Is It Ready for Prime Time?
Methylphenidate absorbed through the skin.
In 2006, Shire Pharmaceuticals released Daytrana for the treatment of AD/HD in children aged 6-12. In 2010 the approval was broadened to include adolescents aged 13 to 17. Individual clinicians have used Daytrana in adults but this is an off label use. Daytrana, previously known as the Methypatch, was developed based on technology from Noven Pharmaceuticals and then sold to Shire Pharmaceutical Company. In 2010 Shire sold the licensing rights back to Noven. The active ingredient, methylphenidate is the same chemical used in Ritalin and Concerta. However, since the Daytrana encases the methylphenidate is in a skin patch, the child or adolescent does not need to swallow a pill.
Skin patches have been used to deliver a variety of medications through the skin. Many women may be familiar with the estrogen/progestone patches used for hormone replacement. Those who have read the Joey Pigza books by Jack Gantos may remember that Joey’s AD/HD medication was in patch form. Considering the dates of that book series, Joey might have been using Catapress-TTS, a patch form of clonidine. (The Carapress TTS patch is not FDA approved for the treatment of AD/HD but is sometimes used as a second-line treatment.) Years ago, I would sometimes use the Catapress-TTS patch as an adjunct treatment for children who had an incomplete response to stimulant treatment. The Catapress-TTS patch was designed to be worn for seven days. However, patients complained of itching and would often pull it off. More recently, there have been advances in the types of skin adhesives and the patch delivery system. Noven Pharmacuetical developed the patch system used in Daytrana and several other medications. Daytrana uses Noven’s Dot Matrix Technology. This system allows smaller patches with a larger amount of drug. The patch has three layers. The outside layer protects the active drug layer from the elements. The middle layer contains the active methylphenidate interspersed with the adhesive. The inner layer is a protective film with is removed and discarded when the patch is applied.
This medication should be used with great caution in individuals who abuse drugs. Daytrana contains methylphenidate which does have abuse potential. Some have said that the patch format leads to a lower abuse potential However, individuals who are determined to abuse stimulants have figured out easy ways to abuse the patch.
Why use a patch? Depending on the medication, there might be several reasons for using a transdermal patch instead of a pill.
- A patch eliminates the need to swallow a pill. Some children have difficulty swallowing pills. Methylphenidate is available in a liquid form, but the liquid preparation is short-acting and may require multiple doses each day.
- A patch may have a longer duration of action than an oral medication. Some medications such as estrogen or clonidine patches, can be worn for several days. A Daytrana patch is not supposed to be used for longer than 9 hours. The effect starts about 2 hours after the patch is applied and continues for about 3 hours after the patch is removed. If one wears the patch for 9 hours one gets about 10 hours of significant drug effect.
- A patch can promote greater flexibility of dose duration. For example, the Daytrana, the methylphenidate patch can be removed earlier on days when one does not need a long duration of action. For children who have problems with appetite suppression, one might remove the patch earlier if the child does not have homework of after-school activities.
- Elimination of first pass drug metabolism. Medications delivered through the skin pass into the blood stream without going through the digestive system. If an oral medication’s absorption is affected by food intake, this could be significant.
What are the disadvantages of a patch?
- Non-compliance. My main problem with the Catapress-TTS patches was that patients would pull them off. Usually this was because of itching. Despite changes in adhesive technology, itching and rash can still be problematic for some individuals.
- Lag time. It is recommended that the Daytrana patch be applied 2 hours before the time one wants to see a drug effect. After the patch is removed, the drug effect gradually wears off over several hours. Some parents wake up early and apply the patch while the child is still sleeping.
- Increased stimulant side effects. When Daytrana was submitted to the FDA, they turned it down in 2003 because its side effect profile was worse than Concerta. Shire and Noven then studied the Daytrana patch when it was applied for 9 hours. This time the studies showed stimulant-type side effects no greater than those seen with other stimulants.
- Skin sensitization. In a study specifically designed to look at skin sensitization. Subjects wore the Daytrana patch on the same site for three weeks. the subjects then had two weeks without the patch. After this they wore the patch again. Under these conditions, at least 13.5% of the subjects were judged to be sensitized to Daytrana. When subjects used Daytrana as directed, none of them spontaneously reported skin sensitization. However, the subjects were not systematically checked for skin sensitization. Thus we do not actually know the true incidence of skin sensitization when Daytrana is used as directed. Theoretically, if one develops a true sensitization to the Daytrana patch, one might also develop a sensitization to oral methylphenidate. If this happened, one might not be able to take methylphenidate pills.
- Variation in skin absorption. Heat can increase the rate of absorption of Daytrana through the skin. The rate of absorption also changes over time even when the medication is used as directed. When Daytrana is administered for several weeks, it is absorbed more quickly and the peak concentrations are higher. Since methylphenidate is metabolized rapidly, this effect is not related to a drug buildup in the child’s system. this may meant that it takes longer to determine the optimal dose.
- Manufacturing problems: There have been multiple product recalls between 2007 and 2011. See below.
Daytrana comes in doses of It should be applied to the hip and the location should be rotated each day.
The patch should stay on while the child is swimming or bathing. However, since heat can increase the drug absorption, the patch should not be exposed to a heating pad, an electric blanket or a heated water bed. If the skin area is already irritated the absorption will also be significantly increased.
The patch comes in sizes that release 10mg (12.5 cm2), 15mg (18.75cm2), 20mg (25 cm2)and 30mg (35.5 cm2) over 9 hours.
Potential side effects, (other than skin sensitization) are the same type of symptoms seen with the oral stimulants. The most common side effects include appetite suppression, insomnia, irritability, stomach upset, and weight loss. Rarer, more severe stimulant side effects could potentially include seizures, cardiac events, elevated blood pressure, tics, psychosis and mania.
Should you use Daytrana? I would not recommend using this medication as a first line treatment for AD/HD. It might fill a niche for children who need a long-acting stimulant but who cannot swallow pills. Often, if a child trouble swallowing the pills, one can help this by understanding the child’s fears about the medication or by teaching the child how to swallow the pills. Some long acting stimulants can be opened and sprinkled onto pudding or put into a glass of water.
Carol Watkins, M.D.
|Patch size (cm2)||Content per patch (mg)||Delivery (mg/hr)||9 hour patch total (mg)||Equivalent short acting methylphenidate (mg)||Equivalent Concerta dose (mg)|
Adapted from: Arnold et al Treating attention-deficit/hyperactivity disorder with a stimulant transdermal patch: the clinical art, Pediatrics 2007 Nov;120(5):1100-6.
|Week one||Week two||Week three||Week four|
|Patch Size||12.5 cm2||18.75 cm2||25 cm2||37.5 cm2|
|Delivered dose (mg/9 hours)||10 mg||15 mg||20 mg||30 mg|
Recommended dosage titration for patients who have not been on methylphenidate in the recent past. The above table adapted from (From official prescribing information pamphlet) link http://www.daytrana.com/documents/daytrana-prescribing-information.pdf If one achieves a good response or encounters significant side effects, one should stop increasing the dose. Depending on my ability to get prompt information about medication response, I might increase the dose more slowly.
There have been multiple product recalls for Daytrana. In 2008, the FDA sent a warning letter about manufacturing practices. Periodic product recalls have continued through 2011. In 2010, Shire sold the licensing rights back to Noven Pharmaceuticals, the company which originally developed the product.
List of Daytrana recalls
2007: Noven discloses to the SEC that the patch has been improved to reduce liner problems. (Meaning that it had prior liner problems.)
July 2007: Noven receives FDA letter containing “observations” regarding its patch manufacturing.
Q3 2007: Two patch recalls. Noven pays $3.3 million to Shire in trigger payments.
January 2008: FDA sends Noven a warning letter re “peel force issues.”
June 2008: Two recalls of Daytrana.
August 2008: Two more recalls of Daytrana. Noven pays Shire $3.7 million in trigger payments.
March 2009: Another recall. Shire gets $3.4 million in trigger payments.
February 2009: Noven receives another FDA “observations” letter regarding the patch.
December 2009: Another Daytrana recall announced by Shire.
2007-2009 recall list from Shire’s Daytrana Patch Recall Is 8th So Far: Time to Pull the Plug? Jim Edwards CBS News Moneywatch December 7, 2009
March 2011: Recall of several batches of Daytrana.
Because of the multiple product recalls, I would recommend only using Daytrana as a second or third line medication treatment for AD/HD.