Scientific Discussion.en.Id

of 9
All materials on our website are shared by users. If you have any questions about copyright issues, please report us to resolve them. We are always happy to assist you.
Information Report
Category:

Documents

Published:

Views: 3 | Pages: 9

Extension: PDF | Download: 0

Share
Description
Description:
Tags
Transcript
  London Medicines Evaluation Network Extended-release methylphenidate  –  a review of the pharmacokinetic profiles available May 2016 Authored by Martin Bradley (martin.bradley@gstt.nhs.uk)  Background Methylphenidate is a central nervous stimulant available in the UK in various licensed immediate, and modified-release, oral, solid dosage forms. It is a schedule 2 controlled drug, licensed for the treatment of attention deficit hyperactivity disorder (ADHD) in children aged over 6 years and adolescents 1  and is the usual first line treatment for this condition for both children and adults 2 , (though initiation in adult patients is outside of the product licence). Most of the products available specify in their Summary of Product Characteristics (SPCs) that in patients whose symptoms persist into adulthood and who have shown clear benefit from treatment, it may be appropriate to continue treatment into adulthood 3,4,5,6 . Methylphenidate, as a stimulant, is also sometimes used off-label for disorders of excessive somnolence e.g. narcolepsy, idiopathic hypersomnia 7 . This review describes a brief background to current NICE recommendations for the use of methylphenidate for the treatment of ADHD and summarises pertinent points with respect the pharmacokinetic differences of the various methylphenidate modified-release products available. In particular this review covers two new products to the UK market Xenidate XL and Matoride XL, as a detailed review of the Medikinet XL, Equasym XL, and Concerta XL products is already available 8 . The National Institute for Health and Care Excellence (NICE) CG72: Attention deficit hyperactivity disorder: diagnosis and management 2   In their clinical guidelines NICE make several recommendations regarding the use of methylphenidate for the management of ADHD: With respect to initiation:   Begin with low doses of immediate-release or modified-release preparations consistent with starting doses in the BNF   Titrate the dose against symptoms and side effects over 4  – 6 weeks until dose optimisation is achieved   Modified-release preparations should be given as a single dose in the morning (or no more than twice a day in adults) and immediate-release preparations should be given in two or three divided doses (or up to four times a day in adults)   Doses should be gradually increased until there is no further improvement and side effects are tolerable  With respect to ongoing treatment and improving adherence: When prescribing methylphenidate for the treatment of children or young people, modified-release preparations should be considered for the following reasons:    Convenience    Improving adherence    Reducing stigma (because the child or young person does not need to take medication at school)    Reducing problems schools have in storing and administering controlled drugs    Their pharmacokinetic profiles; in particular the proportion of medication released in specific time frames and the overall duration of action. For adult patients, modified-release preparations may be preferred to increase adherence and in circumstances where there are concerns about substance misuse or diversion General recommendations from NICE: Prescribers should be familiar with the pharmacokinetic profiles of all the modified-release and immediate-release preparations available for ADHD to ensure that treatment is tailored effectively to the individual’s needs. Following titration and dose stabilisation, prescribing and monitoring should be carried out under locally agreed shared care arrangements with primary care. No recommendations are made with respect to the prescribing of specific brands, though it states : “If there is a choice of more than one appropriate drug, the product with the lowest cost (taking into account the cost per dose and number of daily doses) should be prescribed”.   Modified-release methylphenidate preparations currently available in the UK: The following preparations are currently licensed in the UK (as of April 2016)   Concerta XL tablets   Equasym XL capsules   Medikinet XL capsules   Matoride XL tablets   Xenidate XL tablets  All the modified-release methylphenidate preparations include an immediate-release component as well as an extended-release component. This allows for rapid onset of action while avoiding the need to take further doses during the day to maintain effect. The biphasic release profiles of these products are however not all equivalent and contain different proportions of the immediate-release and modified-release component. The BNF states that “ different versions of modified-release preparations may not have the same clinical effect. To avoid confusion between these different formulations of methylphenidate prescribers should specify the brand to be dispensed ”   1 .  Concerta XL tablets Concerta XL was licensed in the UK in February 2002. It is an oral tablet with an osmotic release system and has internal layers of extended-release methylphenidate, surrounded by a coat of immediate-release methylphenidate 3 . The non-absorbable membrane of the tablet can pass into the faeces unchanged. It is available as 18mg, 27mg, 36mg and 54mg tablets. The manufacturers advise that when initiating, titration should be started at 18mg and proceed with 18mg increments at approximately weekly intervals 3 . The 27mg dose is available for those who wish to prescribe between the 18mg and 36mg doses. When converting patients to Concerta XL from methylphenidate immediate release, the manufacturers recommend a conversion factor of 18mg Concerta XL per 15mg methylphenidate immediate release daily dose 3 . The maximum daily dosage recommended by the manufacturer is 54mg 3 . Medikinet XL capsules Medikinet XL was licensed in the UK in February 2007. These capsules contain immediate release uncoated pellets and extended release coated pellets producing a two-stage release profile 4 . Medikinet XL capsules are available as 5mg, 10mg, 20mg, 30mg, 40mg, 50mg and 60mg. When initiating methylphenidate with Medikinet XL, the manufacturers recommend starting at 10mg once daily, increasing as necessary by weekly increments of 5-10mg 4 . The manufacturers recommend that when converting from immediate release methylphenidate, the total daily dose can be converted 1:1 to Medikinet XL 4 . The maximum daily dosage recommended by the manufacturer is 60mg 4 .  Equasym XL capsules Equasym was licensed in the UK in February 2005. Each capsule contains beads coated with immediate release or extended release methylphenidate. It is available as 10, 20 and 30mg capsules. When initiating methyphenidate with Equasym XL the manufacturers recommend starting at 10mg once daily, increasing as necessary by weekly increments of 5-10mg 9 . The manufacturers recommend that when converting from immediate release methylphenidate, the total daily dose can be converted 1:1 to Equasym XL 9 . The maximum daily dosage recommended by the manufacturer is 60mg 9 .  Comparison of pharmacokinetic profiles of Concerta XL, Medikinet XL and Equasym XL 8   Concerta XL tablets Medikinet XL capsules Equasym XL capsules Composition (percentage immediate/extended release) 22/78 50/50 30/70 Release profile Maximum plasma concentration at 1-2 hours, second peak at 6-8 hours Maximum plasma concentration reached rapidly, second peak at 3-4 hours Maximum plasma concentration at 1.5 hours, followed by a second peak at 6 hours followed by a gradual decline Duration of action Up to 12 hours Up to 8 hours Up to 8 hours Administration Swallow whole with liquid. Must not be chewed, crushed or divided Can be swallowed whole with liquid, or opened and the contents sprinkled onto a small amount (tablespoon) of applesauce or yoghurt and given immediately. Capsules and contents not to be crushed or chewed Can be swallowed whole with liquid, or opened and the contents sprinkled onto a small amount (tablespoon) of applesauce or yoghurt and given immediately. Capsules and contents not to be crushed or chewed Food requirements Can be given with or without food To be taken with or after breakfast To be taken with or after breakfast Frequency Once daily in the morning Once daily in the morning Once daily in the morning Immediate-release methylphenidate equivalent Three times daily Twice daily Twice daily The differing time  – action profiles provided by these long-acting formulations may allow clinicians to target specific periods of the day that are particularly relevant for a patient, facilitating individualisation of ADHD treatment. Recently licensed preparations Matoride XL tablets and Xenidate XL tablets are recent additions to the UK market, and have been granted marketing authorisation on the basis of bioequivalence to Concerta XL tablets as the licensed reference product as opposed to clinical studies. Both are available as 18mg, 36mg and 54mg pro-longed release tablets. Matoride XL tablets and Xenidate XL are presented as biconvex round tablets whereas Concerta XL are capsule shaped tablets of a similar size to the bioequivalent products. Concerta XL, Matoride XL and Xenidate XL 18mg, 36mg and 54mg are yellow, white and red in colouring respectively. Concerta XL and Matoride XL contain lactose 3,5 , and Xenidate XL contains sucrose ,6 .
We Need Your Support
Thank you for visiting our website and your interest in our free products and services. We are nonprofit website to share and download documents. To the running of this website, we need your help to support us.

Thanks to everyone for your continued support.

No, Thanks
SAVE OUR EARTH

We need your sign to support Project to invent "SMART AND CONTROLLABLE REFLECTIVE BALLOONS" to cover the Sun and Save Our Earth.

More details...

Sign Now!

We are very appreciated for your Prompt Action!

x