admin November 30th, 2007
The MHRA report on four Traditional Chinese Medicines that have been found to contain aristolochia acids (the active principle extracted from the herb Aristolochia). These acids are nephrotoxic and carcinogenic, most clearly demostrated in Belgium when over 100 patients developed Aristolochic Acid Nephropathy following the use of a herbal slimming regime. An informative review of the dangers of aristolochic acid has been published in Drug Safety.1 The MHRA have already issued wanrings about the risks of aristolochic acid contamination in Drug Safety Update this month.
The four products are:
- Xiao Qin Long Wan
- Chuan Xiong Cha Tiao Wan
- Bai Tou Weng Wan
- Xie Gan Wan
These products may be available in a variety of different packaging.
Bottom line: If you have been taking any of the above products stop taking them and immediately contact your doctor. There is no safe level of exposure to aristochic acid. Users of Traditional Chinese Medicines should be aware that the risk of contamination is a continuing issue in their safety.
1. Cosyns, JP. Aristolochic Acid and “Chinses Herbs Nephropahthy”: A review of the evidence to date. Drug Safety 2003; 26(1): 33-48
admin November 30th, 2007
The Commission on Human Medicines (CHM) has now advised that the UK marketing authorisations (licences) should be suspended pending the outcome of a full Europe-wide review of the balance of risks and benefits of aprotinin . This review is expected to take at least three months and the licences will be suspended from 7 December until further notice.
Source: MHRA.
This decision is based on the findings of the BART study which was terminated early due to an excess of mortality in the aprotinin arm (relative risk of 1.5 compared to tranexamic acid and animocaproic acid). Other observational data has suggested a similar risk, as well as increased risks of cardiac, cerebrovascular and renal adverse effects. The benefits of reduced bleeding produced by aprotinin are thought to be outweighed by these risks.
Bottom line: The risks attached to aprotinin appear to outweigh its benefits, as noted by previous CHM advice. The CHM advise that “aprotinin should only be used when the likely benefits outweigh any risks to individual patients.” While aprotinin continues to be availible until the suspension of the licences, clinicians should attention to this advice. After the suspension of the UK licences, limited supplies of aprotinin for treatment of individual patients under ‘Specials’ regulations will be permitted. In that case, prescribers will be prescribing an unlicensed medication and take responsibility for its use. A European review of the data should present further information in the new year.
admin November 22nd, 2007
The FDA have drawn attention to reports of suicidal thoughts and aggressive and erratic behavior in patients who have taken varenicline. Varenicline is known by the tradename Chantix in the US market and Champix in the UK. On suicidal thoughts the FDA say:
The manufacturer of Chantix, Pfizer, Inc., recently submitted to FDA postmarketing cases describing suicidal ideation and occasional suicidal behavior. FDA currently is reviewing these cases, along with a number of recent reports in the popular press and internet sites. A preliminary assessment reveals that many of the cases reflect new-onset of depressed mood, suicidal ideation, and changes in emotion and behavior within days to weeks of initiating Chantix treatment. The role of Chantix in these cases is not clear because smoking cessation, with or without treatment, is associated with nicotine withdrawal symptoms and has also been associated with the exacerbation of underlying psychiatric illness. However, not all patients described in these cases had pre-existing psychiatric illness and not all had discontinued smoking.
The case of aggressive and erratic behaviour may have also been associated with comfounding factors, such as alcohol use, and the FDA are continuing to examine additional material supplied by the manufacturer.
The FDA is also evaluating cases of drowsiness that affected the ability to drive, and have recommended that “Patients should use caution when driving or operating machinery until they know how quitting smoking with Chantix may affect them.”
Bottom line:: Although the role of varenicline in these cases of suicidal thoughts and aggression is not conclusively proven, healthcare professionals should be aware of these reported cases. Varenicline is a black triangle medicine in the UK, meaning that any suspected reactions (no matter how trivial) should be reported to the Yellow Card scheme. Drowsiness is a listed adverse reaction of varenicline in the UK; healthcare professionals should warn patients who drive or operate other heavy machinery to be aware of this potential adverse effect.
admin November 20th, 2007
Lumiracoxib has been withdrawn from the UK market after a series of spontaneous reports of liver toxicity collected worldwide. Lumiracoxib was withdrawn in Canada last month, and in August of this year the MHRA imposed some restrictions on the use of lumiracoxib. Further cases have undermined the usefulness of that advice:
Recently, several new cases of serious hepatotoxicity have been identified following exposure to the licensed 100mg dose, and after short duration of treatment (less than one month in some cases). CHM concluded that recently introduced risk minimisation measures (baseline and monthly liver function test monitoring, and contraindications for patients with current or previous hepatic dysfunction) cannot be relied upon to guarantee patient safety, and further restrictions are unlikely to be practical. CHM considered that urgent action was required in order to protect public health, and that suspension of Marketing Authorisation for lumiracoxib was warranted.
A further press release and advice is available at the MHRA website.
Bottom line: Patients who are obtaining benefit from lumiracoxib may continue treatment until they have arranged an appointment with their doctor at the next convenient opportunity, at which alternative treatment can be discussed. Patients who are taking lumiracoxib and who feel unwell should stop taking lumiracoxib immediately seek medical attention. Any adverse effects to lumiracoxib should be reported at yellowcard.gov.uk.
admin November 20th, 2007
The MHRA have responded to the European Medicines Agency statement on strontium ranelate:
Women taking Protelos should be alert to the risk of severe allergic reactions and if they develop a rash, they should stop taking the medicine and consult their doctor immediately. Once Protelos treatment has been stopped it should not be re-introduced.
The EMEA press release is here (PDF). The nature of the reaction is described:
Up to now, 16 cases of ‘drug rash with eosinophilia and systemic symptoms (DRESS)’ in patients treated with Protelos/Osseor, two of which were fatal, have been reported to the EMEA, following a total of around 570,000 patient-years of worldwide exposure. DRESS is a serious and life-threatening condition. The reported serious reactions started within 3 to 6 weeks of the initiation of the treatment, with skin rash, accompanied by a fever, swollen glands, increased numbers of white cells in the blood and effects on the liver, kidneys and lung.
Bottom line: Strontium ranelate has been associated with severe allergic reactions to which prescribers and users should be alert to. Women taking strontium ranelate who develop any form of rash should stop treatment immediately and seek medical advice.
admin November 7th, 2007
Just a short note to direct you to the MHRA’s October and November Drug Safety Updates.