• The Food and Drug Administration (FDA) has approved the labeling
claim that dexmethylphenidate extended release (Focalin XR)
capsules have a 30-minute onset of action in treatment of
attention-deficit/hyperactivity disorder (ADHD), according to a November 12
announcement by Norvartis, which markets the drug.
The approval was based on data from a randomized, multicenter,
double-blind, crossover study in 86 pediatric patients aged 6 to 12 with ADHD.
Patients randomized to the group of 20 mg dexmethylphenidate extended release
had a significantly greater improvement in ADHD symptoms from baseline than
did patients taking placebo at 30 minutes after drug administration. The study
was conducted by Matthew Brams, M.D., and colleagues and published in the
August CNS Drugs.
An abstract of "A Randomized, Double-Blind, Crossover Study of
Once-Daily Dexmethylphenidate in Children With Attention-Deficit Hyperactivity
Disorder: Rapid Onset of Effect" is posted at<cnsdrugs.adisonline.com/pt/re/cns/abstract.00023210-200822080-00006.htm>.
• The safety sections on the labels of citalopram,
escitalopram, and paliperidone extended release have
been changed, the FDA noted on its MedWatch Web site. For citalopram and
esciptalopram, several adverse reactions including abnormal bleeding,
potential interaction with other drugs that also increase risk of bleeding,
and hyponatremia especially in geriatric patients have been added to the"
Precautions" section. For paliperidone, the "Drug
Interactions" section now identifies the drug as a weak inhibitor of
P-glycoprotein at high concentrations. In addition, paliperidone concentration
in blood may be decreased by coadministration of carbamazepine because of
reduction in renal clearance of paliperidone. Dose adjustment may be necessary
if both drugs are prescribed.
Revised labeling safety information can be accessed at<www.fda.gov/medwatch/safety/2008/sep08_quickview.htm>.
• At its October meeting, the Committee for Medicinal Products for
Human Use (CHMP), which advises the European Medicines Agency on new drug
approvals, adopted a positive opinion for eszopiclone (brand
name Lunesta in the United States and Lunivia in Europe) for treating insomnia
in adults. The indications approved by the CHMP were short-term use to treat
difficulty falling asleep, nocturnal awakening, or early awakening.
Eszopiclone is manufactured by Sepracor Pharmaceuticals.
• AstraZeneca announced on November 13 that
quetiapine, in both immediate- and extended-release
formulations, was approved by the European authority for the treatment of
major depressive episodes in bipolar disorder. Quetiapine extended-release
tablets were approved for treating moderate to severe manic episodes in
bipolar disorder. The drugs already carry similar indications in the United
• A record number of serious injuries (20,745) and deaths (4,824)
suspected to be associated with drug therapy were reported to the FDA in the
first quarter of 2008, according to a report released on October 23 by the
Institute for Safe Medication Practices (ISMP), a nonprofit organization that
conducts research on and advocates for medication safety for hospitals,
pharmacists, and consumers. The number of suspected medication-related deaths
was "a 2.6-fold increase from the previous quarter," the ISMP
Varenicline accounted for the largest number of serious injuries and deaths
reported to the FDA during this period. Heparin-related serious injuries were
ranked second, with 779 reports to the agency. During this time, the agency
had issued a massive heparin recall because of possible contamination from
suppliers in China. Medication errors accounted for 7.1 percent of
drug-related serious injuries.
The ISMP regularly monitors drug-related adverse events stored in the FDA's
database known as the Adverse Event Reporting System. These adverse events are
reported voluntarily by physicians, nurses, pharmacists, and drug
• Asenapine was more effective than placebo in the
long-term prevention of relapse in patients with schizophrenia, according to a
randomized, placebo-controlled, double-blind, multicenter trial. The results
were announced by Schering-Plough on October 23. In the study, 700 patients
first took asenapine for up to 26 weeks. At the end of the open-label study,
386 patients who remain stabilized on the drug were randomized to either
placebo or asenapine in a double-blind, controlled phase for another 26 weeks.
No additional details were published.
• Auspex Pharmaceuticals announced in October positive safety data
from a phase 1 clinical trial of SD-254, a selective serotonin
norepinephrine reuptake inhibitor. SD-254 is essentially the same as
venlafaxine except that some hydrogen atoms in the molecule are substituted
with deuterium, an isotope of hydrogen.
According to the company's Web site, this molecular drug design, known as
deuteration, could allow many drugs to preserve their efficacy but alter the
pharmacokinetics and possibly reduce side effects. In this trial, the
pharmacokinetic profile of SD-254 in 16 healthy volunteers appeared to be"
superior to that of venlafaxine," the announcement stated.
• GlaxoSmithKline will publicly disclose its payments to physicians
and limit the annual payment for any one person to $150,000, according to an
October 24 press release. The decision follows several other major
pharmaceutical companies, including Eli Lilly and Merck, that recently
announced plans to post payments and gifts to physicians on their Web sites.
Congress has been discussing but has not passed the Physician Payments
Sunshine Act, which will mandate such disclosure for all drug and device
• Azur Pharma and Elan Corp. will collaborate in the development of
once-daily formulations of clozapine, Azur announced on
November 10. Drug-delivery technologies owned by Elan, intended to manipulate
the pharmaceutical properties of various formulations, had been explored as a
possible vehicle for extended-release clozapine since 2007. Azur currently
manufactures and markets the orally disintegrating clozapine tablets and will
carry out the clinical development of the once-daily formulations.
• The National Institute of Mental Health will fund a clinical trial
on effective approaches to mitigate the metabolic side effects, such as weight
gain, blood glucose increase, and blood lipid increase, of
second-generation antipsychotics in children and adolescents.
The study will recruit overweight youths aged 8 to 17 who have a diagnosis of
either schizophrenia or bipolar disorder and who have gained 10 percent or
more body weight on risperidone, quetiapine, or olanzapine. The patients will
be randomly assigned to three interventions for 24 weeks: adding metformin,
switching to aripiprazole, or continuing on the current treatment. The weight,
metabolic profile, and psychiatric outcomes of the three groups will be
• An investigational drug known as nepicastat, a
dopamine beta hydroxlase inhibitor, will be studied in a randomized,
double-blind, placebo-controlled, phase 2a clinical trial for treatment of
posttraumatic stress disorder (PTSD). The drug is owned and developed by
Synosia Therapeutics. The trial, funded by the U.S. Department of Defense,
will be conducted with veterans of the Iraq war and assess the efficacy and
tolerability of nepicastat in treating PTSD, including symptom improvement,
remission, and quality of life. The trial will be conducted at Veterans
Affairs medical centers in Tuscaloosa, Ala.; Houston; and Charleston, S.C.
Dopamine beta hydroxylase is an enzyme that converts dopamine into
norepinephrine. Nepicastat has been shown to increase dopamine and decrease
norepinephrine concentrations in blood and brain in animal studies, according
to the November 3 announcement by Synosia.
• The National Institute on Aging has given Ceregene Inc., a $5.4
million grant to conduct a phase 2 clinical trial of the company's
CERE-110, a gene therapy "designed to deliver nerve
growth factor (NGF) for the treatment of Alzheimer's disease," Ceregene
announced on November 4. Cere-110 is expected to deliver the gene for NGF
using an adeno-associated virus as a vector and is surgically injected into
the nucleus basalis of Meynert in the brain, where cholinergic cell
degeneration occurs in Alzheimer's disease, the announcement stated. The hope
is to restore the function of these neurons with increased NGF gene
In a previous phase 1 trial, CERE-110 was given to 10 patients with mild to
moderate Alzheimer's disease and appeared to be safe and well tolerated. The
phase 2 trial is expected to begin in early 2009.
• The National Institute on Drug Abuse will fund a clinical trial of
Avigen Inc.'s investigational drug AV411, also known as
ibudilast, for the treatment of opioid withdrawal symptoms,
the company announced on October 15. AV411 is a nonopioid molecule that
suppresses proinflammatory cytokines, such as interlukin (IL)-1 beta, tumor
necrosis beta, and IL-6, according to the announcement. Preclinical studies
indicated that the drug may reduce the behavioral and neurochemical symptoms
of opioid withdrawal. The trial will evaluate safety and efficacy of AV411 for
the treatment of opioid withdrawal symptoms and will be conducted by the New
York State Psychiatric Institute and Columbia University. The drug is also
being investigated for treating neuropathic pain. ▪