In Singapore, BCG vaccine is routinely given to newborns as part of the National Childhood Immunisation Schedule. From January to October this year, HSA received a total of 53 reports of lymphadenitis, out of which 27 cases presented as suppurative lymphadenitis. The cases of suppurative lymphadenitis appeared to have doubled compared to 2010. Studies have revealed that the incidence of suppurative lymphadenitis is dependent on a number of factors including the strain of BCG vaccine and its constituents, host-related factors as well as administration techniques. Healthcare professionals are advised on the role of intradermal administrative technique in administering BCG Vaccine SSI® which is known to be reactogenic and to report any suspected adverse events with the vaccine to the Vigilance Branch of HSA
HSA would like to update on overseas cases of rare and distinct congenital anomalies in infants exposed in utero to chronic high-dose fluconazole during first trimester of pregnancy. In response to several reports of rare, distinct congenital anomalies observed in infants whose mothers had received chronic daily treatment with 400mg to 800mg fluconazole during early pregnancy, the US FDA issued a drug safety communication informing that chronic, high doses of fluconazole may be associated with a rare and distinct set of birth defects in infants born to mothers treated with the drug during the first trimester of pregnancy. This risk does not appear to be associated with a single dose of fluconazole 150mg for treatment of vaginal candidiasis. The US pregnancy category for fluconazole indications (other than vaginal candidiasis) has been changed from category C to D. Healthcare professionals are advised to take into consideration the potential risks with long-term, high-dose use of fluconazole when prescribing the medication to women of child-bearing potential.
The Health Sciences Authority (HSA) would like to alert healthcare professionals to serious cases of bleeding associated with the use of dabigatran and to remind healthcare professionals to closely monitor patients who are prescribed this medication, especially those with renal impairment, as well as elderly patients. The Japanese MHLW had issued a safety advisory to warn of the potential for adverse events with dabigatran (Pradaxa®), following the death of five patients who were the drug. Two clinical cases of major bleeding events in elderly patients were also published in the Archives of Internal Medicine in August 2011. Healthcare professionals are reminded of the contraindications for use stated in the local package insert as well as to maintain close clinical surveillance for signs of bleeding or anaemia is recommended throughout the treatment period, especially in patients with risk factors for bleeding.
HSA would like to update healthcare professionals on the reports it has received relating to the ID-Micro Typing System test cell reagent, ID-DiaCell I-II-III. The ID-Micro Typing System test cell reagent, ID-DiaCell I-II-III, is licensed in Singapore for the detection of antibodies that may be present against the antigens on red blood cells during compatibility testing for blood transfusion. Recently, Bio-Rad received reports of an unexpectedly high number of false positive reactions with the use of test cell reagent (cell III) of the ID-Micro Typing System test cell reagent ID-Diacell I-II-III. Bio-Rad has initiated investigations into the possible reasons that may have resulted in these false positive reactions. Healthcare professionals who require the ID-Micro Typing System test cell reagent ID-Diacell I-II-III are advised to take into consideration the high rate of false positives when using this reagent for diagnostic purposes. It is recommended that all samples tested positive in the antibody screen should be confirmed by an antibody identification test.
HSA would like to draw the attention of healthcare professionals to an increased risk of high grade prostate cancer observed in patients taking 5-alpha reductase inhibitors (5-ARIs) in clinical studies. A recent review of two large, randomised controlled trials, namely the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, by the US Food and Drug Administration (FDA) indicated an increased incidence of high grade prostate cancer in patients treated with finasteride and dutasteride. Although the risk appeared to be low, healthcare professionals are advised to be aware of this safety information and to weigh the benefits-risks of 5-ARIs before prescribing them.
26 Sep 2011: Risk of neonatal extrapyramidal signs and/or withdrawal symptoms with antipsychotic drug use during third trimester of pregnancy
HSA would like to inform healthcare professionals that neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at potential risk of extrapyramidal signs (EPS) and/or withdrawal symptoms following delivery. The US Food and Drug Administration's (FDA) Adverse Event Reporting System database identified 69 suspected cases of neonatal EPS or withdrawal associated with antipsychotic drugs occurring with varying severity anytime from birth to one month after birth. Although the majority of the cases were confounded by other factors, there were some suspected cases which suggest that neonatal EPS and withdrawal may occur with antipsychotic drugs alone. Physicians are advised to consider the benefit versus risk of using antipsychotic drugs on a case-by-case basis.
HSA would like to inform healthcare professionals that neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at potential risk of extrapyramidal signs (EPS) and/or withdrawal symptoms following delivery. The US Food and Drug Administration's (FDA) Adverse Event Reporting System database identified 69 suspected cases of neonatal EPS or withdrawal associated with antipsychotic drugs occurring with varying severity anytime from birth to one month after birth. Although the majority of the cases were confounded by other factors, there were some suspected cases which suggest that neonatal EPS and withdrawal may occur with antipsychotic drugs alone. Physicians are advised to consider the benefit versus risk of using antipsychotic drugs on a case-by-case basis.
HSA would like to update healthcare professionals on the outcome of recent studies investigating the risk of venous thromboembolism (VTE) associated with the use of drospirenone-containing combined oral contraceptives (COCs). In May 2011, the EMA's Pharmacovigilance Working Party announced that although drospirenone-containing COCs are associated with a higher VTE risk than levonorgestrel-containing COCs and that the risk may be similar to that for COCs containing desogestrel or gestodene, the absolute risk of VTE with any COC (including those containing drospirenone) is very small. Based on the latest information available, HSA has concluded that the benefit-risk profile of Yasmin® and Yaz® remains positive when used according to its licensed indications. In its review, HSA has also considered the data from earlier observational studies conducted by academics and post-market surveillance studies undertaken by the company. Currently, Yasmin® and Yaz® are contraindicated in the presence or a history of VTE. Additional warnings on VTE, including risk factors for VTE, are in the process of being updated in the local package inserts of both products.
In October 1999, the first marketed rotavirus vaccine, RotaShield®, was withdrawn in the United States after studies suggested an elevated risk of intussusceptions (IS) which translated to nine additional cases of IS per 100,000 infants vaccinated. Recent data from post-marketing studies in Mexico, Brazil and Australia suggests that the newer generation rotavirus vaccines, Rotarix® and RotaTeq®, are associated with smaller elevated risks of IS compared to RotaShield® but the overall benefit/risk balance of both vaccines remains positive. To date, HSA has received a total of six cases of IS following receipt of rotavirus vaccines. Healthcare professionals are advised to be vigilant of any symptoms indicative of IS following vaccination with Rotarix® and RotaTeq® and to advise parents to seek treatment earlier if the child display any signs and symptoms suggestive of IS.
Recently, counterfeit contact lenses fraudulently labelled as "FreshLook®ColorBlends®" Contact Lenses from CIBA VISION, sold for aesthetic and eye sight correction purposes, were found to be distributed illegally by optical shops in Singapore. These products have been found to be unsafe and of poor quality. The use of such counterfeit products, especially, one that is placed directly on the eye, may seriously affect the user's eyesight and may potentially lead to serious complications such as eye infections, corneal ulcers (open sores in the outer layer of the eye) and blindness. Healthcare professionals are advised to report cases of adverse reaction associated with the use of contact lenses such as severe eye irritation, redness, blurred vision, pain, light sensitivity and unusual discomfort despite good contact lenses hygiene practices to the Vigilance Branch of HSA.
Data from the North American Antiepileptic Drug (NAAED) Pregnancy Registry indicated that the prevalence of oral clefts was 1.2% in infants exposed to topiramate in utero as compared to a prevalence of 0.39% to 0.46% in infants exposed to other AEDs. Relative risk of oral clefts in topiramate-exposed pregnancies in the NAAED Pregnancy Registry was 9.6 (95%CI: 3.6-25.7) when compared to background risk in the population. The UK Epilepsy and Pregnancy Register reported a similar increased prevalence of oral clefts (3.2 %) among infants exposed to topiramate monotherapy in utero which translates to a 16-fold increase in risk of oral clefts in topiramate-exposed pregnancies as compared to the background incidence (0.2%). With this new information, topiramate has been reclassified from Pregnancy Category C to D by the US Food and Drug Administration. The local package insert will be strengthened to include the safety information and healthcare providers are advised to weigh the benefits and risks of Topamax® when prescribing it to women of childbearing potential, including the need to emphasise the importance of using an effective birth control.
HSA would like to update healthcare professionals on the association of venous and arterial thromboembolic events with lenalidomide and thalidomide. From a recent review of overseas post-marketing data, it was observed that patients treated with thalidomide had an increased risk of arterial thromboembolism, in addition to the established risk of venous thromboembolism. The combination of lenalidomide and dexamethsaone has also been associated with an increased risk of venous and arterial thromboembolism (predominantly deep vein thrombosis, pulmonary embolism, MI and cerebrovascular accident). A review of the Celgene pharmacovigilance database found that a total of 493 medically confirmed reports of arterial thromboembolic events associated with lenalidomide have been received. Healthcare professionals are advised to take into consideration the above safety information, the presence of venous and arterial thromboembolic risk factors (eg, smoking, hypertension, hyperlipidaemia) as well as the need for thrombo-prophylaxis, when evaluating if their patients are suitable for treatment with thalidomide or lenalidomide.
HSA is alerting healthcare professionals to overseas cases of rare, but severe liver injury, including two cases of acute liver failure leading to liver transplant in patients treated with dronedarone. The two case reports of liver transplantation occurred at 4.5 and 6 months after initiation of treatment in patients with normal baseline liver function tests. Although both patients were taking concomitant medication, a causal relationship with dronedarone (Multaq®) could not be excluded. Healthcare professionals are advised to perform liver function test monitoring in patients being prescribed dronedarone and to advise their patients to report symptoms of potential liver injury such as sustained new onset abdominal pain, anorexia, nausea, vomiting, fever, malaise, fatigue, jaundice, dark urine or itching.
HSA would like to inform healthcare professionals that emerging data has shown that proton pump inhibitors (PPIs) may cause hypomagnesaemia if taken for prolonged periods of time. This applies especially to treatment duration with PPIs that exceed one year. Low serum magnesium levels can result in serious adverse events including tetany, arrhythmias and convulsions. This risk may be increased for patients on concomitant drugs known to deplete magnesium, such as digoxin and diuretics. Patients who develop hypomagnesaemia, besides requiring magnesium supplementation, may also need to discontinue their PPI therapy.
HSA recommends that healthcare professionals may consider monitoring magnesium levels prior to the initiation of PPI treatment and periodically in patients expected to be on prolonged PPI treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesaemia (eg, diuretics). Patients should be advised to seek immediate care from a healthcare professional if they experience arrhythmias, tetany, tremors, or seizures while on prolonged treatment.
HSA would like highlight the recent changes made to the labelling of fluoquinolones relating to the risk of QT interval prolongation. The CHMP of the European Medicines Agency (EMA) recently performed a review of QT prolongation related to fluoroquinolones, taking into consideration data from in vivo studies, in vitro electrophysiological studies and post-marketing data. From this review, the CHMP concluded that fluoroquinolones may be stratified into three groups depending on their potential for inducing QT interval prolongation. HSA is currently working with drug companies to update the package inserts of all oral and intravenous formulations of fluoroquinolones to strengthen the warnings regarding the potential of QT interval prolongation associated with its use. Healthcare professionals are encouraged to take into consideration the potential of a fluoroquinolone to cause QT prolongation when selecting this choice of therapy for their patients, especially in patients with risk factors.
In order to facilitate access by the public to commonly used medicines, HSA has embarked on a biannual review of Prescription Only Medicine (POM) class medicinal products to identify medicines that may be supplied without a doctor's prescription by pharmacists under exemptions where they are deemed sufficiently safe for use with reduced medical supervision. In the recent review, eight POM active ingredients were assessed to have met the criteria to be granted exemptions for supply without prescription. In additionally, HSA has also developed tools to ensure that all Pharmacy Only (P) medicines and medicines granted exemption for supply of POM without prescription are judiciously dispensed to members of the public These tools include the mandatory record-keeping for the supply of these medicines and the publication of Patient Information Leaflets (PIL) for these medicines at the HSA website. Pharmacists are strongly encouraged to refer to these PILs when counselling their patients on the use and side effects of the medicine.
The Health Sciences Authority (HSA) would like to alert healthcare professionals to local reports of serious skin reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with strontium ranelate (Protos®) received over the past four years, out of which two were associated with a fatal outcome. As early signs of rash and skin reactions may be indicative of a more serious reaction such as SJS and TEN, healthcare professionals are advised to educate their patients on the early recognition of allergic reactions and to seek medical attention promptly. In addition, patients who have stopped treatment due to hypersensitivity reactions should not re-start therapy with strontium ranelate.
The Health Sciences Authority (HSA) would like to update healthcare professionals on the outcome of its recent review of the benefit-risk profile of pioglitazone taking into consideration the new findings of its association with a small increased risk of bladder cancer. HSA with advice from its Pharmacovigilance Advisory Committee (PVAC) and an expert panel of endocrinologists and oncologists has assessed that the benefit-risk profile remains favourable and has put forward additional recommendations to guide doctors on its use so as to minimise the risk of bladder cancer in patients who are prescribed with the medicine. The local package insert of pioglitazone will also be amended accordingly to reflect the additional contraindications, warnings and precautions associated with its use.
HSA would like to inform healthcare professionals of the risk of methaemoglobinaemia associated with the use of benzocaine containing products. A review of the US cases indicated that methaemoglobinaemia may occur following a single administration of the benzocaine spray and may not be related to the amount applied. Of the 319 cases reported in the US, there were seven (2.2%) cases of death, 32 (10%) cases categorized as life-threatening and 216 (67.7%) cases categorized as serious. Healthcare professionals are advised to take note of HSA's advisory when prescribing or managing patients using benzocaine containing products and to report any adverse reactions suspected to be associated with benzocaine containing products to the Vigilance Branch of HSA.
The Health Sciences Authority (HSA) would like to alert healthcare professionals to overseas reports of maternal deaths and serious cardiovascular adverse events associated with the obstetric use of oral and injectable forms of terbutaline. The US FDA had received 16 maternal death reports between 1976 and 2009 and 12 maternal cases of serious cardiovascular events between Jan 1998 and Jul 2009 associated with the obstetric use of terbutaline. Some of the cardiovascular adverse events that were reported in these maternal cases include cardiac arrhythmias, myocardial infarction, pulmonary edema, hypertension, and tachycardia. Healthcare professionals are advised not to use terbutaline for the treatment of prolonged tocolysis due to the unfavorable benefit/risk profile when used for this purpose.
The Vigilance Branch of HSA would like to highlight that quinine sulphate is known to be associated with serious and life-threatening haematological reactions. Healthcare professionals are advised not to use it off-label for the management of nocturnal leg cramps due to its unfavourable benefit-risk profile for this condition.
HSA would like to remind healthcare professionals of the risk of photosensitivity reactions associated with topical ketoprofen. Following the European Medicines Agency's (EMA) review of the safety and effectiveness of topical ketoprofen-containing products, the French medicines regulatory agency (Afssaps) decided to suspend the marketing authorisation of all topical medicines containing ketoprofen in France in December 2009. EMA's Committee for Medicinal Products for Human Use (CHMP) concluded that the risk of serious photoallergic reactions was very low (one case per one million patients treated) and that the benefits of topical ketoprofen-containing products continue to outweigh their risks. Nevertheless, healthcare professionals are reminded to inform their patients on how to use these products appropriately so as to prevent serious skin photosensitivity reactions.
The UK Medicines and Healthcare products Regulatory Agency (MHRA) has recently announced that there have been reports of problems with inserting and removing Implanon® (SOL Limited) and that in some women who have had an unintended pregnancy, Implanon® was found not to have been inserted at all. Between May 2002 to September 2010, SOL Limited has reported a local rate of 0.06 unintended pregnancies per 100 implants distributed. The proper insertion of Implanon® is crucial for its efficacy. Healthcare professionals are strongly encouraged to follow the instructions on the package insert on the proper insertion of Implanon® and to promptly report any cases of contraceptive failures in patients using Implanon® to HSA.
HSA would like to update healthcare professionals on the recent findings of an 11-year follow-up of post-menopausal women in the Women's Health Initiative (WHI) study and remind healthcare professionals of the importance of appropriate use of hormone replacement therapy (HRT).
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