Drug News and FDA Alerts

Drug News and FDA Alerts by Year

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2021 FDA Alerts arrow_drop_down
  • April 16, 2021: Everolimus (Afinitor® and Afinitor/Disperz®) tablets for oral suspension – The FDA updated Prescribing Information to include a new Warning and Precaution: Radiation sensitization and recall, in some cases severe, involving cutaneous and visceral organs (including radiation esophagitis and pneumonitis) have been reported in patients treated with radiation prior to, during, or subsequent to Afinitor/Afinitor Disperz treatment. Updates include advice to monitor patients closely when the drug is administered during or sequentially with radiation treatment. Corresponding updates were made to PI sections on Adverse Reactions, Postmarketing Experience, Patient Counseling information, and Patient Information/Patient Package Insert.
  • March 31, 2021: Lamotrigine (Lamictal®) – FDA updated Prescribing Information Warnings and Precautions summary related to cardiac rhythm and conduction abnormalities: “Based on in vitro findings, Lamictal could cause serious arrhythmias and/or death in patients with certain underlying cardiac disorders or arrhythmias. Any expected or observed benefit of Lamictal in an individual patient with clinically important structural or functional heart disease must be carefully weighed against the risk for serious arrythmias and/or death for that patient.” This replaces the summary from an October 2020 PI update that read, “Avoid Lamictal in patients with underlying cardiac disorders or arrhythmias.”

    Along with the March 31, 2021 PI update, FDA issued and broadly distributed a Drug Safety Communication about lamotrigine. The communication summarized related concerns and announced that FDA will require postmarket safety studies to evaluate whether other sodium channel blockers in the same drug class, as listed in the communication, have similar effects on the heart. The communication advises, “...sodium channel blockers approved for epilepsy, bipolar disorder, and other indications should not be considered safer alternatives to lamotrigine in the absence of additional information.” Specific guidance for health care professionals is provided as well patient messaging that states in part, “Patients should not stop taking your medicine without first talking to your prescriber, because stopping lamotrigine can lead to uncontrolled seizures, or new or worsening mental health problems...”

    AES provided practical guidance for clinicians through a recorded March 11 webinar, Lamotrigine and the Heart, Cause for Concern? and a joint ILAE/AES advisory statement on cardiac effects of lamotrigine in Epilepsy Currents. AES will continue to keep members apprised of related news.
  • February 16, 2021: Phenytoin (Dilantin-125®) – FDA updated the Prescribing Information related to serious dermatologic reactions (severe cutaneous adverse reactions, or SCARs), drug interactions, and use in patients with decreased CYP2c9 function. Updates include the following additions to specific PI sections. Please refer to the full PI for context. 

Section 5.3, Serious Dermatologic Reactions (additions bolded below)

In addition, retrospective, case-control, genome-wide association studies in patients of southeast Asian ancestry have also identified an increased risk of SCARs in carriers of the decreased function CYP2C9*3 variant, which has also been associated with decreased clearance of phenytoin. Consider avoiding DILANTIN as an alternative to carbamazepine in patients who are positive for HLA-B*1502 or in CYP2C9*3 carriers [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.5)].

The use of HLA-B*1502 or CYP2C9 genotyping has important limitations and must never substitute for appropriate clinical vigilance and patient management. The role of other possible factors in the development of, and morbidity from, SJS/TEN, such as antiepileptic drug (AED) dose, compliance, concomitant medications, comorbidities, and the level of dermatologic monitoring have not been studied.

Section 7, Drug Interactions (additions underlined)

Phenytoin is extensively bound to plasma proteins and is prone to competitive displacement. Phenytoin is primarily metabolized by the hepatic cytochrome P450 enzyme CYP2C9 and to a lesser extent by CYP2C19 and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism. ...

Section 8, Use in Specific Populations, Subsection 8.7 Use in Patients with Decreased CYP2C9 Function (new subsection added)

Patients who are intermediate or poor metabolizers of CYP2C9 substrates (e.g., *1/*3, *2/*2, *3/*3) may exhibit increased phenytoin serum concentrations compared to patients who are normal metabolizers (e.g.,*1/*1). Thus, patients who are known to be intermediate or poor metabolizers may ultimately require lower doses of phenytoin to maintain similar steady-state concentrations compared to normal metabolizers. If early signs of dose-related central nervous system (CNS) toxicity develop, serum concentrations should be checked immediately [see Clinical Pharmacology (12.5)].

  • February 5, 2021: Benzodiazepines – clonazepam, diazepam, midazolam, lorazepam, and clobazam (various manufacturers and formulations); FDA announced updates to PI for benzodiazepines, including these used as antiseizure medications. Among the black-box safety warnings now included are:
    • Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death
    • Risk of abuse, misuse, and addiction, which can lead to overdose and death
    • Abrupt discontinuation or rapid dosage reduction after continued use may precipitate acute withdrawal reactions, which can be life-threatening
    As just one example, clobazam changes are detailed, with prominent black box warnings, in its PI and summarized in the corresponding label revision approval letter. Each drug can be searched in the Drugs@FDA database, with links to the PI and letter found for each specific manufacturer and formulation under the header, Approval Date(s) and History, Letters, Labels, Reviews.
  • January 29, 2021: FDA Safety Warning on the Cardiac Effects of LamotrigineAn Advisory from the Ad Hoc ILAE/AES Task Force – A preprint version of this joint ILAE/AES statement is provided here in advance of copublication in Epilepsia Open and Epilepsy Currents to assist AES members in managing clinical care and communications with patients about the October 9, 2020, new safety warning and prescribing information updates related to lamotrigine.
2020 FDA Alerts arrow_drop_down
  • 01/29/21 – FDA Safety Warning on the Cardiac Effects of Lamotrigine: An Advisory from the Ad Hoc ILAE/AES Task Force – A preprint version of this joint ILAE/AES statement is provided here, in advance of copublication in Epilepsia Open and Epilepsy Currents to assist AES members in managing clinical care and communications with patients about the October 9, 2020, new safety warning and prescribing information updates related to lamotrigine.
  • 10/09/20 - Lamotrigine (Lamictal®) – The FDA approved new Warnings and Precautions for the Prescribing Information (PI) regarding cardiac arrhythmias. In vitro testing showed that Lamictal exhibits Class IB antiarrhythmic activity at therapeutically relevant concentrations, so it could slow ventricular conduction (widen QRS) and induce proarrhythmia, including sudden death, in patients with structural heart disease or myocardial ischemia. Avoid the use of Lamictal in patients who have cardiac conduction disorders (i.e., second- or third-degree heart block), ventricular arrhythmias, or cardiac disease or abnormality (i.e., myocardial ischemia, heart failure, structural heart disease, Brugada syndrome, or other sodium channelopathies). Concomitant use of other sodium channel blockers may increase the risk of proarrhythmia. Related updates were made in other sections of the PI, including Pharmacodynamics and Patient Counseling, as well as the Medication Guide.
  • 10/05/20 - Midazolam (Nayzilam®) nasal spray – UCB, Inc. today notified health care professionals and AES of an anticipated temporary shortage of Nayzilam® (midazolam) nasal spray, C-IV, through the end of October 2020, due to a manufacturing delay unrelated to COVID-19. The company states, “UCB, Inc. is committed to restoring the supply of Nayzilam® as soon as possible. Patients or caregivers experiencing difficulty accessing Nayzilam® are encouraged to call ucbCARES® at +1-844-599-2273 for assistance.” As of this post, midazolam nasal spray does not yet appear among reported shortages on the FDA Drug Shortages website, although injectable midazolam is listed as “currently in shortage.”
  • 09/23/20 – Benzodiazepines – The FDA issued a Drug Safety Communication requiring Boxed Warning updates for all benzodiazepine medications to improve the safe use of this drug class and address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions. In addition to the Boxed Warning updates, FDA is requiring the addition of information to the Prescribing Information and Medication Guides for these medications (links are to general FDA lookup sites). The Drug Safety Communication provides details, rationale for the new requirements, and information for health professionals. FDA encourages patients and health care professionals to report side effects of benzodiazepines and other medications to the FDA MedWatch program.
  • 8/31/20 – Cenobamate (Xcopri®) tablets – FDA approved updated Prescribing Information that incorporates a March 10, 2020, Drug Enforcement Administration (DEA) scheduling determination. In an interim final rule, DEA placed cenobamate in schedule V of the Controlled Substances Act. SK Life Science, Inc. filed a supplemental new drug application with FDA on March 11, 2020, to add the final scheduling information to the PI. Additional details are in the FDA approval letter. The drug was initially approved November 21, 2019, with highlights of PI, pending the DEA scheduling determination (See related entry on this page)
  • 8/31/20 – Lamotrigine (Lamictal®) - FDA approved a GlaxoSmithKline supplemental new drug application to provide for addition of the following to the Adverse Reactions; Postmarketing Experience section of the Prescribing Information for several formulations of Lamictal (lamotrigine) tablets: “Renal and Urinary Disorders: Tubulointerstitial nephritis (has been reported alone and in association with uveitis).” Please see the approval letter and the PI for details.
  • 7/31/20 – Cannabidiol [CBD] (Epidiolex®) – The U.S. Food and Drug Administration (FDA) approved Epidiolex (cannabidiol) [CBD] oral solution for the treatment of seizures associated with tuberous sclerosis complex in patients one year of age and older. Epidiolex was previously approved for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome. See details in the updated prescribing information, the FDA approval letter, and an FDA press release
  • 6/26/20 – Fenfluramine (Fintepla®) – FDA announced approval of a new drug application from Zogenix, Inc. that provides for the use of Fintepla (fenfluramine), oral solution 2.5 mg per mL for the treatment of seizures associated with Dravet syndrome in patients 2 years of age and older, as specified in the Prescribing Information. The Medication Guide provides information for patients. The FDA approval letter notes that this drug has an orphan drug designation for this indication and is currently controlled in Schedule IV of the Controlled Substances Act. FDA will transmit a scheduling recommendation to the Drug Enforcement Administration (DEA), but the drug remains a controlled substance while DEA is making its final scheduling decision, at which time revisions to the PI, Medication Guide, and Instructions for Use will be required. In addition, physicians who prescribe, pharmacies that dispense, and patients who receive, fenfluramine (Fintepla) must be certified in the fenfluramine (Fintepla) Risk Evaluation and Mitigation Strategy (REMS) program, as detailed in the FDA approval letter.
  • 6/8/2020 – Topiramate (Topamax®) tablets and sprinkle capsules – FDA approved a supplemental new drug application from Janssen Pharmaceuticals that provides for the addition of serious skin reaction, Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), to the Warnings and Precautions and Patient Counseling Information sections of the Prescribing Information (PI) and to the Medication Guide. See details in the FDA approval letter and updated PI.
  • 05/19/2020 – Valproate – FDA-approved AbbVie supplement applications for revisions to labeling information to reflect new data pertaining to an increased risk of attention-deficit/hyperactivity disorder (ADHD) in children who were exposed to valproate in utero. In addition, Prescribing Information (PI) warning updates include additional descriptive information on birth defects, decreased IQ, and neurodevelopmental disorders following in utero exposure. FDA approval letters and the updated labeling information (PI) are linked from FDA pages for each form of the medication: Depakote (divalproex sodium) delayed-release tabletsDepakote sprinkle capsules (divalproex sodium delayed-release capsules)Depakote ER (divalproex sodium) extended-release tabletsDepakene (valproic acid) capsulesDepakene (valproic acid) oral solution, and Depacon (valproate sodium) injection. The PIs provide supporting data and specific information related to the updates (In each PI, see especially Section 5, Warnings and Precautions, and Section 8.1, Use in Specific Populations – Pregnancy).
  • 04/03/2020 – Levetiracetam Immediate-Release Oral Tablets, USP – FDA re-verified shortage status for various manufacturers. FDA first reported this drug as “Currently in Shortage” on 04/01/2019.
  • 04/02/2020 – Midazolam Injection, USP – FDA first reported status as “Currently in Shortage” with various manufacturers reporting “Demand Increase for the Drug,” one manufacturer reporting “On allocation,” and one manufacturer reporting “Limited supply. On allocation for 2020. Cannot supply market demand.” 
  • 4/1/2020 - Levetiracetam Extended-Release Oral Tablets, USP – FDA re-verified shortage status for various manufacturers. Recent manufacturer reports of potential shortages began 12/03/2019, and FDA first reported this drug as “Currently in Shortage” on 05/28/2019. 
  • 1/24/2020 - Vigabatrin (Sabril®) – The U.S. Food and Drug Administration (FDA) approved a supplemental new drug application from Lundbeck Pharmaceuticals, Deerfield, IL to provide for expanded use of Sabril to patients 2 years of age and older with refractory complex partial seizures (rCPS) and proposed modifications to the related risk evaluation and mitigation strategy (REMS). Previously indicated for Infantile Spasms, the added Sabril indication is for: “Refractory Complex Partial Seizures as adjunctive therapy in patients 2 years of age and older who have responded inadequately to several alternative treatments; SABRIL is not indicated as a first-line agent.” Details are in the updated Prescribing Information for Sabril, with additional information in the FDA approval letter.
  • 1/10/2020 – Diazepam (Valtoco®) nasal spray; FDA approved an application from Neuralis Inc. for a new dosage form (nasal spray) of diazepam, as noted on this page in the FDA-Approved Drugs database. Approved dosage levels are 5 mg, 7.5 mg, and 10 mg. The Prescribing Information provides additional details.
  • 1/10/20 - Recall of Lamotrigine Tablets USP, 100 mg, 100 Count Bottles – Taro Pharmaceuticals U.S.A., Inc. is voluntarily recalling one (1) lot of Lamotrigine 100 mg Tablets, Lot # 331771 (expiration date June 2021) in 100 count bottles, NDC 51672-4131-1 to the consumer level. This single lot of Lamotrigine 100 mg Tablets Lot #331771 (expiration date June 2021) was found to have been cross-contaminated with a small amount of another drug substance (Enalapril Maleate) used to manufacture another product at the same facility. Details and a product label photo are on the US Food and Drug Administration (FDA) page on the recall announcement, and the company press release on the recall provides additional information.
2019 FDA Alerts arrow_drop_down
  • 12/20/19 - The U.S. Food and Drug Administration (FDA) announced a recall of the LivaNova VNS Therapy SenTiva Generator due to an unintended reset error that causes the system to stop delivering VNS therapy. If device replacement is needed, there is a risk associated with additional surgery to replace the generator. LivaNova has received 14 reports of unexpected reset errors. 4 patients have required early revision surgery for failed devices. No deaths related to this issue have been reported. On July 31, 2019, LivaNova implemented additional mitigations and at this time, no reset errors have been observed since the implementation of these mitigations. These additional mitigations are currently under review by the FDA. The full FDA announcement provides details and recommended actions for providers and patients.
  • 12/19/19 - The U.S. Food & Drug Administration (FDA) issued a Drug Safety Communication warning that serious breathing difficulties may occur in patients using gabapentin (Neurontin, Gralise, Horizant) or pregabalin (Lyrica, Lyrica CR) who have respiratory risk factors. These include use of opioid pain medicines and other drugs that depress the central nervous system and conditions such as chronic obstructive pulmonary disease (COPD) that reduce lung function. The elderly are also at higher risk. An FDA portal on the safety communication links to additional details, including data on which the safety concern is based, advice for health care professionals and patients and caregivers, and where to report side effects. In addition to the safety communication, FDA is requiring that 1) new warnings about the risk of respiratory depression be added to the prescribing information of the gabapentinoids, and 2) drug manufacturers conduct clinical trials to further evaluate abuse potential of the gabapentinoids, particularly in combination with opioids, because misuse and abuse of these products together is increasing, and co-use may increase the risk of respiratory depression. Gabapentin and pregabalin are FDA-approved for a variety of conditions, including seizures, nerve pain, and restless legs syndrome. FDA announced in July 2019 the approval of the first pregabalin generics of Lyrica. 
  • 11/21/19 – The U.S. Food and Drug Administration (FDA) approved cenobamate tablets (Xcopri, SK Life Science Inc.) as a new treatment option for partial onset seizures in adults, based on two randomized controlled trials that established safety and efficacy. The FDA announcement was released November 21, and highlights of prescribing Information (PI) are dated 11/2019, pending DEA controlled substance scheduling. It is hoped that cenobamate (Xcopri) will be available in pharmacies shortly after scheduling has been completed.
  • 10/23/19 – The FDA approved a prescribing information (PI) change for Keppra® (levetiracetam). Previously approved only for adjunctive therapy, Keppra indications now include monotherapy for partial-onset seizures in patients 1 month of age and older. The updated PI includes related updates to information on dosing and discontinuation. Recommended dosing is the same for monotherapy and adjunctive therapy. The updated PI includes no change to Keppra indications for use only as adjunctive therapy in the treatment of myoclonic seizures in patients 12 years of age and older with juvenile myoclonic epilepsy (JME) and in the treatment of primary generalized tonic-clonic seizures (GTCS) in patients 6 years of age and older with idiopathic generalized epilepsy. See highlights of the updated PI.
  • 7/31/19 – The FDA approved addition of the following statement to section 5.4 (Warnings and Precautions; Neurotoxicity) of the Prescribing Information (PI) for Sabril (vigabatrin): "Intramyelinic edema (IME) has been reported in postmortem examination of infants being treated for IS with vigabatrin.” See details in the FDA letter of approval and the updated PI.
  • 7/22/19 - A July 22, 2019 announcement from the U.S. Food and Drug Administration, Center for Drug Evaluation and Research (FDA CDER) highlighted the July 19, 2019 approval of multiple applications of first generics of Lyrica (pregabalin) for indications that include “adjunctive therapy for the treatment of partial onset seizures in patients 17 years of age and older.” CDER Director, Janet Woodcock, MD, cited “FDA’s longstanding commitment to advance patient access to lower cost, high-quality generic medicines.” The announcement also summarizes patient Medication Guide warnings required to be dispensed with pregabalin. Details (dosage levels, manufacturers, and indications) about first-time generic drugs approved in 2019, including pregabalin, can be found at this FDA First Generic Drug Approvals 2019 page.
  • 5/17/19 - On May 17, 2019, the Food & Drug Administration approved Nayzilam (midazolam) intranasal spray for the treatment of seizure clusters and acute repetitive seizures that are distinct from the patient’s usual seizure pattern in patients with epilepsy 12 years of age and older. The prescribing information may be found here.
  • 2/26/19 Intravenous Levetiracetam distributed by Dr. Reddy’s Laboratories Inc. A labeling error incorrectly stating the product strength resulted in a Class I recall of 2770 i.v. bags of levetiracetam in 0.54% sodium chloride injection, 1500 mg/100 mL (15 mg/mL), distributed in the US by Dr. Reddy's Laboratories Inc. The February 20, 2019, FDA Enforcement Report states, "the preprinted text on the primary infusion bag and the NDC incorrectly identifies the product as levetiracetam in 0.75% sodium chloride (1000 mg/100 mL). However, the external foil pouch correctly identifies the product as levetiracetam in 0.54% sodium chloride injection (1500 mg/100 mL).” The recall affects bags manufactured by Gland Pharma Limited from lot ABD807 (Exp. 5/20). More here.
  • 2/26/19 - Lamictal (lamotrigine): Health Canada and the European Medicine Agency have recently issued 2 warnings regarding lamotrigine. First, Brugada-type ECG arrhythmogenic ST-T abnormalities and typical Brugada ECG pattern have been reported in patients treated with lamotrigine. The use of lamotrigine should be carefully considered in patients with Brugada syndrome. Second, lamotrigine also has been reported to pass into breast milk, resulting in lamotrigine plasma total levels in neonates and older infants of up to approximately 50% of the mother’s level. Therefore, in some breastfed infants, plasma concentrations of lamotrigine may reach levels at which pharmacological effects occur. The potential benefits of breastfeeding should be weighed against the potential risk of adverse effects occurring in the infant. Should a woman decide to breastfeed while on therapy with lamotrigine, the infant should be monitored for adverse effects, such as sedation, rash, and poor weight gain. More here
  • 1/17/19 - The FDA has cleared the Embrace watch for use in epilepsy patients ages 6 years and older. It was first approved in January 2018 for adults aged ≥ 21 years. The watch detects convulsive seizures by combing information from both electrodermal and accelerometry biosensors. When a seizure is detected, an automated alert can be sent to a caregiver, when the watch detects unusual patterns that may be associated with a convulsive seizure. Clinical trials have demonstrated accuracy rates greater than 95% for detecting generalized convulsive seizures. More here.
2018 FDA Alerts arrow_drop_down
  • 11/11/18 - The FDA approved new prescribing information for Vimpat (lacosamide). In addition to the previously known 0.4% risk of first-degree AV block (PR interval >200 msec) observed in preclinical trials, additional cardiac risks have been identified. "In the post-marketing setting, there have been reports of cardiac arrhythmias in patients treated with VIMPAT, including bradycardia, AV block, and ventricular tachyarrhythmia, which have rarely resulted in asystole, cardiac arrest, and death. Most, although not all, cases have occurred in patients with underlying proarrhythmic conditions, or in those taking concomitant medications that affect cardiac conduction or prolong the PR interval. These events have occurred with both oral and intravenous routes of administration and at prescribed doses as well as in the setting of overdose. Vimpat should be used with caution in patients with underlying proarrhythmic conditions such as known cardiac conduction problems (e.g., marked first-degree AV block, second-degree or higher AV block, and sick sinus syndrome without pacemaker), severe cardiac disease (such as myocardial ischemia or heart failure, or structural heart disease), and cardiac sodium channelopathies (e.g., Brugada Syndrome). VIMPAT should also be used with caution in patients on concomitant medications that affect cardiac conduction, including sodium channel blockers, beta-blockers, calcium channel blockers, potassium channel blockers, and medications that prolong the PR interval. The PI PDF is attached here.
  • 11/12/18 - The FDA approved new prescribing information (PI) for VIMPAT[BOLD], which now contains additional serious warnings about cardiac arrhythmias including ventricular arrhythmias. VIMPAT is indicated for the treatment of partial-onset seizures in patients 4 years of age and older. Additional information regarding the updated PI is located here.
  • 10/18/18 - The FDA approved new labeling for oral Dilantin [BOLD} (phenytoin) suspension. Section 5.6 of the Prescribing information indicates, "Cases of bradycardia and cardiac arrest have been reported in Dilantin-treated patients, both at recommended phenytoin doses and levels and in association with phenytoin toxicity. Most of the reports of cardiac arrest occurred in patients with underlying cardiac disease." It is important not to confuse this warning with the existing concerns for intravenous phenytoin or fosphenytoin. The updated labeling information is located here.
  • 9/1/2018 - The FDA has extended the labeling for Fycompa (perampanel). It is now indicated for the treatment of focal onset seizures with or without progression to bilateral tonic-clonic seizures in children as young as age 4 years. This indication includes both monotherapy and adjunctive therapy. The revised PI can be located here.
  • 8/20/18 - The FDA approved Diacomit (stiripentol) for the treatment of seizures associated with Dravet syndrome in persons 2 years of age and older. Diacomit is approved for use as an adjunct to clobazam, with which it has a drug-drug interaction. It is available as capsules or oral powder for suspension and is not scheduled. Prescribing information is located on the FDA CDER website here
  • 8/8/18 - The FDA has launched a new medication guide database to replace the current medication guide webpage. Features of the new database include active ingredient and brand name search for medication guides, download capabilities to CSV and Excel spreadsheets, streamlined data entry for faster database updates, and improved mobile device usability. Click here to view the new medication guide database.
  • 7/18/18 - The FDA updated the prescribing information (PI) for Lamictal (lamotrigine) to include the extremely rare occurrence of hemophagocytic lymphohistiocytosis in 8 cases worldwide since 1994. The revised PI states, "Hemophagocytic lymphohistiocytosis (HLH) has occurred in pediatric and adult patients taking Lamictal for various indications. HLH is a life-threatening syndrome of pathologic immune activation characterized by clinical signs and symptoms of extreme systemic inflammation. It is associated with high mortality rates if not recognized early and treated. Common findings include fever, hepatosplenomegaly, rash, lymphadenopathy, neurologic symptoms, cytopenias, high serum ferritin, and liver function and coagulation abnormalities. In cases of HLH reported with Lamictal, patients have presented with signs of systemic inflammation (fever, rash, hepatosplenomegaly, and organ system dysfunction) and blood dyscrasias. Symptoms have been reported to occur within 8 to 24 days following the initiation of treatment." Providers should review the new PI which provides further guidance on differential diagnosis and treatment. HLH has signs which may overlap with other diagnoses including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson syndrome, and toxic epidermal necrolysis. The July 2018 revised PI can be located here.
  • 6/25/2018 - The FDA approved Epidiolex (cannabidiol) for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients two years of age and older. This new antiepileptic drug will be available shortly after the Drug Enforcement Agency issues a scheduling determination 90 days after the FDA-approval date. Additional information is located here and the PI is here.
  • 5/10/2018 - The FDA approved an extension to the indication for Briviact (brivaracetam). Briviact is now indicated for the treatment of partial onset seizures in children four years of age and older, and in adults. The i.v. formulation is not approved for children ages four to 15 years. Additional information for download is located here.
  • 4/27/2018 - The FDA approved the Medtronic Deep Brain Stimulation (DBS) System for Epilepsy. The device delivers electrical pulses to a location inside the brain which is involved in seizures. The system consists of a pulse generator (IPG) implanted under the skin of the upper chest, and two leads implanted in the brain. The Medtronic DBS System for Epilepsy helps reduce the frequency of seizures in epilepsy patients who have frequent, disabling, partial-onset seizures and have not responded well to antiepileptic medications. Additional information is located here.
  • 4/25/2018 The FDA is providing health care providers with preliminary information concerning magnetic resonance (MR) thermometry reliability with magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) devices.

    The FDA is currently evaluating data, which suggests that potentially inaccurate MR thermometry information can be displayed during treatment. For example, MR parameters such as voxel size (measurement of the image resolution or detail) and MR image acquisition time (e.g., up to 8 seconds) may contribute to inaccurate MR thermometry readings and potential errors in the ablation assessment. In addition, MRgLITT devices may not account for the continued thermal spread of energy to the surrounding tissue (as the target ablation area returns to its baseline temperature), which may result in an underestimation of thermal damage.

    The FDA reviewed Medical Device Reports (MDRs) and literature reports which describe adverse events, such as neurological deficits (e.g., focal motor deficits, aphasia, cognitive changes), increased intracerebral edema or pressure, intracranial bleeding, and/or visual changes (e.g., visual field deficits, blurry vision) when these devices were used to treat intra-cranial lesions. Several of these reports note which events required urgent medical and/or surgical intervention, and may have been associated with patient deaths. However, it is unclear at this time, whether an inaccuracy of MR thermometry directly caused or contributed to these events. Additional information is located here
  • 4/25/2018 - The FDA has issued a new warning that the medication Lamictal (lamotrigine) for seizures and bipolar disorder can cause a rare, but very serious reaction that excessively activates the body’s infection-fighting immune system. This can cause severe inflammation throughout the body and lead to hospitalization and death, especially if the reaction is not diagnosed and treated quickly. As a result, the FDA is requiring a new warning about this risk be added to the prescribing information in the lamotrigine drug labels. Additional information is located here
  • 4/10/2018 - The FDA approved the use of Afinitor (everolimus) for the adjunctive treatment of adult and pediatric patients aged two years and older with tuberous sclerosis complex (TSC)-associated focal-onset seizures. Additional information is located here.
2017 FDA Alerts arrow_drop_down
  • 11/02/2017 - The FDA expanded the approval for Vimpat oral tablets and solution to include children. The approval is now for the treatment of partial-onset seizures in patients age 4 and older as monotherapy or adjunctive therapy. Vimpat injection remains approved for this indication only for patients 17 years and older. More information is available here.
  • 08/2017 - Health Canada updated the Keppra monograph to add warnings for pancytopenia and rhabdomyolysis and is available here. The risk of pancytopenia has been included in the warnings and precautions sections of the Canadian product monograph for Keppra (levetiracetam). The risk of rhabdomyolysis/blood creatine phosphokinase increase has been included in the post-market adverse drug reactions section.
  • 08/17/2017 - The FDA approved an extension of the indication for eslicarbazebine (Aptiom). Aptiom is now indicated down to age 4 years for both monotherapy and adjunctive therapy for the treatment of partial (focal) onset seizures. The updated prescribing information can be found here.
  • 08/15/2017 - The FDA approved an extension on the indication for brivaracetam (Briviact) Briviact is now indicated for both monotherapy and adjunctive therapy for persons age 16 years and above for the treatment of partial (focal) onset seizures. The updated prescribing information can be found here.
  • 07/26/2017 - The FDA approved an important change to the Fycompa (perampanel) prescribing information. Perampanel is now approved as monotherapy for patients 12 years of age and older who have partial (focal)-onset seizures both with and without progression to generalized tonic-clonic seizures. This new, expanded FDA indication does not include monotherapy for primary generalized tonic-clonic seizures, where perampanel is still approved as adjunctive treatment. This is the first antiepileptic drug (AED) to receive approval for monotherapy use under the FDA's new rule granting a monotherapy indication based solely on the results of randomized controlled trials of adjunctive therapy for partial (focal)-onset seizures. Additional information regarding the prescribing information is located here.
  • 03/28/2017 - The FDA announced an update to the Vimpat (lacosamide) prescribing information to include a warning about rare cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS; formerly known as multiorgan hypersensitivity). Additionally, cardiogenic shock has been added as an effect of Vimpat overdose. More information is available here.
  • 03/07/2017 - The FDA sent a letter to Sunovion asking that Prescribing Information be updated to include the occurrence of toxic epidermal necrolysis (TEN) with the use of Aptiom. This is in addition to the warnings of Stevens-Johnson Syndrome (SJS) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRWSS) listed in the current Prescribing Information. More here.
  • 02/20/2017 - VistaPharm, Inc is recalling more than 12,000 units of Phenytoin Oral Suspension, USP 100 mg/ 4 mL, 50 unit dose cups of 4 mL per case, Rx only, according to the US Food and Drug Administration’s (FDA) latest Drug Enforcement Report (February 15, 2017).  The recall was initiated on January 18, 2017, due to, 'CGMP Deviations: Purified water used to manufacture the drug products may have been contaminated with Burkholderia cepacia,' according to the FDA.  The affected products were distributed throughout the United States. Known lot numbers include 428700 (Exp. 11/17) and 409500 (Exp. 06/17). On February 2, 2017, the FDA designated the recall a class II, meaning that exposure might cause temporary health problems, but is unlikely to cause injuries of a serious nature.
  • 02/07/2017 - Health Canada has published a review that concluded that there may be a link between the use of levetiracetam (Keppra) and the risk of acute kidney injury. The current product information for Keppra informs that cases of acute kidney injury have been reported in patients treated with levetiracetam. Health Canada has requested that the other manufacturers of levetiracetam-containing products also update their product information with the same wording. More information is available here.
  • 01/05/2017 - The FDA has issued a new class warning for the use of benzodiazepines concomitantly with opiates.
    This would include AEDs such as Onfi (clobazam), Klonopin (clonazepam), Ativan (lorazepam), Diastat (rectal diazepam) and others. The warning states, "concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.' Please see the attached prescribing information regarding Onfi (clobazam)." More information here and here. Find Onfi prescribing information here.
2016 FDA Alerts arrow_drop_down
  • 12/12/2016 - Health Canada carried out a safety review after learning that the European Medicines Agency was looking into a potential interaction between levetiracetam and methotrexate. The interaction between the two drugs may lead to higher amount of methotrexate in the blood, which may cause serious side effects. The side effects, which can be fatal, include sudden (acute) kidney failure.
  • 11/18/2016 - FDA recalls of Clonazepam Tablets, USP, 0.5 mg, a drug used to treat certain seizure and panic disorders. The recall affects certain packages. More information here.
  • 11/7/2016 - Health Canada has indicated a potential link to respiratory depression—including sedation, somnolence, and loss of consciousness—in patients treated with gabapentin, particularly in patients having lung, kidney, or nervous system diseases that impact breathing, as well as in those that are elderly, or using other drugs that can affect breathing such as opioids, or in those are at higher risk of serious breathing problems. Additional information concerning the risk of respiratory depression has been added to the Warnings and Precautions section of the Canadian product monograph (CPM) for Neurontin (gabapentin). Concomitant use of CNS depressants with gabapentin is also a contributing factor. More information here.
  • 10/18/2016 - EMA recommends measures to ensure safe use of Keppra oral solution. More information here.
  • 10/17/2016 - FDA approves Carnexiv - i.v. carbamazepine, marketed by Lundbeck. More information here.
  • 10/6/2016 - FDA recalls lamotrigine tablets, USP, 150 mg, due to misprinted tablets. The medication (NDC 29300-113-05) was packaged in 500-count bottles. More information here.
  • 9/26/2016 - Zarontin (ethosuximide) - Defective Capsules Associated with Reduced Efficacy (Increased Frequency of Seizures). More information here.
  • 8/31/2016 - Levetiracetam may rarely be associated with acute renal failure. Recently, the Ministry of Health, Labour, and Welfare in Japan reported that a patient treated with levetiracetam developed acute renal failure within 90 days of the initiation of the treatment. The condition resolved after discontinuation of levetiracetam. In Japan, the prescribing information for levetiracetam now lists acute renal failure as one of the serious adverse reactions. Currently, no specific monitoring is recommended with levetiracetam, but obtaining baseline renal tests before initiation of levetiracetam and periodically thereafter could be done to assess renal function.
  • 8/30/2016 - Lamotrigine Orally Disintegrating Tablet 200 mg by Impax: Recall - Incorrect Labeling of Blister Cards. More information here.
  • 8/16/2016 - GlaxoSmithKline (GSK) is advising healthcare providers that POTIGA (ezogabine) Tablets, CV, 50mg, 200mg, 300mg, and 400mg will no longer be commercially available after June 30, 2017. GSK intends to permanently discontinue the product due to the very limited usage of the medicine and the continued decline in new patient initiation. Discontinuation is not due to efficacy or safety reasons. Read more. [PDF]
  • 8/15/2016 - In an enforcement letter the week of August 1st, the FDA ordered a recall of Divalproex 100 mg delayed-release tablets manufactured by Teva, Inc. due to failed specifications. The recall number is D-1449-2016 and code information is Lot #: 02D163, Exp. 9/2017.
  • 5/29/2016 - A new boxed warning has been added to the prescribing information for ezogabine: "Potiga (ezogabine) can cause retinal abnormalities with funduscopic features similar to those seen in retinal pigment dystrophies, which are known to result in damage to the photoreceptors and vision loss. Macular abnormalities characterized as vitelliform lesions have also been observed. All patients taking Potiga should have baseline and periodic (every 6 months) systematic visual monitoring by an ophthalmic professional. Testing should include visual acuity, dilated fundus photography, and optical coherence tomography." Click here to download. [PDF]
  • 4/18/2016 - Study in Neurology finds pregabalin may be linked to major birth defects. View the Pubmed citation
  • 4/12/2016 - The FDA issues overview, "FDA Regulation of Marijuana: Past Actions, Future Plans." Click here to download. [PDF]
  • 4/6/2016 - The FDA and the manufacturer updated the prescribing information for Zonegran (zonisamide) to include a warning about Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) also known as multiorgan hypersensitivity. Download the revised prescribing information here. [PDF]
  • 2/19/2016 - FDA approves Briviact (brivaracetam) as an add-on treatment to other medications to treat partial-onset seizures in patients age 16 years and older with epilepsy. Click here for more information.