New Patch May Broaden Use of ADHD Therapy

The Food and Drug Administration's approval of a transdermal methyl-phenidate patch for the treatment of attention-deficit hyperactivity disorder in children could broaden use of the drug for patients who need it.

“Some patients may have difficulty swallowing the tablets, and patients may prefer to use the patch,” Dr. Joseph Biederman, professor of psychiatry at Harvard Medical School, Boston, said in an interview. “So it's a technology that may allow physicians to expand the repertoire of choices.”

Dr. Thomas Laughren, director of the FDA's division of psychiatric products in Rockville, Md., agreed. During a meeting of the FDA's Psychopharmacologic Drugs Advisory Panel in December, the agency heard from several advisers and others that a “substantial fraction” of children have difficulty taking pills, Dr. Laughren said during a media teleconference sponsored by the FDA. “They felt that this would be an important addition to the available treatments for ADHD.”

Dr. Richard Gorman said in an interview that he also thinks that another dosage form will open use of the drug for patients who have had difficulty with methylphenidate in the past. “Whether it will be widely accepted or not I think is still an open question,” said Dr. Gorman, chairman of the section of clinical pharmacology and therapeutics for the American Academy of Pediatrics.

It is important to note that use of a patch by young children would require intervention by a responsible adult at specific times twice a day, compared with just once a day for oral forms of methylphenidate, said Dr. Gorman, a pediatrician in private practice in Baltimore. The approval applies to children aged 6–11 years.

Approval of the patch—called Daytrana and codeveloped by Shire Pharmaceuticals Inc. and Noven Pharmaceuticals Inc.—had been widely expected after the panel's endorsement. But the panel, citing the patch's potential to cause sensitization to methylphenidate, questioned how strong the warnings on the label would be.

Sensitization can occur with any medication delivered using a transdermal patch. People sometimes develop antibodies to the medication in transdermal patches, and when they are later challenged with an oral version of the medication, they may experience an allergic reaction. Theoretically, this could prevent a child who had used the methylphenidate patch from ever taking an oral form of the medication.

Dr. Laughren said such a sensitization reaction had never been seen in 765 patients exposed to methylphenidate patches in short-term trials. In one case that had been thought to involve sensitization, further study showed that sensitization did not occur. However, a separate provocation study with treatment for an extended period of time indicated that sensitization could be a possibility.

At the panel meeting, a spokesperson for Shire Pharmaceuticals cited two studies of children aged 6–12 years with ADHD—a 2-day laboratory classroom study of 93 children and a pivotal multicenter outpatient study of 274 children that compared the patch with oral methylphenidate (Concerta) and placebo over 7 weeks. Significant improvements in behavior were seen within 2 hours of application of the patch (left on for 9 hours) and persisted for 3 hours after removal, the company said.

The label instructions call for the patch to be left on for a maximum of 9 hours, but Dr. Biederman said that it can be left on for longer than 9 hours for a longer duration of effect. “We know from the early studies that the patch continues to work for about 2 hours after it's removed,” he said. “So it may permit clinicians and families to actually vary the duration of effect, depending on the individual needs of the particular day, week, or month.”

Normally, the patch is to be applied to alternating areas of the child's thighs each morning and removed later that day. But in the provocation study, patches were applied to a single area and left on continuously for days at a time, and 13% of patients did develop sensitivity.

For that reason, the label of the product as it will be released contains advice for physicians on how to recognize and manage sensitization. Redness at the patch site is very common and does not by itself indicate sensitization. The patch will be available in four dosages: 10 mg, 15 mg, 20 mg, and 30 mg.

The Food and Drug Administration's approval of a transdermal methyl-phenidate patch for the treatment of attention-deficit hyperactivity disorder in children could broaden use of the drug for patients who need it.

“Some patients may have difficulty swallowing the tablets, and patients may prefer to use the patch,” Dr. Joseph Biederman, professor of psychiatry at Harvard Medical School, Boston, said in an interview. “So it's a technology that may allow physicians to expand the repertoire of choices.”

Dr. Thomas Laughren, director of the FDA's division of psychiatric products in Rockville, Md., agreed. During a meeting of the FDA's Psychopharmacologic Drugs Advisory Panel in December, the agency heard from several advisers and others that a “substantial fraction” of children have difficulty taking pills, Dr. Laughren said during a media teleconference sponsored by the FDA. “They felt that this would be an important addition to the available treatments for ADHD.”

Dr. Richard Gorman said in an interview that he also thinks that another dosage form will open use of the drug for patients who have had difficulty with methylphenidate in the past. “Whether it will be widely accepted or not I think is still an open question,” said Dr. Gorman, chairman of the section of clinical pharmacology and therapeutics for the American Academy of Pediatrics.

It is important to note that use of a patch by young children would require intervention by a responsible adult at specific times twice a day, compared with just once a day for oral forms of methylphenidate, said Dr. Gorman, a pediatrician in private practice in Baltimore. The approval applies to children aged 6–11 years.

Approval of the patch—called Daytrana and codeveloped by Shire Pharmaceuticals Inc. and Noven Pharmaceuticals Inc.—had been widely expected after the panel's endorsement. But the panel, citing the patch's potential to cause sensitization to methylphenidate, questioned how strong the warnings on the label would be.

Sensitization can occur with any medication delivered using a transdermal patch. People sometimes develop antibodies to the medication in transdermal patches, and when they are later challenged with an oral version of the medication, they may experience an allergic reaction. Theoretically, this could prevent a child who had used the methylphenidate patch from ever taking an oral form of the medication.

Dr. Laughren said such a sensitization reaction had never been seen in 765 patients exposed to methylphenidate patches in short-term trials. In one case that had been thought to involve sensitization, further study showed that sensitization did not occur. However, a separate provocation study with treatment for an extended period of time indicated that sensitization could be a possibility.

At the panel meeting, a spokesperson for Shire Pharmaceuticals cited two studies of children aged 6–12 years with ADHD—a 2-day laboratory classroom study of 93 children and a pivotal multicenter outpatient study of 274 children that compared the patch with oral methylphenidate (Concerta) and placebo over 7 weeks. Significant improvements in behavior were seen within 2 hours of application of the patch (left on for 9 hours) and persisted for 3 hours after removal, the company said.

The label instructions call for the patch to be left on for a maximum of 9 hours, but Dr. Biederman said that it can be left on for longer than 9 hours for a longer duration of effect. “We know from the early studies that the patch continues to work for about 2 hours after it's removed,” he said. “So it may permit clinicians and families to actually vary the duration of effect, depending on the individual needs of the particular day, week, or month.”

Normally, the patch is to be applied to alternating areas of the child's thighs each morning and removed later that day. But in the provocation study, patches were applied to a single area and left on continuously for days at a time, and 13% of patients did develop sensitivity.

For that reason, the label of the product as it will be released contains advice for physicians on how to recognize and manage sensitization. Redness at the patch site is very common and does not by itself indicate sensitization. The patch will be available in four dosages: 10 mg, 15 mg, 20 mg, and 30 mg.

The Food and Drug Administration's approval of a transdermal methyl-phenidate patch for the treatment of attention-deficit hyperactivity disorder in children could broaden use of the drug for patients who need it.

“Some patients may have difficulty swallowing the tablets, and patients may prefer to use the patch,” Dr. Joseph Biederman, professor of psychiatry at Harvard Medical School, Boston, said in an interview. “So it's a technology that may allow physicians to expand the repertoire of choices.”

Dr. Thomas Laughren, director of the FDA's division of psychiatric products in Rockville, Md., agreed. During a meeting of the FDA's Psychopharmacologic Drugs Advisory Panel in December, the agency heard from several advisers and others that a “substantial fraction” of children have difficulty taking pills, Dr. Laughren said during a media teleconference sponsored by the FDA. “They felt that this would be an important addition to the available treatments for ADHD.”

Dr. Richard Gorman said in an interview that he also thinks that another dosage form will open use of the drug for patients who have had difficulty with methylphenidate in the past. “Whether it will be widely accepted or not I think is still an open question,” said Dr. Gorman, chairman of the section of clinical pharmacology and therapeutics for the American Academy of Pediatrics.

It is important to note that use of a patch by young children would require intervention by a responsible adult at specific times twice a day, compared with just once a day for oral forms of methylphenidate, said Dr. Gorman, a pediatrician in private practice in Baltimore. The approval applies to children aged 6–11 years.

Approval of the patch—called Daytrana and codeveloped by Shire Pharmaceuticals Inc. and Noven Pharmaceuticals Inc.—had been widely expected after the panel's endorsement. But the panel, citing the patch's potential to cause sensitization to methylphenidate, questioned how strong the warnings on the label would be.

Sensitization can occur with any medication delivered using a transdermal patch. People sometimes develop antibodies to the medication in transdermal patches, and when they are later challenged with an oral version of the medication, they may experience an allergic reaction. Theoretically, this could prevent a child who had used the methylphenidate patch from ever taking an oral form of the medication.

Dr. Laughren said such a sensitization reaction had never been seen in 765 patients exposed to methylphenidate patches in short-term trials. In one case that had been thought to involve sensitization, further study showed that sensitization did not occur. However, a separate provocation study with treatment for an extended period of time indicated that sensitization could be a possibility.

At the panel meeting, a spokesperson for Shire Pharmaceuticals cited two studies of children aged 6–12 years with ADHD—a 2-day laboratory classroom study of 93 children and a pivotal multicenter outpatient study of 274 children that compared the patch with oral methylphenidate (Concerta) and placebo over 7 weeks. Significant improvements in behavior were seen within 2 hours of application of the patch (left on for 9 hours) and persisted for 3 hours after removal, the company said.

The label instructions call for the patch to be left on for a maximum of 9 hours, but Dr. Biederman said that it can be left on for longer than 9 hours for a longer duration of effect. “We know from the early studies that the patch continues to work for about 2 hours after it's removed,” he said. “So it may permit clinicians and families to actually vary the duration of effect, depending on the individual needs of the particular day, week, or month.”

Normally, the patch is to be applied to alternating areas of the child's thighs each morning and removed later that day. But in the provocation study, patches were applied to a single area and left on continuously for days at a time, and 13% of patients did develop sensitivity.

For that reason, the label of the product as it will be released contains advice for physicians on how to recognize and manage sensitization. Redness at the patch site is very common and does not by itself indicate sensitization. The patch will be available in four dosages: 10 mg, 15 mg, 20 mg, and 30 mg.