Dr. Helm,
I don’t have the energy. It really would require a novel. I will say that so many long term doctor/patient relationships were ruined because of the change in that old product, the nay-saying, the patient blaming. We not only had to quickly find something to titrate to while trying to avoid epilepticus, toxicities, and allergic reactions- We also had to find doctors that were willing to listen to us over the stats and drug company and do some research of their own.
We did find them.

I know that all of us here at Pharmalot are very sorry for your loss and hope that you are able to find comfort and good memories with your family and friends.

If a patient is stable and seizure free on one generic brand, it can be difficult for the prescriber and/or pharmacist to ensure that the patient remains on that specific generic brand.

2. As I understand it, AED ANDA testing only tests blood levels on healthy humans, not on epileptic patients. It would likely not be ethical to test on epileptic patients. Is this correct, and if so, does this change things?

Question:
Can any of the medical/FDA professionals tell us if it is possible for an AED equivalent to to have bioequivalent blood levels but a different CNS penetration level than the originator and/or a different generic brand of an EAD drug?

3. Between outsourcing and increased mail order dispenses, it seems as though many prescription medicines are in shipping and handling channels for longer peroids of time. Would the additional potential for tampering and exposure to adulterating elements be a variable that might be precipitating increases in break through seizures?

Do I plan to sue anyone, absolutely not..

Too many misteps along the way. I blame the healthcare system, my mother never rcved the appropriate medical tests,.. Thats the medicaid system for you.

Evidence (and experience) show otherwise…

See the following as a starting point:
Epilepsia. 2008 Mar;49(3):446-54. Epub 2007 Nov 21.
Prevalence and cost of nonadherence with antiepileptic drugs in an adult managed care population.

Epilepsia. 2009 Mar;50(3):501-9. Epub 2008 Oct 3.
Impact of nonadherence to antiepileptic drugs on health care utilization and costs: findings from the RANSOM study.

I can’t explain why this occurs, but I can tell you that many times in the ER I saw children actively seizing who had no (or impossibly low) measurable levels of their antiepileptic medications in their blood, given that their parent/guardian swore that they received their medicines on the prescribed schedule.

For a time after the adverse event (seizure) the patient and family will be adherent, but the adherence behavior in some patients seems to decay over time. It is a phenomenon without a name as far as I know - maybe “event-generating adherence decline syndrome.” How about EGADS for short? (This is also common in diabetes, asthma, and a number of other costly conditions)

In my opinion the Dilantin issues were real, though some may have had seizures for reasons other than the pharmacokinetics changes. The older seizure meds seem particularly vulnerable to variability in delivery and seem to need blood/CSF levels nearer the levels associated with toxicity for effect.

My perception is that most of the newer meds have longer half-lives, better availability, and generally less toxicity than the older meds. Some still have weird and troubling interaction profiles. The new ones are also much more likely to be used off-label. (Some seem to generate more than 75% of their revenue from conditions which are not associated with seizures - and where there is not good evidence supporting effectiveness. For those uses, what’s wrong with the generic?)

As the newer ones were going generic, there seemed to have been a lot of money thrown around to the AAN and other interests to fight (or at least cloud the issues) on behalf of PhRMA.

Another possibility if increased seizures are perceived is that physician’s instill a belief in their patient that the generic is inferior. This could affect adherence - particularly if a physician is insistent that the patient should only be treated with the brand which has become much more costly to the patient. (Or if they take the generic a sense of fatalism about the poor control outcome may lead to hopelessness and apathy.)

Sadly, as a physician, I can say that we are not that good at actually determining (scientifically) WHY something happened. We often let our biases color our conclusions about an observation. If we think generics are inferior, and a patient has a seizure we blame the generic, when in fact there may be another cause.

As always, more study IS needed. I would not want anyone to suffer poor seizure control due to a difference in manufacturing - though the variations there (if any are significant) are probably much less than the variations that occur with co-adminstration of food/beverages, other med interactions, stress, sleep, infection, etc. in a single patient over time.

However, I (and all of us really) have a problem when the study hypotheses are poorly formulated because of particular biases we can’t see around.

Someone has taken a drug and maintained good seizure control for a decade or two, and all of a sudden because he was switched to a generic, he has forgotten his dosing schedule?

Medications do not have NTIs, people do.

I think I may have seen you once or twice along the way, Doc.

I’ve reviewed a few cases where after changing to a generic from a brand a patient was alleged to have worsened seizure control. In all cases, I noticed that the patient’s use of the medication was less consistent after the change. If a patient only takes the generic half of the time, and previously took the brand more than 80% of the time, the results aren’t surprising.

Seizures are bad. But, poor adherence to medications which may reduce their occurence is not a fault of the FDA or the manufacturers (brand or generic). Unfortunately, for some patients, adherence routinely falls over time, until another event occurs.

At that time, Sid Wolfe/Public Citizen noted that it was one of the worst examples of repeat offending and systemmic irresponsibility he had ever seen. He suggested then that, given W-L’s attacks on generics, W-L ought to “look in the mirror”

http://www.citizen.org/publications/release.cfm?ID=5555

Plus ca change?