Compendium Of Pharmaceuticals Research Articles

Identification of Environmental Compounds That May Trigger Early Female Puberty by Activating Human GnRHR and KISS1R.

There has been an alarming trend toward earlier puberty in girls, suggesting the influence of an environmental factor(s). As the reactivation of the reproductive axis during puberty is thought to be mediated by the hypothalamic neuropeptides kisspeptin and gonadotropin-releasing hormone (GnRH), we asked whether an environmental compound might activate the kisspeptin (KISS1R) or GnRH receptor (GnRHR). We used GnRHR or KISS1R-expressing HEK293 cells to screen the Tox21 10K compound library, a compendium of pharmaceuticals and environmental compounds, for GnRHR and KISS1R activation. Agonists were identified using Ca2+ flux and phosphorylated extracellularly regulated kinase (p-ERK) detection assays. Follow-up studies included measurement of genes known to be upregulated upon receptor activation using relevant murine or human cell lines and molecular docking simulation. Musk ambrette was identified as a KISS1R agonist, and treatment with musk ambrette led to increased expression of Gnrh1 in murine and human hypothalamic cells and expansion of GnRH neuronal area in developing zebrafish larvae. Molecular docking demonstrated that musk ambrette interacts with the His309, Gln122, and Gln123 residues of the KISS1R. A group of cholinergic agonists with structures similar to methacholine was identified as GnRHR agonists. When applied to murine gonadotrope cells, these agonists upregulated Fos, Jun, and/or Egr1. Molecular docking revealed a potential interaction between GnRHR and 5 agonists, with Asn305 constituting the most conservative GnRHR binding site. In summary, using a Tox21 10K compound library screen combined with cellular, molecular, and structural biology techniques, we have identified novel environmental agents that may activate the human KISS1R or GnRHR.

Approved and Off-Label Use of Prescribed Psychotropic Medications among Federal Canadian Inmates.

To examine psychotropic medication prescription practices in federal Canadian penitentiaries. 468 files were drawn from a purposive sample of thirteen Canadian federal institutions representing the five regions, different security levels, and male and female designated facilities. Information on the names of all psychotropic medications prescribed, indications for use, dosage, frequency, and route of administration was retrieved. Designation of approved or off-label use of medications was determined by consulting: (1) the Health Canada (2016) Drug Product Database, (2) the Canadian Compendium of Pharmaceuticals and Specialties 2016, and (3) the American Hospital Formulary Service Drug Information 2016. Prescription rates were examined by gender, Indigenous ancestry, drug class, institutional infractions, and current offence. 36.2% of prescriptions for psychotropic medication were coded as 'off-label'. Anxiolytic/hypnotics drugs were the psychotropic drugs most commonly used for off-label purposes. There were no differences in the prevalence of approved versus off-label prescriptions based on Indigenous ancestry or gender, and no pattern of elevated off-label prescription practices for offenders involved in institutional misconducts or those sentenced for the most serious crimes. The rates of prescribing 'off-label' psychotropic medication are not elevated relative to other correctional settings or to rates cited in Canadian surveys conducted in the community.

Does a history of suicide attempt predict higher antipsychotic dosage in schizophrenia?

Antipsychotic dosage is generally adjusted by physicians depending on the stability of the patient and the response to that particular drug. Our hypothesis is that patients with previous suicide attempt are prescribed higher doses of antipsychotics. We examined the dosage and patterns of antipsychotic use in regard to past suicidal behaviour. For this study, 304 subjects with schizophrenia spectrum disorders between the ages of 18 and 75 were recruited. A cross-sectional assessment was used for this study, in which data were collected from each patient through an interview and self-report questionnaires. The percentages of the Compendium of Pharmaceuticals and Specialties (CPS) maximum recommended daily dose were applied to standardize antipsychotic dosages across different treatments. We compared the standardized dosage of antipsychotics in schizophrenics with previous suicide attempts and those who have never attempted suicide. Applying the ANCOVA, our preliminary results show no significant difference (P = 0.467) in antipsychotic dosage in the attempters and non-attempters. The prescribed clozapine dosage fails to show a significant relationship with suicidal history (P >0.05). In summary, our analysis does not show antipsychotic dosage adjustment based on past suicide attempt, after controlling for the current suicidal ideation and hopelessness.

Information for Physicians and Pharmacists About Drugs That Might Cause Dry Mouth: A Study of Monographs and Published Literature

Over three-quarters of the older population take medications that can potentially cause dry mouth. Physicians or pharmacists rarely inform patients about this adverse effect and its potentially severe damage to the teeth, mouth and general health. The objectives of this study were to (1) identify warnings in the literature about dry mouth associated with the most frequently prescribed pharmaceutical products in Canada; and (2) consider how this information might be obtained by physicians, pharmacists and patients. Monographs on the 72 most frequently prescribed medications during 2010 were retrieved from the Compendium of Pharmaceuticals and Specialties (CPS, a standard drug information reference for physicians and pharmacists), the National Library of Medicine's 'DailyMed' database, directly from the manufacturers, and from a systematic search of biomedical journals. The CPS provided monographs for 43% of the medications, and requests to manufacturers produced the remaining monographs. Mentions of dry mouth were identified in 61% of the products (43% amongst CPS monographs; an additional 43% amongst manufacturers' monographs; 7% in the DailyMed database and 7% from biomedical journals); five medications had contradictory reports in different monographs. Nearly two-thirds (61%) of the most commonly prescribed medications can cause dry mouth, yet warnings about this adverse effect and its potentially serious consequences are not readily available to physicians, pharmacists, dentists or patients.

CPhA and other health care professions

The results of a 2010 survey of CPhA members revealed that one of the most highly valued roles for the CPhA to play was to represent the perspective of pharmacists to other health care professionals. This was an astute observation—pharmacy represents one piece of a very complex health care puzzle, and so strengthening relationships with Canada’s physicians, nurses, dentists, mental health workers and other practitioners is a key step towards improving real interdisciplinary care across Canada. The CPhA devotes a great deal of effort to engaging with other health care providers to provide pharmacists’ views on key health-related issues. Contacts with other health provider organizations have allowed the CPhA to build coalitions on key issues, strengthen and promote the role of the pharmacist and advocate more strongly with governments on the need for patient-centred care. Ongoing dialogue with the broader health community also helps provide valuable intelligence and information on developments of interest and concern to the pharmacy community. Although examples of engagement with other health care providers occur on a daily basis, here are some noteworthy instances of recent interdisciplinary efforts: Following decades of resistance to increasing scopes of practice for pharmacists, more recent statements by the Canadian Medical Association (CMA) have promoted the idea of enabling allied health professionals such as pharmacists to practise to the full extent of their training and ability. As a leading member of HEAL, a coalition of 40 health provider organizations, discussions have already begun about positioning and messaging for the 2015 election, in an attempt to have the parties discuss relevant issues surrounding health care. Through its strong partnership with the Canadian Nurses Association (CNA), CMA and the Health Action Lobby (HEAL), the CPhA has been a contributor to the Council of the Federation’s effort to promote team-based models of care throughout Canada, with an eye to ensuring that models of care include pharmacists where warranted. There have been weekly discussions and updates between CPhA, CMA, CNA and HEAL representatives to update each other on the progress of the Council of the Federation and relevant developments. The Canadian Medical Association and CPhA will shortly issue a joint policy statement on the need for e-prescribing in Canada, which will speak to the benefits of and need for investment in e-prescribing. We also work with other health provider groups to advocate for greater progress on the implementation of electronic health records in Canada. The CPhA is a leading member of the G-7, a group of 7 allied health professional organizations that discuss issues relevant to our joint sectors. Recent discussions within the G-7 have helped inform efforts by pharmacy to advocate with third-party insurers for better coverage of pharmacy-related services. The CPhA led an effort among 8 national health provider organizations to oppose federal elimination of supplemental health benefits for refugees. These efforts helped restore supplemental benefits, including pharmacy benefits, to approximately one-third of refugees in Canada. Although not directly advocacy related, the therapeutic information provided to other medical practitioners via CPhA’s various publications and products (e.g., the Compendium of Pharmaceuticals and Specialties, Therapeutic Choices and e-Therapeutics+) is an invaluable source of information for practitioners on evidence-based drug therapy. One important note is that our partners in other health organizations recognize the key role and contribution that pharmacists play in the health field. They recognize the accessibility, the relevance and the expertise that pharmacists bring to the health system, which is why the CPhA is called upon so frequently to discuss and participate in issues of relevance to the Canadian health care system. Although this is not an overly visible or celebrated function of the national association, it is a responsibility that the CPhA takes very seriously and will continue to prioritize in the years to come. ■

Pharmacotherapy in Type 1 Diabetes

Pharmacotherapy in Type 1 Diabetes

Off-label drug use in pediatric anesthesia and intensive care according to official and pediatric reference formularies

In pediatric practice, the official drug label often does not accurately reflect the contemporary use of many drugs prescribed to children. Therefore, clinicians frequently use contemporary drug references as a source of prescribing information instead of national formularies. The objective of this study was to compare drug prescriptions between two national formularies and two commonly used contemporary pediatric reference guidelines in the operating room/postanesthetic care unit (OR/PACU), pediatric intensive care unit (PICU), and neonatal intensive care unit (NICU). We performed a retrospective chart review of patients admitted over a one-month period to the NICU and PICU, and for one week during the same month, we reviewed charts of patients in the OR/PACU. The data collected included patients' demographic information, drugs prescribed, and dosage information. We assessed conformity with two national formularies, the Canadian Compendium of Pharmaceuticals and Specialties (CPS) and France's 2009 Dictionnaire Vidal (Vidal), and two contemporary pediatric references, the Hospital for Sick Children Handbook and Formulary and the Lexi-Comp Pediatric Dosage Handbook. Across the three clinical units, 59.7% (95% confidence interval [CI] 57.1-62.1%) of prescriptions were identified as being off-label, as defined by the CPS formulary. The odds of having an off-label prescription would have been substantially lower if the contemporary pediatric references (odds ratio [OR] = 0.074; 95% CI 0.065-0.084) or Vidal (OR = 0.70; 95% CI 0.63-0.77) had been used to define the label (both P < 0.001 compared with the CPS). Drugs are less likely to be off-label if prescribed according to a contemporary pediatric reference rather than according to national formularies. Methodologies used to compile contemporary references might serve as templates to inform a drug's official label.

Are Excipients Really Inert Ingredients? A Review of Adverse Reactions to Excipients in Oral Dermatologic Medications in Canada

Whereas several literature reviews have discussed the role of excipients in drug-related reactions, no article has focused specifically on those found in oral dermatologic medications. The Compendium of Pharmaceuticals and Specialties (CPS) was used to reference the inert ingredients found in oral dermatologic medications. An extensive literature review was subsequently conducted using PubMed and MEDLINE to document adverse reactions to these excipients. Sixty-three oral dermatologic medications were reviewed. Lactose was commonly used as a filler. Several medications indicated that they were dye, tartrazine, or gluten free. Three medications were found to contain soybean oil and one was found to contain peanut oil. Although there are documented reactions to excipients in other products in the literature, few reports outline reactions to excipients in oral dermatologic medications. Whether this low frequency is accurate or whether it is due to a lack of reporting remains unknown. If the latter reasoning is correct, dermatologists must be more aware of these possible reactions. This article serves as a reference guide for dermatologists to aid in prescribing medications to individuals with known sensitivities and to assist in working up patients with suspected reactions to inert ingredients.

New challenges to medicare beneficiary access to mAbs

Precision binding of monoclonal antibodies (mAbs) to biological targets, their relative clinical success, and expansion of indications following initial approval, are distinctive clinical features. The relatively high cost of mAbs, together with the absence of a regulatory pathway to generics, stand out as distinctive economic features. Based on both literature review and primary data collection we enumerated mAb original approvals, supplemental indications, and off-label uses, assessed payer formulary management of mAbs, and determined new challenges to Medicare beneficiary access to mAbs. We found that the FDA has approved 22 mAbs and 30 supplemental indications pertaining to the originally approved mAbs. In addition, there are 46 off-label use citations in officially recognized pharmaceutical compendia. Across Part B carriers and Part D plans, we found considerable variation in terms of coverage and conditions of reimbursement related to on- and off-label uses of mAbs. Our results point to four major challenges facing mAb developers, health care providers, Medicare beneficiaries, payers, and policymakers. These include administrative price controls, coverage variation, projected shift from physician- to self-administered mAbs, and comparative effectiveness. We suggest more systematic use of “coverage with evidence development” as a means of optimally addressing these challenges.

Error in the Compendium of Pharmaceuticals and Specialties, 2008 edition

A potentially serious error has been identified in the Compendium of Pharmaceuticals and Specialties (CPS), 2008 edition, in the Clin-Info section, Calculations and Dosing Tools, p. L3.[1][1] The square brackets in the first equation for body surface area (BSA) should enclose both the numerator and

Documentation of Pediatric Drug Safety in Manufacturers??? Product Monographs

To describe the provision of pediatric drug safety information in a national formulary of manufacturers' drug product monographs. We performed a cross-sectional evaluation of comprehensive product monographs contained in the 2005 Canadian Compendium of Pharmaceuticals and Specialities (CPS). We abstracted data describing indications for prescription, statements about pediatric safety, available preparations, and provision of dosing guidelines. For each monograph we classified pediatric safety data as either present, present but limited or absent. We then described the pediatric safety data in CPS monographs for drugs listed in the published formulary of the Hospital for Sick Children, Toronto, Ontario, Canada. A total of 2232 product monographs were screened; 684 were excluded and 1548 (66%) were further analyzed. 1462 (94%) had indications that did not exclude children. Pediatric safety information was present in 592 (38%), present but limited in 148 (10%), and absent in 808 (52%) drug monographs. Safety statements were absent in 224 (14%) drug monographs that provided both dosing guidelines and formulations suitable for administration to children, and in 214 (52%) of 411 drugs in the pediatric hospital formulary. We evaluated a widely available national source of pediatric prescribing information. Safety data for children was not mentioned in more than half of the product monographs. Moreover, the provision of safety data was discordant with indications for prescription, the availability of pediatric formulations, and dosing guidelines within the monographs, and with inclusion in a pediatric hospital formulary. Our study suggests that the presentation of pediatric safety data in drug product monographs can be improved to better inform prescribing and to optimize pharmacotherapy in children.

Is Gentamicin Ototoxic to the Fetus?

BackgroundGentamicin is used in pregnancy to treat infections that cause complications to the mother and fetus if left untreated. In 2003, Schering, the manufacturer of Garamycin Injectable, amended the product monograph in the Compendium of Pharmaceuticals and Specialties to state that gentamicin should be avoided in pregnancy due to cases of “total irreversible bilateral congenital deafness” in babies exposed to gentamicin in utero. Because we have identified, after an intensive literature search, only two cases over many years of availability, it is questionable whether the outcome can be attributed to drug use rather than other factors. ObjectivesThe main objective of this study was to determine whether any infant exposed in utero to intravenous gentamicin and born between January 2002 and April 2006 at Victoria General Hospital demonstrated audiologic deficits on routine hearing testing. Such testing has been universally available since late 2001. Our secondary objectives were to examine patterns of gentamicin use, including indication, dosage, duration, and to determine whether or not monitoring of serum gentamicin levels was done. MethodsWomen who had received gentamicin were identified through pharmacy records and their charts reviewed for factors that might contribute to fetal deafness including substance abuse, use of other potentially ototoxic medications, genetic predisposition, and intrauterine infections. We reviewed audiology test result and the infants’ charts for potential confounding factors, including prematurity, low birth weight, low Apgar scores, anoxia, hyperbilirubinemia, sepsis, and meningitis. ResultsFifty-two charts were reviewed, 40 of which documented live births. There was no case of hearing loss documented. Of the eight fetal losses, six (11.5%) were preterm births before viability, and two were elective terminations. Pyelonephritis was the main indication for gentamicin use (48%), followed by chorioamnionitis (31%) and other miscellaneous indications (21%). Three times daily dosing was used for a mean duration of 2.7±2.3 days, resulting in an average cumulative dose of 764±600 mg gentamicin. The average gestational age at exposure was 28 weeks. Maternal serum gentamicin levels were obtained in 72.5% of cases, and no trough level was above 2 mg/L. Other potentially ototoxic medications were administered to the mother in 17.5% of pregnancies, and to 17.5% of babies in the immediate newborn period. With the exception of one infant who died before additional testing could be carried out, all the infants passed hearing tests, 89% on initial screening. ConclusionIn utero exposure to gentamicin did not cause an increase in audiologic impairment in the infants tested in this cohort.

Chlorambucil Induced Angioedema of the Tongue in a Patient with Lymphoma.

A Caucasian female, born in 1941, was first seen in November 2002 because of tiredness, weight loss and splenomegaly. She was taking glyburide, procylidine and venlafaxine for diabetes, parkinsonism and depression. Physical examination, revealed marked splenomegaly but no lymphadenopathy. Flowcytometry of peripheral blood showed a monoclonal B cell lymphoproliferative disorder consistent with marginal zone lymphoma. She was treated with chlorambucil 6 mg daily and prednisone 25 mg daily. She responded well to therapy. Chemotherapy was discontinued in December 2003. In April 2005 she was admitted to the hospital with pneumonia. She had pancytopenia and marked splenomegaly. Bone marrow apirate showed infiltration with marginal zone lymphoma cells. She was prescribed Chlorambucil 6 mg daily for management of her recurrent lymphoma. She took her first 6 mg of Chlorambucil at 8:00 PM of May 18, 2005 and woke up around 5:30 AM with grossly swollen tongue. She was brough to Emergency ward at 06:45 hr with grossly swollen, tender tongue protrudinng form her widely opened mouth. Angioedema of the tongue was diagnosed and she was given epinephrin, IV Benadryl, Solumedrol and morphine. By 10:00 hr, she was in moderate respiratory distress. She was taken to OR at 10:20 for urgent intubation or tracheotomy. Endoscopy revealed ++ oropharyngeal and supraglotic edema. A nasotracheal tube was inserted at 11:00 hr. The picture included was taken one hour after intubation.(16 hrs after taking chlorambucil). She was given Solumedrol 125 mg IV Q 12 hr. By 24 hours after intubation her tongue had receded into her mouth and she was extubated. Her serum C1 inhibitor was 0.13 g/L (normal 0.15–0.35) and functional C1 esterase inhibitor was 87% (normal >67%). Immunoglobulines, C3 & C4 were normal. Her lymphoma was treated with 6 courses of R-CVP regimen. She has not received any more chlorambucil and she has not had any more angioedema or anaphylactic reaction of any kind. In May 2005 her C1 inhibitor was 0.38 g/L and functional C1 esterase inhibitor was 96%.Discussion: on the day before experiencing angioedema of the tongue, she had not taken any unusual food or any other new medication. The time sequence and subsequent course of this case strongly suggest that the angioedema of the tongue was due to Chlorambucil. The literature does not show any report of chlorambucil induced angioedema. However, angioedema is listed as one of the adverse reactions of Chlorambuci both in AHFS Drug Information and in Compendium of Pharmaceuticals and Specialities. Following communication with GlaskoSmithKline, the manufacturer of Chlorambucil, I was told that, they are not aware of any published report, but they have reports of angioedema induced by Chlorambucil in their file. I was told that they are not in position to reveal the number of such reactions. [Display omitted]

Drug information resources used by nurse practitioners and collaborating physicians at the point of care in Nova Scotia, Canada: a survey and review of the literature

BackgroundKeeping current with drug therapy information is challenging for health care practitioners. Technologies are often implemented to facilitate access to current and credible drug information sources. In the Canadian province of Nova Scotia, legislation was passed in 2002 to allow nurse practitioners (NPs) to practice collaboratively with physician partners. The purpose of this study was to determine the current utilization patterns of information technologies by these groups of practitioners.MethodsNurse practitioners and their collaborating physician partners in Nova Scotia were sent a survey in February 2005 to determine the frequency of use, usefulness, accessibility, credibility, and current/timeliness of personal digital assistant (PDA), computer, and print drug information resources. Two surveys were developed (one for PDA users and one for computer users) and revised based on a literature search, stakeholder consultation, and pilot-testing results. A second distribution to nonresponders occurred two weeks following the first. Data were entered and analysed with SPSS.ResultsTwenty-seven (14 NPs and 13 physicians) of 36 (75%) recipients responded. 22% (6) returned personal digital assistant (PDA) surveys. Respondents reported print, health professionals, and online/electronic resources as the most to least preferred means to access drug information, respectively. 37% and 35% of respondents reported using "both print and electronic but print more than electronic" and "print only", respectively, to search monograph-related drug information queries whereas 4% reported using "PDA only". Analysis of respondent ratings for all resources in the categories print, health professionals and other, and online/electronic resources, indicated that the Compendium of Pharmaceuticals and Specialties and pharmacists ranked highly for frequency of use, usefulness, accessibility, credibility, and current/timeliness by both groups of practitioners. Respondents' preferences and resource ratings were consistent with self-reported methods for conducting drug information queries. Few differences existed between NP and physician rankings of resources.ConclusionThe use of computers and PDAs remains limited, which is also consistent with preferred and frequent use of print resources. Education for these practitioners regarding available electronic drug information resources may facilitate future computer and PDA use. Further research is needed to determine methods to increase computer and PDA use and whether these technologies affect prescribing and patient outcomes.

Cannabinoids for Pain Management: What is their Role?

In the popular press, many Canadians claim to be using herbal cannabis (marijuana) to control symptoms such as pain, nausea, muscle spasm, anorexia and anxiety that may be associated with diseases like AIDS/HIV, multiple sclerosis, epilepsy and chronic pain. Surveys of patients with chronic pain, multiple sclerosis and epilepsy suggest that approximately 10% to 12% of these patients are active cannabis users, and up to 36% have tried using herbal cannabis or its derivatives to control symptoms they experience with these diseases (1-3). On the other hand, the prescription cannabinoids available have, to date, only limited use in the management of pain. Neither nabilone (Cesamet, Valeant Canada limitee/Limited) nor dronabinol (Marinol, Solvay Pharma Inc, Canada) have pain as an indication according to the Canadian Compendium of Pharmaceuticals and Specialties (4), while Sativex (GW Pharma Ltd, United Kingdom) is only indicated for neuropathic pain in multiple sclerosis. Although there is a large and growing preclinical literature regarding potential therapeutic uses of cannabinoids, there are few studies on the clinical efficacy of natural and synthetic cannabinoids as analgesics. Previous available studies have involved only small numbers of subjects and were often of limited quality (5). An overview of the rapidly developing basic science relevant to potential analgesic actions of cannabinoids (6), which includes a review of the endogenous cannabinoid system; evidence of antinociceptive, antihyperalgesic and anti-inflammatory actions; and a review of the pharmacokinetics of cannabinoids (7) is presented in this special issue. Reviews of the current literature assist in understanding the possible toxic effects (8), safety (9) and risks of addiction (10) of cannabinoids. As with all pharmacologically active agents, currently available cannabinoids are associated with adverse effects, and it is important to be aware of these effects as clinicians begin to consider these agents in the treatment of pain. Examples include effects on drowsiness, attention and cognition, the possibility of exaggerating existing psychoses or provoking others long-term, postural hypotension and tachycardia. Further understanding the roles of the cannabinoid receptors (CB1 and CB2) and the development of new cannabinoid receptor agonists will allow us to maximize the analgesic efficacy and minimize the side effects caused by the cannabinoids. Development of novel agonists, which do not cross the bloodbrain barrier, alternative methods of delivery (ie, transdermal, buccal, rectal, etc), and further elaboration of ways to manipulate the endogenous cannabinoid system are all exciting areas of research that will lead to compounds exhibiting greater efficacy, and potentially fewer adverse effects. However, it will likely be several years before such compounds will be clinically available and, right now, we need to be familiar with the currently available compounds. The purpose of the present supplement to Pain Research & Management is to provide Canadian clinicians and researchers with comprehensive reviews of the current basic and clinical science regarding cannabinoids, along with up-to-date reviews of the literature relevant to safety, toxicity and the risk of addiction related to cannabinoids. The authors of the present supplement have developed an algorithm for use by clinicians in the assessment and treatment of chronic pain when cannabinoid compounds are considered. In addition, guidelines for the use of the two oral cannabinoid compounds that are currently available by prescription in Canada are provided. It is not possible to make recommendations about the buccal administered cannabinoid compound because information is limited. The use of smoked herbal cannabis should be discouraged; there is significant controversy regarding this route of delivery. There is no question that smoking is toxic, but can patients limit their risk by minimizing the dose? Do the benefits outweigh the risks in some cases? The answers to these questions await further study and, until inexpensive, safer and efficient methods of delivery are available, it is probable that some patients with pain and other symptoms will seek relief by smoking cannabis. Others may receive existing preparations for off-label use. It is the goal of the present supplement to assist clinicians, researchers and policy makers with these issues. EDITORIAL

Limitations to antiarrhythmic drug use in patients with atrial fibrillation.

Of the antiarrhythmic agents currently marketed in Canada, 5 are commonly used to treat atrial fibrillation (AF). The impact of contraindications, warnings and precautions for the use of these drugs in patients with AF is not known. We evaluated the proportion of patients with AF for whom contraindications, warnings and/or precautions might limit the use of these commonly prescribed drugs and the proportion of patients actually receiving antiarrhythmic drugs despite the presence of contraindications and/or warnings. A total of 723 patients with electrocardiographically confirmed, new-onset paroxysmal AF who were enrolled in the Canadian Registry of Atrial Fibrillation were used in this analysis. The 1996 Compendium of Pharmaceuticals and Specialties was used to obtain contraindications, warnings and precautions for use of 5 antiarrhythmic drugs: flecainide, quinidine, sotalol, amiodarone and propafenone. Proportions of patients with contraindications, warnings and/or precautions for use of any of these drugs owing to comorbid conditions or concomitant drug therapy were calculated, regardless of whether the drugs had been prescribed. We then calculated the proportion of patients taking each antiarrhythmic drug at 3 months despite contraindications and/or warnings. At baseline, when conditions for contraindications and warnings were combined, 414 (57%), 235 (33%), 327 (45%), 285 (39%) and 272 (38%) patients had restrictions for the use of flecainide, quinidine, sotalol, amiodarone and propafenone respectively. Among 465 patients actually taking these medications at 3-month follow-up, 33.3% (2/6), 83.3% (40/48), 36.4% (92/253), 64.1% (25/39) and 34.5% (41/119) respectively had contraindications and/or warnings against their use. The burden of comorbid disease among patients with AF was noteworthy: 404 (56%) had structural heart disease, which included 227 (31%) with ischemic heart disease, 158 (22%) with left ventricular systolic dysfunction and 106 (15%) with heart failure. The high burden of comorbid disease and concomitant drug use in a large proportion of patients with AF limits the suitability of existing antiarrhythmic drugs. Over one-third of patients with new-onset AF received antiarrhythmic drugs despite the presence of contraindications or warnings. Although such restrictions may not preclude the use of these drugs, the results demonstrate the need for new antiarrhythmic drugs with fewer limitations.

Canadian Standards Association Standard CAN/CSA/Z264.1-02:2002: A New Voluntary Standard for Spacers and Holding Chambers Used with Pressurized Metered-Dose Inhalers

A new Canadian standard (CAN/CSA/Z264.1-02:2002) has been published with the purpose of helping to ensure the safety, efficacy and functionality of spacers and/or holding chambers. They are prescribed for use by spontaneously breathing patients for the treatment of various respiratory diseases where medication is delivered to the lungs using pressurized-metered dose inhalers. This consensus standard was developed with the support of pharmaceutical companies and manufacturers of spacers and holding chambers, and with the help of clinicians, retail pharmacists and representatives of patient advocate bodies associated with respiratory diseases and the dissemination of information related to the treatment and the delivery of inhaled medications. Advice was also sought from expert groups outside of Canada to ensure that the standard would be relevant internationally. Whereas monographs in the pharmaceutical compendia and guidance documents published by regulatory bodies provide information that is largely about the drug product and inhaler, this is the only standard whose focus is primarily on these add-on devices. The purpose of the present review is to highlight the main features of the standard for clinicians by describing its scope, the tests that are intended to assure the robustness of the construction of these devices, the type of testing that is specified to establish in vitro efficacy, and the recommendations for the marking and labelling of the device and its associated packaging. Manufacturers who test their products to this Canadian Standards Association standard will be able to provide performance information about add-on devices to the clinician, facilitating an informed decision when selecting devices for patients.

Where physicians look for information on drug prescribing for children

Despite the important role of drug therapy in children, there is often a lack of readily available information regarding the indications and dosing regimens for medications in paediatrics. To collect data on where family physicians obtain this prescribing information. A structured questionnaire was mailed to 500 family physicians in Ontario. Questionnaires were returned by 261 (52%) family physicians, 217 (83%) of whom identified themselves as currently involved in the care of children. Most (87%) reported that the Compendium of Pharmaceuticals and Specialties (CPS) was the source that they most commonly consulted for drug information in children. The available sources of information on prescribing for children were thought to be not adequate by 40% and not readily available by 27%. Sixty-one per cent reported being moderately confident (in doubt part of the time) about their decisions regarding drug prescribing in this age group. The majority (70%) had learned most of what they know about prescribing in paediatrics during practice, while 69% and 62% reported they had little or no teaching during undergraduate and postgraduate (internship or residency) medical education, respectively. Although it is recognized that for a number of drugs used in children the CPS does not reflect the current standard of care in paediatrics, it is currently the source most commonly referred to by family physicians. Further work should be done in the provision of useful information on paediatric drug therapy to family physicians.

The physician's role and responsibility in reporting adverse drug events in children

The physician's role and responsibility in reporting adverse drug events in children

The carbohydrate and caloric content of concomitant medications for children with epilepsy on the ketogenic diet.

The ketogenic diet for children with refractory epilepsy requires a strict control of the amount of ingested carbohydrates. This can be altered by medication prescribed for the epileptic syndrome or for intercurrent illnesses. The goal of this paper is to compile the carbohydrate and caloric content of commonly used medications in this population. We compiled a list of frequently used medications with the help of Canadian manufacturers and the Compendium of Pharmaceuticals and Specialties. We also tested a worst case scenario calculation based on the weight of the tablet. We list the carbohydrate and caloric content of 790 medications studied. Our worst case scenario gives an over-estimate in all cases, making adjustments based on this calculation in an emergency setting safe. We propose this list as a tool for physicians, dietitians, nurses and pharmacists. The list can easily be adjusted, based on local practices and reviewed periodically.