annually. 40 'high-risk' pregnant smokers who expressed interest in stopping smoking. As has been found in the general population, 'quit' rates with NRT use were low. Only three of the participants in this study, who became abstinent with patch use during pregnancy, were still abstinent at birth. The circumstances of two of these women, and a third woman who used patches to 'control' her smoking despite researcher advice, are detailed here. Only one of the two women 'abstinent at delivery' was still abstinent 3 months after birth, the last contact point of the study. Although health providers intuitively regard pregnancy as an appropriate time for women to stop smoking, the stressors during pregnancy seem to militate against cessation. This study does not indicate that use of NRT will provide an easier solution. It may be more fruitful to institute a concerted lifestyle approach with both the woman and her partner (or significant household members), and continue this support and education postnatally if cessation has not been achieved. Health professionals should also support better-targeted public health campaigns and tobacco-control initiatives generally, because, undoubtedly, the social environment is a major determinant of initiation and continuation of smoking.

Australian Drug Evaluation Committee (ADEC) 40th Anniversary

The 40th anniversary of the Australian Drug Evaluation Committee, commonly known as ADEC, occurred in late July 2003. ADEC first met on Thursday 25 July 1963, under the Chairmanship of Dr Edgar Thomson, in the boardroom at the Royal Prince Alfred Hospital, Sydney. The Committee was composed of seven members eminent in the fields of clinical medicine and pharmacology. ADEC has met regularly since and its August 2003 meeting was its 229th meeting. Australia was centrally involved in the recognition of the teratogenicity of thalidomide. William McBride’s letter published in the Lancet in December 1961 attracted the world’s attention. In 1963, to a large extent as a result of the thalidomide experience, discussions took place between the Australian Department of Health and senior Australian clinicians on ways and means of more effectively exerting control over drugs causing serious adverse effects. The thalidomide experience had brought home to Australian health officials that there were not only benefits but also potential risks from the use of therapeutic compounds. As a result of these discussions, the then Minister for Health established an independent body, the ADEC, to advise on the safety of new drugs being imported into Australia and to formulate measures for the evaluation of possible adverse affects of drugs that were being used in Australia. The functions given to the new Committee were: • to make medical and scientific evaluations of such therapeutic substances that the Minister referred to it for evaluation; • to make medical and scientific evaluations of other therapeutic substances if, in the opinion of the Committee, it would be desirable to do so; and • to furnish such advice to the Minister as the Committee considered necessary related to the importation into, and the distribution within, Australia of therapeutic substances that were the subject of evaluations made by it. ADEC met three times during 1963. These meetings laid the foundations for what would become the evaluation process for new drug substances in Australia. General topics discussed at these early meetings included the functions of the ADEC, the definition of a new drug, details of the future Australian drug evaluation process using comparisons with international practice at the time and the role of the individual medical practitioner in drug safety surveillance. Standards for submission of data for importation of medicines into Australia were introduced as a result of the early recommendations of the Committee. The Committee also sought to ensure that companies were required to provide information about risks, as well as benefits, in promotional material for health professionals. The early ADEC made a number of important decisions in relation to individual product groups. Drug substances discussed by the Committee in 1963 included Enovid® 1, the first oral contraceptive approved by the US FDA, which was of great interest to the pharmaceutical industry at the time. In the wake of thalidomide, any drug with such widespread potential use in women of childbearing years encountered a rather cautious regulatory environment. ADEC advised of the need for medical supervision of patients using oral contraceptives. Interestingly, ADEC was not convinced of a cause and effect relationship between use of oral contraceptives and thrombosis at that time. It was 3 or 4 years later before studies in Europe showed convincingly the link between high-dose oestrogens and thrombotic events. The early ADEC also acted to discourage the use of some long-acting sulphonamides, which were widely used in general practice at the time. These sulphonamides were causing StevensJohnson syndrome, especially in children. There had been 19 cases reported in Australia, mainly in children, with four deaths. In 1964, ADEC undertook a detailed review of five Australian reports to it of deaths in patients using sympathomimetic drugs to treat severe asthma. Subsequently, the Committee published a warning in the January 1965 issue of the Medical Journal of Australia. This warning was an important stimulus to studies in the UK and elsewhere of the association between pressurised

Australian Drug Evaluation Committee (ADEC) 40th Anniversary

Australian Drug Evaluation Committee (ADEC) 40th Anniversary

The Australian Drug Evaluation Committee has recommended for approval Pharmion's thalidomide

The Australian Drug Evaluation Committee has recommended for approval Pharmion's thalidomide

The Australian Drug Evaluation Committee has recommended the approval of a new indication for methyl aminolevulinate ['Metvix'; PhotoCure

The Australian Drug Evaluation Committee has recommended the approval of a new indication for methyl aminolevulinate ['Metvix'; PhotoCure

The Australian Drug Evaluation Committee (ADEC) has recommended the approval of methyl aminolevulinate

The Australian Drug Evaluation Committee (ADEC) has recommended the approval of methyl aminolevulinate

Risk classification systems for drug use during pregnancy: are they a reliable source of information?

In several countries, risk classification systems have been set up to summarise the sparse data on drug safety during pregnancy. However, these have resulted in ambiguous statements that are often difficult to interpret and use with accuracy when counselling patients on drug use in pregnancy. The objective of this study was to compare and analyse the consistency between and the criteria for risk classification for medications used during pregnancy included in 3 widely used international risk classification systems. All 3 systems use categories based on risk factors to summarise the degree to which available clinical information has ruled out the risk to unborn offspring, balanced against the drug's potential benefit to the patient. Drugs included in the risk classification systems from the US Food and Drug Administration (FDA), the Australian Drug Evaluation Committee (ADEC) and the Swedish Catalogue of Approved Drugs (FASS), were reviewed and compared on basis of the risk factor category to which they had been assigned. Agreement between the systems was calculated as the number of drugs common to all 3 and assigned to the same risk factor category. In addition, evidence on teratogenicity and adverse effects during pregnancy was retrieved using a MEDLINE search (from 1966 up to 1998) for common drugs classified as teratogenic. Differences in the allocation of drugs to different risk factor categories were found. Risk factor category allocation for 645 drugs classified by the FDA, 446 classified by ADEC and 527 classified by FASS was compared. Only 61 (26%) of the 236 drugs common to all 3 systems were placed in the same risk factor category. Analysis of studies on the safety of common drugs during pregnancy of drugs classified as X by the FDA indicated that the variability in category allocation was not only attributable to the different definitions for the categories, but also depended on how the available scientific literature was handled. Differences in category allocation for the same drug can be a source of great confusion among users of the classification systems as well as for those who require information regarding risk for drug use during pregnancy, and may limit the usefulness and reliability of risk classification systems.

Population Pharmacokinetics and Pharmacodynamics: An Underutilized Resource

A meeting was convened in Canberra, Australia, at the request of the Australian Drug Evaluation Committee (ADEC), on December 3-4, 1997 to discuss the role of population pharmacokinetics and pharmacodynamics in drug evaluation and development. The ADEC was particularly concerned about registration of drugs in the pediatric age group. The population approach could be used more often than is currently the case in pharmacokinetic and pharmacodynamic studies to provide valuable information for the safe and effective use of drugs in neonates, infants, and children. The meeting ultimately broadened to include discussion about other subgroups. The main conclusions of the meeting were: 1. The population approach, pharmacokinetic and pharmacodynamic analysis, is a valuable tool both for drug registration purposes and for optimal dosing of drugs in specific groups of patients, 2. Population pharmacokinetic and pharmacodynamic studies are able to fill in the gaps' in registration of drugs, for example, to provide information on optimal pediatric dosing. Such studies provide a basis for enhancing product information to improve rational prescribing, 3. Expertise is required to perform the population studies and expertise, with a clinical perspective, is also required to evaluate such studies if they are to be submitted as part of a drug registration dossier Such expertise is available in the Australasian region and is increasing. Centers of excellence with the appropriate expertise to advise and assist should be encouraged to develop and grow in the region, 4. The use of the population approach by the pharmaceutical industry needs to be encouraged to provide valuable information not obtainable by other techniques. The acceptance of population pharmacokinetic and pharmacodynamic analyses by regulatory agencies also needs to be encouraged, and 5. Development of the population approach to pharmacokinetics and pharmacodynamics is needed from a public health perspective to ensure that all available information is collected and used to improve the way drugs are used. This important endeavor needs funding and support at the local and international levels.

Book Reviews

Journal of Paediatrics and Child HealthVolume 27, Issue 5 p. 314-314 Book Reviews First published: October 1991 https://doi.org/10.1111/j.1440-1754.1991.tb02547.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Book reviewed in this article: JOLLY'S DISEASE OF CHILDREN 6th edition, edited by Malcolm I. Levene FITS AND FAINTS by John B. P. Stephenson MEDICINES IN PREGNANCY by the Congenital Abnormalities Subcommittee of the Australian Drug Evaluation Committee; 1989 Volume27, Issue5October 1991Pages 314-314 RelatedInformation

Nocturnal Cramps, Quinine, and Thrombocytopenia

To the Editor.— I read with some interest the article by McGee,1regarding muscle cramps. Of particular note was the discussion on the use of quinine for the treatment of nocturnal cramps. While not wishing to comment further on the efficacy of quinine, I would like to point out McGee's comment that it is on the meager weight of this scientific evidence and single-blind testimonies that quinine remains the most recommended drug for muscle cramps, because there is a need for some further discussion on the adverse effects of this drug. The Adverse Drug Reactions Section of the Australian Therapeutic Goods Administration receives voluntary reports on suspected adverse reactions to drugs, forwarded by medical practitioners, hospitals, pharmacists, dentists, and other health professionals. These are reviewed by The Australian Adverse Drug Reactions Advisory Committee, a subcommittee of the Australian Drug Evaluation Committee. The Australian Adverse Drug Reactions Advisory Committee has

Letters to the Editor

EDITORIAL COMMENT: The Minis guide warns that methaemoglobinaemia is a contraindication to the prescription of prilocaine hydrochloride (Citanest). The Report of Suspected Adverse Drug Reactions (No. 6, October 1983 — December 1986) published by the Australian Drug Evaluation Committee considers 17 reports of suspected adverse reactions to prilocaine hydrochloride but methaemoglobinaemia does not appear in the 31 complications listed! The author has reported the cases described in his letter to the Australian Drug Evaluation Committee.

How Are Drugs Made Available in Australia?

The release of prescription drugs in Australia for use by the medical profession is complicated because in practice there is a two-tier system determining availability. The first tier, for new drugs, involves evaluation for safety and efficacy prior to marketing. The final decision is made by the Australian Drug Evaluation Committee (ADEC) serviced by the Department of Health. In the second, much more unusual step, a decision is made by a different committee on whether the now-approved drug is to be included on the government-subsidized drug list (Pharmaceutical Benefits Scheme—PBS). Because the PBS list is unusually extensive for a country without a nationalized health service (1,184 items, including all forms and strengths of over 600 drugs) and because a large proportion of prescriptions are written for drugs on the PBS, the PBS Committee making the listing decisions has a major influence on prescribing patterns. In addition, the government is able to exert considerable pressure on drug prices.

Introduction and use of investigational anticancer agents in Australia

Medical Journal of AustraliaVolume 141, Issue 4 p. 237-239 Special Article Introduction and use of investigational anticancer agents in Australia First progress report First published: 01 August 1984 https://doi.org/10.5694/j.1326-5377.1984.tb132761.xCitations: 1 Reprints: The Secretary, Anticancer Subcommittee AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract The Anticancer Subcommittee of the Australian Drug Evaluation Committee was established in 1978 to facilitate the obtaining of data on, and the supply of, investigational anticancer agents for use by Australian oncology units. The present report outlines the way in which the usage of specific drugs has developed. Citing Literature Volume141, Issue4August 1984Pages 237-239 RelatedInformation

Anti‐Cancer Subcommittee

Medical Journal of AustraliaVolume 140, Issue 3 p. 149-150 Australian Drug Evaluation Committee Anti-Cancer Subcommittee Aims and policies First published: 01 February 1984 https://doi.org/10.5694/j.1326-5377.1984.tb103945.xCitations: 1 Reprints: The Secretary, Anti-Cancer Subcommittee, PO Box 100, Woden, ACT 2606. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume140, Issue3February 1984Pages 149-150 RelatedInformation