adr.org.uk

admin December 17th, 2007

EMEA have issued a warning about suicidal ideation and suicide attempts associated with varenicline [PDF]:

The European Medicines Agency (EMEA) has concluded that updated warnings to doctors and patients are needed to increase awareness of cases of suicidal ideation and suicide attempts reported in patients using Champix (varenicline), a medicine indicated for smoking cessation in adults.

The Committee for Medicinal Products for Human Use (CHMP) has been closely monitoring the safety of Champix since it was first authorised in the European Union (EU) in September 2006. As part of the routine pharmacovigilance activities, all adverse reactions for Champix are analysed on a regular basis. Cases of suicidal ideation and suicide were reviewed in July, October and November 2007.

At its December 2007 meeting, the CHMP concluded that there is a need to update the product information for Champix to warn doctors and patients that depression has been reported in patients who are trying to stop smoking using Champix. The symptoms of this depression may include suicidal ideation and suicide attempt.

A Q&A on varenicline [PDF] is also available.

Additional link: MHRA announcement.

Bottom line: Although reports of suicidal ideation and suicide attempts have been associated with varenicline, there is no conclusive evidence of a link. Other confounding factors may have lead to the association, such as the cessation of smoking or a pre-disposition to depression. However, enough spontaneous reports have arisen to warrant warning patients and prescribers of the possibility of depressive symptoms. Heallthcare practitioners should advise their patients of these reported symptoms, and advise them to immediately stop treatment, and seek medical help, if suicidal thoughts are experienced.

• EMEA
• Comments Off

admin December 14th, 2007

EMEA have withdrawn lumiracoxib from the European market due to its effects on the liver [PDF]:

The liver safety of lumiracoxib has been monitored continuously since its launch in 2005. In August 2007, the product information was updated with contraindications for patients with potential liver problems and advice to doctors that they should frequently monitor patients treated with lumiracoxib for liver reactions. More spontaneous reports of serious liver problems have been received since then, which have increased the concerns regarding hepatic safety for lumiracoxib. In addition, the CHMP considered that the proposed measures to reduce the risk for liver reactions can not assure adequate patient safety, and are not considered realistic given the approved clinical indication.

Consequently, the CHMP is now recommending the withdrawal of the marketing authorisations.

EMEA have issues a Q&A [PDF], including the following points:

What are the recommendations for patients and prescribers?

Patients who are currently taking lumiracoxib and have signs of possible problems with their liver should see their doctor immediately. The signs to watch out for are: feeling sick; vomiting; loss of appetite; tiredness; stomach pains; dark urine; itching; or yellowing of the skin.

Patients who are currently taking lumiracoxib and who are feeling well should make an appointment to see their doctor as soon as is convenient, so that the doctor can change their prescription.

Doctors should stop prescribing lumiracoxib. Alternative treatments should be used as appropriate, based on each patient’s symptoms and individual risk profile.

• EMEA
• Comments Off

admin December 14th, 2007

Carbamazepine’s propensity to skin rashes is well known, with 5-20% of patients developing skin rashes which can lead to drug withdrawal. It is also associated relatively rarely with more serious skin reactions such as exfoliative dermititis, Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The FDA have issued information about a genetic susceptibility, mainly present in patients with an Asian/South Asia ancestory, and are advise that patients with such ancestory should be screened prior to treatment.

Dangerous or even fatal skin reactions (Stevens Johnson syndrome and toxic epidermal necrolysis), that can be caused by carbamazepine therapy, are significantly more common in patients with a particular human leukocyte antigen (HLA) allele, HLA-B*1502. This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including South Asian Indians. Genetic tests for HLA-B*1502 are already available. Patients with ancestry from areas in which HLA-B*1502 is present should be screened for the HLA-B*1502 allele before starting treatment with carbamazepine. If they test positive, carbamazepine should not be started unless the expected benefit clearly outweighs the increased risk of serious skin reactions. Patients who have been taking carbamazepine for more than a few months without developing skin reactions are at low risk of these events ever developing from carbamazepine. This is true for patients of any ethnicity or genotype, including patients positive for HLA-B*1502.

Further details, and evidence, are available from the FDA website. The FDA have provided a list of areas with higher prevalences of HLA-B*1502 (although many regions of Asia have not been studied), although they suggest the following figures to be no more than a rough guide in deciding which patients to screen:

• 10-15% or more of patients may carry the allele in parts of China, Thailand, Malaysia, Indonesia, the Philippines, and Taiwan.
• South Asians, including Indians, appear to have intermediate prevalence of HLA-B*1502, averaging 2 to 4%, but higher in some groups.
• HLA-B*1502 appears to be present at a low frequency, <1%, in Japan and Korea.

Bottom Line: Although SJS and TEN rarely occur (1 to 6 cases per 10,000 new users ) they can be permanently disabling, and even fatal. Asian patients, including South Asian Indians, appear to have a tenfold increased risk of such serious skin reactions, and testing provides an indication of this increased risk to aid in risk benefit decisions about the appropriateness of therapy. Patients who have already taken carbamazepine for a few months without skin reactions, are at low risk of such reactions.

• FDA
• Comments Off

admin December 12th, 2007

The use of medicines in children is a dangerous activity. Physical and physiological differences between children and adults, and the comparative lack of data for drug use in children makes decisions about dosing complex. Often specifically licensed childrens preparations are not available, further increasing the dangers of dosing errors due to calculation errors. Conroy et al have published a systematic review of interventions to reduce the risk of dosing errors in children.

What they studied
The authors searched mainstream literature databases, and databases such as Pharmline up to October 2006, as well as hand searches of specific drug safety journals from 1995 to 2006. Criteria for selection were that the articles should report an intervention, and that the intervention should be related to dose calculations. Non-specific interventions, such as computerised physician order entry (CPOE), were also included.

What they found
From an initial 3302 articles, they found 28 relevant articles. Lack of hetoerogenity study methodology and outcomes did not allow the researchers to perform a statistical summary of the articles. Most studies used a reduction in error rates as an outcome, and most studies gave positive results. The most common intervention was related to CPOE (electronic prescribing), used in 14 studies.

• Electronic prescribing
• Other computer aids
• Unit dose dispensing systems
• Education/risk management programmes
• Smart pumps

Electronic prescribing had a variable rates of reduction of errors, which the authors suggest could be due to differing outcome measures (e.g. reductions in calculation errors compared to more general reductions in prescribing errors), and the settings of studies (small specialised settings such as neonatal units versus larger hospital populations). Differences in electronic prescribing systems, such as the level of decision support for prescribers, were also hard to determine. One study CPOE study even demonstrated an increase in the mortality rate following intervention.

Limitations
The authors note that non-beneficial, or negative, interventions were unlikely to be published, and noted several methodological issues related to the study of medication errors. However, they did not critically analyse the studies or attempt comparison of the results.

What the study adds
This review is a useful summary of the current evidence base for reducing medication errors in paediatrics. It highlights the difficulties in designing interventional studies in this area, and the lack of research in this field. Although error reductions were reported in some studies, some interventions may carry risks. The authors argue that further research is required to demonstrate the effectiveness of medication error reduction interventions on clinical outcomes and mortality. Care should be taken when interventions are implemented in different healthcare settings from that they were originally studied in.

1. Conroy S, Sweis D, Planner C, Yeung V, Collier J, Haines L, Wong ICK. Interventions ro reduce dosing errors in children. Drug Safety 2007; 30(12): 111-1125. [abstract]

• Patient Safety
• Comments Off

admin December 12th, 2007

The FDA has completed its review of the safety of omeprazole and esomeprazole, in the wake of two studies that appeared to show higher rates of cardiac events in those treated with the proton pump inhibitors (PPIs). Both of these studies were small, one had differences in the baseline cardivascular status of the subjects, and both studies failed to adaquately define or verify heart problems, such as heart attacks making evaluations of the safety of either drug in these studies difficult. FDA analysis of 14 other studies of omeprazole showed no apparent increase in the risk of cardiovascular adverse drug reactions.

Bottom line: The FDA analysis seems to discount fears of potential adverse cardiovascular effects of PPIs. Prescribers should be reassured that such drugs can be prescribed in those with cardiovascular disease, especially considering that they are commonly co-prescribed with aspirin in order to reduce the risks of gastrointestinal bleeding.

• FDA
• Comments Off

admin December 11th, 2007

The following are three posters this unit recently presented at ISOP 2007 in October of this year:

Cox AR, Anton C, Marriott JF, Ferner RE. The paradox of low prescribers who are high reporters: correlates of spontaneous reporting of adverse drug reactions within primary care. Drug Safety 2006; 30(10): 977-978
(Presented at the 7th Annual Meeting of ISoP Bournemouth – UK, 21-24 October 2009)

Download PDF of Poster

McDowell SE, Coleman JJ, Ferner RE. Rhabdomyolysis and statins – an analysis of spontaneous case reports using a three-diensional classification scheme. Drug Safety 2006; 30(10): 979
(Presented at the 7th Annual Meeting of ISoP Bournemouth – UK, 21-24 October 2009)

Download PDF of Poster

Ormerod S, McDowell SE, Coleman JJ, Ferner RE. Ethnic differences in the risks of adverse reactions to drugs used in the treatment of psychoses: systematic review and meta-analysis. Drug Safety 2006; 30(10): 975-976
(Presented at the 7th Annual Meeting of ISoP Bournemouth – UK, 21-24 October 2009)

Download PDF of Poster

• Our research
• Comments Off

admin December 11th, 2007

The National Academies Press has published Challenges for the FDA:The Future of Drug Safety, Workshop Summary, which is the result of a one-day symposium in March of this year. The text is free online.

• FDA
• Comments Off

admin December 11th, 2007

The MHRA Annual Conference will be held in Birmingham this year.

• Events , MHRA
• Comments Off

admin December 11th, 2007

The NPC draw attention to a FDA document on the safety of salmeterol in children, and provide extensive links on material to help prescribers.

• FDA
• Comments Off

admin December 11th, 2007

The NPSA have issued two booklets about the safe dispensing of medicines.

1. A guide to the design of the dispensing environment.

2. A guide to the design of dispensed medicines.

A BMJ news report summerises the key points as:

• Designing dispensaries that encourage a safe and effective flow of work
• Patients’ waiting areas that allow for confidential discussions about their drugs
• Using bar codes on drug packs to aid accuracy checking
• Ensuring that dispensing labels are clearly laid out, with text in a size that patients can read easily
• Placing labels on packaging in a way that does not obscure important information or, where this is not possible, on smaller packets and tubes, using “flag” labels, and
• Directly labelling containers rather than outer packaging.

• Patient Safety
• Comments Off