adr.org.uk

admin November 7th, 2008

This month’s Drug Safety Update has been published. Direct link here. Items include:

• Varenicline: adverse psychiatric reactions, including depression
• Tigecycline: new formulation affects compatibility
• Reporting by community pharmacists is encouraged for OTCs
• Ezetimibe and possible increased risk of cancer: results of SEAS study
• Rimonabant: European suspension of marketing authorisation
• Inhaled anticholinergics: recent published data for risk of death or stroke
• Paracetamol use in infancy: no strong evidence for asthma link
• Device bulletin: use of in vitro diagnostic devices with other medical equipment
• Herbal medicines: packaging shows MHRA approval

• MHRA
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admin November 7th, 2008

Recently this website has suffered a suspected attack leading to the website becoming temporarily unavailable due to a lack of bandwidth. We have therefore blocked a number of IP addresses and removed the Pronouncing Drug Names material from the site in order to maintain our web presence.

We apologise for any inconvenience this may cause our readers.

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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.

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admin October 24th, 2008

Rimonabant’s marketing licence has been suspended by the Eurpean Medicines Evaluation Agency because of an increased risk of psychiatric disorders, and concerns about its effectiveness:

Following the assessment of the available information on the benefits and risks of Acomplia including data from studies completed since it was granted marketing authorisation, the CHMP confirmed at its 20-23 October meeting, that there is an approximate doubling of the risk of psychiatric disorders in obese or overweight patients taking Acomplia compared to those taking placebo.

The CHMP considered that the new data from post-marketing experience and ongoing clinical trials indicated that serious psychiatric disorders may be more common than in the clinical trials used in the initial assessment of the medicine. The CHMP was also of the opinion that these psychiatric side effects could not be adequately addressed by further risk minimisation measures.

In addition, the CHMP noted, that the effectiveness of Acomplia in clinical practice is more limited than was expected on the basis of the clinical trials, because available data indicate that patients generally take Acomplia only for a short period.

Prescribers should not issue any prescriptions for Acomplia and should review the treatment of patients currently taking the medicine. Patients who are currently taking Acomplia should consult their doctor or pharmacist at a convenient time to discuss their treatment. There is no need for patients to stop treatment with Acomplia immediately, but patients who wish to stop can do so at any time.

EMEA press release. [PDF]
EMEA Questions and Answers. [PDF]
MHAR Page.
MHRA letter to healthcare professionals.[PDF]

• EMEA , MHRA
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admin September 22nd, 2008

Readers may be aware of the recent news story concerning the use of antibiotic in pregnancy. The NPC blog has an informative post with useful links within it on this subject.

The prescription of antibiotics for women in spontaneous preterm labour whose waters have not broken and who have no evidence of infection has been associated with an increase in functional impairment and cerebral palsy in their children, according to a recent study. However, no association was found in women whose waters had broken. The Commission on Human Medicines (CHM) has reviewed the results and advises that any association is unlikely to be directly to the antibiotic but rather due to a number of factors involved in the natural history of pre-term labour.

• teratogenicity
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admin September 22nd, 2008

Readers may be interested to know that the charity APRIL (Adverse Psychiatric Reactions Information Link) are running a study day on the 6th of November 2008 in London.

Adverse psychiatric side effects of medicines: What’s your responsibility?

Venue: Friends House, Euston Road, London NW1 2BJ

Date: Thursday 6 November 2008

Time: 9.00 am to 5.00 pm registration from 8.30 am

Speakers and Panel include:

Professor Munir Pirmohamed Professor of Pharmacogenetics, Liverpool University. Leader in ADR Research

Professor David Healy Professor of Psychological Medicine University of Wales Author of The Antidpressant Era and peer reviewed studies of SSRI Suicide risk

Charles Medawar Founder Social Audit, Specialist Medicines Policy & Drug Safety co-author Medicines out of Control

Dr Anita Holdcroft Emeritus Professor of Anaesthesia, Imperial College London.

Professor Heather Ashton Emeritus Professor Clinical Psychopharmacology Newcastle University

Dr Joanna Moncrieff Sen.Lecturer/Hon.Consultant Psychiatrist, member of the Critical Psychiatry Group

Dr Simon Maxwell Edinburgh Uni/ British Pharmacological Soc. Med Schools Council Safe Prescribing Working Group

Dr Andrew Herxheimer Former editor Drug and Therapeutics Bulletin

Nigel Meadows H.M.Coroner Manchester City District

Bob Johnson James Nayler Foundation psychiatrist author of Emotional Health

Dr John Halliday Pharmacology & Therapeutics Sub Dean King’s College, London

Programme includes morning break out session - Coming Off Medicines ‘how to prepare and cope with withdrawal’ – session participants will include Professor David Healy, Professor Heather Ashton, Dr Joanna Moncrieff, nurse Adam J Hugroo and psychologist Dr Bob Johnson who will discuss “A review of talking cures for psychoses”

Delegates will include health professionals, GP’s, nurses, psychiatrists, psychologists, practice managers & service users, - all those concerned with patient care and patient safety

Cost: £125

Concessions including carers & un-funded health professionals, £25

Un-funded nurses, students & service users £5

Lunch is not provided, reasonably priced food available

Further details are available at the APRIL website.

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admin September 12th, 2008

Readers are reminded that adverse reactions to vaccines can be reported to the Yellow Card Scheme via the Yellow Cards in the BNF, and online. The following is a letter related to the Human papillomavirus (HPV) immunisation programme from the MHRA.

2 September 2008

Dear Colleague

Human papillomavirus (HPV) immunisation programme – reporting adverse reactions via the Yellow Card Scheme

The routine immunisation programme for HPV vaccine, Cervarix, is commencing across the UK. I am writing to clarify arrangements for reporting suspected adverse reactions (ADRs) via the Yellow Card Scheme and to seek your help in optimising the value of reporting in relation to Cervarix.

Many adolescents will be immunised with the vaccine over a relatively short time in the coming months. Following the specific guidance outlined below will help us monitor the safety of Cervarix vaccine effectively. The most common side-effects have been established in clinical trials and these are listed in the product information (available via http://emc.medicines.org.uk). However, as with all vaccines and medicines used in the UK, it is important that the MHRA monitors the safety of Cervarix during routine use.

How to report a suspected ADR

• Please report via the Yellow Card Scheme ADRs that you suspect may have been caused by Cervarix.
  We strongly encourage you to report online at www.yellowcard.gov.uk If you need a paper form, these are available in the BNF.
• Please report only reactions that you suspect may be related to the vaccine and not those associated with the injection process or procedure – see below.

Faints and panic attacks
Fainting (or vasovagal syncope) and panic attacks, including mass episodes, can occur during, following, or even before, vaccination. The clinical features of such events are described in chapter 8 of the ‘Green Book’. It is important that procedures are in place to avoid injury from faints and to ensure that any sudden loss of consciousness is distinguished from a possible anaphylactic reaction (see below). Faints or panic attacks occurring during or very shortly after vaccination are usually a psychogenic response to the needle injection and not a true side-effect of the vaccine.

If having considered this advice, you wish to report an episode which may have been psychogenic, please include only the main diagnosis or event as the suspected reaction (e.g. ‘faint’ or ‘panic attack’). Any associated symptoms (such as loss of consciousness, injury, limb jerking or tingling, difficulty in breathing, hyperventilation etc) should not be reported as a suspected adverse reaction. If necessary, they can be included as ‘additional information’ on the form.

Anaphylaxis and other allergic reactions
Anaphylaxis is a very rare side-effect of most vaccines. It is essential that we distinguish between reports of anaphylaxis and less serious allergic reactions or psychogenic events. The ‘Green Book’ gives further guidance on this. If you suspect a true case of anaphylaxis, please report it as such via the Yellow Card Scheme. We may need to contact you for confirmation. When reporting less severe allergic reactions please report only as ‘allergic reaction’ or other relevant description. Any signs or symptoms of anaphylaxis or other allergic reactions should be reported only as ‘additional information’ on the Yellow Card.

If you require further information on the role of the MHRA and the Yellow Card Scheme, please visit www.mhra.gov.uk. Further information on the vaccine can be found at www.mhra.gov.uk/HPVvaccine.

Remember, every Yellow Card report matters. Thank you for your help in monitoring the safety of this important new vaccine.

Yours faithfully,

Professor Kent Woods, Chief Executive

• MHRA , Yellow Card Scheme
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admin September 12th, 2008

The FDA have posted details of a warning by the manufacturer of rituximab concerning a case report of progressive multifocal leukoencephalopathy:

Genentech informed healthcare professionals of revisions to prescribing information for Rituxan regarding a case of progressive multifocal leukoencephalopathy (PML) leading to death in a patient with rheumatoid arthritis who received Rituxan in a long-term safety extension clinical study. The patient developed a JC virus infection with resultant PML and death 18 months after taking the last dose of Rituxan. Healthcare professionals treating patients with Rituxan should consider PML in any patient presenting with new onset neurologic manifestations. Additionally, consultation with a neurologist, brain MRI and lumbar puncture should be considered as clinically indicated.

The manufacturer’s letter [PDF] provides further details of the case:

The case of JC virus infection with resultant PML and death was reported in an RA patient treated with Rituxan and was diagnosed approximately 18 months after the last dose of Rituxan. This case was confounded by the patient’s development of oropharyngeal cancer, which was treated with chemotherapy (a platinum containing regimen) and radiation therapy 9 months prior to the development of PML. The patient had longstanding RA treated with immunosuppressants and a complex medical and rheumatologic history including Sjogren’s syndrome and undetectable complement C4 levels. Treatment for RA included methotrexate, steroids, and a TNF antagonist prior to Rituxan therapy; and methotrexate and steroids during and after Rituxan therapy.

The Rituxan package insert WARNING section on PML has previously noted reports of PML in patients with hematologic malignancies and autoimmune diseases for which Rituxan is not approved. It has been updated to reflect the case of PML in an RA patient treated with Rituxan and is enclosed [PDF] for your reference [See WARNINGS and PRECAUTIONS: 5.4 Progressive Multifocal Leukoencephalopathy (PML)].

• FDA
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admin September 10th, 2008

The MHRA have published September’s Drug Safety Update, which includes:

Drug safety advice
Fentanyl patches: serious and fatal overdose from dosing errors, accidental exposure, and inappropriate use
Yellow Card scheme update
Please report suspected adverse reactions to vaccines

Hot topic
Introduction of human papillomavirus immunisation in the UK

Stop Press
Viracept: update on carcinogen contamination (ethyl mesylate)
Natalizumab (Tysabri): progressive multifocal leukoencephalopathy
Monthly round-up of letters to healthcare professionals
Intrathecal drug pumps: missing propellant
Caffeine for apnoea of prematurity: correction
Recall of reagent for paracetamol levels

Other information from the MHRA
Patient Information Leaflet of the month: Prostasan (saw palmetto)
Azithromycin reclassification: pharmacy availability to treat chlamydia

• MHRA
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admin August 22nd, 2008

The FDA have issued an Early Communication about an Ongoing Safety Review concerning a potentially increased risk of cancer associated with Simvastatin and Ezetimibe when used in combination (Vytorin).

FDA informed healthcare professionals that the Agency is investigating a report from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of a possible association between the use of Vytorin and a potentially increased incidence of cancer. Vytorin is a combination product of simvastatin and ezetimibe used to decrease the production of cholesterol by the liver and inhibit the absorption of cholesterol in the intestine to reduce LDL-cholesterol levels and reduce the risk of cardiovascular events. Recently, FDA obtained preliminary results from the SEAS trial. The clinical trial tested whether lowering LDL-cholesterol with Vytorin would reduce the risk of cardiovascular events in individuals with aortic stenosis. A lower overall cardiovascular risk was not found with Vytorin. However, there was an additional observation that a larger percentage of subjects treated with Vytorin were diagnosed with and died from all types of cancer combined when compared to placebo during the 5-year study.

FDA anticipates receiving a final SEAS study report in about 3 months and the Agency’s review and evaluation of the clinical trial data and other relevant information should take approximately 6 months. FDA will communicate its conclusions and recommendations at that time. Healthcare professionals and caregivers should continue to monitor patients taking Vytorin and report side effects from the use of this drug to the Agency.

The risk reported in the SEAS trial is noted here:

An adverse event attributable to cancer was noted more frequently in the ezetimibe/simvastatin arm, as compared with placebo (9.9% vs. 7.0%, p = 0.03). Cancer deaths were also more frequent in the ezetimibe/simvastatin arm (4.1% vs. 2.5%, p = 0.05). On further scrutiny, these differences did not seem to be related to any particular type of cancer and did not become significantly larger with more prolonged treatment.

There is already controversy about this news in the media, with the democratic chairman of the U.S. House of Representatives Energy and Commerce Committee getting confused by an apparent discrepancy in cancer figures. This is a red herring related to two snapshots of the trial data release from two differing sources. It should not be taken as evidence of harms being hidden, although it is a shame that calm rational discussion of the possible risk may be derailed by confusion about figures.

As the FDA notes there are two large ongoing trials (IMPROVE-IT and SHARP) being undertaken of the simvastatin/ezetimibe combination, and the full results of the SEAS study are not yet available. Interim data from IMPROVE-IT and SHARP do not show this result. Therefore some caution is required in interpretation of these preliminary results from SEAS.

The FDA are therefore not advising patients to stop or switch treatment, and nor are they suggesting there is a causal relationship between the combination and cancer. They expect to finish their review in 6 months time.

In years gones by regulators may have avoided statements related to associations that where not proven. Improvements in transparency and communications mean that regulators are attempting to be open about their decision making processes. That means sharing information about potential adverse effects - even when proof does not exist. Hopefully, the media and public will accept this for what it is, rather than being alarmed by the information provided.

• FDA
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