Free Expert Witness Designation - District Court of Colorado - Colorado

Case 1:03-cv-02608-WDM-MJW

Document 68-2

Filed 11/20/2006

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EXHIBIT "A"

Case 1:03-cv-02608-WDM-MJW

Document 68-2

Filed 11/20/2006

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FROM

Maxim D. Hammer, M.D. Assistant Professor of Neurology University of Pittsburgh Medical Center Department of Neurology 200 Lothrop St, PUH C-419 Pittsburgh, PA 15213 November 11, 2006 Julie Sweeney Pietragallo, Bosick & Gordon The thirty-eighth floor One Oxford Centre Pittsburgh, PA 15219 Lorna Fooshee v Mylan Pharmaceuticals, Inc

DATE TO

RE

Dear Ms. Sweeney, I did have the opportunity to review all of the documents you have provided, including: Death Certificate 10/29/2001; Coroner's Report and Investigation; WALMART pharmacy documents; Peak Vista CHC Medical Records; Community Health Center/Visit Notes; Prescription dated 9/24/2001; Medication bottle labels; Laboratory records; Patient care report; Memorial Hospital medical records; Emergency care records; Academic neurology medical records; records from "Neurology consultants"; Co Springs Family Record; Expert report of Jerome Skelly, PhD; Expert report of Marvin Meyer, PhD; Expert report by Joel Freiman, MD; Expert report by Charles Marable, MD; Expert review by Leppik, MD; Expert review by Mozayani-Posey PhD; Expert review by Bartling, Pharm D; Second Ammended Complaint/Allegations; Mylan's response to Allegations. 1. The cause of death is not clear to me. I reject the coroner's assumption that the cause of death was seizure. There was no autopsy. There may have been a concomitant undiagnosed medical condition. A seizure may produce death if aspiration results in respiratory arrest, although this is a rare outcome for seizure. Alternate causes of death: polycythemia with pulmonary embolism. I have tabulated his red blood cell counts from 1990 to 2001. There is a rise in his hemoglobin and hematocrit counts between 1990 and 1997. There were no measurements between 1997 and 2001 until the ER visit of 10/18/2001, when the levels were increased even further and for the first time, out of the normal range. Polycythemia predisposes to blood clot formation, and blood clot formation can lead to fatal outcomes such as pulmonary embolism. 2. In general, seizures, in a patient with epilepsy, can be triggered by multiple factors. A sudden drop in medications may cause seizures. However, other causes such as infections, lack of sleep, alcohol or other drug use, stress, and

Case 1:03-cv-02608-WDM-MJW

Document 68-2

Filed 11/20/2006

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physical overactivity, can also trigger seizures. Finally, patients with epilepsy may still have seizures despite the absence of any of the above triggering factors. 3. It is not clear why Mr. Fooshee had increased seizure frequency just prior to his death. Let us assume that the increased seizure frequency was related to the decreased serum phenytoin levels. There are three possible reasons for a fall in the serum phenytoin levels: the switch to generic (which may have occurred anytime between 9/25/01 and 10/21/01, or may not have occurred at all); the decrease in daily dose (this was ordered 10/18/2001); noncompliance (there is previous documentation of noncompliance---see page N0103). a. If he switched to generic between the day he filled the prescription (9/25/01) and the day he had an elevated drug level (10/12/01), then the switch to generic caused a rise (not a fall) in the serum phenytoin level. Therefore, the switch to generic was not the reason his levels fell subsequently. The reason for the fall in levels would have been either the order to decrease the daily dose; or noncompliance for whatever reason. b. If he switched to generic between the day of the elevated level (10/12/01) and the day of his death (10/22/01), then the generic formulation may have been a factor in his decreased serum levels. Lowering the daily dose would then have been a second factor occurring at the same time. Noncompliance is a possible third factor. c. If he filled the generic prescription, but never starting using those pills, then the switch to generic never occurred and is eliminated as a possibility. d. My conclusion is that using strict logic, I cannot infer, from the data that I have reviewed, that the generic formulation is to blame for the patient's decreased serum phenytoin levels. I believe within a reasonable degree of medical certainty, that the cause in the decreased drug levels are far more likely to be related to the decrease in the dose from 500 mg a day to 400 mg a day. 4. With respect to the issue of bioequivalence of Mylan's phenytoin and Dilantin Kapseals: the testimonies of Drs. Skelly, Meyer, and Freiman (especially Skelly's) quite eloquently justify the FDA's approval of Mylan's generic phenytoin based on rigorous controlled medical trials. At the same time, as described especially by Dr. Marable, there have been reports of nonequivalence in the medical literature. My own opinion is that whatever change in bioequivalence that might empirically occur in any given patient can easily be managed by careful and appropriate monitoring of the blood level. I believe that switching from trade name to generic phenytoin is perfectly acceptable, as long as drug levels are closely monitored initially to determine the necessity for dose adjustments. 5. I believe that dropping the daily dose from 500 to 400mg was irresponsible, given the kinetics of phenytoin (with an expected sharp dropoff in serum level following a small dose decrease); and the fact that the patient had marginal seizure control even on 500mg a day. A better approach would have been to simply repeat a level.

Case 1:03-cv-02608-WDM-MJW

Document 68-2

Filed 11/20/2006

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All of the opinions expressed in my report are stated within a reasonable degree of medical certainty.

Maxim D. Hammer, M.D.