Are generic drugs as safe and effective as name brand drugs?

Use of generic drugs has the potential to reduce annual consumer spending on prescriptions by billions.  A study published in the New England Journal of Medicine and discussed in the New York Times’ Economix blog in 2012 looked at Medicare Part D expenditures and correlated them with drug prescribing patterns. The regions of the United States with the highest Medicare expenditures were those where more name brand drugs were prescribed.  But, are generic drugs as safe and effective as name brand drugs?

Generic medications become available after brand name drugs go off patent (usually 10 to 14 years after coming to market). The pharmaceutical industry maintains that the high cost of brand name drugs relates to the research and development required to innovate and bring new products to market.   Advertising and promotion are also, no doubt, a major factor.

A generic drug is a drug that has been determined to be the bioequivalent of a brand name drug in terms of its active ingredient.   Standards for proving bioequivalence are defined by the FDA and are similar to standards used in Canada, Japan and Europe.  Here’s what the FDA website says about bioequivalence:

One way scientists demonstrate bioequivalence is to measure the time it takes the generic drug to reach the bloodstream and its concentration in the bloodstream in 24 to 36 healthy, normal volunteers. This gives them the rate and extent of absorption-or bioavailability-of the generic drug, which they then compare to that of the pioneer drug. The generic version must deliver the same amount of active ingredients into a patient’s bloodstream in the same amount of time as the pioneer drug.

The following graph illustrates the bioavailability of two drugs, Drug A and Drug B. The statistics may be difficult to understand, but to be determined bioequivalent the 90% confidence interval of the ratios of the mean bioavailability, or “area under the curve” (AUC), of the two drugs and their peak concentrations (Cmax) must be in the ranges of 80 to 125%.  In more concrete terms, analyses of numerous studies of bioequivalence have shown that differences in blood concentrations of the active ingredients of branded versus generic drugs are generally less than 4 percent.

Are generic drugs as safe and effective as name brand drugs?

Once a generic drug is deemed to be bioequivalent by these statistical standards it is not required to go through the same extensive clinical safety and efficacy trials, as a newly innovated brand name drug applying for its initial patent.

What are some pitfalls of using generics? The inactive ingredients in generics compared with branded drugs are not required to be the same. Therefore allergies to these fillers and inactive compounds can be an issue. Also, special consideration should be taken when changing from a branded drug to a generic drug, or when changing between generics, if the drug has a narrow therapeutic index. Some drugs with narrow therapeutic indices include thyroid medications, anti-epileptics and warfarin.

Here are some examples of issues that come up with generics:

The adhesive contained in a fentanyl transdermal patch differs depending on whether the patch is generic or brand name. Some of my patients have developed allergies to the adhesive in the brand name patch (as opposed to the generic,) others complain that the generics don’t stick as well.

Along the lines of narrow therapeutic index—I can recall two separate instances in which a patient was changed to a new warfarin generic drug product. In each case the patient’s PT and INR (coagulation test) had been stable for months, but after the change their levels of anti-coagulation became too high. This took some detailed history-taking to figure out. One review of the literature suggested that generic warfarin and Coumadin products are equally effective and safe and uphold the FDA’s criteria for bioequivalence, yet the authors still suggested that patients limit switches amongst warfarin products and brand and monitor anti-coagulation after making changes.

If a product is deemed bioequivalent then it is also deemed “interchangeable” and pharmacists are not required to inform physicians when they change a patient from brand to generic, or when they change from one generic to another.

Another patient, who reports a high level of drug sensitivity, noticed that a particular generic of nortriptyline used for chronic insomnia was more effective for him than others.

Thyroid medication is known to vary amongst the generics and Synthroid brand in terms of clinical effects. While the FDA has deemed these various products to be bioequivalent and interchangeable many endocrinologists disagree.  In attempt to address this issue in 2004 a Joint Statement was issued by the major endocrinology professional societies making recommendations on the topic.

The most recent controversy regarding generics has to do with biological drugs, or “biologics.” Because of the inherent complexity of these innovator drugs, which are derived from living cells, the concept of “biosimilar” has replaced bioequivalent for the generic products being developed.  As reported in the New York Times, the pharmaceutical industry is currently engaged intense lobbying to prevent biosimilar generic biologics from coming to market as competition to the numerous, ultra-expensive biologics whose patents will be expiring in the near future.

The science behind the FDA approval process for generic drugs is rigorous. My advice, it can be smart to try a generic. There is no evidence that these products are of lower quality, or less effective than name brand products—though they are not required to go through clinical efficacy trials. However, be wary of minor fluctuations in the clinical effects of your medications when switching between name brand and generic, and amongst different generics, and be aware that your pharmacist may change your generic from one manufacturer to another without your knowledge (the pill should look different).

What is your experience with generic medications versus name brand products?

Juliet K. Mavromatis is an internal medicine physician who blogs at Dr Dialogue.

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  • http://www.facebook.com/beau.ellenbecker Beau Ellenbecker

    “The pharmaceutical industry maintains that the high cost of brand name drugs relates to the research and development required to innovate and bring new products to market.”

    Right….. Only the universities do the research not the drug companies. And it took a whole lot of innovation to put to generic drugs into a combo pill and sell it at trade name prices under patent protection. Or to take the same drug and get a new patent every time you figure out a different way to get it into the body (See Imitrex and all its derivatives). Same drug, much larger price.

  • http://www.facebook.com/beau.ellenbecker Beau Ellenbecker

    This is well written and presents both sides. I liked that. However you didn’t mention that many of the generics out there are made by the same companies that make the trade name, just like in the food industry.

  • drg

    you did not mention the quality control problems in the manufacturing process for generics. Lipitor generic was found to have glass most recently and overall generic manufacturers many were closed down for awhile for quality control problems.
    But my impression is that with the little money they make–cents per pill–that there is no incentive for improvement–or even incentive to manufacture at all because of little profit. And the other related point is that there is a shortage of many generics.

  • http://www.facebook.com/people/Steven-Reznick/100000549195050 Steven Reznick

    The generic factories and production plants are rarely if ever inspected by the FDA for quality and consistency.Many of these production plants are overseas. The FDA does not perform any bioequivalency tests. It depends on the manufacturer to submit data that the tests have been performed by labs the manufacturer has hired and the tests are performed appropriately and the results presented are accurate and reliable. Much like the fox watching the chicken coop.

  • SBornfeld

    Some of the problems with specific generics apparently “make the rounds” unofficially. An old friend who’s a psychiatrist referred to a specific generic manufactured by a specific manufacturer (and no, neither Chinese nor Indian) that it was apparently well-known “must-to-avoid”. Anecdotal, yes–but wouldn’t YOU listen?

    • http://euonymous.wordpress.com euonymous

      So glad to see that you and others have included remarks about some generics being untrustworthy. As someone who must take Coumadin and who has had horrible reactions to the “generic equivalent” — I believe no generic should be sold without testing and regular FDA monitoring. Mind you, I am a frugal Yankee, so I completely support the availability of less expensive generics, but only when they have been proven to be bioequivalent.

    • drg

      So what is making you hold back from telling us the specifics?

      • SBornfeld

        For one, it was told to me in confidence by a personal friend. Secondly–creeping senility. I remember the name of the company, but not the medication.

  • http://twitter.com/sunjayd Sunjay R Devarajan

    Thanks for posting this. I definitely think we could be a lot smarter about how we approach generics, because it is simply irresponsible in this day and age to be actively prescribing branded medications without evaluating if a generic could be substituted. I have seen adverse effects most often, however, with antiepileptics (as you have mentioned above), and really any psychiatric medications like Lithium. Patient feedback is really important in making sure it all works out.

  • Rose

    I have to take several medications and each time the gp prescribes the generic, and each time I have to check the ingredients. Several generics have artificial colourings in that cause my asthma to flare up or a nasty urticaria rash, others have lactose in that I am intolerant to, the brand names do not have these ingredients in and seem to work much better.

    Also my father was on warfarin and each month the tablets were a different make, we could not stabilise his INR and in the end he had to stop taking them, I think you have just explained why!

  • bill10526

    Revenue has to be found to pay for the manufacture and distribution of any drug (the generic costs.) and to fund the development of new drugs. Moving to Generics transfers development costs from those buying the generics to others, total societal costs are not reduced and are probably increased.

    Societal costs could be reduced with more rational regulations and curbing litigation. “If only I had known …” rings hollow when patients fight to get into clinical trials.