- Clobazam (e.g. Onfi, Sympazan) - November 28, 2023 - The FDA released a drug safety communication warning that in rare cases clobazam can cause Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). DRESS is a rare but serious reaction that can be life-threatening if not diagnosed and treated quickly. The current FDA labeling for clobazam does not include mention of DRESS, although it does include risk of similar symptoms in subsection 5.6 Serious Dermatological Reactions. The FDA is now requiring manufacturers to add information about DRESS to both the Prescribing Information and the Medication Guide (details of the exact content are not currently available).
- Levetiracetam (e.g. Keppra, Spritam) - November 28, 2023 - The FDA released a drug safety communication warning that in rare cases levetiracetam can cause Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). DRESS is a rare but serious reaction that can be life-threatening if not diagnosed and treated quickly. Subsection 5.5, of the Warnings and Precautions from the current FDA Prescribing Information includes information about the risk of symptoms similar to those of DRESS and subsection 6.2, Post Marketing Experience, does include mention of DRESS among a list of other adverse reactions identified post-approval. The FDA is now requiring manufacturers to add new warnings about DRESS to both the Prescribing Information and the Medication Guide (details of the exact content are not currently available).
- Levetiracetam (Keppra®) - August 17, 2023 - The FDA approved updates to the Prescribing Information (PI). The updates are to Section 6, Adverse Reactions: Section 6.2 Post marketing Experience: The following were added to the list of adverse reactions reported in patients receiving Keppra worldwide: “obsessive-compulsive disorders (OCD)” and “worsening of seizures including in patients with SCN8A mutations.”
- July 26, 2023 - The World Health Organization Committee on Essential Medicines has updated the core list of essential medicines to include levetiracetam and remove phenytoin. Essential medicines are those that satisfy the priority healthcare needs of a population. They are selected with due regard to disease prevalence and public health relevance, evidence of efficacy and safety, and comparative cost-effectiveness. Full details of the Expert Committee’s recommendations, describing the additions, changes and removal of medicines, and decisions not to recommend medicines are available in the executive summary.
- Felbatol (Felbamate) - June 12, 2023 - Felbamate oral suspension and tablets have been discontinued by Mylan Specialty, a Viatris Company, which is one of seven manufacturers of felbamate. Brand Felbatol continues to be available. Difficulties obtaining certain generic felbamate products have been reported by some patients and advocacy groups, and the impact of the discontinuation on existing shortages is not known at this time.
- Ganaxolone (Ztalmy®)- June 23, 2023 - The FDA updated the Prescribing Information (PI) with information on the use of Ztalmy® in patients with hepatic impairment. The PI was updated with new sections: Section 2.3: Dosage for Patients with Severe Hepatic Impairment and Section 8.6: Hepatic Impairment, which provide information on dosage adjustments during titration and maintenance for patients with severe hepatic impairment. Section 12.3 Pharmacokinetics, Specific Populations, Patients with hepatic impairment was also updated.
- Brivaracetam (Briviact) - May 17, 2023 - The FDA approved updates to the Prescribing Information (PI). The updates are to Section 8, Use in Specific Populations: Section 8.1 Pregnancy: The risk summary was updated from "no data available" to "insufficient to identify a risk of major birth defects, miscarriage, or other maternal or fetal outcomes associated with Brivaracetam use during pregnancy." Section 8.2 Lactation: The risk summary was updated from "no data available" to "brivaracetam is present in human milk. There is insufficient information on effects in breastfed infant or on milk production."
- Lacosamide (Motpoly XR) – May 4, 2023 - The FDA approved a new drug application for Lacosamide (Motpoly XR) extended-release capsules, 100 mg, 150 mg, and 200 mg for the treatment of partial-onset seizures in adults and in pediatric patients weighing at least 50 kg. As specified in the Prescribing Information (PI), the recommended dose range is 200 to 400 mg given once daily. AES Treatments Committee Note: In 2017, the International League Against Epilepsy (ILAE) revised the operational classification of seizure types. The current terminology for ‘partial-onset seizure’ is ‘focal seizure’.
- Topiramate (Topamax®) – May 3, 2023 – The FDA approved Prescribing Information (PI) updates to add progestin-only contraceptives to Subsection 7.4, Contraceptives under Section 7, Drug Interactions. The updated subsection reads: “The possibility of decreased contraceptive efficacy and increased breakthrough bleeding may occur in patients taking contraceptive products with Topamax®. Patients taking estrogen-containing or progestin-only contraceptives should be asked to report any change in their bleeding patterns. Contraceptive efficacy can be decreased even in the absence of breakthrough bleeding [see Clinical Pharmacology (12.3)].”
- Lacosamide (Vimpat®) – April 28, 2023 – The FDA approved Prescribing Information (PI) updates, described in the approval letter as related to the “use of alternate initial dosing (loading dose) for initiation of lacosamide treatment in partial onset seizure patients ≥1month to <17 years of age and in primary generalized tonic-clonic seizure patients ≥4 to <17 years, across all formulations.” Details are found in the updated PI, Dosage and Administration [Section 2], in Subsection 2.1, Table 1, and in particular in the newly added Subsection 2.2, Alternate Initial Dosage Information to Achieve the Maintenance Dosage in a Shorter Timeframe, and in the related Table 2.
In addition, updates related to loading dose and pediatric indications were made to Warnings and Precautions [Section 5], Adverse Reactions [Section 6], Use in Specific Populations, [Section 8, Subsections 8.6 and 8.7] related to renal impairment and hepatic impairment, and the Medication Guide [Section 17].
- Fenfluramine hydrochloride (Fintepla®) oral solution – April 17, 2023 – The Prescribing Information (PI) has been updated to remove Section 9 Drug Abuse and Dependence. Fintepla oral solution is no longer subject to the Controlled Substance Act (CSA) based on a December 2022 DEA Final Rule that removes fenfluramine from the schedules of the controlled substance act. The manufacturer is beginning the process of updating the compendia in states where they hold licensure. Once this process is completed, in most cases prescribers will be able to write a prescription for a full year's supply, versus the current limitation of six months, although the Fintepla Risk Evaluation and Mitigation Strategies (REMS) Program still requires cardiac monitoring via echocardiogram and cardiovascular status assessments every six months.
- Carbamazepine (Carbatrol®) – April 11, 2023 – The FDA updated the Prescribing Information (PI) to add hyperammonemia to Adverse Reactions, under the Metabolism subsection which now reads, “Metabolism: Fever and chills, decreased levels of plasma calcium leading to osteoporosis, and hyperammonemia have been reported.” Additional PI updates to the Warnings and Precautions, Adverse Reactions, Drug Interactions, and Use in Specific Populations sections, as well as the addition of a Medication Guide, were based on approved labeling of the listed drug, Tegretol®, the PI for which was last updated March 20, 2018.
- Divalproex sodium (Depakote) - February 24, 2023 – The FDA approved revisions to Drug Interactions [Section 7] in the Prescribing information (PI) to include interactions with methotrexate and cannabidiol. Revisions include:
Methotrexate was added in Effects of Co-Administered Drugs on Valproate Clearance [Subsection 7.1] under the heading, Drugs for which a potentially important interaction has been observed: Methotrexate may decrease serum valproate levels and potentially result in increased frequency of seizures or bipolar symptoms. Prescribers should monitor serum valproate concentrations and clinical response when adding or discontinuing methotrexate and adjust valproate dosage, if necessary.
Cannabidiol was added in a new subsection [7.4]: Concomitant administration of valproate and cannabidiol has been associated with an increased risk of ALT and/or AST elevation. This has been manageable by dose reduction or, in more severe cases, by discontinuation of one or both drugs. Liver function, including serum transaminase and total bilirubin levels, should be monitored during concomitant treatment [see Warnings and Precautions (5.1)].
The Drug Interactions PI updates were made for extended-release oral tablets, delayed-release oral tablets, and delayed-release capsule formulations of divalproex sodium. The referenced extensive updates to the Medication Guide are included only in the PI for the extended-release oral tablet formulation, where all three formulations are listed.
- Benzodiazepine class – January 13, 2023 – The FDA approved Prescribing Information (PI) updates related to use of all benzodiazepines in the class during late pregnancy and breastfeeding. See the updated PI for clobazam as one example of the changes made to Warnings and Precautions [Section 5] and Use in Specific Populations [Section 8], as well as corresponding updates to Patient Counseling Information [Section 17] and the Medication Guide. New risk summaries and clinical considerations information include:
Use of benzodiazepines late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in newborns.
Pregnant females should be advised of the risks, be asked to inform their healthcare provider if they become pregnant and be encouraged to enroll voluntarily in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant while on a benzodiazepine.
Breastfeeding patients should be advised to inform their healthcare providers of the use of benzodiazepines and should be instructed to monitor their infants for excessive sedation, poor feeding, and poor weight gain, and to seek medical attention if they notice these signs.