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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.

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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.

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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.

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admin December 10th, 2007

Readers may be interested in the FDA’s new Drug Safety Newsletter.

Rituximab (marketed as Rituxan): Progressive Multifocal Leukoencephalopathy (PML)
Modafinil (marketed as Provigil): Serious Skin Reactions
Temozolomide (marketed as Temodar): Aplastic Anemia
Deferasirox (marketed as Exjade): Early safety findings.

[PDF here]

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admin December 6th, 2007

The FDA have requested that manufacturers update prescribing information for desmopressin to include warnings about severe hyponatremia and seizures. Children treated with desmopressin intranasal formulations for primary nocturnal enuresis (PNE) are particularly susceptible, and for that reason such formulations are no longer indicated for the treatment of primary nocturnal enuresis.

Bottom line: The indication of primary nocturnal enuresis (PNE) was removed from all desmopressin nasal spray products in the UK in April of this year and the risk of hyponatremia was discussed in Drug Safety Update (Vol 1: Issue 2) in September 2007. This news acts as a reminder of the risk of hyponatraemia and the need to monitor therapy appropriately.

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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.

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admin November 6th, 2007

News from the FDA:

The U.S. Food and Drug Administration (FDA) today announced that, at the agency’s request, Bayer Pharmaceuticals Corp. has agreed to a marketing suspension of Trasylol, a drug used to control bleeding during heart surgery, pending detailed review of preliminary results from a Canadian study that suggested an increased risk for death.

FDA requested the suspension in the interest of patient safety based on the serious nature of the outcomes suggested in the preliminary data. FDA has not yet received full study data but expects to act quickly with Bayer, the study’s researchers at the Ottawa Health Research Institute, and other regulatory agencies to undertake a thorough analysis of data to better understand the risks and benefits of Trasylol.

There are not many treatment options for patients at risk for excessive bleeding during cardiac surgery. Thus, FDA is working with Bayer to phase Trasylol out of the marketplace in a way that does not cause shortages of other drugs used for this purpose.

Until FDA can review the data from the terminated study it is not possible to determine and identify a population of patients undergoing cardiac surgery for which the benefits of Trasylol outweigh the risks. Understanding that individual doctors may identify specific cases where benefit outweighs risk, FDA is committed to exploring ways for those doctors to have continued, limited access to Trasylol.

The MHRA also state:

The UK Commission on Human Medicines will advise this week on any formal regulatory action and appropriate advice to UK prescribers. In the meantime, and as a precautionary approach, our advice is that aprotinin should only be used after careful consideration in individual cases where, for example, the risk of blood loss during surgery is considered to be particularly high (for example, redo CABG (coronary artery bypass graft surgery), where there is no suitable alternative, and only when the likely benefits outweigh any risks to individual patients.

Aprotinin is indicated for the prevention of major blood loss during coronary artery bypass graft surgery. Since 2006, the safety of aprotinin has been kept under review within Europe due to emerging evidence of adverse effects on the kidney as well as a possible increased risk of heart and cerebral disorders and death. On the basis of the evidence of kidney dysfunction, action was taken within Europe last year to restrict the usage of aprotinin only as a preventative to reduce blood loss in patients undergoing cardiopulmonary bypass in the course of coronary artery bypass graft surgery who are at increased risk of blood loss or blood transfusion. As the evidence of an increased risk of death and heart and cerebral disorders was inconclusive, no further action was taken until more data are available.

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admin October 30th, 2007

On October 19, 2007, FDA was notified of the Data Safety Monitoring Board’s (DSMB) recommendation to stop patient enrollment in the aprotinin (marketed as Trasylol by Bayer, Inc.) treatment group arm of the: Blood conservation using antifibrinolytics: A randomized trial in a cardiac surgery population (BART) study. The preliminary findings suggest that, compared to the antifibrinolytic drugs, epsilon-aminocaproic acid and tranexamic acid, aprotinin increases the risk of death.
[...]
[the] FDA anticipates re-evaluation of the overall risks and benefits of Trasylol. This re-evaluation may result in the need to revise the labeling or other regulatory actions. Until this process has been completed, healthcare providers who are considering use of Trasylol should be aware of the risks and benefits described in the labeling for Trasylol and the accumulating data suggesting Trasylol administration increases the risk for death compared to other antifibrinolytic drugs.

FDA early warning.

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admin October 17th, 2007

The FDA have issued a warning about pancreatitis associated with exenatide. In a review of 30 spontaneous reports of pancreatitis associated with exenatide, 27 had risks factors associated with pancreatitis, 22 patients improved on withdrawal of the drug, and a further 5 cases seemed to provoked by a change to a higher dosage. The FDA advise:

Healthcare providers should be alert to the signs and symptoms of acute pancreatitis. Symptoms include persistent severe abdominal pain that can radiate to the back and may be accompanied by nausea and vomiting. Acute pancreatitis is typically confirmed by the presence of elevated levels of serum amylase and/or lipase and characteristic findings by radiological imaging.

Discontinue Byetta if pancreatitis is suspected. If pancreatitis is confirmed, do not restart Byetta unless an alternative etiology for the pancreatitis is identified.

Suspected adverse drug reactions associated with exenatide can be reported in the UK to the Yellow Card scheme. As exenatide is a black triangle drug, any reactipn, no matter how trivial, should be reported.

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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.

More at the FDA.

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