Details of the Dear Healthcare Professional Letters can be found on the Health Professionals Portal (HPP). HPP was developed for all healthcare professionals in Singapore. Dentists, medical doctors and pharmacists are required to log in at http://www.hpp.moh.gov.sg/.

Listing  

19 Dec 2008: Reports of pure red cell aplasia in patients treated with Cellcept® (mycophenolate mofetil) [Roche]                                                                                                      Roche, in consultation with HSA, updates healthcare professionals about new safety information on pure red cell aplasia (PRCA) associated with the use of Cellcept®  (mycophenolate mofetil, MMF). Forty-one cases of pure red cell aplasia have been reported in patients treated with MMF in combination with other immunosuppressive agents, of which 16 cases are considered to be possibly related to MMF. The mechanism for MMF-induced PRCA as well as the relative contribution of other drugs in a multiple-drug immunosuppression regimen are unknown. In some cases PRCA was found to be reversible with dose reduction or cessation of MMF therapy. However, reduced immunosuppression in transplant patients may place the graft at risk. Roche will be updating the product information to include this new safety information.

20 Oct 2008: Recall of Hot/Cold Packs
The Health Sciences Authority's (HSA) laboratory tests on hot/cold gel packs found that gel packs from 4 companies, Tyco Healthcare, Assisted Living, Lifeline Corporation and OSIM International, contained ethylene glycol, a highly toxic substance that may be harmful if swallowed. A total of 10 hot/cold gel packs were identified to contain ethylene glycol.  Following this finding, the 4 companies have undertaken a voluntary recall of the 10 affected products from retail shops and pharmacies from 16 October 2008. Healthcare professionals are advised to be vigilant for patients who may present with symptoms of ethylene glycol poisoning after using hot/cold packs.

7 Oct 2008: New Formulation of Eltroxin® (Levothyroxine) tablets[GlaxoSmithKline]                                                                                                                                     Eltroxin® (Levothyroxine) is indicated as replacement therapy for hypothyrodism. GlaxoSmithKline (GSK), in consultation wtih HSA, informs physicians of a change in formulation and appearance of Eltroxin® 50mcg and 100mcg tablets.  The reformulation involved only the excipients, with the active ingredient remaining unchanged as in the previous formulation. In view of the narrow therapeutic index of Levothyroxine and variability between patients' pharmacokinetic profiles, some patients may experience a change in clinical effect when switched between brands or formulations.  Doctors are advised to be vigilant for symptoms suggestive of adverse reactions or loss of clinical control in patients using the reformulated Eltroxin® tablets.  Dose adjustments and thyroid function tests should be conducted when necessary. 

19 Sep 2008: US FDA's actions on products manufactured by two Ranbaxy's manufacturing plants in India
The Health Sciences Authority (HSA) updates healthcare professionals on the recent warnings issued by the US Food and Drug Administration (FDA) to two of Ranbaxy's manufacturing plants in India due to deviations from manufacturing standards. No recall of products has been initiated by US. Locally, there is also no product recall initiated and patients taking Ranbaxy products are advised to continue their drug therapy till further notice.

18 Sep 2008: First case of Progressive Multifocal Leukoencephalopathy (PML) in Rheumatoid Arthritis patient  treated with Mabthera®(Rituximab)[Roche]                                                                                                                                                                              Roche updates hematologists, medical oncologists and rheumatologists about new safety information regarding use of Mabthera®. A case of progressive multifocal leukoencephalopathy (PML) leading to death, had been reported in a patient who received Mabthera® for the treatment of rheumatoid arthritis (RA) in a long-term safety extension clinical study. This is the first case of PML reported with a labelled use of Mabthera®. PML was diagnosed approximately 18 months after the last dose of Mabthera® and 9 months after treatment with chemotherapy and radiation for oropharyngeal cancer. Roche urges physicians treating patients with Mabthera® to consider the possibility of PML in any patient presenting with new onset neurologic manifestations. In patients who develop PML, Mabthera® should be discontinued and reductions or discontinuation in concomitant immunosuppressive therapy and appropriate treatment including antiviral therapy should be considered.

 14 Jul 2008: Important safety information regarding the combined use of  bevacizumab (Avastin®) and sunitinib malate                                                                                                                                 Roche updates oncologists about new safety information regarding the combined use of  bevacizumab (Avastin®) and sunitinib malate. This new information arose from a Phase I dose-escalation study, combining Avastin and escalating doses of sunitinib malate, in patients with metastatic renal cell carcinoma (mRCC) and another Phase II trial of sunitinib with or without Avastin. Five of 12 patients at the highest sunitinib malate dose level in the Phase I study and 2 patients in the Phase II trial exhibited microangiopathic haemolytic anaemia (MAHA). Currently, there is insufficient clinical data to draw any firm conclusion about the safety of combining Avastin with sunitinib malate and this drug combination is not indicated for any disease state.

12 Jun 2008: Reports of acute pancreatitis and renal impairment associated with  exenatide (Byetta®) [Eli Lilly]                                                                                                                                             Eli Lilly updates healthcare professionals of the new safety information on acute pancreatitis and renal impairment associated with the use of Byetta®. As of 31 December 2006, the US FDA has reviewed 30 post-marketing reports of acute pancreatitis in patients treated with Byetta®. In some reports, symptoms of pancreatitis began or worsened after the dose of Byetta® was doubled. There were also reports describing serious complications including dehydration and renal failure; suspected ileus; phlegmon; and ascites. In 3 reports, symptoms of acute pancreatitis returned when Byetta® was restarted while in another 22 reports, symptoms of acute pancreatitis improved after Byetta® was discontinued. Rare events of altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure and acute renal failure, sometimes requiring hemodialysis have also been reported. Although causal relationships between Byetta® and acute pancreatitis and renal impairment have not been fully established, Eli Lilly will be updating the package insert for Byetta® to reflect these safety information.

03 Jun 2008: Use of Trasylol® (Aprotinin) Tablets via Restricted Access Program                     Trasylol® (Aprotinin) was placed under restricted access program following the interim findings of BART (Blood Conservation Using Antifribinolytics Randomized Trial). Recently, in May 2008, the final results of the BART were published in an issue of the New England Journal of Medicine. As such, Bayer in consultation with HSA issued a Dear Healthcare Professional Letter for the purpose of updating prescribers with regards to the status of Trasylol® in Singapore. In addition, this letter was to remind prescribers that Trasylol® is only indicated for the purpose of reducing perioperative blood loss and the need for blood transfusion in adult patients undergoing cardiopulmonary bypass in the course of coronary artery bypass graft surgery who are at an increased risk for blood loss and blood transfusion.

26 May 2008: Abacavir sulfate-containing medicinal products, (Ziagen® Tablets and Oral Solution; Kivexa® Tablets; Trizivir® Tablets)-Communication on results pertaining to abacavir from the D:A:D study [GlaxoSmithKline]
GlaxoSmithKline (GSK) updates healthcare professional on the results of The Data Collection of Adverse Effects of Anti-HIV Drugs Study (D:A:D Study) pertaining to abacavir sulfate-containing medicinal products, Ziagen®, Kivexa® and Trizivir®. The study's recent analysis of 33,347 patients revealed that 192 of the 517 patients who developed their first myocardial infarction (MI) during the study had taken abacavir in the 6 months prior to the event. The relative risk of myocardial infarction associated with the recent use of abacavir was 1.9 (95% CI, 1.47-2.45; p=0.0001) and the absolute myocardial infarction rate was 6.1/1000 patient years of exposure for those recently exposed to abacavir. However, previous comparative clinical trials sponsored by GSK have not shown increased risk for myocardial infarction with abacavir containing medicinal products. Based on all currently available data, no definitive conclusion can be drawn on the potential association between abacavir use and the risk of myocardial infarction.

22 Apr 2008: Reports of progressive multifocal leukoencephalopathy  in mycophenolate mofetil (CellCept(®) [ROCHE]                                                                                                    Progressive multifocal leukoencephalopathy (PML)  is a rare, progressive, demyelinating disease of the central nervous system (CNS) that usually leads to death or severe disability. Isolated cases of PML have been described in kidney, heart and lung transplant patients, and in SLE patients, receiving CellCept® . The case reports received have been associated with confounding factors, in particular the nature of the underlying disease, concomitant immunosuppression and latency between the use of CellCept® and the onset of PML, even though the contributory role of CellCept® cannot be excluded. Roche recommends physicians to consider PML in the differential diagnosis of patients reporting neurological symptoms following treatment with CellCept(®.

15 Apr 2008: HSA alerts on wider spread of harmful illegal health products
Since the alert on the illegal product Power 1 Walnut was issued in Feb 08, HSA has detected 3 more of such products adulterated with glibenclamide and sildenafil. To date, there are 30 confirmed cases and 59 suspected cases reported and HSA assessed that illegal products adulterated with high doses of glibenclamide may not be limited to these 4. As such, HSA urges healthcare professional to be on the alert for patients who present with unprovoked hypoglycaemia and to check carefully if patient has consumed complementary medicinal products or illegal products.

01 Apr 2008: Tykerb® (lapatinib) and new safety information on hepatotoxicity [GlaxoSmithKline]
GlaxoSmithKline in consultation with HSA has issued a Dear Healthcare Professional Letter informing healthcare professionals of the new safety information on hepatotoxicity with the use of Tykerb® (lapatinib). From GlaxoSmithKline's worldwide safety database, 39 cases of hepatotoxicity were identified, of which 38.5% of the subjects were receiving lapatinib monotheraphy while 53.8% were receiving lapatinib in combination with other chemotherapies, such as capecitabine. Majority of the key cases were from clinical trials, which yielded a crude incidence of 0.4% for hepatobiliary events in the entire lapatinib clinical program while 7 cases of hepatotoxicity were from spontaneous sources. There have been 13 incidences of death with reported liver-related events in the Tykerb® clinical trial program. However, due to these patients' medical conditions and underlying cancer, it is difficult to ascertain Tykerb's® role in these cases. The hepatotoxicity frequency however is rare and reversible. As such, healthcare professionals are advised to monitor their patients' liver functions before initiating treatment and at approximately monthly intervals thereafter or as clinically indicated.  Tykerb® should be discontinued and not restarted in patients with severe changes in liver function.

01 Apr 2008: Updated information on the risk of suicidal ideation and behaviour with Lamictal® tablets and chewable dispersible tablets [GlaxoSmithKline]
GlaxoSmithKline, in consultation with HSA, has issued a Dear Healthcare Professional Letter to inform physicians of a trend towards higher incidence of suicidal ideation and behaviour with Lamictal® (lamotrigine) tablets and chewable dispersible tablets compared to placebo suggested by an pooled analysis of 35 double-blind clinical trials. In the subset analysis of bipolar disorder trials, the rate of events were numerically, but not statistically significantly, greater for lamotrigine (29/1212 [2.4%]) compared with placebo (19/1054 [1.8%]). In the subset analysis of epilepsy trials, there were no statistically significant differences in the rate of events between lamotrigine and placebo. Although the number of suicidal ideation and behaviour events was too low (6/1073 [0.6%] on lamotrigine and 2/805 [0.3%] on placebo) to allow a definitive comparison between treatment groups, the relative rate reported from this lamotrigine analysis is consistent with a possible class effect reported by the US Food and Drug Administration, based on their meta-analysis of 11 anticonvulsant drugs including lamotrigine. In view of the trend towards higher incidence of suicidal ideation and behaviour compared to placebo, GlaxoSmithKline will be working with HSA to update the prescribing information for Lamictal® tablets and chewable dispersible tablets to reflect this new safety finding.

17 Mar 2008: Peripheral neuropathy seen with the combination treatment of Sebivo® (telbivudine) with pegylated interferon alfa-2a [Novartis]
Sebivo® (telbivudine) is indicated for the treatment of HBeAg-positive and HBeAg-negative chronic hepatitis B in patients who have compensated liver disease, evidence of viral replication and active liver inflammation, and who are nucleoside analogue naive. In a pilot clinical trial, 8 cases of peripheral neuropathy were reported out of the 48 patients treated wtih telbivudine and a standard dose of pegylated interferon alfa-2a. The time to onset for the event was approximately 2 to 6 months. In contrast, the rate of peripheral neuropathy in the 2-year pivotal study with telbivudine monotherapy was uncommon. As the risk of developing peripheral neuropathy appears to be increased in the telbivudine and peyglated-interferon alfa-2a combination, Novartis is working with HSA to update the product information for Sebivo®  to reflect this new finding.

25 Feb 2008: Reports of hepatic failure with Exjade® (deferasirox) [Novartis]
Novartis, in consultation with HSA, has issued a Dear Healthcare Professional Letter to inform physicians of recent reports on hepatic failure in patients prescribed Exjade® (deferasirox). Exjade® is indicated for the treatment of chronic iron overload. As of 31 October 2007, there are a total of 24 international reports of hepatic failure - 21 post-marketing reports and 3 reports from clinical studies. Most  of these reports involved patients with significant co-morbidities, including liver cirrhosis and multi-organ failure. Even though the causal relationship between Exjade® and hepatic failure has not been fully established, Novartis will be updating the package insert for Exjade® to reflect this important safety information as a precautionary measure.

14 Feb 2008: HSA warns about an illegal health product, Power 1 Walnut
The Health Sciences Authority (HSA) has detected the presence of glibenclamide and sildenafil in an illegal health product, Power 1 Walnut. The product is labelled as being manufactured by Guangzhou Xinkauili Limited Company. It claims to contain only natural herbal ingredients and is marketed for sexual enhancement. Based on our preliminary investigations, the product is likely to have been illegally brought into Singapore. Healthcare professionals are advised to be on the alert for patients who present with hypoglycaemia and to check carefully the medication history for consumption of Power 1 Walnut or other complementary medicinal products.

31 Jan 2008:  Myfortic® (mycophenolate sodium) - Labelling update on teratogenic risk [Novartis]
Novartis would like to inform healthcare professionals of the increased risk of congenital malformation in children of patients treated with Myfortic® during pregnancy. Novartis has in its Dear Healthcare Professional Letter, reminded healthcare professionals of several precautions to take regarding the use of Myfortic® in pregnancy.