admin March 19th, 2008
The FDA’s Winter 2008 Drug Safety Newsletter has been published. Contents include:
Exenatide (marketed as BYETTA): Acute Pancreatitis
PHOSPHODIESTERASE TYPE 5 (PDE5) INHIBITORS: Sildenafil citrate (marketed as VIAGRA and REVATIO), vardenafil hydrochloride (marketed as LEVITRA), and tadalafil (marketed as CIALIS): Sudden Hearing Loss
TUMOR NECROSIS FACTOR ALPHA (TNF-α) ANTAGONISTS: Infliximab (marketed as REMICADE), etanercept (marketed as ENBREL), and adalimumab (marketed as HUMIRA): Serious Skin Reactions
New Molecular Entity (NME) – 3 Years Later: Duloxetine (marketed as CYMBALTA)
Feature Article: Pharmacogenomics and Its Role In Drug Safety
admin March 19th, 2008
The FDA have announced in an early communication that ongoing safety monitoring has identified a possible increased risk of stroke in patients who take tiotropium.
Boehringer Ingelheim reported to the FDA that it has conducted an analysis of the safety data from 29 placebo controlled clinical studies (“pooled analysisâ€). In 25 of the clinical studies, patients were treated with Spiriva HandiHaler. In the other 4 clinical studies patients were treated with another formulation of tiotropium approved in Europe, Spiriva Respimat. The 29 clinical studies included approximately 13,500 patients with COPD. Based on data from these studies, the preliminary estimates of the risk of stroke are 8 patients per 1000 patients treated for one year with Spiriva, and 6 patients per 1000 patients treated for one year with placebo. This means that the estimated excess risk of any type of stroke due to Spiriva is 2 patients for each 1000 patients using Spiriva over a one year period.
It is important to interpret these preliminary results with caution. FDA has not confirmed these analyses. Pooled analyses can provide early information about potential safety issues. However, these analyses have inherent limitations and uncertainty that require further investigation using other data sources. This early communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs.
No causal relationship is as yet proven. The FDA are currently reviewing post-marketing data and further data from the UPLIFT study will be available in June of this year.
Bottom line: There is no proven link between stroke and tiotropium at present. However, healthcare professionals should be aware that any suspected adverse effects to tiotropium can be reported via the Yellow Card scheme.
admin March 14th, 2008
Prezista (darunavir) has had warnings added in relation to hepatotoxicity by the FDA:
FDA and Tibotec Therapeutics notified healthcare professionals of changes to the WARNINGS section of the prescribing information for Prezista (darunavir) tablets regarding the risk of hepatotoxicity. In clinical trials and postmarketing experience, drug induced hepatitis has been reported in patients receiving combination therapy with Prezista/ritonavir. Appropriate laboratory testing should be conducted prior to initiating therapy with Prezista/ritonavir and patients should be monitored during treatment. Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pretreatment elevations of transaminases, especially during the first several months of Prezista/ritonavir treatment.
Darunavir is currently a black triangle drug in the United Kingdom, meaning that any adverse effects, no matter how trivial, should be reported to the Yellow Card scheme.
admin March 14th, 2008
The FDA have issued warnings related to Erythropoiesis Stimulating Agents (ESAs):
Increased Mortality and/or Tumor Progression section of the Aranesp and EPOGEN/PROCRIT labeling to update information describing the results of two additional studies showing increased mortality and more rapid tumor progression in patients with cancer receiving ESAs. Based on the results of these studies, the prescribing information has been revised as follows: ESAs shortened overall survival and/or time to tumor progression in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers when dosed to target a hemoglobin of ≥ 12 g/dL.
admin February 28th, 2008
FDA news:
Biogen Idec, Elan and FDA notified healthcare professionals of reports of clinically significant liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, occurred as early as six days after the first dose of Tysabri. The combination of transaminase elevations and elevated bilirubin without evidence of obstruction is recognized as an important predictor of severe liver injury that may lead to death or the need for a liver transplant in some patients. Tysabri should be discontinued in patients with jaundice or other evidence of significant liver injury. Physicians should inform patients that Tysabri may cause liver injury.
admin February 11th, 2008
FDA issued an early communication about an ongoing safety review regarding Botox and Botox Cosmetic. FDA has received reports of systemic adverse reactions including respiratory compromise and death following the use of botulinum toxins types A and B for both FDA-approved and unapproved uses. The reactions reported are suggestive of botulism, which occurs when botulinum toxin spreads in the body beyond the site where it was injected. The most serious cases had outcomes that included hospitalization and death, and occurred mostly in children treated for cerebral palsy-associated limb spasticity. Use of botulinum toxins for treatment of limb spasticity (severe arm and leg muscle spasms) in children or adults is not an approved use in the U.S
FDA
admin February 2nd, 2008
The FDA have updated the prescribing information for varenicline:
FDA informed healthcare professionals and consumers of important revisions to the WARNINGS and PRECAUTIONS sections of the prescribing information for Chantix regarding serious neuropsychiatric symptoms experienced in patients taking Chantix. These symptoms include changes in behavior, agitation, depressed mood, suicidal ideation, and attempted and completed suicide. While some patients may have experienced these types of symptoms and events as a result of nicotine withdrawal, some patients taking Chantix who experienced serious neuropsychiatric symptoms and events had not yet discontinued smoking. In most cases, neuropsychiatric symptoms developed during Chantix treatment, but in others, symptoms developed following withdrawal of Chantix therapy. See the FDA Information for Healthcare Professionals Sheet for recommendations and considerations for healthcare professionals on using Chantix therapy for patients.
admin January 18th, 2008
The FDA have issued warnings about the potential confusion between edetate disodium instead of edetate calcium disodium, and the unlicenced use of edetate disodium for chelation therapy.
There have been cases where children and adults have died when they were mistakenly given Edetate Disodium instead of Edetate Calcium Disodium (Calcium Disodium Versenate) or when Edetate Disodium was used for “chelation therapies” and other uses that are not approved by the FDA. As a result, FDA is reviewing the benefit/risk profile of Edetate Disodium to determine if the benefits for its intended use continue to outweigh the serious risks.
Further information.
Q&A.
admin January 8th, 2008
The FDA have issued advice about bisphosphonates and severe musculoskeletal pain.
The severe musculoskeletal pain may occur within days, months, or years after starting a bisphosphonate. Some patients have reported complete relief of symptoms after discontinuing the bisphosphonate, whereas others have reported slow or incomplete resolution. The risk factors for and incidence of severe musculoskeletal pain associated with bisphosphonates are unknown.
This severe musculoskeletal pain is in contrast to the acute phase response characterized by fever, chills, bone pain, myalgias, and arthralgias that sometimes accompanies initial administration of intravenous bisphosphonates and may occur with initial exposure to once-weekly or once-monthly doses of oral bisphosphonates. The symptoms related to the acute phase response tend to resolve within several days with continued drug use.
Bottom line: Patients who present with severe musculoskeletal pain who are taking bisphophonates may benefit from a temporary or permanent cessation of therapy.
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.
An example of toxic epidermal necrolysis (TEN).
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.