Untoward Effects of Generic Carbamazepine Therapy

Comparative Bioavailability of a Generic Phenytoin and Dilantin

“…Four "well-known published reports of clinical non-equivalence with breakthrough seizures or increased seizure frequency upon generic substitution" were cited. Three were letters to the editor or other nonrefereed communications (Mac-Donald, 1987;Koch and Allen, 1987;Sachdeo and Belendiuk, 1987). Serum levels were not available for two reports (MacDonald, 1987;Sachdeo and Belendiuk, 1987), and the third report showed remarkable wide swings that suggested the possibility of noncompliance (Koch and Allen, 1987).…”

“…Three were letters to the editor or other nonrefereed communications (Mac-Donald, 1987;Koch and Allen, 1987;Sachdeo and Belendiuk, 1987). Serum levels were not available for two reports (MacDonald, 1987;Sachdeo and Belendiuk, 1987), and the third report showed remarkable wide swings that suggested the possibility of noncompliance (Koch and Allen, 1987). The fourth report was an article describing a "therapeutic failure" of generic primidone (PRM) (Wyllie et al, 1987).…”

Comparative Bioavailability of a Generic Phenytoin and Dilantin

“…Four "well-known published reports of clinical non-equivalence with breakthrough seizures or increased seizure frequency upon generic substitution" were cited. Three were letters to the editor or other nonrefereed communications (Mac-Donald, 1987;Koch and Allen, 1987;Sachdeo and Belendiuk, 1987). Serum levels were not available for two reports (MacDonald, 1987;Sachdeo and Belendiuk, 1987), and the third report showed remarkable wide swings that suggested the possibility of noncompliance (Koch and Allen, 1987).…”

“…Three were letters to the editor or other nonrefereed communications (Mac-Donald, 1987;Koch and Allen, 1987;Sachdeo and Belendiuk, 1987). Serum levels were not available for two reports (MacDonald, 1987;Sachdeo and Belendiuk, 1987), and the third report showed remarkable wide swings that suggested the possibility of noncompliance (Koch and Allen, 1987). The fourth report was an article describing a "therapeutic failure" of generic primidone (PRM) (Wyllie et al, 1987).…”

Ionic Liquids: New Forms of Active Pharmaceutical Ingredients with Unique, Tunable Properties

“…The existence of polymorphs also results in Intellectual Property (IP) protection challenges, as the synthesis of a new polymorph is a valid reason to obtain patent protection. For example, several clinical failures were reported for carbamazepine due to different polymorphs of the branded and generic drug, , and for which crystal engineering studies found as many as 13 new crystalline phases . The pharmacokinetics and cognitive-enhancing nootropic activity of the drug latrepirdine (Dimebon), that exists in 6 polymorphic forms, demonstrated that only one of the latrepirdine polymorphs showed significant nootropic activity, while five other patent-protected polymorphs did not provide any statistically significant therapeutic effect .…”

Therapeutic Basis of Generic Substitution of Antiseizure Medications

“…Specifically, the AUC and C max of generic ASMs are only required to be within a range of 80% to 125%. However, at a C max of 81% of the normal therapeutic range, doses that are too low may result in breakthrough seizures and failure of ASM therapy, resulting in an increase in the frequency of seizures (Atif et al, 2016;Hartley et al, 1990Hartley et al, , 1991Jain, 1993;Koch and Allen, 1987;Meyer et al, 1992;Sachdeo and Belendiuk, 1987;Welty et al, 1992). In fact, twothirds of physicians report that they have treated a patient who experienced a breakthrough seizure after switching from a brand-name ASM to a generic Fitzgerald and Jacobson, 2011;Guberman and Corman, 2000;Wilner, 2004).…”

Comparative Bioavailability of a Generic Phenytoin and Dilantin

“…Four "well-known published reports of clinical non-equivalence with breakthrough seizures or increased seizure frequency upon generic substitution" were cited. Three were letters to the editor or other nonrefereed communications (Mac-Donald, 1987;Koch and Allen, 1987;Sachdeo and Belendiuk, 1987). Serum levels were not available for two reports (MacDonald, 1987;Sachdeo and Belendiuk, 1987), and the third report showed remarkable wide swings that suggested the possibility of noncompliance (Koch and Allen, 1987).…”

“…Three were letters to the editor or other nonrefereed communications (Mac-Donald, 1987;Koch and Allen, 1987;Sachdeo and Belendiuk, 1987). Serum levels were not available for two reports (MacDonald, 1987;Sachdeo and Belendiuk, 1987), and the third report showed remarkable wide swings that suggested the possibility of noncompliance (Koch and Allen, 1987). The fourth report was an article describing a "therapeutic failure" of generic primidone (PRM) (Wyllie et al, 1987).…”

Ionic Liquids: New Forms of Active Pharmaceutical Ingredients with Unique, Tunable Properties

“…The existence of polymorphs also results in Intellectual Property (IP) protection challenges, as the synthesis of a new polymorph is a valid reason to obtain patent protection. For example, several clinical failures were reported for carbamazepine due to different polymorphs of the branded and generic drug, , and for which crystal engineering studies found as many as 13 new crystalline phases . The pharmacokinetics and cognitive-enhancing nootropic activity of the drug latrepirdine (Dimebon), that exists in 6 polymorphic forms, demonstrated that only one of the latrepirdine polymorphs showed significant nootropic activity, while five other patent-protected polymorphs did not provide any statistically significant therapeutic effect .…”

Therapeutic Basis of Generic Substitution of Antiseizure Medications

“…Specifically, the AUC and C max of generic ASMs are only required to be within a range of 80% to 125%. However, at a C max of 81% of the normal therapeutic range, doses that are too low may result in breakthrough seizures and failure of ASM therapy, resulting in an increase in the frequency of seizures (Atif et al, 2016;Hartley et al, 1990Hartley et al, , 1991Jain, 1993;Koch and Allen, 1987;Meyer et al, 1992;Sachdeo and Belendiuk, 1987;Welty et al, 1992). In fact, twothirds of physicians report that they have treated a patient who experienced a breakthrough seizure after switching from a brand-name ASM to a generic Fitzgerald and Jacobson, 2011;Guberman and Corman, 2000;Wilner, 2004).…”

Comparative Bioavailability of a Generic Phenytoin and Dilantin

“…Four "well-known published reports of clinical non-equivalence with breakthrough seizures or increased seizure frequency upon generic substitution" were cited. Three were letters to the editor or other nonrefereed communications (Mac-Donald, 1987;Koch and Allen, 1987;Sachdeo and Belendiuk, 1987). Serum levels were not available for two reports (MacDonald, 1987;Sachdeo and Belendiuk, 1987), and the third report showed remarkable wide swings that suggested the possibility of noncompliance (Koch and Allen, 1987).…”

“…Three were letters to the editor or other nonrefereed communications (Mac-Donald, 1987;Koch and Allen, 1987;Sachdeo and Belendiuk, 1987). Serum levels were not available for two reports (MacDonald, 1987;Sachdeo and Belendiuk, 1987), and the third report showed remarkable wide swings that suggested the possibility of noncompliance (Koch and Allen, 1987). The fourth report was an article describing a "therapeutic failure" of generic primidone (PRM) (Wyllie et al, 1987).…”

Ionic Liquids: New Forms of Active Pharmaceutical Ingredients with Unique, Tunable Properties

“…The existence of polymorphs also results in Intellectual Property (IP) protection challenges, as the synthesis of a new polymorph is a valid reason to obtain patent protection. For example, several clinical failures were reported for carbamazepine due to different polymorphs of the branded and generic drug, , and for which crystal engineering studies found as many as 13 new crystalline phases . The pharmacokinetics and cognitive-enhancing nootropic activity of the drug latrepirdine (Dimebon), that exists in 6 polymorphic forms, demonstrated that only one of the latrepirdine polymorphs showed significant nootropic activity, while five other patent-protected polymorphs did not provide any statistically significant therapeutic effect .…”

Therapeutic Basis of Generic Substitution of Antiseizure Medications

“…Specifically, the AUC and C max of generic ASMs are only required to be within a range of 80% to 125%. However, at a C max of 81% of the normal therapeutic range, doses that are too low may result in breakthrough seizures and failure of ASM therapy, resulting in an increase in the frequency of seizures (Atif et al, 2016;Hartley et al, 1990Hartley et al, , 1991Jain, 1993;Koch and Allen, 1987;Meyer et al, 1992;Sachdeo and Belendiuk, 1987;Welty et al, 1992). In fact, twothirds of physicians report that they have treated a patient who experienced a breakthrough seizure after switching from a brand-name ASM to a generic Fitzgerald and Jacobson, 2011;Guberman and Corman, 2000;Wilner, 2004).…”