|Shire Pharmaceuticals recently released Daytrana for the treatment of AD/HD in children aged 6-12. Daytrana, previously known as the Methypatch, was developed based on technology from Noven Pharmaceuticals. 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 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 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. (Clonidine 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.
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 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.
- 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.
- 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 judeged 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 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.
- New Drug: We do not have controlled studies of the effect of this medication after seven weeks. I am always cautious about using a new medication or a new medication delivery system.
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 is irritated the absorption will also be significantly increased.
The patch comes in sizes that release 10mg, 15mg, 20mg and 30mg over 9 hours.
Potential side effects, (other than skin sensitization) are the same type of symptoms seen with the oral stimulants. the more 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 small 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. Daytrana needs further study including extended time, controlled studies in which the skin sensitization is assessed systematically for each patient. If you do not ask about a side effect, you will usually get a lower incidence than if you always look for a specific side effect. When researchers did not specifically ask about sexual side effects with the SSRI antidepressants, they got a very low spontaneous report of this side effect. When later studies specifically asked everyone about sexual side effects, the incidence went up drastically.
Shire and Noven Pharmaceuticals are currently working on a patch which would deliver amphetamine. At present it is in the pre-clinical (very early) stages of development.