Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions.

We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release.

Myasthenia gravis exacerbation or unmasking associated with telithromycin treatment.

Telithromycin, a new ketolide antibiotic, has been implicated in the exacerbation or unmasking of myasthenia gravis. This retrospective study presents two clinical reports and summarizes eight other suspected cases notified to the French pharmacovigilance system, highlighting a potentially life-threatening risk of telithromycin treatment in myasthenic patients. An important common feature was that, in seven cases, symptomatology occurred within 2 hours of first telithromycin intake--notably in cases of severe exacerbation.

[Clinically significant toxicity and tolerance of the main antibiotics used in lower respiratory tract infections]. / Toxicité et tolérance cliniquement significatives des principales familles antibiotiques utilisées pour le traitement des infections des voies respiratoires basses.

The purpose of this article was not to review all reported adverse reactions of antibiotics used in the treatment of lower respiratory tract infections but rather to focus either on those which might have an impact on observance, efficacy, and resistance, or on rare but life-threatening adverse effects such as torsade de pointe. The latter are mostly predictable and prescribers should adhere to precautions and contraindications. For new antibiotics, the number of patients enrolled in phase I to III clinical trials is far to small to detect such rare adverse effects and large post registration tolerance surveys are mandatory. ss-lactams are well tolerated. The risk of anaphylactic reaction is magnified by patient reports and can be reduced by skin testing. Macrolides are well tolerated as well. The risk of cardiac toxicity should be reduced by assessing individual susceptibility and avoiding drug interactions. The tolerance to telithromycin, a new ketolide, is similar to that of macrolides. Serious toxic reactions such as convulsions, tendon rupture, torsade de pointe, and hypoglycemia are associated with the use of fluoroquinolones. Most of these adverse reactions can be often circumvented by avoiding exposure patients at risk. Quinupristin/dalfopristin can induce arthralgia and myalgia and the major adverse effects of linezolid are IMAO like reactions, reversible myelosuppression, and peripheral neuropathy. Most of the adverse antibiotic reactions are reported when precautions of use in susceptible patients are not taken into account. When they are, the safety/risk ratio is good.

Pill esophagitis caused by telithromycin: a case report.

A large number of oral drugs have been reported to cause pillinduced esophagitis in the medical literature. To our knowledge, this is the first reported case in which telithromycin was the cause of pill-induced esophagitis. In this report, we describe a male patient who admitted to the hospital with dysphagia and retrosternal pain after taking telithromycin (Ketek for acute sinusitis. He had a history of swallowing the film tablet with at least a glass of water and lying down immediately after taking the drug. An upper endoscopic examination demonstrated a deep ulceration of 1 cm diameter in the middle of the esophagus surrounded by relatively normal mucosa. Lansoprazole 30 mg was started. His symptoms improved seven days after cessation of the drug. The esophagus was completely normal in control endoscopy after two weeks. Telithromycin may cause esophageal lesions; therefore, patients should be educated by physicians about the drug's side effects and should drink at least 100 ml water after swallowing the medication. Drug administration should be in the upright position.