The Ministry of Health, Labour and Welfare (MHLW) and the Pharmaceuticals and Medical Devices Agency (PMDA) have announced that the package insert for azithromycin (Zithromax®) has been updated to include the risk of acute generalized exanthematous pustulosis as a clinically significant adverse reaction. Azithromycin is an antimicrobial used for a number of bacterial infections caused by strains of genus Staphylococcus, Streptococcus, Pneumococcus, Neisseria gonorrhoeae, Moraxella (Branhamella) catarrhalis, Haemophilus influenzae, Legionella pneumophila, Peptostreptococcus, Prevotella, Chlamydia, and Mycoplasma. One case of acute generalised exanthematous pustulosis has been reported in Japan. A causal relationship could not be excluded in this case. In addition, the company core datasheet (CCDS) has been updated.
The Saudi Food and Drug Authority (SFDA) has updated the summary of product characteristics and patient information leaflet for doxycycline to include the risk of fixed drug eruptions (FDE). Doxycycline is a tetracycline broad-spectrum antibiotic with bacteriostatic characteristics. It is used as treatment or prophylaxis against a wide range of susceptible strains of gram-negative and gram-positive bacteria and other microorganisms. The SFDA initiated the investigation based on a signal observed in a published case report examining potential associations between doxycycline and risk of FDE. As a result, the SFDA reviewed the available evidence related to this safety issue including screening of the WHO global database of Individual Case Safety Reports, VigiBase. In addition, a literature review was conducted. The SFDA concluded that the available evidence suggests a probable association between doxycycline and FDE.
Paracetamol (modified- or prolonged-release)
The EMA has recommended that modified- or prolonged-release paracetamol products should be suspended from the market. This is in view of the risks to patients from the complex way these medicines release paracetamol into the body after an overdose. Paracetamol is a medicine that has been widely used for many years to relieve pain and fever in adults and children. The review of modified-release paracetamol has been carried out by the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC). The PRAC evaluated published studies and reports of overdose with these medicines, consulted experts in the management of poisoning and assessed how overdose with paracetamol is managed in the EU and other parts of the world. In many cases, it may not be known whether an overdose of paracetamol involves immediate-release or modified-release products, making it difficult to decide what type of management is needed. The committee could not identify a way to minimise the risk to patients, or a feasible and standardised way to adapt the management of paracetamol overdose across the EU to allow for treatment of cases that involve modified-release preparations. It concluded that the risk following overdose with these medicines outweighs the advantage of having a longer-acting preparation.
The MHLW and the PMDA have announced that the package insert for warfarin has been updated to include the risk of calciphylaxis as a clinically significant adverse reaction. Warfarin is used for treatment and prevention of thromboembolism (including venous thrombosis, myocardial infarction, pulmonary embolism, brain embolism and, slowly progressive cerebral thrombosis). Eleven cases associated with calciphylaxis have been reported in Japan and there is an overseas report published in the literature describing calciphylaxis with the use of warfarin. In addition, package inserts in Europe and the United States have been revised.
Health Canada has carried out a safety review to look at the potential risk of QT interval prolongation with the use of over-the-counter (OTC) desloratadine-containing products. This safety review was triggered by a signal publication in the WHO Pharmaceuticals Newsletter No.2, 2015, describing cases of abnormal heart rhythm suspected to be associated with the use of loratadine and desloratadine. Desloratadine is used to relieve symptoms of seasonal allergy or allergy caused by pollen or dust (hay fever). At the time of the review, Health Canada had received 10 Canadian reports of abnormal heart rhythm suspected to be associated with desloratadine use. In addition, Health Canada reviewed 13 international reports of abnormal heart rhythm suspected to be associated with the use of desloratadine that were provided by the manufacturer. A search in the WHO database of Individual Case Safety Reports, VigiBase identified 35 cases of abnormal heart rhythm suspected to be associated with desloratadine use. A link between the use of desloratadine and the abnormal heart rhythm could not be established, as there was not enough information in the reports to draw conclusions. Published scientific studies have shown that desloratadine is not associated with abnormal heart rhythm in humans.
The MHLW and the PMDA have announced that the package inserts for diclofenac preparations (Voltaren® and Rectos®) have been updated to include the risk of gastrointestinal stenosis and obstruction as clinically significant adverse reactions. A total of five cases of gastrointestinal stenosis or obstruction associated with the use of diclofenac have been reported in Japan. In addition, the company core datasheet (CCDS) has been updated.
Health Canada is working with the Drug Safety and Effectiveness Network to further investigate the extent of ondansetron (Zofran®) use during pregnancy and the risk to the foetus. Health Canada has requested that manufacturers submit information they may have regarding birth defects and use of ondansetron during pregnancy. At the time of the review, Health Canada had received 14 reports of birth defects in the newborn babies of mothers treated with ondansetron. Findings from published scientific studies were inconsistent and inconclusive. There were concerns with study design, and the majority had a number of limitations such as use of concomitant medications. Available information were not sufficient to establish a link between the use of ondansetron during pregnancy and the risk of birth defects. Health Canada will continue to monitor safety information involving the use.
Health Canada has concluded in a review that there is not enough evidence to confirm a link between incretin-based therapies and pancreatic cancer. During the last few years, a small number of studies have found a possible link between the use of incretin-based therapies and an increased risk of pancreatic cancer. This led Health Canada to conduct a review. At the time of the review, 15 cases of pancreatic cancer that may have been linked to the use of incretin-based therapies had been reported to Health Canada. Although some non-clinical studies using animal or human models have suggested that the use of incretin-based therapies may be linked to an increased risk of pancreatic cancer, results from clinical trials and many studies looking at the patterns, causes, and effects of health and disease conditions in people, do not support this link.
The HPRA has issued advice to health-care professionals on monitoring the international normalised ratio (INR) more closely in patients concurrently treated with vitamin K antagonists. A signal of a potential drug interaction leading to a reduced INR has recently been identified with co-administration of direct-acting antivirals and vitamin K antagonists. The case reports on which the signal was based were reviewed by the EMA’s PRAC. The PRAC has recommended that the product information of direct-acting antivirals should be updated to include a recommendation for close monitoring of INR in patients treated with vitamin K antagonists, as liver function may change during treatment with direct-acting antivirals. While no change in the pharmacokinetics of warfarin is expected, close monitoring of INR is recommended with all vitamin K antagonists.
The MHLW and the PMDA have announced that the package inserts for warfarin and miconazole (Florid®) have been updated to include a contraindication of administering warfarin and miconazole concomitantly due to increased risk of bleeding. The package inserts for other antifungal drugs (voriconazole, itraconazole, fluconazole and fosfluconazole) have also been updated to include precautions about concomitant administration with warfarin. A total of 41 cases associated with serious bleeding during concomitant administration or, after discontinuation of concomitant administration of miconazole and warfarin have been reported in Japan. Due to the contraindication of concomitant administration of miconazole and warfarin, the use of other azole drugs, including those recommended as first-line treatments is expected. Thus, MHLW/PMDA considered that caution is also required for concomitant administration of warfarin and other azole antifungal drugs.
2016 © THE PHARMA WORLD. All Rights Reserved.