Medicines Healthcare Products Regulatory Agency
Advice to healthcare professionals:
- caution should be used if long-acting formulations of methylphenidate are to be used interchangeably due to the differences between formulations in dosing frequency, administration with food, amount and timing of the modified-release component, and overall clinical effect
- follow specific dosage recommendations for each formulation
- if considering a switch to another long-acting preparation:
- consult with the patient (and their parent or caregiver if relevant) to discuss the reasons for this and the possible changes they may experience in symptom management and side effects (and what to do if these occur)
- consider patient preferences such as their individual needs, dose frequency, possible side effects, or other issues related to the patients condition
- reiterate the instructions for use for the newly prescribed formulation, especially whether it should be taken with or without food
- clinical guidance advises to prescribe these long-acting formulations of methylphenidate by specifying brand name or by using the generic drug name and name of the manufacturer
- report any suspected adverse drug reactions associated with methylphenidate or other medicines on a Yellow Card
Advice to provide to patients or parents and caregivers:
- there are differences between long-acting methylphenidate medicines in how they release the medicine to manage ADHD symptoms and in the instructions on how to take them
- we have asked doctors and pharmacists to be cautious when switching patients between different long-acting formulations of methylphenidate
- carefully read and follow the advice in the Patient Information Leaflet that comes with your medicine and speak to a healthcare professional if you are concerned about side effects or are concerned about your childs health or medicines
- it is especially important to follow advice on how much methylphenidate to take and to follow instructions on when and how to take it these can affect how well the medicine works for your ADHD
About methylphenidate
Methylphenidate is used as part of a comprehensive treatment programme for attention deficit hyperactivity disorder (ADHD) in children and adolescents aged between 6 and 18 years and in adults. It is authorised only after other treatment measures, such as counselling and behavioural therapies, have proven insufficient to manage symptoms.
Methylphenidate is available in the UK in immediate-release and long-acting formulations taken orally (tablets or capsules). Long-acting medicines are those labelled as prolonged-release, modified-release, or sustained-release formulations.
Review and updates to advice
A recent European procedure looked at differences between Medikinet XL and other long-acting formulations of methylphenidate and the impact on safety and efficacy when switching to and from products. This procedure concluded that caution is advised if long-acting formulations of methylphenidate are used interchangeably due to the differences between formulations in frequency of dosing, administration with food, and plasma drug concentration achieved. These updates will be made to the UK Summary of Product Characteristics (SmPC) for Medikinet XL. We have considered this, together with the safety data for all long-acting methylphenidate medicines, and agree with this position.
We also considered reports and queries from patients, carers and healthcare professionals in the UK regarding concerns of lack of effect and increased adverse effects when switching between long-acting formulations of methylphenidate. We sought the views of the Paediatric Medicines Expert Advisory Group of the Commission on Human Medicines on these concerns.
We are alerting healthcare professionals to the need to use caution when prescribing or dispensing long-acting methylphenidate preparations and to adequately counsel patients as required.
We will continue to monitor safety information and will seek to introduce this wording in other long-acting methylphenidate formulations as appropriate.
We note this advice is consistent with existing clinical guidance from the Specialist Pharmacy Service on prescribing modified-release methylphenidate preparations by brand.
Information on how formulations differ
All long-acting methylphenidate preparations include an immediate-release component as well as a modified-release component. This means methylphenidate is released in two phases (biphasic). This allows for rapid onset of action and a slower extended release, avoiding the need to take further doses during the day to maintain effect. It is possible that several formulations will need to be tried before one is found that suits an individual.
The biphasic-release profiles of these products are not all equivalent and contain different proportions of the immediate-release and modified-release components. The differing timeaction profiles provided by long-acting formulations of methylphenidate allow clinicians to target specific periods of the day that are particularly relevant for a patient, facilitating individualisation of ADHD treatment. Transferring to another formulation can result in changes in symptom management at key time periods during the day.
The response to methylphenidate varies greatly from patient to patient and therefore the doctor will need to increase or decrease a dose to find one that suits the patient (dose-finding phase). A number of long-acting methylphenidate preparations are available, Medikinet XL, Ritalin LA, Equasym XL, Concerta XL and generics, and they differ from each other in several aspects, including:
- their available dose strengths
- the ratio of immediate-release and modified-release methylphenidate
- mechanism of release
- pharmacokinetics
- plasma concentration-time profiles and bioavailability
- their dependence on the presence or absence of food at the time of ingestion
Due to these differences, changing preparations means that the dose may have to be adjusted to avoid the potential for overdose or underdose.
Advice on switching of methylphenidate products
Switching between different preparations may result in concerns from patients and parents or caregivers.
No single formulation meets the requirements of all patients with ADHD and the unique characteristics of each agent should be matched to the individual needs of the patient.
Switching between formulations with differing pharmacokinetics can also be associated with differences in adverse events or patient experiences of effectiveness in both paediatric and adult patient groups.
Frequent switching between different products should be avoided. Once a patient is established on a product, prescribers may wish to maintain them on that specific product. In such cases, prescribing by specifying brand or manufacturer may be appropriate. This is consistent with existing guidance from the Specialist Pharmacy Service and in the BNF and BNF for Children.
Changes to medication should only be made in the context of individual review and should be communicated to patients, who should be advised to report any changes to their symptoms or development of side effects.
Report suspected adverse drug reactions on a Yellow Card
Please continue to report suspected adverse drug reactions to the Yellow Card scheme.
Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:
- the Yellow Card website
- the Yellow Card app; download from the Apple App Store or Google Play Store
- some clinical IT systems for healthcare professionals (EMIS, SystmOne, Vision, MiDatabank, and Ulysses)
When reporting please provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset timing, treatment dates, and product brand name.
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