• The Food and Drug Administration (FDA) has set up a consumer-education Web
site about direct-to-consumer (DTC) prescription drug advertisements. Three
types of DTC advertisements are described: product claims in which a drug, the
condition it treats, and its benefits and risks are described; reminder ads in
which only the drug name but no indication is given; and help-seeking ads in
which a disease or condition is described but no specific drug is mentioned.
The Web site encourages consumers to report inappropriate drug ads to the
FDA's Division of Drug Marketing, Advertising, and Communications, the
division responsible for regulating postmarketing promotions of prescription
The DTC Web site can be accessed at<www.fda.gov/cder/ethicad/index.htm>.
• The FDA issued two warning letters last month to the India-based generic
drug manufacturer Ranbaxy Laboratories Ltd. and an import alert for its
products from two plants in India. The agency was concerned about"
deviations from U.S. current Good Manufacturing Practice
requirements" at facilities in Dewas and Paonta Sahib. The import alert
means that these products can be blocked from importation into the United
States. However, the Ranbaxy products named in the announcement have not been
recalled, and the FDA advised consumers to continue taking their medications.
Among the drugs affected by the alert are gabapentin and
nafazedone hydrochloride. Ranbaxy Laboratories announced two
days later that it retained Rudy Guiliani, the former New York City mayor, to
advise it on legal issues in this matter.
• The FDA requested additional data to evaluate the new drug application for
paliperidone palmitate intramuscular injection, according to
an announcement in August by Johnson and Johnson Pharmaceutical Research and
Development. The agency issued a "complete response letter" to the
manufacturer. This letter is in the new format that replaces the approvable
and not-approvable letters previously issued in response to new drug
applications. The product is being developed as a once-monthly injectable
formulation of the oral paliperidone tablets to treat schizophrenia. The
company said the agency did not require additional studies, which suggests
that the approval may come soon.
• Researchers at 15 sites are recruiting patients for a clinical trial to
test the effectiveness of a two-drug combination for major-depression. The
Combining Medication to Enhance Outcome of Depression (CO-MED) trial has been
designed to further the evidence for depression treatment on the basis of the
Sequenced Treatment Alternatives to Relieve Depression (STAR*D)
study. This randomized, single-blind (patients), active-controlled trial will
compare the effectiveness of a single drug with a two-drug combination in
adults with major depression. All drugs tested in the trial are approved
antidepressants. The primary outcome measured is remission rate after six
months of treatment. The total number of patients planned for the study is
The study is funded by the National Institute of Mental Health. The
principal investigators are John Rush, M.D., a professor of clinical sciences
and psychiatry, and Madhukar Trivedi, M.D., a professor of psychiatry, both at
the University of Texas Southwestern Medical Center.
Detailed CO-MED study information can be accessed at<clinicaltrials.gov/ct2/show/NCT00590863>.
• Concerns about neuropsychiatric adverse effects of
montelukast, a leukotriene receptor inhibitor to treat asthma
and allergy, may be unfounded, a study sponsored by the American Lung
Association (ALA) indicated.
The FDA issued an alert earlier this year to health care professionals and
the public, noting that it suspects a link between the drug and
psychiatric/behavioral symptoms such as depression, suicidal thoughts, and
anxiousness based on postmarketing reports (Psychiatric News, May
16); Merck had added warnings about the symptoms to the drug's package
insert. However, the ALA study, led by Janet Holbrook, Ph.D., M.P.H., found no
evidence to support this adverse effect.
The authors reanalyzed pooled data on 1,352 patients, including children as
young as age 6, who participated in three previous randomized, double-blind,
placebo-controlled, clinical trials of montelukast. The emotional well-being
of participants in these trials, measured by quality-of-life scales, showed no
deterioration after taking montelukast in either adults over 24 weeks or
children over 16 weeks, and no difference between the active-treatment and
placebo groups. The authors acknowledged that these trials had not been
designed to detect psychiatric disturbances, and this analysis did not
entirely rule out possible rare psychiatric adverse effects of the drug. As of
September 19, the study was scheduled for publication in the Journal of
Allergy and Clinical Immunology.
• Children with autism who took risperidone at doses of up to
3.5 mg a day did not appear to have impairment in their cognitive performance,
a randomized, double-blind study in the June Journal of Child and
Adolescent Psychopharmacology showed.
Thirty-eight children aged 5 to 17 with autism and severe behavior
disturbance (29 boys and nine girls) were randomly assigned to treatment with
either risperidone 0.5 mg to 3.5 mg a day (n=20) or placebo (n=18) for eight
weeks. Risperidone did not lead to significant decline in cognitive
performance from baseline. Patients' performance on certain tests was
better in the risperidone group than in the placebo group.
The study was led by Michael Aman, Ph.D., a professor of psychology and
psychiatry at the Nisonger Center at Ohio State University and funded by
grants from the National Institute of Mental Health.
An abstract of "Cognitive Effects of Risperidone in Children
With Autism and Irritable Behavior" is posted at<www.liebertonline.com/doi/abs/10.1089/cap.2007.0133>.
• After a voluntary recall in June, Shire announced in late August that
additional lots of methylphenidate transdermal system
(marketed as Daytrana) have been recalled because of problems
with the release liner, which could make it difficult for patients or parents
to remove the liner before applying the patch on the skin. Indicated for the
treatment of attention-deficit/hyperactivity disorder (ADHD), the patches are
manufactured by Noven Pharmaceuticals Inc. for Shire. Because the voluntary
recalls were not related to safety issues, Shire advised patients to continue
using the patches unless the release liners cannot be removed or the patches
are damaged upon opening. The lot numbers of the recalled products are
2750211, 2764111, 2764211, and 2819811.
• Pfizer has announced that it will pay Medivation Inc. up to $725 million
for the rights to develop and market the experimental drug dimebolin
hydrochloride for Alzheimer's disease (AD). The drug is in phase
3 development for mild-to-moderate Alzheimer's disease and has shown
promising results in clinical trials for Huntington's disease as
• Preliminary results from a phase 3 clinical trial indicated that a
long-acting formulation of clonidine developed by Sciele
Pharma Inc. and Addrenex Pharmaceuticals improved ADHD symptoms significantly
more than placebo, according to an announcement by the two companies. The
randomized, double-blind, placebo-controlled, eight-week study evaluated 228
ADHD patients aged 6 to 17.
• A Phase 2b trial of AZD3480 (also known as TC-1734), an
experimental drug being developed by AstraZeneca and Targacept Inc. for
treatment of AD, yielded inconclusive results, the companies announced in
September. In the 12-week, randomized, placebo-controlled trial in patients
with mild-to-moderate AD, neither AZD3480 nor the active comparator donepezil
produced an improvement that was statistically significantly different from
placebo in primary outcome of AD symptoms. The primary outcome was measured by
the Alzheimer's Disease Assessment Scale-Cognition Scale (ADAS-Cog).
The molecule is also being investigated for treating cognitive dysfunction
in schizophrenia and adult ADHD. AstraZeneca said it will announce the fate of
the drug's clinical development in December.
•Duloxetine hydrochloride has been approved by the European
drug regulatory agency for treatment of generalized anxiety disorder, Eli
Lilly and Co. and Boehringer Ingelheim announced on August 22. The drug
already carries this indication in the United States. ▪