Physicians are invited to provide feedback on their experiences with the new generic methylphenidate-based product with a progressive delivery system, Novo-Methylphenidate ER-C, a medication approved by Health Canada in March as a generic for ConcertaTM. CADDRA received some anecdotal reports from families and physicians of behavioural changes in patients when Concerta was switched to the generic formulation. While we are aware these changes could also be attributed to other factors, we have decided to provide doctors with a way of providing feedback on their experiences with the generic – both positive and negative – through an online comment form. Physicians are also reminded that adverse medication reactions must be reported to the Health Canada through the Canada Vigilance Program.
Bioequivalence does not mean clinical equivalence for all products and this may be the case for ADHD treatment with psychostimulants delivered with a slow release mechanism. CADDRA has expressed its concerns to Health Canada in a number of letters; has submitted feedback to the Health Canada consultative process on comparative bioavailability standards: formulations used for systemic effects; and will present its concerns and recommendations regarding bioequivalence requirements for modified release dosage forms at a workshop in June organised by Health Canada’s Scientific Advisory Panel on Bioequivalence Requirements for Modified-Release Dosage Forms
The actual delivery mechanism of Novo-Methylphenidate ER-C has not been described. This medication is not delivered via the OROS pump system, which is utilized for ConcertaTM. The visual appearance of the medication is very similar to ConcertaTM capsules. However, unlike ConcertaTM, Novo-Methylphenidate ER-C can easily be divided, crushed and powered, which could potentially increase its abuse potential. It is important to know that abuse potential is reduced if the medication is a non stimulant or a long-acting psychostimulant delivered in a non-crushable format. It has been shown that inhalation or injection of immediate-released methylphenidate-based or amphetamine-based medication can induce a pleasurable sensation, increasing the abuse potential. All long duration stimulants including Methylphenidate ER can be crushed releasing Methylphenidate (MPH). While Concerta cannot be crushed there are ways of extracting both the external layer and using the osmotic pump to release the internal drug.
As with all other generic products, Novo-Methylphenidate ER-C was made available in Canada after demonstrating bioequivalence to ConcertaTM according to Health Canada criteria. However, clinical equivalence to the original product has not yet been established. Bioequivalence does not mean clinical efficacy equivalence. Clinical equivalence data is needed to ensure that the generic formulation will in fact have the same effect for patients. This is particularly a concern because of the different delivery system employed by the generic medication. We know that time necessary to obtain the maximal concentration (Tmax) is earlier with the generic medication, but we don’t know if that will influence the side effects profile, onset and duration of action of Novo-Methylphenidate ER-C compared to ConcertaTM. For the time being, we don’t have enough data to comment on its clinical efficacy. As things now stand, we will need to wait for clinical experience to offer clarity.
Methylphenidate is a drug with an extraordinarily tight correlation between the pharmacokinetic curve and the attention or deportment at that time. In other words, if you know the pK curve you have a very good idea of the behaviour of the drug. If patients are warned of the change and are titrated accordingly they would hopefully be able to report if there were modest changes in symptoms between the morning and afternoon. However, patients may be unaware that a substitution has taken place and express a change in symptom control not knowing why. Physicians should look into the possibility that Concerta may have been substituted with Novo-Methylphenidate ER-C.
Pharmacists have the right to substitute an innovative or original product for a generic product. They have to make sure that the generic product is likely to produce the expected therapeutic effect, similar to the trademark medication. If the pharmacist believes that the generic product will produce a therapeutic effect similar to the original, he can decide to proceed to a substitution. Pharmacists that consider a substitution must analyze the clinical situation of the patient, taking into account the current medication profile, actual clinical considerations specific to the patient and his or her treatment history. It is logical that close follow-up would have to be put in place and that a discussion with the prescribing physician could be required. A patient has the option to reject the proposed substitution. If the patient is covered by a public medication insurance program, or in certain cases of private insurance programs, he or she may be required to pay more for the original product. Physicians may decide to write do not substitute on the prescription.
In general, CADDRA welcomes any new pharmaceutical products into the marketplace as it has been our collective clinical experience that no one medication is right for every patient, and the more variety of medications that we have available, the better off our patients will be. We also welcome low cost alternative medications to the marketplace, as many of our patients are unable to afford some of the longer-acting preparations that are available.
Only clinical experience will help answer the questions of clinical efficacy and abuse potential. In the meantime, CADDRA recommends that Novo-Methylphenidate ER-C be considered an additional ADHD treatment option, instead of a product that can automatically replace ConcertaTM. Each case is unique and it is crucial to personalize treatment taking into account the needs of each patient.