Impact of a Forced Dose-Equivalent Levothyroxine Brand Switch on Plasma Thyrotropin: A Cohort Study.

Background: Patients with primary hypothyroidism are treated with levothyroxine (LT4) to normalize their serum thyrotropin (TSH). Finding the optimal dosage is a long-lasting process, and a small change can have major impact. Currently, limited data are available on the impact of dose-equivalent substitution between brands. This study aimed to determine the effect of the shortage of the LT4 brand Thyrax® in the Netherlands and the resulting dose-equivalent switch to another brand on plasma TSH concentrations in a large cohort of patients. Methods: Observational cohort study. Two registries representative for the Dutch population containing prescription and laboratory test data: the Nivel Primary Care Database and the PHARMO Database Network. Patients using at least 25 µg Thyrax daily for one year or longer were included. Two cohorts were formed: a switch cohort consisting of patients who switched from Thyrax to an alternative brand, and a Thyrax cohort including patients who continued to use Thyrax. Patients in the switch cohort did switch from Thyrax to a different brand of LT4 in 2016 and had two consecutive TSH measurements on the same dose of LT4, one before and one 6 weeks after the switch. Patients in the Thyrax cohort had two consecutive TSH measurements on the same dose of Thyrax that were 6 weeks apart. Results: In the Thyrax cohort, 19% of euthyroid patients using ≤100 µg had a TSH level outside the reference range at the subsequent measurement compared with 24% in the switch cohort (p < 0.0001). For patients using >100 µg Thyrax, these figures were 24% and 63%, respectively (p < 0.0001). Furthermore, patients using >50 µg Thyrax were four to five times more likely to become hyperthyroid after a dose-equivalent switch to a different brand compared with patients who stayed on Thyrax. Conclusions: In euthyroid patients continuing the LT4 product Thyrax at the same dose, TSH was out of range in 19-24% at least 6 weeks later. A dose-equivalent switch from Thyrax to other LT4 brands induced biochemical signs of overdosing in an even larger proportion (24-63%) of patients. The results indicate that a dose-equivalent LT4 brand switch may necessitate a dose adjustment in a large number of patients.

[Discontinuation of SSRIs and SNRIs]. / Het afbouwen van SSRI's en SNRI's.

Interruption or abrupt discontinuation of the use of antidepressants may lead to withdrawal symptoms. These are most common with selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs).There is insufficient scientific evidence about the prevalence of antidepressant withdrawal symptoms and how to optimally discontinue antidepressants. The multidisciplinary document 'Discontinuation of SSRIs & SNRIs' offers a rationale and suggestions for the gradual tapering of these antidepressants. The following factors are consistently named as risk factors for the occurrence of withdrawal symptoms: (a) the patient experiences withdrawal symptoms in case of non-compliance or skipped doses; (b) a previous attempt to stop was unsuccessful; and (c) the patient is being treated with higher doses than the smallest effective dose of SSRIs or SNRIs. In patients with one or more risk factors, a tapering schedule with non-linear dose-reduction steps should be considered. The speed at which these steps are taken, should be adjusted depending on occurrence of withdrawal symptoms. Shared decision-making by patient and physician is the best way to select a tapering schedule.

Trends in antithrombotic drug use and adherence to non-vitamin K oral anticoagulants in the Netherlands.

BACKGROUND: Non-vitamin K oral anticoagulants (NOACs) became available in the Netherlands in 2008, providing another antithrombotic treatment besides vitamin K antagonists (VKAs) and antiplatelet agents (APAs). OBJECTIVE: To describe the patterns of antithrombotic drug use between 2008 and 2013 by examination of dispensing data form community pharmacies in the Netherlands; to determine the concomitant use of NOACs with VKAs and APAs and switching between the drug classes; and to compare adherence to NOACs with adherence to APAs. SETTING: An observational retrospective study was conducted using routinely collected dispensing data from Dutch community pharmacies. METHODS: For each calendar year, the numbers of NOAC, VKA, and APA users were calculated. Adherence was determined for NOACs and APAs by the percentage of days covered by medication (PDC). Information on the prescribed daily dose of VKAs was unavailable. MAIN OUTCOME MEASURES: Comparison of age, sex, and co-medications of users of the three drug classes; concomitant use of different antithrombotic drug classes and switching between these in each year; and mean PDC and percentages of all users with a PDC above 80 %. RESULTS: NOAC use increased during the study period to 29,687 users in 2013. In that year there were 484,024 VKA users and 1313,032 APA users. Compared with users of VKAs, NOAC users were slightly younger and more frequently used antiarrhythmic drugs and beta blockers as co-medications. Substantial numbers of patients were dispensed potentially harmful combinations in 2013: 820 subjects were dispensed NOACs together with VKAs, and 684 subjects were dispensed NOACs, VKAs, and APAs concomitantly. Mean adherence to NOACs was 84.2 % compared with 87.3 % to APA. One in four NOAC users had a PDC lower than 80 % compared with one in five APA users. CONCLUSION: Our findings show increasing use of NOACs by outpatients. The number of patients taking potentially harmful combinations of antithrombotic drugs was substantial. Adherence to NOACs in daily practice may be suboptimal to prevent thrombotic events.

[Multidisciplinary guideline 'Recognition and treatment of chronic pain in vulnerable elderly people']. / Multidisciplinaire richtlijn 'Herkenning en behandeling van chronische pijn bij kwetsbare ouderen'.

Chronic pain in vulnerable elderly people is still poorly recognized and treated, both at home and in hospitals and care and nursing homes. Vulnerable elderly people experience and express pain differently to relatively healthy adults, especially when they suffer from cognitive impairment or specific conditions. Determining the nature and severity of the pain requires the use of pain assessment instruments that have been validated for use in vulnerable elderly people. Effective treatment of pain demands careful diagnosis and pharmacological and non-pharmacological interventions that have proven effectiveness in vulnerable elderly people. The combination of multiple morbidity and poly-pharmacy increases the chance of side-effects and complications. In addition, the pharmacokinetic and pharmacodynamic characteristics of many drugs are different in vulnerable elderly people. The advice is to start with a lower dose of pain medication and gradually build up a level on the basis of pain relief and side-effects ('start low, go slow!').

[Correct use of methotrexate]. / Correct gebruik van methotrexaat.

Insufficient knowledge about the correct dosage and potential implications of overdose have played an important role in recent accidents involving methotrexate (MTX). Therefore, it is important that the prescribing physician as well as the pharmacist and pharmacist's assistant have sufficient knowledge of the usual dosages, precautionary measures, side-effects, interactions and contraindications of MTX, to ensure a correct dosing regimen is prescribed. For nearly all indications, MTX is prescribed in a weekly dose of 5-30 mg and preferably in combination with 5 mg folic acid twice a week on a day that MTX is not used. The toxic dose of MTX lies very close to the effective MTX dose. It is therefore important to look out for signs of toxicity.

[Methotrexate: safe if prescribed correctly]. / Methotrexaat veilig, mits juist voorgeschreven.

Methotrexate (MTX) is an effective medicine that can be safely used for the treatment of rheumatic arthritis and severe cases of psoriasis. For nearly all indications MTX is prescribed as a weekly dose. As a result of prescription errors, miscommunication, failing pharmacovigilance and lack of knowledge, fatal incidents have occurred due to prescriptions for a dosage once daily instead of once weekly. To prevent such incidences in the future, a balanced automatic pharmacovigilance, clear instructions for the use of MTX on the prescription and good patient information are needed.