7 replies to this topic

[CallMeLucky]

Cited from:

AEI  OUTLOOK  SERIES

Dangerous Substandard Medicines

An Increasing Global Problem

By Roger Bate,  Julissa Milligan, Lorraine Mooney

http://www.aei.org/outlook/101061

Glivec. Glivec® is an innovator drug used to treat chronic  myeloid leukemia. In the last two and a half years, case studies involving  comparatively well-off patients from middle-income countries have demonstrated  that copy drugs are ineffective in treating chronic myeloid leukemia in some  patients. These copy medications are not proven generics and are not required to  pass stringent bioequivalence tests prior to use in hospitals and  pharmacies.[14] Some of these medications, such as Imatib, are produced by large  reputable pharmaceutical manufacturers--in this case India's Cipla, whose  pharmaceuticals regularly pass FDA inspections and meet international regulatory  standards (none of Cipla's antibiotics or antimalarials failed basic tests in  our study discussed above).

While Glivec® has demonstrated a "high hematologic, cytogenetic, and  molecular response rate and favorable long-term safety profile,"[15] five  reported case studies suggest that copy versions, which contain a slightly  different version of the active ingredient,[16] are ineffective in some cases.  In all five studies, the patient experienced a relapse after switching from the  original to the generic medication, and then improved again when put back on the  original drug. In one case, an older patient in fragile condition was unable to  recover even after the reintroduction of the innovator drug, and he died after  the reintroduction.

[Happycat]

Interesting. I wondered how they got around the patent issue. I'll have to check into the structure of Imatib, since they mention it is ever so slightly different. I'll bet they replaced a hydrogen-bonding atom with a non-hydrogen bonding one, which could very well change the ability to bind to the amino acids in the bcr-abl protein.  Either that or they changed the formulation.

Note the key sentence - "These copy medications are not proven generics and are not required to pass stringent bioequivalence tests prior to use in hospitals and pharmacies."  I would not take any generic that was not required to pass bioequivalence tests.

Generics that have been approved by the FDA should be fine, though. The FDA is pretty tough on generics requirements.

I would assume a generic approved for use in most European countries would be okay, too.  Did the article state the problem was generics in developing countries only?

Traci

[Trey]

There are at least two Indian "generic imatinib" drugs from Veenat and Cipla.  They do NOT comply with U.S. patent law, so cannot be exported to Western countries.  India does not recognize patents the way most the rest of the world does.

[Marnie]

So do the Indian drugs work as well??  Not interested in heading to India for meds, but curious.  Are they safe?  Have they been tested?  Are they the same med?

Marnie

[Trey]

People in India use them successfully.  They are likely good quality drugs, and the few cases cited do not prove much since there are many variables, including poor PCR procedures, lack of compliance by the patient, etc, that could account for the small number of issues.  No doubt there are some problems with some manufacturers of certain generic drugs around the world.  Veenat has some type of FDA tentative approval to sell their generic imatinib in the U.S. when the Novartis patent expires in 2015.  And Western companies will also enter the generic market when the time comes.  When Jan 2015 arrives, there will be a lot of people switching to generic imatinib.

[knoppl]

Generic drugs in general can have up to a 20% difference in how effective they are. My husband is on a medication that he cannot be on generically as it is not as effective and his family doctor is the one that told us about he 20%. Not sure if this related directly to the Gleevec effectiveness.

[Susan61]

Hi:  I heard the same thing from someone else with regard to Generic.  My opinion is that if name brand got me to where I am,then do not switch me and take a chance.  My issue will be money when my husband retires, and we are not with our regular insurance.  Then again with all the changes going on, who knows what we will be able to get or afford in the future.

Susan

[Happycat]

Checked into this a little bit.  The compound imatinib can crystallize out of solution in different forms.  Meaning that the crystal "shape" is different, so one might look like little needles and one might look like squares.

Novartis sells the beta-form, which is thermodynamically more stable.  Cipla and other generic houses sell the alpha-form. I did not go digging around to see if the alpha vs. beta form has different activity, solubility, stability, etc.  The supposition in the literature is that the alpha-form is responsible for the difference some people have noted in outcomes with generic vs. Novartis imatinib.  If the beta-form is more stable than the alpha, it could be something as simple as reduced shelf-life for the alpha-form.

No clinical studies have ever been done on alpha vs. beta, so there is no definitive proof that one performs better than the other.  Novartis did all of their studies on the beta form.

Traci