Questions about complementary and alternative medicine to the Regional Medicines Information and Pharmacovigilance Centres in Norway (RELIS): a descriptive pilot study

Background: Provision of clinically relevant information about complementary and alternative medicine (CAM) to health care professionals is not well described. The aim of the study was to assess questions about CAM to the Regional Medicines Information and Pharmacovigilance Centres in Norway (RELIS). Methods: All question-answers pairs (QAPs) in the RELIS database indexed with alternative medicine from 2005-2010 constituted the study material. A randomly selected sample of 100 QAPs was characterized with regard to type of question (category, patient-specific or general), occupation and workplace of enquirer, the type of information search performed (simple or advanced), and if the answers contained information to provide factual or consultative replies (facts about or advice on clinical use of CAM, respectively). Proportions were compared with Fisher’s exact test with significance at the 0.05 level. Results: One thousand and thirty-eight (7.7%) out of 13 482 questions involved CAM. Eighty-two out of 100 questions concerned products containing one or more herbs, vitamins and minerals as well as other substances. Thirty-eight out of 100 questions concerned the category documentation (substance identification and/or literature reports about clinical effects), 36 interactions, 16 adverse effects, 9 pregnancy and lactation, and 1 question concerned contraindications. Sixty-three questions were patient-specific and 37 general. Fifty-four questions came from physicians, 33 from pharmacists and 13 from others (including nurses, midwives, students, CAM practitioners, and the public). Pharmacists asked more frequently about interactions while physicians asked more frequently about adverse effects (p < 0.05). Seventy-six of the questions came from outside hospital, mainly general practice and community pharmacies. Fifty-nine answers were based on a simple and 41 on an advanced information search. Thirty-three factual and 38 consultative answers were provided. In 29 answers, search provided no information. Lack of information to provide an answer was not significantly different between patient-specific (31.7%) and general questions (24.3%). Conclusions: General practice and community pharmacies are the main sources for questions about CAM to RELIS. Physicians are concerned about adverse effects while pharmacists are concerned about interactions. Lack of information to provide answers to patient-specific and general questions about CAM represents a problem

Breastfeeding women in need of information about antiemetics for nausea and vomiting during pregnancy: a review of inquiries to a medicines information service

Introduction: The medicines information service, SafeMotherMedicine, regularly receives inquiries from breastfeeding women asking about antiemetics for nausea and vomiting during pregnancy (NVP) or hyperemesis gravidarum (HG). However, treatment guidelines for NVP or HG do not address the use of antiemetics in women who are breastfeeding while becoming pregnant again. Our objective was to characterize inquiries to describe the need for lactation risk information among women with NVP or HG and also to raise awareness of this topic.Method: We conducted a review of inquiries to the Norwegian web-based medicines information service, SafeMotherMedicine.Results: In total, 97 inquiries addressing the use of antiemetics for NVP or HG during breastfeeding were identified. The following medications were addressed in the inquiries (n = 97): meclizine (51%), metoclopramide (33%), promethazine (16%), ondansetron (9%), and others (6%). The breastfed child was older than 6 months and 1 year in 96% and 71% of the inquiries, respectively. There was a preponderance of general inquiries (unclear motivation/double checking) (64%); however, one-third of the inquiries were generated by restrictive information from sources such as product information.Conclusion: Based on our small review of spontaneous inquiries, there seems to be an information need about the use of antiemetics during lactation among women breastfeeding an older infant whilst suffering from NVP or HG. Addressing such use in guidelines for NVP and HG and/or other easily available information sources may be considered in order to balance out the restrictive information provided by the manufacturers. This could avoid potential unnecessary weaning of breastfeeding in an otherwise challenging situation

Review of Clinical Questions Submitted to Norwegian Drug Information Centres Concerning Administration and Dosage to Older Patients of Relevance to Patient-Centric Care

Patient-centric care entails optimising healthcare provision to patients based on their perspective and opinion. It involves appropriate treatment at a reasonable cost and a focus on patient characteristics in the decision-making process to make it more personally useful. The optimisation of medicines in the older population is a challenge due to physiological changes, comorbidity, and polypharmacy. Furthermore, patient-centric care is difficult to achieve due to the high proportion of patients with dementia and frailty. Decision support concerning the appropriateness of indication, formulation, dose, administration, co-prescribing, and length of treatment to older patients is frequently in demand. In the current study, we aimed to review clinical questions concerning administration and dosage to older patients of relevance to patient-centric care. We analysed questions concerning medicines to patients 65 years or older in the database of the network of Norwegian drug information centres from 2010 to 2020. The analysis included the distribution of drugs, diseases, and recurring topics among the questions. Through a Boolean search that combined the indexed categories of “older” and “administration and dosage”, we retrieved 84 question-answer pairs. Questions about psychotropic and cardiovascular drugs in relation to therapy, adverse drug reactions, and pharmacokinetics dominated, and more than 60% of the questions came from physicians. Topics relevant to patient-centric pharmacotherapy were drug withdrawal (10 questions), drug formulation (8 questions), drug initiation (8 questions), and switching drugs (5 questions). One question concerned drug withdrawal and switching, and one question drug formulation and switching. Answers provided decision support regarding appropriate formulations of drugs to patients with dementia who chew capsules or tablets, the use of parenteral administration in patients who refuse to take oral formulations, and the pharmacokinetics of transdermal or rectal drug administration. The results highlight the importance of including pharmacological factors in the assessment of the acceptability and appropriateness of oral and parenteral medicine to older patients.publishedVersio

Short communication: Distribution of psychotropic drugs into lipoproteins

Under embargo until: 2020-12-01Aim: The aim of this pilot study was to investigate whether psychotropic drugs frequently analyzed in a routine therapeutic drug monitoring laboratory bind to low-density lipoproteins/very-low-density lipoproteins (LDL/VLDL) in human serum. Methods: Drug concentrations in 20 serum sample pools containing one psychotropic drug each, and in the LDL/VLDL fractions extracted from the same samples, were measured by triple quadrupole liquid chromatography tandem mass spectrometry. The membrane permeability of the drugs was measured using a Parallel Artificial Membrane Permeability Assay. Results: Of the 20 antidepressants, antipsychotics, and antiepileptics examined, 7 drugs were detected in both the pooled serum samples and in the LDL/VLDL fraction. Binding of drugs to LDL/VLDL significantly correlated with high octanol: water partition coefficient (logP), high degree of protein binding, and a low polar surface area. The drugs found in LDL/VLDL, with the exception of aripiprazole, were also characterized by high or intermediate membrane permeability. Conclusions: The present results indicate that psychotropic drugs with certain characteristics bind to LDL/VLDL in blood. This further implies that lipoproteins could play an important role in drug transport.acceptedVersio

Relationship Between Time Consumption and Quality of Responses to Drug-Related Queries : A Study From Seven Drug Information Centers in Scandinavia

Paid Open Acces

Intracellular Cytidine Deaminase Regulates Gemcitabine Metabolism in Pancreatic Cancer Cell Lines

Cytidine deaminase (CDA) is a determinant of in vivo gemcitabine elimination kinetics and cellular toxicity. The impact of CDA activity in pancreatic ductal adenocarcinoma (PDAC) cell lines has not been elucidated. We hypothesized that CDA regulates gemcitabine flux through its inactivation and activation pathways in PDAC cell lines. Three PDAC cell lines (BxPC-3, MIA PaCa-2, and PANC-1) were incubated with 10 or 100 µM gemcitabine for 60 minutes or 24 hours, with or without tetrahydrouridine, a CDA inhibitor. Extracellular inactive gemcitabine metabolite (dFdU) and intracellular active metabolite (dFdCTP) were quantified with liquid chromatography tandem mass spectrometry. Cellular expression of CDA was assessed with real-time PCR and Western blot. Gemcitabine conversion to dFdU was extensive in BxPC-3 and low in MIA PaCa-2 and PANC-1, in accordance with their respective CDA expression levels. CDA inhibition was associated with low or undetectable dFdU in all three cell lines. After 24 hours gemcitabine incubation, dFdCTP was highest in MIA PaCa-2 and lowest in BxPC-3. CDA inhibition resulted in a profound dFdCTP increase in BxPC-3 but not in MIA PaCa-2 or PANC-1. dFdCTP concentrations were not higher after exposure to 100 versus 10 µM gemcitabine when CDA activities were low (MIA PaCa-2 and PANC-1) or inhibited (BxPC-3). The results suggest a regulatory role of CDA for gemcitabine activation in PDAC cells but within limits related to the capacity in the activation pathway in the cell lines. SIGNIFICANCE STATEMENT The importance of cytidine deaminase (CDA) for cellular gemcitabine toxicity, linking a lower activity to higher toxicity, is well described. An underlying assumption is that CDA, by inactivating gemcitabine, limits the amount available for the intracellular activation pathway. Our study is the first to illustrate this regulatory role of CDA in pancreatic ductal adenocarcinoma cell lines by quantifying intracellular and extracellular gemcitabine metabolite concentrations.publishedVersio

Perceptions of generic medicines and medication adherence after percutaneous coronary intervention: a prospective multicentre cohort study

Objective: To determine patient perceptions of generic medicines 2 and 6 months after percutaneous coronary intervention (PCI), and to determine whether these perceptions moderate medication adherence. Design: Prospective multicentre cohort study with repeated measures of perceptions of generic medicines and medication adherence. Setting: The CONCARDPCI study conducted at seven large referral PCI centres in Norway and Denmark between June 2017 and May 2020. Participants: A total of 3417 adults (78% men), using both generic and brand name medicines, with a mean age of 66 years (SD 11) who underwent PCI were followed up 2 and 6 months after discharge from hospital. Main outcome measures: Perceptions of generic medicines were the main outcome. The secondary outcome was medication adherence. Results: Perceptions of generic medicines were significantly more negative at 2 than at 6 months (1.10, 95% CI 0.41 to 1.79, p=0.002). Female sex (−4.21, 95% CI −6.75 to −1.71, p=0.001), older age (−0.12, 95% CI −0.23 to −0.02, p=0.020), lower education level (overall p<0.001), ethnicity (overall p=0.002), Norwegian nationality (10.27, 95% CI 8.19 to 12.40, p<0.001) and reduced self-reported health status (0.19, 95% CI 0.09 to 0.41, p=0.003) were significantly associated with negative perceptions of generic medicines. There was no evidence to suggest that perceptions of generic medicines moderate the association between sociodemographic and clinical variables and medication adherence (p≥0.077 for all covariates). Moreover, self-reported medication adherence was high, with 99% scoring at or above the Medication Adherence Report Scale midpoint at both time points. There were no substantial correlations between negative perceptions of generic medicines and medication non-adherence at 2 months (r=0.041, 95% CI 0.002 to 0.081, p=0.037) or 6 months (r=0.038, 95% CI −0.005 to 0.081, p=0.057). Conclusions: Mistrust and uncertainty about the safety and efficacy of generic medicines remains in a sizeable proportion of patients after PCI. This applies especially to those of lower socioeconomic status, older age, female sex, immigrants and those with poorer mental health. However, this study demonstrated a shift towards more positive perceptions of generic medicines in the longer term.publishedVersio