Are there problems that present due to the safe and equivalent rating given to generic medications?

The more sensitive population that is in need of precise and careful care by their physician might not be adequately represented by the Food and Drug Administration (FDA) rating. While generic medication has good result for many, this is not the case for every person.

The 20% delivery difference of active ingredients that the FDA allows in generics is necessary because the inactive ingredients (fillers and or bulking agents) vary as compared to the brand medication counterpart. Different inactive ingredients in generics do affect how a sensitive person, such as allergy prone, immune deficient, or known atypical metabolizer, will respond to the active ingredients in the generic.

Poor metabolizers do not respond typically to many medications as far as how the medications will deliver in their system. Poor metabolizers will likely be prone to side effects, sometimes dangerous ones that are more than slightly adverse as far as health and safety. Generic medication will confound things in cases where the inactive ingredients have possibility of change from month to month. This is because the resulting difference in delivery of the active ingredient might drastically vary from month to month.

The FDA represents that it simply provides a safety rating for the generic. The FDA feels resulting problems from the rating are not the fault of the agency. In order to achieve a successful FDA safety rating, the generic is only required to be tested on normal subjects. The FDA safety rating involves an abbreviated process as compared to how safety has historically been verified.

Evaluation of how generics affect the more sensitive population is not required by the FDA. There is not a specific reporting program in place in order that insurance might be required to report adverse effects from use of generics. Those who are covered by insurance and accept the forced switch from brand to generic, and then have to go back to brand due to adverse health consequences from the switch, are quietly involved in a questionable generic experiment.

Insurance companies point to the FDA rating of generics, in order to insist that even atypical responders make a switch to generic. The FDA allows this and does not address the problem that their safe and equivalent rating is causing. The FDA represents that it does not regulate the practice of medicine, but only the safety rating on generics.

The FDA is regulating the practice of medicine if, in fact, the insurance companies are using the safe and equivalent rating as medical fact across all types of illnesses. The insurance companies apply generic medication policy in medical cases where the rating of equivalency should never be medically applied. Since there can be a dramatic difference in response between brand and generic medication, for those who have health issues or sensitivity — brand medication and the generic counterparts can act as if they are two entirely different medications.

The FDA allowed difference in delivery and performance between brand medication and generic medication is bad medicine for many who desperately need the same delivery of their medication, every time. While brand medications have the same active and inactive ingredients every time, generic medication counterparts realistically can have inactive ingredients that differ every month, impacted in huge part according to what the generic supplier and pharmacy have opted to purchase and provide to their customers. Therefore the generic medication delivery of the needed active ingredient can drastically differ according to the variability in inactive ingredients.

The generic medication difference is in the… “Active ingredients, bulking agents, preservatives, coatings, shelf life instabilities, manufacturer glitches.” (Susan Okie, M.D., Multinational Medicines-Ensuring Drug Quality in an Era of Global Manufacturing, 8/2009)

The FDA process of regulating generic medications has actually gone a little backward.

“Before 1984, generic-drug makers were obliged to conduct the same safety and efficacy tests that had been required of the original brand-name manufacturers to receive Food and Drug Administration (FDA) approval for marketing.” But then: “The Hatch-Waxman Act allowed abbreviated process for generic drugs to receive FDA approval and allowed generic drug manufacturers to apply for FDA approval and conduct tests before relevant patents expired.” *

Furthermore: “Companies seeking approval of generic drug are not required to conduct chemical trials of its safety or efficacy, but most submit results of a study in healthy volunteers with product absorption comparative to brand – medication counter part.” *

So, even if it is true, that generic medication is safe and equivalent for those who are already healthy. What about those who are not quite the picture of perfect health or perfect response to treatment? The FDA might not have the ability to care, and insurance companies may be prone to look the other way in favor of their pharmacy benefits bottom line. There are avenues of expression that paint a vivid picture of generic medication’s effect upon the population in need of good medicine.

People’s Pharmacy provides multiple years’ worth of reports of adverse response to generics by people who had been successfully treated with brand named medication, but forced to switch to generic. Another site formerly called CrazyMed has provided a bird’s eye view of the effect of generic medication upon those with forms of depression and psychosis. Reading the posts from either source overwhelms due to the number of posters’ who had to experiment with the generic medication that they were forced to switch to.

Everyone talks about saving at the pharmacy, but some people who have been inclined to switch to generic from brand have big problems. They are likely visiting the doctor more frequently and perhaps requiring more inpatient stays. I do wonder how many might have done themselves in due to the psychosis that revisits them while experimenting with generics that do not give the same results.

The problem of metabolism and how delivery of generic medication can vary, coupled with the other problem of special interest’s control over delivery and quality of medication products — begs an important question. What is the point of medicating if the special interests are just going to end up taking the good initial result away from the person being medicated?

About the issue of poor metabolism and autism.

Many drugs that are used to treat those within the autism spectrum interact with CYP2D6. CYP2D6 receives a lot of attention with regard to research on how drugs metabolize in the system. Poor metabolizers of the CYP2D6 enzyme, who are tried on medications that interact with CYP2D6, might experience increased plasma concentrations that can increase the risk of serious adverse consequences.

“CYP2D6 is considered a low-capacity, high-affinity enzyme and CYP2D6 will preferentially metabolize drugs at lower concentrations. As the concentration of a drug increases, the metabolism spills over to CYP3A4 and CYP1A2, which are high-capacity, low-affinity enzymes. Thus if a drug that has several metabolic pathways but relies on CYP2D6 as its major pathway is given to a patient with poor CYP2D6 activity, the other P-450 enzymes that are high capacity, low affinity will clear the drug, but clearance will be slower and less efficient, and drug levels will increase, increasing the risk for adverse drug reactions. Four phenotypes are identified: poor metabolizers (PM), ultrarapid metablizers (UM), intermediate metabolizers (IM) and normal metabolizers (NM)”. (Pharmacy Times)

The antidepressants that are metabolized by CYP2D6 are ones that are used frequently, and they include: cimetidine (Tagamet), the selective serotonin reuptake inhibitors (SSRIs) and some tricyclic antidepressants.

“…Paroxetine (Paxil) appears to have the greatest ability to inhibit the metabolism of CYP2D6 substrates. This is followed by fluoxetine (Prozac) and norfluoxetine; sertraline (Zoloft) and desmethylsertraline; fluvoxamine (Luvox), nefazodone (Serzone) and venlafaxine (Effexor); clomipramine (Anafranil), and amitriptyline (Elavil)…Although sertraline appears to be less likely than the other SSRIs to inhibit CYP2D6, inhibition may still occur at doses greater than 50 mg. The clinical significance of the inhibition of tricyclics by SSRIs or cimetidine is subject to variation in enzyme activity between individuals, the degree to which the patient metabolizes and co-ingestion of other enzyme inhibitors“. (HealthandDNA.com)

Some feel that as many as half of the patients who take medications are probably not experiencing any type of benefit from them due to metabolism issues, while most likely being exposed to potential danger from side effects. One source expresses the thought that at some point, medical professionals might let go of the one pill fits all mindset. Many obstacles will detour that process. There is hesitation by doctors to utilize CYP2D6 testing since there are no clear guidelines about how they should act upon the information provided by the test.

Additionally: “The ability of test developers to prove that their tests are accurate and useful is one major obstacle. Other obstacles include the reluctance of drug makers to encourage or develop tests that could limit the use of their drugs and the possibility that insurers might not pay for the tests. However, drug makers are “starting to realize that their medicines might not be approved or paid for without better evidence that they work,” according to the Times (Pollack, New York Times, 12/30/08)”. (Medicalnewstoday.com)

In many cases of autism I am personally convinced that the metabolism issue is a significant factor with regard to failure of medication tries. Additionally, the tries might actually contribute to worsening.

Many autism affected children begin using medications at a very early age and one analysis “… included 75 children enrolled in the long-term Collaborative Programs of Excellence in Autism. The study found that 52% used at least 1 psychotropic medication between the ages of 3 and 12 years and 20% had taken 4 or more.” (Medscape.com)

Learning what I have about the metabolism issue from personal experience, I often become curious about the consequences with regard to how many children were doing well on a brand medication, and then suffered a worsening — simply because they had been switched to a generic that was deemed safe and equivalent by the FDA.

Families trust the rating and may never consider that the switch to generic is what caused the worsening. For those within the autism spectrum this might be a huge issue.

Generic medication and brand medication might very likely be considered neither safe or equivalent where a switch would be concerned, for those within the very sensitive autism population.