Dear E-druggers,
This is in response to the questions about the registration status of
certain drugs namely terfenadine, astemizole, guar gum, and temafloxacin.
The status in the U.S. for these drugs:
1. Terfenadine: This antihistamine has been associated with a number of
serious adverse drug interactions including some fatalities. The problem
with terfenadine almost always have been observed when the drug has been
co-administered with the anti-fungal drug ketoconazole and macrolide
antibiotics such as erythromycin.
Ketoconazole interferes with the metabolism of terfenadine leading to
prolongation of QT interval resulting in life-threatening ventricular
arrhythmias. On the basis of adverse drug experience reports
and clinical
pharmacologic studies, the U.S. Food and Drug Administration required
labeling changes contraindicating simultaneous use of terfenadine and
ketoconazole and/or erythromycins.
Recently, with the availability of a safer alternative, FDA proposed to
the manufacturer to withdraw terfenadine from the market (Please see an
earlier email posted on terfenadine in the E-Drug). As far as I know
terfenadine has always been available by prescription in the U.S.
2. Astemizole: Concomitant use of astemizole with ketoconazole and/or
erythromycin has been associated with similar life-threatening cardiac
arrhythmias. Simultaneous use of these drugs are contra-indicated. This
drug is available by prescription and the FDA has presently not issued any
notice to the manufacturer to pull this drug from the market unlike
terfenadine.
3. Guar gum: This product was used as an OTC weight control product. Guar
gum products are intended to expand in the stomach when hydrated. It was
later found that if insufficient water was ingested with the product, guar
gum could swell in the esophagus, rapidly forming a heavy, viscous,
adhesive mass.
A well documented report of a death attributed to surgical treatment of
guar-gum-associated esophageal obstruction led to a recall of weight
control products containing this ingredient.
1989, FDA's adverse drug experience monitoring center (now
pharmacovigilance division) received several reports of esophageal
obstruction associated with guar gum. The receipt of these additional
reports led to an investigation that identified 17 cases. Evaluation of
these case series resulted in a product recall and a reclassification of
weight control products containing guar gum as "not being generally
recognized as safe and effective."
4. Temafloxacin: This oral antibiotic was approved in the U.S. in January
1992 and launched in the market in mid-February. When approved by the FDA
the drug was already being used in Argentina, Germany, Italy, Ireland,
Sweden, and the U.K.
During the first three months of temafloxacin use, the FDA received
approximately 50 reporst of serious adverse events including three deaths.
These side effects included hypoglycemia in elderly patients as well as a
constellation of multi-system organ involvement characterized by hemolytic
anemia, frequently associated with renal failure, markedly abnormal liver
function tests, and coagulopathy.
Evaluation of these reports resulted in reclassification of the
registration status of temafloxacin and within four months after its
launch in the U.S. market, the drug was withdrawn from the U.S. and the
world market.
All the above cases emphasize the importance of having a system to
monitor adverse reactions association with the use of drugs. All countries
need a strong pharmacovigilance system and the WHO Collaborating Center in
Uppsala, Sweden helps in setting up such programs.
I hope the above is useful. Thanks and good luck!
Syed Rizwanuddin Ahmad, MD, MPH
Washington, DC
Email: srahmad@essential.org
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