Seeing first hand all the different reactions patients have to medications and how these reactions can differ wildly when using the generic version of a medication. How can a medication be called a generic version if the adverse events experienced differ so much from the original medication? Could this be due to the other agents present in the medication and not the principal agent itself?
An adverse event profile of a given product to a given patients could considerably vary from what you read in the Patient Information leaflet. Reason behind could be: patient individual sensitivity, underlying diseases, concomitant medications and - as you said - other ingredients of the tablet. Generic version means that the drug was approved by Health Authorities based on some limited data - usually bioequivalence trials. It is also very much depends on the drug class, mode of action. If you have a specific question - ie name of active ingredient - i could help further.
Generic drugs are required by law to be bioequivalent to the brand name product, however, they can use different excipients, binders and other inert ingredients. The variable adverse reactions could be due to these changes, even though the generic gives the same blood levels.
That kind of response is also observable between two different original medications. It depends not only of the formulation (bioavailability) but preety much on the individual characteristics of the subject. There are reported cases in which adverse effects are monitored even in original medicines, because they are always compared with the first one, often the reference.
Not only the ingredients but also the manufacturing of tablets determine the rate and location of release of the medication. There are many factors that affect this and bioequivalence studies should determine differences. In principal even with the original drug having two 200mg tablets and one 400mg tablet might have different adverse effects.
The genetic differences may be one of the reasons causing variability of drug response (Pharmacogenetics). The genetic differences of drug metabolizing enzymes responsible for eliminating a given drug between patients may cause toxic levels of the drug, adverse effects or loss of effect regardless of being generic or original drug
I agree with Patrick Woster. As long as the generic drug product is bioequivalent, there must be equivalent responses with respect to the active ingredient; bioequivalence has to mean equivalent extent and rate of drug absorption. If the excipients differ, they could lead to a difference in response. Certainly there are reports in the literature of adverse responses to some of the dyes that are used to colour tablets. Of course this applies to the innovator as well as the generic product.
Generics are bioequivalent (in the US) this means they yield 80-120% of the API under std conditions. More often they yield 90-110% (or better). Excipients may be an answer, genetics may be an answer, but it could be that your data set is not real -perhaps it is just a collection of recollections and anecdotal observations? What data set(s) are you referring to that indicates a significant difference in adverse events between generic and original named product?
If really there wide differences in adverse effects between a generic and an original brand (bearing in mind the enormous task of establishing the facts), then we will have to look at multitudes of factors that constitutes patient's variability, formulation variability and pharmacy variability (storage, shelf life, etc).
Can I also suggest the following paper which summarises some of the issues that can impact on perceptions of generic drugs and also where brand prescribing is deemed necessary, with a particular UK slant:
Duerden, MG & Hughes, DA. Br J Clin Pharmacol 2010;70(3): 335 - 341
Formulation differences etc as discussed above are important as indeed is the information provided to patients when a generic is first supplied. Subtle differences in appearance of both packaging, colour or shape can impact on patient perception as well as an inherent concern that "cheaper alternatives" will be inferior.
It's important to remember that formulation changes in "brands" can lead to the same sorts of problems being experienced by patients.
The differences between excipients used in generic and brand medicines as well as manufacture processes often give significative differences in treatment response. You also must not forget that patients idiosyncrasies can lead into differences to same treatments.
Basically (theoretically) the simplified AIC doesn' t need preclinical tests for generics but only pharma-grade ingredients and validated procedures comprehensive of manifacturing.
Nevertheless the quality of the final product is not always good and can be quite approximate in the formulation (although the actives are the same) .
Therefore I believe generics (biosimilar) can lead to different PK and bioavailability profiles (a tolerance up to 20% can be accepted)but I don' t think this drawback can actually lead stronger side effects than the medications as off targets effects of the pharmacologically active ingredient..
To Salvatore: I contrary think that these draw backs may lead to serious adverse effects of a drug entity.
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