1. Switching to Generic Antiepileptic Drugs (AEDs)
Mitra Habibi, PharmD
Clinical Pharmacist, Clinical Assistant Professor
College of Pharmacy
University of Illinois at Chicago

2. Antiepileptic Drugs (AEDs)
The first AED, Phenobarbital was discovered in 1912
Since then >20 more AEDs have been approved
The brand name – the name given to the new drug by the manufacturer
The generic name – the chemical name for that specific drug

3. Brand Drugs
Once a drug is discovered, the manufacturer gets patent protection from the Food and Drug Administration (FDA) for about 20 years
Usually takes about 6-7 years for a drug to reach the market
Studies to check how the drug works in the body
making sure the drug is safe and effective in treating seizures
The remaining years, no generic company can make the drug
Currently, all AEDs approved before 2005 are available in generic form

4. Antiepileptic Drugs Felbamate 1993 Phenobarbital 1912 Gabapentin 1994
Phenytoin 1938
Primidone 1954
Ethosuximdie 1960
Carbamazepine 1974
Clonazepam 1975
Valproic acid 1978
Felbamate 1993
Gabapentin 1994
Lamotrigine 1994
Topiramate 1996
Oxcarbazepine 1999
Levetiracetam 1999
Zonisamide 2000
Pregabalin 2005
Lacosamide 2008
Rufinamide 2008
Vigabatrin 2009
Ezogabine 2010
Clobazam 2011
Perampanel 2012
Eslicarbazepine 2013
Brivaracetam 2016

5. Brand Drugs Once the patent protection for a brand drug expires
Other companies can apply to get permission from the FDA to make/sell the generic form of the drug
These companies do not need to repeat all the initial animal and human/patient studies that the original company had to complete to show safety/efficacy of the drug
Significantly decreasing the cost of making generic medications
As a result, generic drugs are sold at a lower price compared to brand, decreasing overall cost

6. Brand drugs
In order to get FDA approval to bring generic form of the drug to the market, the generic drug company must show that their generic form:
Has the same active material as the brand drug
The inactive material can be different (color/taste/form)
Be identical in strength
to have the same amount of drug, for example: 100mg tablets
Have the same dosage form (tablets, capsules, etc.)
The same administration (be taken by mouth or given by injections)

7. Generic Drugs In addition: The generic drug should:
Have the same use (example: partial seizures)
Be manufactured under the same standards
Tested in a group of healthy volunteers to show no significant difference in
Maximum blood level between the brand and generic forms of the drug
Total amount of drug absorbed by the body

8. Generic Drugs Concerns about switching brand/generic AEDs
Not enough drug absorbed, possible loss of seizure control
Too much drug absorbed, experiencing side effects

9. Generic AEDs
Researches have checked to see if there are significant differences
Reviewed > 83,000 patients taking generic AEDs
Reviewed type of generic form filled at previous month
Compared to generic form filled ~ 3 months earlier
Reviewed if both AEDs were from the same generic company or not
Looked for increased risk of having seizures
Found out no additional risk for seizures with generic drugs
even if AEDs were switched to different generic company
Kesselheim et al., Neurology 2016;87:

10. Generic AEDs Other examples:
Researches have compared lamictal (lamotrigine)
Differences in brand lamictal versus generic lamotrigine
Differences between two different generic forms of lamotrigine
Patients in many different centers across U.S. were tested
Patients had similar blood levels, similar total drug absorption
overall difference of <3% which was not significant
Ting et al., Epilepsia 2015;56:
Privitera et al., Lanct Neurol 2016;15:

11. Generic AEDs
Other researchers have also looked at differences in AED blood levels in individual patients for
Topiramate (Topamax), levetiracetam (Keppra), Lamotrigine (Lamictal)
Noticed day-to-day differences in blood levels even if patient had remained on the same brand product
Concluded that these differences in blood levels may not be related to brand-generic substitution
Contin M, et al., Epilepsy Research 122:79-83

12. Generic AEDs Important to note that:
Some AEDs more sensitive to dose changes and subsequent blood levels
Phenytoin – complex metabolism (small changes in dose results in significant changes in blood level)
Carbamazepine – variable absorption with different formulations
There is also the issue of patient “outliers”

13. Generic drugs
Pharmacies can change generic suppliers depending on cost and/or which generic drug is available
Brand medications are substituted for generic forms as a cost- saving measure
Insurance companies in general will not approve brand version if generic form available
If offered, the co-pay cost may be substantially higher for patients
This practice will continue

14. Generic AEDs Some issues:
May cause concerns in patients (am I going to have more seizures?, am I going to have side effects?)
If switched between different generic companies, may cause confusion
Looking different (shape, size, color)
However, the investigations in switching brand to generic AEDs shown to be safe
Resulting in similar medication absorption and blood levels

15. Generic AEDs Tell your physician if you notice any difference
Ideal situation
To remain on the same product/generic company
Tell your physician if you notice any difference
Most concerns can be addressed by monitoring patients closely and adjusting the dose based on:
changes in blood levels, changes in seizure frequency