Drug Alerts and FDA News

 

2018

  • 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 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

  • 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

  • 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 depressionincluding sedation, somnolence, and loss of consciousnessin 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.

2015

  • 12/21/2015 - Drug interactions between AEDs and antivirals for hepatitis C. Recently, new antivirals (e.g., asunaprevir, daclatasvir, sofosbuvir, telaprevir, vaniprevir) and the endothelin receptor antagonist (macitenta) were approved for the treatment of hepatitis C. AEDs which induce the CYP3A4 isozyme (e.g., phenobarbital and phenytoin) increase the metabolism of antivirals, causing a significant reduction of the serum concentrations of the antivirals and the endothelin receptor antagonist. The antivirals and the endothelin receptor antagonist, with interferon, are necessary to eradicate the hepatitis C virus. Clinicians should be aware of this serious drug-drug interaction to optimize hepatitis C treatment. Providers are advised to consult with a pharmacist or use appropriate drug information resources to check any potential drug-drug interactions between AEDs and hepatitis C treatment agents.
  • 12/4/2015 - On Dec 4, 2015, the FDA approved updated Prescribing Information (PI) for Oxtellar (oxcarbazepine). Serious, potentially life-threatening, dermatologic reactions such as toxic epidermal necrolysis (TEN) and Stevens Johnson syndrome (SJS) have occurred in adults and children treated with oxcarbazepine. Median time of onset was 19 days. Patients with Human Leukocyte Antigen (HLA) allele B*1502 may be at increased risk.  The HLA-B*1502 allele is present in 2-15% of patients from various countries with Han Chinese ancestry. Prior to initiating oxcarbazepine treatment, testing for  HLA-B*1502 should be considered in patients of Asian ancestry. Oxcarbazepine should be avoided in patients positive for HLA-B*1502, unless the benefits clearly outweigh the risks. Click here for the prescribing information. [PDF]
  • 9/30/2015 - On August 28, 2015, the FDA approved updated Prescribing Information (PI) for Tegretol (carbamazepine). Information about the risk of serious dermatologic reactions such as toxic epidermal necrolysis (TEN) and Stevens Johnson syndrome (SJS) are presented. Among patients of Chinese ancestry, there is a strong association of developing SJS/TEN with the HLA-B*1502 gene variant. Prior to initiating Tegretol treatment, testing for  HLA-B*1502 should be performed in patients with ancestry in which HLA-B*1502 may be present (many Asian countries). The PI now states Tegretol should not be used in patients positive for HLA-B*1502 unless the benefit clearly outweighs the risks. Please see the full PI for additional information about this, as well as the use carbamazepine with other drugs such as phenytoin which may increase the risk of cutaneous reactions in patients with HLA-B*1502, the risks of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and the risk of SJS/TEN and DRESS among patients of European, Korean, Japanese and other ancestry who carry the HLA-A*3101 allelic variant. Click here for the prescribing information. [PDF]
  • 9/28/2015 - The FDA and Pfizer issued an updated PI for Neurontin (gabapentin) in September 2015. The update is to section 5.2 of the PI which states "Neurontin can cause anaphylaxis and angioedema after the first dose or at any time during treatment. Signs and symptoms in reported cases have included difficulty breathing, swelling of the lips, throat and tongue and hypotension requiring emergency treatment. Patients should be instructed to discontinue Neurontin and seek immediate medical care should they experience signs and symptoms of anaphylaxis or angioedema."  Click here to download the prescribing information. [PDF]
  • 8/28/2015 - FDA approved a monotherapy indication for eslicarbazepine. The indication reads, "Aptiom (eslicarbazepine acetate) is indicated for the treatment of partial-onset seizures as monotherapy or adjunctive therapy." The recommended maintenance dose is 800 mg to 1600 mg once daily, depending on clinical response and tolerability. Click here to download the prescribing information. [PDF]
  • 6/19/2015 - FDA approved perampanel (Fycompa) for the adjunctive treatment of Primary Generalized Tonic-Clonic Seizures (PGTCS) in patients age 12 years and older. 
  • 6/17/2015 - FDA Determines Ezogabine Labeling Adequate to Manage Risks Based on reviews of additional safety reports from patients treated with the anti-seizure drug ezogabine (brand name Potiga), the US Food and Drug Administration has determined that the potential risks of vision loss due to pigment changes in the retina and of skin discoloration can be adequately managed by following the current recommendations in the ezogabine labeling. To further explore any potential long-term consequences of these pigment changes, FDA has required the ezogabine manufacturer, GlaxoSmithKline, to conduct a long-term observational study.  The FDA recommends that health care professionals should continue to follow the recommendations provided in the Boxed Warning, FDA’s most serious type of warning, and the Warnings and Precautions and Indications and Usage sections of the labeling.
  • 6/16/2015 - The FDA has worked with the manufacturer of fosphenytoin (Cerebyx) to update the prescribing information. Studies in patients of Chinese ancestry have found a strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA B gene, in patients using carbamazepine. Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin. Consideration should be given to avoiding CEREBYX as an alternative for carbamazepine patients positive for HLAB*1502.
  • 5/22/2015 - IV Levetiracetam – Shortage identified May 21, 2015   Earliest anticipated release date: June 2015
  • 5/7/2015 - IV Valproate Sodium – Shortage identified May 7, 2015    Earliest anticipated release date: Late May 2015 
  • 4/20/2015 - Blue Cross Blue Shield Association has changed its policy to state that responsive neurostimulation may be considered medically necessary for patients with medication-refractory partial epilepsy who meet certain criteria. 
  • 3/25/2015 - Depakote PI update - "On March 10th, the FDA and the manufacturer updated the label for divalproex (Depakote) to include new and updated warnings about cytopenias, coagulopathies, and DRESS. The new prescribing information reads in section 5.8, 'Valproate is associated with dose-related thrombocytopenia ... and  ... decreases in other cell lines and myelodysplasias.  Because of reports of cytopenia, inhibition of secondary phase of platelet aggregation, and abnormal coagulation parameters (e.g., low fibrinogen, coagulation factor deficiencies, acquired VonWillebrand's disease) measurements of complete blood counts and coagulation parameters are recommended before initiating therapy and at periodic intervals.' In addition in section 5.12, the term Multi-organ Hypersensitivity Reaction has been changed to Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and a completely revised description of DRESS and its severity is provided along with recommendations on how to evaluate it and to stop Depakote." The March 2015 PI is attached here and is also available on the FDA website.
  • 3/17/2015 - Levetiracetam (Keppra) - The FDA, working with the manufacturer, has updated the prescribing information for levetiracetam (Keppra). New warnings include behavioral abnormalities and psychotic symptoms, somnolence and fatigue, red blood cell and white blood cell count decreases, as well as significant diastolic blood pressure increases in 17% of children aged 1 month to <4 years. Read more.
  • 3/11/2015 - The US Food & Drug Administration, working with the manufacturer, has made changes to the prescribing information (PI) for Vimpat with regard to overdoses with the medication. The updated PI contains the wording, 'Following single acute overdoses of 1,000 mg or greater of Vimpat, cardiac conduction disorders and seizures, including generalized tonic-clonic seizures and status epilepticus have been observed.'  The updated PI can be found here.

Past FDA News, Updates, & Press Announcements

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.

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