The Following Letter was Disseminated in December, 1996 to Pharmacists and Contains Important Information Relating to Bioinequivalent Generic Tablets.

If you are confused regarding Eldepryl® Capsules, selegiline HCl tablets, bioequivalence issues, AB ratings and such, it is not surprising. You have been bombarded with letters and fact sheets with all sorts of messages. Let us put all that aside for one moment and just deal with one issue - your patient. You know better than anyone about your Parkinson's Disease patient, generally elderly, receiving multiple medications and carefully maintained on Eldepryl® Capsules after being cautiously titrated with levodopa to ensure efficacy and to limit side-effects.

The manufacturers of selegiline HCl tablets base their claim of bioequivalence upon measurements of metabolites and not the active moiety; parent selegiline. Somerset does not agree with the basis of the claims for bioequivalence and is in litigation with the FDA over this matter. Not surprisingly, the generic manufacturers will not address the real issue, that is, their products do not deliver equivalent blood levels of parent selegiline. In fact, none of these marketed tablet products are bioequivalent with Eldepryl® Capsules. Your patient's selegiline levels will fluctuate dramatically when transferred from Eldepryl® Capsules to the various generic products. Just look at the variability in parent selegiline blood levels from studies conducted with the generic tablets.

This variability can lead to safety and efficacy problems in your patient population in whom drugs must be carefully monitored. Just imagine the impact on Sinemet® blood levels with these wildly fluctuating selegiline levels. Is this acceptable for your patient? Would it be acceptable if you were the patient? The Technical Advisory Committee to the Illinois Formulary did not think so. On 11/22/96, after careful review of the bioequivalency data, the Committee unanimously declined recommending that generic selegiline tablets be included in the Illinois Formulary for the Drug Product Selection Program. Additionally, the New Jersey Drug Utilization Review Committee has not considered adding generic selegiline HCl tablet formulations to the New Jersey Formulary since in New Jersey, it is illegal to substitute generic selegiline HCl tablets for Eldepryl® Capsules.

Moreover, you must note that the FDA's New Drug Division of Neuropharmacological Drug Products has mandated and Somerset has agreed to issue a Dear Doctor Letter notifying physicians of rare reports of hypertensive reactions occurring in patients receiving Eldepryl® Capsules at the recommended dose (5mg bid) associated with ingestion of tyramine-containing foods. FDA has stated that these risks significantly increase when patients are exposed to higher doses of selegiline. FDA has further recommended that careful monitoring is required for those patients who are transferred from one selegiline preparation to another.

We know that the ultimate decision is yours and will be based on the best interest of your patient. We know that Eldepryl® Capsules have no equivalent. In addition please know that Somerset is continuing to engage in Parkinson's Disease research and provides educational materials, financial discounts and support to numerous Parkinson's Disease patients, groups and foundations. Your patients deserve the best and that is Eldepryl® Capsules from Somerset Pharmaceuticals, Inc.

The evidence is clear. As demonstrated on the previous graph, the generic selegiline HCl tablets are bioinequivalent to Eldepryl® Capsules with respect to the pharmacologically active moiety; parent selegiline.

For more information relating to Eldepryl® Capsules or support programs provided for Parkinson's Disease patients call Somerset Professional Services at 1-800-892-8809.

Sincerely,

A. Michael Stevens
Director of Marketing

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The Following Letter was Disseminated in August, 1996 to Pharmacists and Contains Important Information Relating to Non-Interchangable Generic Selegiline Tablets.

Somerset Pharmaceuticals, Inc. manufactures and markets Eldepryl® Capsules (selegiline hydrochloride) for the treatment of patients with late stage Parkinson's disease. In May 1996, Somerset voluntarily discontinued the marketing of Eldepryl® Tablets out of concern for patient safety due to the escalating availability of illegally marketed and counterfeit products.

Some of your patients now receiving Eldepryl® Capsules may become aware that generic tablet versions of selegiline are now available.

Please be aware that the FDA reconfirmed today that these generic tablet versions are not AB rated to Eldepryl® Capsules and are not AB rated to the previously marketed Eldepryl® Tablets. As such, generic tablets may not be substituted for Eldepryl®.

Because Eldepryl® Tablets were removed at Somerset's initiative from the US marketplace in May, due to concern about counterfeit copies, they are no longer on the "Prescription Drug Product List" in FDA's "Orange Book" publication. Accordingly, generic manufacturers cannot legally make claims that their medications are AB rated to Eldepryl® Tablets. They also cannot make AB rating claims to Eldepryl® Capsules because FDA does not confer AB ratings to different dosage forms (ie, tablet or capsule). Additionally, these generic tablet forms have not demonstrated bioequivalency or therapeutic equivalency to Eldepryl® Capsules. Therefore, generic tablet forms cannot be substituted or interchanged for Eldepryl® Capsules.

We hope this information is useful in addressing any questions you may receive about generic selegiline, as well as in clearing up potential confusion regarding generic substitutions. Generic selegiline tablets cannot be substituted for Eldepryl® Capsules and are not AB rated to Eldepryl® Capsules or to the discontinued Eldepryl® Tablets.

As always, please do not hesitate to call Somerset's Department of Professional Services at 1-800-892-8889 with comments or questions.

Sincerely,

Cheryl Blume, Ph.D.
Executive Vice President and Chief Operations Officer