NEW YORK, May 02 (Reuters) -- In rare cases, the prescription antihistamine terfenadine can increase the risk of heart arrhythmias and cardiac death when taken in combination with certain antibiotics, and according to a report earlier this week, even grapefruit juice.
Now, an analysis of the top-selling nonsedative antihistamines in 17 countries suggests that other, similar drugs may also carry the risk of cardiac problems. However, the number of adverse reactions are small, on the order of 0.25 per million defined daily doses sold, according to a letter in this week's issue of The Lancet. Terfenadine, which is sold under the name Seldane, and other newer antihistamines are popular because they can be used to treat hayfever and allergies without the sedative side effects of older drugs.
"The data indicate that some of the alternatives to terfenadine may have similar problems, suggesting that thorough consideration of the comparative benefit risk profile of all non-sedating antihistamines is wise," wrote Marie Lindquist and Ralph Edwards, of the Uppsala, Sweden-based World Health Organization (WHO) Collaborating Center for International Drug Monitoring.
The researchers looked at the number of doses of terfenadine, acrivastine (Semprex-D), astemizole (Hismanal), cetirizine (Zyrtec), and loratadine (Claritin) taken between 1986 to 1996 in countries around the world, and the reported side effects of the drugs, including heart arrhythmias, cardiac arrest, sudden cardiac death, and other heart problems. Terfenadine, loratadine, and astemizole had the most reported side effects.
"On the basis of existing data from the WHO and IMS databases, we were able to provide rapidly a measure of the international spontaneous report levels, allowing comparison between drugs," they wrote. "These crude rates reflect doctors' concerns with these products, but do not provide a definitive answer."
However, it does suggest that other drugs may have similar problems, they concluded. While such drugs are prescription-only in the U.S., they are available over-the-counter in many countries. The U.K. moved last week to make terfenadine prescription-only, France recently discontinued the drug, and the Food and Drug Administration recommended in January that terfenadine products be removed from the market.
Terfenadine and astemizole block cardiac muscle potassium channels, which has been linked to cardiac arrhythmias, according to the letter. Loratadine has not been shown to block the channels.
As previously reported by Reuters, a Canadian study found that grapefruit juice interfered with the metabolism of terfenadine, resulting in higher concentration of the drug in the blood. However, there have been no reported cases of heart problems linked to consuming the drug with grapefruit juice.
SOURCE: The Lancet (1997;349:1322)
