admin November 30th, 2009
The Yellow Card Centre West Midlands has issued re:Action number 38:
HPV vaccination
Varenicline and self-harm
Uncomfortable ulcers: Nicorandil-induced genital ulcers.
[PDF]
admin October 6th, 2009
Angioedema is a rare serious adverse drug reaction (ADR) to angiotensin-converting enzyme inhibitors (ACE-I), with an incidence of 0.1% to 1.0%. If untreated it can be life-threatening. Debate exists over the safety of switching to an angiotensin-II receptor blocker (ARB), due to case reports of angioedema, and the mechanism of ARB-associated angioedema. The DoTS system of ADR classification provides a structured template for examining the Dose and Time relationship, and potential Susceptabilities to an ADR.
Here is a poster we are presenting at the International Society of Pharmacovigilance conference this week.
Angioedema associated with angiotensin-II receptor blockers: a DoTS classification
and analysis [PDF].
admin October 24th, 2008
We draw our readers attention to an interesting paper examining European and US regualtory actions concerned with the safety of the new wave of biological agents published in JAMA. The full text is free.
admin April 21st, 2008
Our unit has recently had a brief guide to the assessment, management and reporting of ADRs.
Cox AR. Assessing, managing and reporting adverse drug reactions may better equip us to minimise medicines-related harm. Pharmacy in Practice 2008;18(2):57-61
A PDF version is here, courtesy of Medicom. (Note this version contains a correction referred to in the following edition of Pharmacy in Practice.
admin February 5th, 2008
Duphaston is to be withdrawn for commerical reasons:
Duphaston/Duphaston HRT (dydrogesterone) is to be withdrawn from the market from March 2008 for commercial reasons.
Duphaston was licensed for use in several indications, including threatened or recurrent miscarriage, dysfunctional uterine bleeding, and hormone replacement therapy.
A Public Assessment Report available for download below reviews evidence for the efficacy of progesterone and dydrogesterone in the maintenance of pregnancy in women with threatened miscarriage or recurrent miscarriage.
For several decades, progesterone and progestogens (such as dydrogesterone) have been used to maintain early pregnancy.
The public assessment report is here [PDF].
admin October 12th, 2007
The NPCi blog documents the recent withdrawal of lumiracoxib▼ (Prexige®) in Canada and argue that:
The concern about lumiracoxib’s▼ potential for rare but serious, even fatal liver reactions must feature in prescribing decisions about the drug, along with the increased risk of thrombotic events seen with all coxibs (note that all coxibs are now contraindicated for people with established ischaemic heart disease, cerebrovascular disease and peripheral artery disease, and individual risk assessment is appropriate for patients with risk factors for cardiovascular events)
admin September 18th, 2007
Johnson and Johnson and the FDA have informed healthcare professionals of the risks of sudden death, QT prolongation and Torsades de Pointes(TdP) in patients treated with haloperidol, especially when given intravenously, or at doses higher than recommended. They report:
There are at least 28 case reports of QT prolongation and TdP, some with fatal outcome in the context of off-label intravenous haloperidol. Healthcare professionals should consider this new risk information when making individual treatment decisions for their patients.
admin September 3rd, 2007
Following consultation with the MHRA and other European regulators, the manufacturer of the osteoarthritis drug lumiracoxib (Prexige), is writing to health professionals to inform them of new restrictions on the prescribing of lumiracoxib. Concern was raised worldwide after rare reports of serious liver reactions; mostly relating to daily doses that are higher than licensed in the EU.
The new measures include regular liver monitoring for patients taking lumiracoxib. In addition, lumiracoxib should not be used in patients with current liver disease or those thought to be at possible risk because of their previous history or other medicines.
The balance of risks and benefits of lumiracoxib in the treatment of osteoarthritis will be further evaluated by European Regulatory Authorities in September. Any updated advice will be issued following that evaluation.
admin July 13th, 2007
The Japan Institute of Pharmacovigilance has written to the BMJ concerning a editorial concerning oseltamivir. The letter states the following:
On 16 June 2007 the Japanese Ministry of Health Labour and Welfare announced that by 31 May 2007 it had received 1377 reports of adverse reactions since 2001, when marketing of oseltamivir started in Japan.
Of these, 567 were serious neuropsychiatric cases, 211 showing abnormal behaviour. The number of deaths reported was 71. These are not only “adverse events” but also “adverse reactions” to oseltamivir because many doctors classed and reported them as probably related or that causality could not be ruled out.
The letter is correct to note that spontaneous reports to regulatory authorities are not adverse events (any event that occurs after the use of a drug with no assessment of causality), since the suspicion of the doctor that the drug was the cause of the event makes them adverse reactions (events that are suspected to be causally-related to the use of a drug). However, it is also important to note that such suspicions are not clear evidence of causality. It is over-simplistic to accept the decision of a doctor to report to a spontaneous reporting system as evidence of causality. Firstly, spontaneous reporting schemes specifically ask for doctors to report possible reactions, not those they have clear causality for. Secondly, the assessment of causality is highly variable between clinicians, especially if the judgement is based on non-expert opinions without the use of a standard algorithm. For this reason, the more cautious interpretation of Dr Simon R J Maxwell may well be the more sensible approach:
Before 2007, there had already been more than 100 reports of neuropsychiatric events (including delirium, convulsions, and encephalitis) with oseltamivir in children, almost entirely from Japan, which has the highest usage of oseltamivir worldwide. However, these disturbing events had to be seen in the context of the millions of prescriptions worldwide and the fact that abnormal behaviour could also be due to flu or disease related complications. Indeed, a Food and Drug Administration (FDA) review of clinical trial and postmarketing data concluded that these events were not clearly drug related but might be related to higher rates of flu related encephalitis in Japan. Since last November, the FDA has required that doctors be warned that patients should be closely monitored for signs of abnormal behaviour throughout the treatment period and the European Medicine Evaluation Agency (EMEA) took similar steps in February.
The controversy about oseltamivir is a further reminder that, although common adverse effects of a drug may emerge in prelicensing studies, the detection of rarer and potentially more serious events has to await exposure of large numbers of patients. In the UK, oseltamivir is a “black triangle” drug, so it remains under more intensive surveillance. Doctors and other healthcare professionals should report all minor as well as serious adverse events via the yellow card scheme.
It is also notable that the Japan Institute of Pharmacovigilance is non-profit making organisation that argues against the use of flu vaccine and anti-pyretics, as well as publishing articles suggesting that “High cholesterol level makes a long life“. Things you may wish to bear in mind when assessing their views on drug safety.
admin July 13th, 2007
The BMJ has published the WISDOM Trial of HRT in postmenopausal women aged 50 to 69 years-of-age (mean age 62.8 SD 4.8).
Key points:
Combined hormone therapy (n=2196) was compared with placebo (n=2189):
- significant increase in the number of major cardiovascular events (7 v 0, P=0.016)
- significant increase in venous thromboembolisms (22 v 3, hazard ratio 7.36 (95% CI 2.20 to 24.60))
- no statistically significant differences in numbers of breast or other cancers (22 v 25, hazard ratio 0.88 (0.49 to 1.56)), cerebrovascular events (14 v 19, 0.73 (0.37 to 1.46)), fractures (40 v 58, 0.69 (0.46 to 1.03)), and overall deaths (8 v 5, 1.60 (0.52 to 4.89)).
Comparison of combined hormone therapy (n=815) versus oestrogen therapy (n=826) outcomes:
- no significant differences.
The study authors argue that this trial is consistent with the Womens’ Health Initiative trial, showing increased risks associated with HRT when used in older post-menopausal women. It is less useful in casting light on the risk to women who are younger and who are using HRT to deal with menopausal symptoms. An accompanying editorial argues that:
So postmenopausal hormone therapy has come full circle.9 It was originally used to treat menopausal symptoms, and now the indications for use are again hot flushes, night sweats, and vaginal dryness. It is the best treatment we have at present for these symptoms. Hot flushes and night sweats are mostly self limiting, and current advice recommends short term use with the lowest dose needed for relief of symptoms. Healthy women in early menopause are at a low absolute risk whether they take hormones or not, and they are unlikely to face substantially increased risks when using hormones for a few years.
Long term use of hormone replacement therapy to prevent chronic disease is no longer recommended, because available randomised evidence shows that the negative outcomes outweigh the positive benefits.