Med Check

• The Committee for Medicinal Products for Human Use, the review committee for the European Agency for the Evaluation of Medicinal Products, has recommended that olanzapine pamoate monohydrate long-acting injection be authorized for marketing as a treatment for schizophrenia.

The olanzapine powder for injectable suspension is manufactured by Eli Lilly and Co. and has not yet been approved in the United States. The brand name of the product marketed in Europe is Zypadhera, and the dosages are 210 mg, 300 mg, and 405 mg, according to the company's September 25 announcement. In clinical trials the long-acting olazapine injection was given at intervals of once every two or four weeks.

Although the side effects of the olanzapine injection in clinical trials were generally similar to those of oral olanzapine, serious adverse events“ with signs and symptoms consistent with olanzapine overdose” have been reported in 0.7 percent of all injections and 1.4 percent of patients in the clinical trials so far, the company stated. These symptoms included mild to severe sedation, coma, delirium, extrapyramidal symptoms, ataxia, and possible convulsion.

•Risperidone long-acting injection (Risperdal Consta) has been approved by the U.S. Food and Drug Administration (FDA) for administration in the deltoid muscle in the arm to treat schizophrenia, according to an October 9 announcement from its maker Johnson and Johnson. It had previously been approved for injection in the gluteal muscle. The deltoid injection should be given through a smaller and shorter needle than the needle intended for the gluteal injection. The two sizes of needles are now included in the product package.

• The FDA has approved quetiapine fumarate extended-release tablets (Seroquel XR) for the acute treatment of depressive episodes in bipolar disorder and manic and mixed episodes in bipolar I disorder, as well as for the maintenance treatment of bipolar I disorder as an adjunct to lithium or divalproex, AstraZeneca announced on October 10.

The indication for bipolar depression was supported by an eight-week, randomized, placebo-controlled clinical trial in 280 patients. The indication for treating acute bipolar manic and mixed episodes was supported by a randomized, placebo-controlled clinical trial that evaluated patients' change from baseline in Young Mania Rating Scale scores at week 3. Before these indications were approved, quetiapine extended-release had been approved for treatment of schizophrenia, and the immediate-release formulation had been approved for bipolar depression.

• The FDA will systematically review brand names of drugs to reduce the chance of medication errors, the agency announced on October 8.

As more and more drugs go on the market, some proprietary drug names sound or look so alike that patients are at risk of being given the wrong medication, which accounts for about one-fourth of the estimated 1.5 million Americans harmed by medication errors every year, according to a 2006 Institute of Medicine report. The FDA plans to implement a pilot project to review and study new propriety drug names voluntarily submitted by manufacturers as a way to minimize the risk of mix-ups. A manufacturer can request this drug-name review as early as completion of the product's phase 2 clinical development.

• Lilly announced on October 7 that it settled lawsuits with 32 states and Washington, D.C., regarding allegations of illegal marketing and promotion of its product olanzapine (Zyprexa) for a total of $62 million. The lawsuits alleged that the company marketed the drug for off-label indications. In addition to the payment, the company agreed to hand over information on health care professionals who had been paid more than $100 a year for promotional activities, such as speaking or consulting arrangements, to the states' attorneys general.

• GlaxoSmithKline settled a class-action lawsuit with U.S. insurers for $40 million, the company announced on October 2. The lawsuit alleged that the company had suppressed information about the risks of paroxetine for children and adolescents, including suicidal thoughts and behaviors. The settlement will go to insurance companies for past claims they paid out for paroxetine use by children and adolescents. The company admitted no liability in the settlement.

• Cephalon announced on September 29 that it would settle all criminal and civil suits filed by the U.S. Attorney's Office, Department of Justice, other federal agencies, and the attorneys general of Massachusetts and Connecticut over illegal off-label promotions of three of its products, tiagabine, modafinil, and oral transmucosal fentanyl citrate.

As part of the settlement, Cephalon pleaded guilty to a criminal misdemeanor charge for violating the U.S. Food, Drug, and Cosmetic Act, according to an October 10 Associated Press report. The company will pay more than $400 million to the federal and state governments. In addition, it will enter a five-year, corporate-integrity agreement with the Department of Health and Human Services to disclose on a Web site by January 21, 2010, all payments to physicians.

• Sepracor Corp., the maker of eszopiclone (Lunesta), is substantially cutting back on direct-to-consumer (DTC) advertisements that promote the sleep-aid drug, according to a report in the October 6 Boston Globe. Sepracor has spent nearly $300 million on DTC ads for this drug alone, as estimated by Nielson Media Research, making it the most heavily advertised drug in the United States. DTC advertising has come under growing criticism, and a recent New England Journal of Medicine report on a study conducted in Canada questioned whether the profit return is worth the investment in DTC advertising. Falling revenue and profits have also put the squeeze on DTC spending.

• Labopharm Inc. announced on September 22 that it submitted a New Drug Application (NDA) to the FDA for its product DDS-04A, a proprietary, once-daily formulation of trazodone, for treatment of major depression. The company conducted five pharmacokinetics studies and a phase 3, placebo-controlled clinical trial in 400 patients with depression to support the NDA.

• Lundbeck A/S, a Danish pharmaceutical company, announced on September 15 that it submitted an NDA to the FDA for sertindole (Serdolect), a second-generation antipsychotic drug, for the treatment of schizophrenia. Sertindole had previously been marketed but was withdrawn in the late 1990s because of concerns over cardiac risks of prolonging QT interval and causing arrhythmia. In 2005, the European regulatory agency approved the drug's reentry into the market. Sertindole inhibits central dopamine D₂ and serotonin 5HT₂ receptors as well as 1-adrenergic receptors.

• Lilly announced on October 1 that it has initiated a second phase 3 clinical trial of LY450139, a gamma-secretase inhibitor being developed for treating Alzheimer's disease. The multinational, randomized, placebo-controlled trial is expected to enroll more than 1,000 patients with mild to moderate Alzheimer's. Gamma secretase is involved in the production of beta amyloid, a substance in the brain implicated in the pathology of Alzheimer's. The trial will evaluate whether the drug is effective in slowing the progression of disease symptoms. ▪