The European-wide review of the anti-obesity drug sibutramine (Reductil) has concluded and an opinion reached recommending the suspension of the licence for the medicine across Europe.

Evidence suggests that there is an increased risk of non-fatal heart attacks and strokes with this medicine that outweighs the benefits of weight loss, which is modest and may not be sustained in the long term after stopping treatment.

Prescribers are advised not to issue any new prescriptions for Reductil and to review the treatment of patients taking the drug.

Pharmacists are asked to cease dispensing the medicine. People who are currently taking Reductil are advised to make a routine appointment with their doctor to discuss alternative measures to lose weight. There are no health implications if people wish to stop treatment before seeing their doctor.

The EMEA document [PDF] and Questions and Answers [PDF]

The European Medicines Agency has completed a review of efalizumab (Raptiva) after concerns about its safety. The Agency’s Committee for Medicinal Products for Human Use (CHMP) has concluded that the benefits of efalizumab do not outweigh its risks, and that the marketing authorisation should be suspended across the EU.

Efalizumab is used to treat adults with moderate to severe chronic plaque psoriasis (a disease that causes red, scaly patches on the skin) who have not responded to, or who are unable to take, other treatments for psoriasis (including ciclosporin, methotrexate, and PUVA).

This medicine was reviewed after reports of serious side effects, including three confirmed cases of progressive multifocal leukoencephalopathy (PML, a rare but serious disorder of the central nervous system) in patients who had received efalizumab for more than 3 years; two of these patients died.

Although psoriasis is a disabling condition that can cause social and psychological problems for patients, it is very rarely life-threatening. The Committee concluded that the risk of PML is unacceptable for patients taking efalizumab. They recommended that the marketing authorisation should be suspended until there is adequate new evidence to identify a group of patients in which the benefits of efalizumab outweigh its risks.

EMEA press release [PDF].

EMEA Q&A on efalizumab [PDF].

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]

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.

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.

The MHRA has also put up a page of material related to this decision, cardiovascular disorders, eye disorders and fracture risks. The issue is also covered in this month’s Drug Safety Update.

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.

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.

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.

Read on…

Advice for patients taking rimonabant:

• If you are taking an anti-depressant, go and see your GP.
• If you start to experience symptoms of depression, go and see your GP.
• If you have had depression, continue your treatment. Next time you see your GP, discuss your treatment.

EMEA documentation relating to rimonbant.

MHRA press release.