The U.S. Food and Drug Administration (FDA) granted final marketing
approval to two new products indicated for use in psychiatric disorders. Both
represent treatment options that significantly differ from medications already
on the market.
The FDA granted final approval April 6 to a joint application submitted by
Shire PLC and Noven Pharmaceuticals to market the companies' methylphenidate
transdermal system (MTS) under the brand name Daytrana.
The new patch to treat attention-deficit/hyperactivity disorder (ADHD) is
indicated for use in children aged 6 to 12. Noven will manufacture the
product, while Shire will be responsible for marketing and distributing it
MTS, the first non-oral ADHD medication, will be available in four dosage
strengths, with individual skin patches containing a total of either 27.5 mg,
41.3 mg, 55 mg, or 82.5 mg. Of the total amount of methylphenidate available
in the patch, the nominal dose of the drug absorbed through the skin over the
course of the recommended wear-time of nine hours will be 10 mg, 15 mg, 20 mg,
or 30 mg. (The product will be labeled according to the dose of
methylphenidate absorbed, not the total dose available in the patch.) The
companies said the product should be on pharmacy shelves in June.
Prescribers are reminded in the new product's labeling that because
absorption of methylphenidate through the skin is subject to significantly
less first-pass metabolism through the patient's liver, "a much lower
dose of Daytrana on a mg/kg basis compared to oral dosages may still produce
higher exposures of methylphenidate with transdermal administration compared
to oral administration." As such, patients may achieve comparable
symptomatic control on lower doses of MTS than oral forms of
"The FDA's approval of Daytrana offers an important new option in the
treatment of ADHD in children," said Robert Findling, M.D., in a press
release issued by Shire. Findling, a lead investigator in the MTS clinical
trials program, is a professor of psychiatry and director of the Division of
Adolescent and Child Psychiatry at Case Western Reserve University School of
"Daytrana," Findling continued, "has been shown to be
effective and generally well tolerated in clinical studies and offers ADHD
treatment in the convenient form of a patch."
It is, however, contraindicated in patients with marked anxiety, tension,
and agitation, as well as in those known to be hypersensitive to
methylphenidate. In addition, the MTS should not be used in patients who have
glaucoma or tic disorders, or who have taken a monoamine oxidase inhibitor
within 14 days of wearing an MTS patch.
Its label will include existing warnings regarding sudden death in patients
taking CNS stimulants who have known or occult structural cardiac
abnormalities. The label will also warn of the potential for patients wearing
MTS patches to develop a contact sensitization. Local redness at the site of
patch application is common, the label notes; however, if redness is
accompanied by edema, papules, or vesicles and does not significantly improve
within 48 hours, sensitization should be suspected. Use of the MTS should be
discontinued if sensitization is suspected.
In clinical trials, the MTS was shown to be effective in reducing symptoms
associated with ADHD as measured by the ADHD Rating Scale—IV. Children
in clinical trials wearing the active patch showed twice the amount of symptom
improvement as children wearing a placebo patch. The most common adverse
events in patients wearing the patch during clinical trials included those
known to be associated with methylphenidate, such as decreased appetite,
insomnia, nausea, vomiting, weight loss, tic, and affect lability.
The FDA granted final approval on April 13 of a joint application from
Alkermes and Cephalon to market a long-acting, injectable formulation of
naltrexone under the brand name Vivitrol.
It is the only once-monthly medication for alcohol dependence and is
indicated for patients who are able to abstain from drinking in an outpatient
setting and are not actively drinking when initiating treatment.
Vivitrol "ensures [that] patients get the benefit of medication over
the entire month," said Richard Rosenthal, M.D., chair of psychiatry at
St. Luke's—Roosevelt Hospital Center and a professor of psychiatry at
Columbia University College of Physicians and Surgeons.
Rosenthal, who participated in Vivitrol clinical trials, added, "With
Vivitrol, physicians have a new option to help treat patients with alcohol
dependence, and patients have new hope to help them in their battle with this
Vivitrol will be available as a single dose of 380 mg of naltrexone for
intramuscular injection to be administered once a month. The product is
expected to be on pharmacy shelves by the end of June and will be jointly
marketed by Alkermes and Cephalon.
Efficacy of the long-acting injection was demonstrated in clinical trials,
with patients receiving injectable naltrexone achieving significantly greater
reduction in heavy drinking days than those administered a placebo
The most common adverse events noted with the injection were nausea,
vomiting, headache, dizziness, fatigue, and injection-site reactions.
Because naltrexone has the capacity to cause cellular injury in the liver
at higher doses, the drug is contraindicated in patients with acute hepatitis
or liver failure, and its use in patients with active liver disease should
follow careful consideration of both risks and potential benefits.
Because naltrexone is a potent opioid antagonist, the drug should not be
used in patients receiving opioid analgesics, those with physiologic
dependence on opioids, or those in acute opioid withdrawal.
Prescribing information for Daytrana is posted at<www.daytrana.com>;
prescribing information for Vivitrol is posted at<www.vivitrol.com>.▪