If terfenadine is banned, why not astemizole, too?
FDA’s action raises questions
The Food and Drug Administration’s proposed ban on the antihistamine terfenadine begs a question: Why not ban astemizole, as well? Both second-generation antihistamines accumulate in the blood when taken with the antifungals ketoconazole and itraconazole, as well as with some macrolide antibiotics, and in both instances QT prolongation and fatal torsades de pointes are the possible results.
"I’m really perplexed astemizole was left on the market," says Steven Miesel, PharmD, assistant director of pharmacy at Fairview Health System in Minneapolis.
"They’re two peas in a pod as far as these cardiac abnormalities go," adds Nancy Jordan, PharmD, director of drug information services for Holyoke (MA) Hospital.
Rusty May, PharmD, who runs the drug information center at the Medical College of Georgia in Augusta, says astemizole has a longer half-life than terfenadine, but the drugs are similar in safety. "Safetywise, I see no reason why anybody would want to use [astemizole]. There are safer options," he says.
While he isn’t sure how many serious drug interactions have occurred with terfenadine or astemizole, May says there is a large number of cases in which the antihistamines are prescribed with the forbidden drugs. In fact, a pharmacy technician at the Medical College recently had two prescriptions filled one for Seldane, the other for erythromycin. "It’s a potentially dangerous combination," he says. "Why not just avoid it if you can?"
FDA’s silence perplexes
For its part, the FDA is silent on the subject of astemizole. Officially, the agency says it’s proposing a ban on terfenadine because Hoechst Marion Roussel, marketers of the drug, just introduced an alternate product, fexofenadine (Allegra). Fexofenadine, the active metabolite of terfenadine, does not affect cardiac function the way the parent drug does. The agency says with fexofenadine on the market, a good reason no longer exists to keep terfenadine on the shelves.
"That is something we’re going to be looking into," says Larry Sasich, PharmD, a research analyst at Public Citizen, a lobbying group in Washington, DC, started by consumer advocate Ralph Nader. "If you read the boxed warnings for the drugs, arguably you could say the astemizole warning is worse than terfenadine’s." With apparently equal toxicity and risk, Sasich says it "makes no sense " to leave astemizole on the market if terfenadine is pulled.
Besides those drugs, Sasich has a few other suggestions for hospitals wishing to trim their formularies of hazardous products. He shares some of the same reservations as do the pharmacists in Drug Utilization Review’s cover story this month. (See p. 49.)
• Metformin (Glucophage)
Phenformin was run out of town in 1977 under the FDA’s "imminent hazard" clause, after numerous associations with severe lactic acidosis. Metformin isn’t as fat-soluble as phenformin, another drug for diabetes, and that’s the primary reason it’s less likely to cause the potentially fatal side effect. Still, patients with kidney dysfunction are at risk. Plus, metformin is in the uncomfortable position of being named on 63 adverse drug reaction (ADR) reports that resulted in death, Sasich says. There’s no evidence metformin caused or contributed to those deaths, however.
Among sulfonylurea antidiabetics, Public Citizen lists glyburide (but not glipizide) as a "Do Not Use" product, based on evidence that the former causes hypoglycemia twice as often as does the latter. Public Citizen’s research shows the sulfonylurea least likely to cause hypoglycemia is tolbutamide.
• Tramadol (Ultram)
"The FDA was totally irresponsible when they approved that product," Sasich says. First marketed in Germany more than 20 years ago, the non-addicting painkiller tramadol clocked a modest number of reported ADRs in Europe about 400. But in its first year on the U.S. market, more than 500 tramadol ADRs were received by the FDA, Sasich says. That prompted a change in the product’s labeling most importantly, a warning that the drug could cause seizures. "Nothing I’ve seen shows it’s as good as plain Tylenol with codeine," Sasich says. Pharmacist Meisel adds, "Any drug that’s God’s gift to mankind is not going to take 18 years to get here."
• Pentoxifylline (Trental)
"A totally useless drug," Sasich says. That pretty much sums up Public Citizen’s opinion of the only drug on the market for poor circulation in the legs.
• Bromocriptine (Parlodel)
Once marketed as a postpartum lactation suppressant, bromocriptine has been discredited in maternity wards since 1988, with the company finally withdrawing that indication in the United States in 1994. The body doesn’t need a supplement to suppress lactation. It does the deed on its own. Aside from unnecessary use, there’s another reason hospitals should stop using bromocriptine in postpartum women, Sasich says. The drug may be linked to an increase risk of strokes and heart attacks. Bromocriptine is, however, effective in Parkinson’s disease.
• Calcium channel blockers
Sasich says there’s a disturbing trend in the treatment of hypertension in the United States: the heavy use of calcium channel blockers when there’s no evidence that as a class they lower the risk of diseases such as stroke and heart failure. Diuretics and beta-blockers, on the other hand, have been proven to prevent such complications.
• Flurazepam
Actually, any sleeping medication with active metabolites is a poor choice for a hospital formulary. Choose Ambien, BuSpar, or Serax instead, Sasich says.
• Fluoroquinolones
While not exactly a "dangerous" group of drugs, an unusual post-marketing side effect has turned up with the fluoroquinolone antibiotics: inflammation and even ruptures of weight- bearing tendons, most especially the Achilles tendon. While the fluoroquinolones have long been associated with damage to developing cartilage and thus aren’t recommended for use in children, adolescents, or pregnant women these tendon ruptures are occurring in adults.
Among U.S.-approved products, the World Health Organization lists the antibiotic ciprofloxacin as the worst offender, with 21 reported cases; ofloxacin is close behind at 16 cases. Those two products, however, dominate the fluoroquinolone market.
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