Each state has rules concerning generic substitutions. The chart presented here indicates which states allow for generic substitution by pharmacists. However generic substitution is not permitted when "Brand Only" or similar wording is indicated by the prescriber. The chart also notes which states mandate generic substitution under those circumstances. It indicates which states allow dispensing of a brand name medication if that is requested by a patient.

Also listed are states which mandate dispensing the brand name medication if that is what is indicated by the prescriber. Each state's specific wording requirements for prescriptions are given in the far right column. For the two states where a specific exception is made for anticonvulsant medications (Hawaii) or narrow therapeutic range medications (North Carolina), which includes antiepileptic drugs, that indication is given in bold type. Any questions should be referred to your pharmacist.

State Laws or Statutes Governing Generic Substitution by Pharmacists
State	Allows for Generic Substitution by Pharmacists if "Brand Only" Not Indicated by Physician	Mandates Generic Substitution by Pharmacists if "Brand Only" Not Indicated by Physician	Allows for Brand if Requested by Patient	Mandates Brand Only if Indicated by Physician	To Ensure Brand Name Only, Physician Must Indicate the Following on the Written Prescription OR Communicate Orally
Alabama	√		√	√	Sign the prescription signature line labeled "May not Substitute" or "Dispense as Written".
Alaska	√		√	√	In the physician's handwriting, the words "Brand Medically Necessary" must appear on the prescription.
Arizona	√		√	√	Clearly display on the prescription "DAW" or other wording indicative of Substitution not Permitted.
Arkansas	√		√	√	In the physician's handwriting, indicate that the product ordered should not be substituted.
California	√		√	√	In the physician's handwriting, the words "Do not substitute" must appear on the prescription.
Colorado	√		√	√	In the physician's handwriting, the words "Dispense as Written" must appear on the prescription.
Connecticut	√		√	√	In the physician's handwriting, indicate that the product ordered should not be substituted.
Delaware	√		√	√	Sign the prescription signature line labeled "May not Substitute" or "Dispense as Written".
Florida		√	√	√	In the physician's handwriting, the words "Medically Necessary" must appear on the prescription.
Georgia	√		√	√	In the physician's handwriting, the words "Brand Necessary" must appear on the prescription.
Hawaii		√	√	√	In the physician's handwriting, the words "Brand Medically Necessary" must appear on the prescription. Mandates Brand Only for Anticonvulsant Medications.
Idaho	√		√	√	Physician must indicate "Brand Only" by checking the "Brand Only" box on the prescription.
Illinois	√		√	√	Sign the prescription signature line labeled "May not Substitute" or "Dispense as Written".
Indiana	√		√	√	Sign the prescription signature line labeled "May not Substitute" or "Dispense as Written".
Iowa	√		√	√	Physician shall communicate to Pharmacist that product should not be substituted.
Kansas	√		√	√	In the physician's handwriting, the words "Dispense as Written" must appear on the prescription.
Kentucky		√	√	√	In the physician's handwriting, the words "Do not substitute" must appear on the prescription.
Louisiana	√		√	√	Physician must indicate "Brand Only" by checking the "Dispense as Written or DAW" box on the prescription.
Maine		√		√	In the physician's handwriting, the words "Dispense as Written", "DAW", "Brand", or "Brand Neccessary" must appear on the prescription.
Maryland	√		√	√	Physician shall communicate to Pharmacist that product should not be substituted.
Massachusetts		√		√	In the physician's handwriting, the words "No substitution" must appear on the prescription.
Michigan	√		√	√	In the physician's handwriting, the words "Dispense as Written" or "DAW" must appear on the prescription.
Minnesota		√	√	√	In the physician's handwriting, the words "Dispense as Written" or "DAW" must appear on the prescription.
Mississippi	√		√	√	Physician shall communicate to Pharmacist that product should not be substituted.
Missouri	√		√	√	Sign the prescription signature line labeled "May not Substitute" or "Dispense as Written".
Montana	√		√	√	In the physician's handwriting, the words "Brand Medically Necessary" must appear on the prescription.
Nebraska	√		√	√	In the physician's handwriting, the words "Dispense as Written", "DAW" or similar statements must appear on the prescription.
Nevada		√	√	√	In the physician's handwriting, the words "Dispense as Written" must appear on the prescription.
New Hampshire	√		√	√	Physician must specify that the Brand is Medically Necessary.
New Jersey		√	√	√	Physician must initial next to the option "Do not Substitute" on the prescription.
New Mexico	√		√	√	In the physician's handwriting, the words "No substitution" or "No sub" must appear on the prescription.
New York		√		√	In the physician's handwriting, "DAW" must appear on the prescription.
North Carolina	√		√	√	Sign the prescription signature line labeled "May not Substitute" or "Dispense as Written". Narrow Therapeutic Range Drugs must be dispensed as originally prescribed.
North Dakota	√		√	√	In the physician's handwriting, the words "Brand Necessary" must appear on the prescription.
Ohio	√		√	√	In the physician's handwriting, the words "Dispense as Written" or "DAW" must appear on the prescription.
Oklahoma	√		√	√	Physician shall communicate to Pharmacist that product should not be substituted.
Oregon	√		√	√	In the physician's handwriting, the words "No substitution" or "N.S" must appear on the prescription.
Pennsylvania	√		√	√	Physician shall communicate to Pharmacist that product should not be substituted.
Rhode Island		√	√	√	In the physician's handwriting, the words "Dispense as Brand Name Necessary" must appear on the prescription.
South Carolina	√		√	√	Sign the prescription signature line labeled "May not Substitute" or "Dispense as Written".
South Dakota	√		√	√	In the physician's handwriting, the words "Brand Necessary" must appear on the prescription.
Tennessee		√	√	√	In the physician's handwriting, the words "Dispense as Written", "DAW", or other language of intent must appear on the prescription.
Texas	√		√	√	In the physician's handwriting, the words "Brand Necessary" or "Brand Medically Necessary" must appear on the prescription.
Utah	√		√	√	Sign the prescription signature line labeled "May not Substitute" or "Dispense as Written" OR in the physician's handwriting, the words "Dispense as Written" must appear on the prescription.
Vermont		√	√	√	In the physician's handwriting, the words "Brand Necessary" or "No substitution" must appear on the prescription.
Virginia	√		√	√	In the physician's handwriting, the words "Brand Necessary" must appear on the prescription.
Washington		√	√	√	Sign the prescription signature line labeled "May not Substitute" or "Dispense as Written".
West Virginia		√	√	√	In the physician's handwriting, the words "Brand Medically Necessary" must appear on the prescription.
Wisconsin	√		√	√	In the physician's handwriting, the words "No substitutions" or "N.S" must appear on the prescription.
Wyoming	√		√	√	In the physician's handwriting, the words "Brand Medically Necessary" must appear on the prescription.

Submitted on: 04/25/07
Reviewed by: Steven C. Schachter, MD

Medicaid's rules concerning generic substitutions for anticonvulsant medications (AEDs) are presented in this chart. Where indicated, a state has a Preferred Drug List (PDL) that includes AEDs. Where known, any AEDs that are not on the PDL for a state are listed. Some AEDs require Prior Approval (PA) before Medicaid will cover their use. Approval must be requested by the prescribing physician. Please read the "Unique Medicaid Features" column carefully for your state. Any questions should be directed to those authorities.

Submitted on: 04/25/07
Reviewed by: Steven C. Schachter, MD

Powepoint Presentation : Generic and Brand Name AEDs – Considerations for Clinicians. To save the presentation to your computer, Right Click and choose Save Target as...

Generic and Brand Name AEDs – Considerations for Clinicians Powerpoint Presentation

Background

In 1984, the Hatch-Waxman Act gave generic drug companies greater access to the market for prescription drugs and gave innovator companies greater patent life for branded products. The patent gives a company the sole right to sell the drug while the patent is in effect. When patents or other periods of exclusivity expire, manufacturers can apply to the Food and Drug Administration (FDA) to sell generic versions of the drug. In order to market a generic product, companies must submit an abbreviated new drug application (ANDA) to the FDA. The ANDA process does not require the generic drug manufacturer to repeat costly animal and clinical research on ingredients or dosage forms already approved for safety and effectiveness, thereby reducing the costs associated with generics. This process applies to drugs that were first marketed after 1962. ¹

Reduction of Healthcare Costs and the Regulatory Process

Payers, including the government, and formularies, need to reduce healthcare costs. The U.S. Congressional Budget Office estimates that generic drugs save consumers $8 - $10/ million a year at retail pharmacies. ¹ These savings are particularly important for seniors who are on a fixed income. The ANDA process allows manufacturers to sell generic formulations at a lower price than brand name medications. To continue to lower costs, the FDA has pledged to continue to make the generic drug approval process more efficient.

In order to obtain FDA approval, a generic drug must contain the same active ingredients as the innovator drug, though inactive ingredients may vary. The generic formulation must be identical in strength, dosage form, and route of administration and must have the same use indications as the original marketed drug. The generic drug must be bioequivalent to the innovator drug; meet the same batch requirements for identity, strength, purity, and quality; and must be manufactured under the same strict standards required for innovator products.

Regulatory Process for Generics in US

Bioequivalence

A generic drug can substitute for the brand name drug if it has been shown to be bioequivalent to the brand name drug. Two formulations of the same drug are claimed bioequivalent if the ratio of the mean of the primary pharmacokinetic parameters, AUC (amount of drug absorbed) and Cmax (rate of absorption), is within 80% - 125%, with 90% assurance. The FDA, however, does not indicate that a generic drug can be substituted by another generic drug, even though both of the generic drugs have been shown to be bioequivalent to the same brand name drug. Bioequivalence studies are generally performed on a limited number of healthy volunteers, and not on patients. Further, doses used in these studies may not yield clinically relevant ranges of serum concentrations of the drug. Specifically, the bioequivalence of antiepileptic drug generics are not tested on patients with epilepsy. ² And bioequivalence does not guarantee that a generic will produce the same therapeutic effect or result in the same adverse effects as the branded drug.

Issues for Generics Specific to Epilepsy

The characteristics of epilepsy and the potential serious ramifications of therapy failure must be considered. Epilepsy is not like other medical conditions, such as elevated cholesterol, because of the seriousness of seizure events. Epilepsy patients are particularly vulnerable to the disadvantages of generic products, since slight deviations in the serum concentrations of AEDs can be the difference between keeping a patient seizure free and the occurrence of a breakthrough seizure. A breakthrough seizure after a long remission can have significant psychosocial and physical consequences for the epilepsy patient in areas of life such as employment and driving, and could lead to injury.

Antiepileptic drugs have a high potential for central nervous system-related adverse events. This is usually related to the serum concentration of the drug. Some AEDs have narrow a therapeutic index, which is defined by the FDA as less than a two-fold difference between the minimum toxic concentration and the minimum effective concentration. Carbamazepine, phenytoin, and sodium valproate in particular have narrow therapeutic indices. Individual patients may have an even narrower difference between efficacy and toxicity.

The rate and extent of absorption or bioavailability often differs between different generic versions of branded products, and each differs from the branded formulation itself. Changes in the bioavailability of an AED in a particular patient can have serious effects for that patient. For example, a slight increase in phenytoin bioavailability can lead to a marked increase in serum level and thus to adverse effects, especially when the level is more than 15/mg/L. 3

Titration is particularly important when treating a patient with AEDs. Management regimens may become very complex, with titration sometimes taking weeks in order to avoid adverse effects. Patients need their medication to be consistent during titration so that prescribed changes of dose have predictable consequences. During the titration period, if there is a switch to a generic or if one generic is changed to another when a prescription is refilled, there is a potential for a change in seizure control. In addition, AEDs must be managed to account for drug interactions with other medications, such as hormonal contraceptives. A change in serum concentration of one drug may lead to changes in serum concentrations of co-medications.

Generics are susceptible to changes over time. Excipients and colorants used in generic products may differ from the brand, potentially causing problems. In 2000, there were more than 26 different generic preparations for five brand name AEDs, with multiple suppliers and formulations. ³ Pharmacies may change supplier depending on price and availability. For reasons discussed above, it is desirable for physicians to be able to use a single-source generic during initiation, titration, and maintenance of AED therapy; however, patients and physicians generally do not have any indication of a change from one refill to another unless they specifically ask. Patients can also become confused by changes in their medication. Generic names are not as easy to remember, spell, or pronounce as branded names. In addition, generic products usually differ in appearance from the brand and from other generic versions of the same product.

Generics are substituted for branded medicines as a cost-saving measure. Yet the savings associated with a generic may be offset by costs associated with office visits, lab tests, emergency room visits, or hospitalizations when the generic provokes seizures or adverse effects.

Clinical Experience and the Literature

There is a paucity of literature comparing generic substitutions to AEDs. Most papers are case reports, case series, or letters to the editor; and the majority concern carbamazepine, phenytoin, and valproate. These reports document breakthrough seizures or adverse events when switching from a branded AED to a generic. The reports are both anecdotal and retrospective. In a survey of neurologists, 56% of 301 respondents reported adverse events, and 68% reported breakthrough seizures in at least one patient switched from a branded to a generic AED. ⁴ Burkhardt et al identified eight adult patients whose seizures were worsened after switching from branded phenytoin to generic phenytoin. ⁵ For patients taking branded PHT, the mean total PHT concentration was 17.7 + 5.3 mg/L. Following a change to generic PHT, it was 12.5 + 2.7 mg/L. Following a switch back to the branded PHT, it was 17.8 + 3.9 mg/L. The authors concluded that brand and generic PHT do not yield equivalent concentrations in some patients.

The few blinded, controlled studies reported in the literature have evaluated relative pharmacokinetics of a brand vs generic formulation. In these trials, only one generic version was studied. No controlled studies have mirrored clinical practice by evaluating safety, efficacy, and compliance with the therapeutic regimen when multiple generic versions are used in succession.

Professional Societies Recommendations

The American Academy of Neurology (AAN) has a number of recommendations regarding generic substitution for AEDs: ⁶

• such substitutions can be approved only if the safety and efficacy of treatment is not compromised
• specific pharmacokinetic information about each AED generic should be made available to physician, and they should avoid switching between formulations of AEDs
• labeling should identify specific manufacturers and pharmacists should be required to inform patients and physicians when switching a patient between manufacturers
• organizations that encourage or mandate substitution of AEDs should evaluate their responsibility for problems arising from their policies.

The Academy recognized that further research on the impact of generic substitution is required.

Like the AAN, the Epilepsy Foundation (EF) is seriously concerned about mandatory substitution of a generic AED without prior approval of the patient and treating physician.⁷ Because changing from one formulation of an AED to another can usually be accomplished, and risks minimized, if physicians and patients monitor blood levels, seizures, and toxicity, the EF maintains that the individual and physician should be notified and give their consent before a switch in medications is made, whether it involves generic substitution for brand name products, or generic to generic substitutions.