Methylphenidate Extended-Release Tablets (Concerta—Alza)
By William T. Elliott, MD, FACP,
and James Chan, PharmD, PhD
The fda has approved an extended-release form of methylphenidate for the treatment of attention deficit hyperactivity disorder (ADHA). Methyl-phenidate has been available for more than 30 years for this indication; however, the drug is a short-acting stimulant with a duration of action of 1-4 hours, and the necessity for frequent dosing has limited its usefulness in children. A currently available extended-release formulation has a duration of action of about eight hours. The newly approved formulation is a once-daily preparation due to a novel drug delivery system (osmotic controlled-release) developed by Alza. The new product will be marketed by Alza and McNeil under the trade name Concerta.
Indications
Methylphenidate extended-release tablets (Concerta) are indicated for the treatment of ADHA. Efficacy has been established in children 6-12 years of age.1 Methylphenidate should be a part of a total treatment program that may include psychological, educational, and social measures.1
Dosage
Concerta is administered orally once daily in the morning. The tablets may be administered without regard to food and must be swallowed whole and not chewed, divided, or crushed.1 The recommended starting dose for patients not currently taking methylphenidate is 18 mg once daily. Dose can be adjusted in 18 mg increments up to a maximum of 54 mg per day. Adjustments may proceed at roughly weekly intervals.1 For patients who are taking methylphenidate 5 mg two or three times a day, or methylphenidate SR 20 mg/d, the Concerta dose is 18 mg every morning. Those on 10 mg two or three times daily, or methylphenidate SR 40 mg/d, the Concerta dose is 36 mg every morning. For those taking 15 mg two or three times daily or 60 mg of methylphenidate, SR the Concerta dose is 54 mg per day.1
Patients should be advised that the tablet remains intact during its passage through the gastrointestinal (GI) tract and not to be alarmed to notice the intact tablets in the stool.
Concerta is supplied as 18 mg and 36 mg.
Potential Advantages
A pharmacokinetic study indicated that the plasma concentration time profile of Concerta more closely reflected that of intermediate-release methylphenidate dosed three times daily compared to the SR formulation (i.e., Ritalin SR).2 In addition, Concerta provides a lower peak concentration compared to the IR and SR formulations.2
Potential Disadvantages
Concerta is only available in doses of 18 mg and 36 mg. Since there is marked individual variability in dose-response, it is not clear if there is sufficient dose flexibility for individual titration to optimize response. The effectiveness of Concerta longer than four weeks has not been studied in controlled clinical trials.1
Comments
Concerta is a novel drug delivery system. The tablet is made up of an osmotically active trilayer core surrounded by a semipermeable membrane with an immediate release overcoat. After oral administration, the overcoat dissolves releasing a portion of the dose. As water permeates the core of the tablet through the semipermeable membrane, the osmotically active polymer excipients expand pushing the drug through a laser-drilled orifice in a controlled rate.1 There is a gradual increase in plasma concentration with a peak at 6-8 hours. This formulation appears to be more similar to multiple dosing of the IR formulation than the SR formulation.2 There are currently no published studies comparing Concerta with the other SR form of methylphenidate and IR methylphenidate. The manufacturer labeling describes controlled studies comparing Concerta with IR methylphenidate dosed three times a day. However, the primary comparison of interest in all these trials was Concerta vs. placebo.1
The cost for Concerta is $2.20 for a 18 mg tablet and $2.30 for 36 mg. This compares to $1.33 for a 20 mg tablet of Ritalin SR and $1.10 for the generic formulation.
Clinical Implications
Methylphenidate is commonly used to treat ADHD. Controlled-release formulations have improved compliance because of the problematic midday dose that usually occurs during school hours.
In addition, data suggest that there may be a greater abuse potential with IR compared to a controlled-release formulation.3 Concerta may offer an advantage over the SR (Ritalin SR) formulation, which shows a fall-off in efficacy earlier than a three times a day regimen with the IR formulation. Patients stabilized on a three times a day regimen of IR methylphenidate in whom compliance with the midday dose is problematic may benefit from Concerta.
References
1. Concerta Product Information. Alza Pharmaceuticals. July 2000.
2. Modi NB, et al. J Clin Pharmacol 2000;40:379-388.
3. Kollins SH, et al. Exp Clin Psychopharmacol 1998;6(4): 367-374.
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