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Claritin's patent will expire in December. Schering hopes Clarinex will catch on before then
Many people will probably see Schering-Plough's newest product, Clarinex (desloratadine), as an attempt to extend the loratadine (Claritin) gravy train. After all, the first patent on loratadine expires in December of this year, and the company plans to launch desloratadine, another nonsedating antihistamine, this month.
Desloratadine is an active metabolite of loratadine. According to package inserts, the two drugs are quite similar, as would be expected. Both are indicated for treatment of seasonal allergic rhinitis symptoms (both nasal and non-nasal), although loratadine is approved for patients as young as two years. Desloratadine is indicated for patients 12 years and older.
Schering has already received an approvable letter for chronic idiopathic urticaria for desloratadine, an indication approved for loratadine, and Food & Drug Administration response is pending on an allergic rhinitis indication.
Although Schering could argue that the new drug is a more purified form of loratadine, the company prefers not to compare the two products. According to William O'Donnell, a spokesman for Schering, desloratadine "is a new chemical entity." He also said the drug relieves both nasal and non-nasal symptoms consistently and effectively for 24 hours. "It helps address concerns that currently available medications don't relieve."
Pharmacists and third parties, however, will likely be closely comparing the two drugs. Both loratadine and desloratadine are selective H1 antagonists and are more effective than placebo at relieving allergy symptoms. Unlike loratadine, desloratadine absorption is not dramatically increased by food. Desloratadine levelsand those of its major active metabolite, 3-hydroxydesloratadinewere increased by cytochrome P-450 inhibitors, but not to the same extent that loratadine levels were.
A curious occurrence with desloratadine is that about 7% of study subjects were "slow metabolizers" of the drug, according to the labeling. While the half-life in most patients was 27 hours, in these patients the half-life was 50 hours or more. The slow metabolizers were exposed to six times more loratadine than the other study subjects. One would expect more side effects as a result, but this was not proven in the pharmacokinetic studies.
In clinical trials of desloratadine, frequency of side effects was quite low, even lower than reported in loratadine trials, and no serious adverse events occurred. The study results did not identify or separate slow metabolizers from the rest of the population, so it is uncertain just how many of those experiencing side effects were in this group. Furthermore, researchers still have no way to predict which patients will turn out to be slow metabolizers. Race may be a factor: 20% of 276 black study participants fell into the slow-metabolizing group.
Since terfenadine (Seldane) was removed from the market, QT prolongation has been a concern with any drug introduction. Desloratadine, when given at nine times the recommended daily dose of 5 mg, raised corrected QT (QTc) by only 8 milliseconds (normal values for QTc range from 0.38 to 0.44 seconds). However, it is unknown whether the slow metabolizers will be in more danger of QT prolongation, particularly when taking liver enzyme inhibitors.
Another potential concern for the slow-metabolizing group is tumor formation. In carcinogenicity studies, rodents given five to seven times the human dose of desloratadine developed significantly more hepatocellular tumors than the controls. This may not be a problem for the general population, but those who accumulate much larger than average levels of desloratadine may be at higher risk.
Schering may have to win over R.Ph.s still upset about last year's albuterol shortage. Manufacturing problems held up the approval of desloratadine and stalled production of albuterol. Alan Wong, R.Ph., who owns a Medicine Shoppe in Orinda, Calif., agreed that the shortage did not do much for Schering's image. "I will stock it," he said of desloratadine, "just to see how it moves."
Wong doesn't believe desloratadine will sell well "unless they manage to get it on formularies and under the price of the generics." Schering anticipated this and is actually pricing the product lower than loratadine. At $1.83 a day, the new drug is about 40 cents cheaper than the loratadine Wong gets from his wholesaler.
Jillene Lewis. Will Clarinex take over the mantle of Claritin?. Drug Topics 2002;2:15.