What are the severe side effects of Felbatol. How should Felbatol be used safely. What precautions should be taken when using Felbatol. Who should avoid taking Felbatol. How does Felbatol work to control seizures. What are the common side effects of Felbatol. When should you seek immediate medical attention while taking Felbatol.

Understanding Felbatol: An Anticonvulsant Medication for Severe Seizures

Felbatol, also known by its generic name felbamate, is a potent anticonvulsant medication used in the treatment of severe seizures. This drug is primarily prescribed for individuals with epilepsy who have not responded well to other antiepileptic medications. Due to its potential for serious side effects, Felbatol is typically reserved as a last-resort option when other treatments have failed to control seizures effectively.

How does Felbatol work?

Felbatol works by altering the activity of certain neurotransmitters in the brain. It is believed to enhance the effects of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter that helps to reduce excessive neuronal firing. Additionally, Felbatol may block sodium channels and N-methyl-D-aspartate (NMDA) receptors, further contributing to its anticonvulsant properties.

Important Safety Warnings and Precautions for Felbatol Use

Before considering Felbatol as a treatment option, it is crucial to understand the significant risks associated with its use. The medication carries a black box warning, the most serious type of warning issued by the U.S. Food and Drug Administration (FDA), due to the potential for life-threatening adverse effects.

Who should not take Felbatol?

• Patients with existing liver problems
• Individuals with a history of blood disorders
• Those who can adequately control their seizures with other medications
• Patients who have previously experienced adverse reactions to Felbatol

Is Felbatol safe for everyone? No, Felbatol is not suitable for all patients with epilepsy. Due to its potential for severe side effects, it should only be used in cases where the benefits clearly outweigh the risks. Your healthcare provider will carefully evaluate your medical history and current condition before prescribing this medication.

Severe Side Effects of Felbatol: Blood and Liver Complications

The most serious concerns associated with Felbatol use are its effects on the blood and liver. These potentially fatal complications necessitate close monitoring and immediate medical attention if symptoms arise.

Blood and Bone Marrow Problems

Felbatol can cause severe blood disorders, including:

• Aplastic anemia
• Leukopenia (low white blood cell count)
• Thrombocytopenia (low platelet count)

These conditions can lead to an increased risk of infections, anemia, and bleeding problems. Patients taking Felbatol should be vigilant for signs such as unexplained fever, sore throat, easy bruising or bleeding, and unusual fatigue.

Liver Complications

Felbatol has been associated with severe liver injury, which can be life-threatening in some cases. Symptoms of liver problems may include:

• Persistent nausea or vomiting
• Abdominal pain
• Jaundice (yellowing of the skin or eyes)
• Dark urine
• Unexplained fatigue

Can liver problems occur even after stopping Felbatol? Yes, it’s important to note that blood and liver complications can develop even after discontinuing the medication. For this reason, patients may need to undergo blood tests for an extended period after stopping Felbatol.

Proper Usage and Administration of Felbatol

To maximize the benefits and minimize the risks of Felbatol, it is essential to follow the prescribed dosage and administration instructions carefully.

Dosage Forms and Administration

Felbatol is available in two forms:

1. Tablets: Usually taken 3 to 4 times daily
2. Oral suspension: Must be shaken well before each use and measured with a special device

The medication can be taken with or without food, but taking it with food may help reduce stomach upset. Your doctor will likely start you on a low dose and gradually increase it to find the most effective and safe dosage for your condition.

Important Guidelines for Felbatol Use

• Do not stop taking Felbatol abruptly without consulting your doctor, as this may worsen seizures
• If you miss a dose, take it as soon as you remember, unless it’s almost time for the next dose
• Never double up on doses to make up for a missed one
• Keep all medical and laboratory appointments for regular monitoring

How long does it take for Felbatol to become effective? The time it takes for Felbatol to reach its full therapeutic effect can vary from person to person. Some patients may notice improvements in seizure control within a few weeks, while others may require several months of treatment before experiencing significant benefits.

Common Side Effects and Management Strategies

While the severe side effects of Felbatol are of primary concern, patients may also experience several less serious but still bothersome side effects. Understanding these potential effects and how to manage them can improve your overall experience with the medication.

Frequently Reported Side Effects

• Drowsiness and dizziness
• Nausea and vomiting
• Diarrhea or constipation
• Insomnia
• Headache
• Blurred or double vision
• Loss of appetite
• Hiccups

Are these side effects permanent? In most cases, these side effects are temporary and may subside as your body adjusts to the medication. However, if they persist or worsen, it’s important to consult your healthcare provider.

Managing Common Side Effects

To help alleviate some of the common side effects associated with Felbatol:

• Take the medication with food to reduce gastrointestinal discomfort
• Stay well-hydrated to help with constipation
• Avoid driving or operating heavy machinery if experiencing drowsiness or dizziness
• Maintain a consistent sleep schedule to help with insomnia
• Use over-the-counter remedies for headaches, as approved by your doctor

Monitoring and Follow-up Care for Felbatol Patients

Due to the potential for serious side effects, patients taking Felbatol require close medical supervision and regular monitoring.

Required Medical Tests

Your healthcare provider will likely order the following tests before and during Felbatol treatment:

• Complete blood count (CBC) to monitor for blood disorders
• Liver function tests to check for signs of liver damage
• Kidney function tests
• Serum electrolyte levels

How often should these tests be performed? Initially, these tests may be conducted every two weeks. As treatment progresses and if results remain stable, the frequency may be reduced to monthly or as determined by your healthcare provider.

Signs Requiring Immediate Medical Attention

While taking Felbatol, it’s crucial to be aware of symptoms that may indicate a serious problem. Seek immediate medical care if you experience:

• Persistent fever or sore throat
• Unusual bleeding or bruising
• Severe fatigue or weakness
• Yellowing of the skin or eyes
• Dark urine or clay-colored stools
• Severe abdominal pain
• Persistent nausea or vomiting
• Skin rash or hives

Drug Interactions and Precautions with Felbatol

Felbatol can interact with various medications, potentially altering their effectiveness or increasing the risk of side effects. It’s essential to inform your healthcare provider about all medications, supplements, and herbal products you are taking.

Common Drug Interactions

Felbatol may interact with:

• Other antiepileptic drugs (e.g., carbamazepine, phenytoin, valproic acid)
• Oral contraceptives
• Certain antibiotics
• Warfarin and other blood thinners
• Monoamine oxidase inhibitors (MAOIs)

Can Felbatol affect the effectiveness of birth control pills? Yes, Felbatol may decrease the effectiveness of hormonal contraceptives. If you are using oral contraceptives, discuss alternative or additional birth control methods with your healthcare provider.

Special Precautions

Certain groups of patients may require extra caution when using Felbatol:

• Pregnant women: Felbatol may pose risks to the developing fetus
• Breastfeeding mothers: The drug can pass into breast milk
• Elderly patients: May be more susceptible to side effects
• Patients with kidney problems: May require dosage adjustments

Is it safe to consume alcohol while taking Felbatol? It’s generally advisable to avoid alcohol while taking Felbatol, as it may increase the risk of side effects and potentially interfere with seizure control. Always consult your healthcare provider regarding alcohol consumption while on this medication.

Alternative Treatments and Future Directions in Epilepsy Management

Given the significant risks associated with Felbatol, it’s important to consider alternative treatment options for managing severe epilepsy. Advances in epilepsy research continue to provide new possibilities for patients who have not found success with traditional therapies.

Alternative Antiepileptic Medications

Several newer antiepileptic drugs may be considered before resorting to Felbatol:

• Levetiracetam (Keppra)
• Lamotrigine (Lamictal)
• Topiramate (Topamax)
• Zonisamide (Zonegran)
• Perampanel (Fycompa)

These medications often have more favorable side effect profiles compared to Felbatol, though their efficacy may vary depending on the individual and the specific type of epilepsy.

Non-Pharmacological Approaches

In some cases, non-drug treatments may be considered, either alone or in combination with medications:

• Vagus nerve stimulation (VNS)
• Responsive neurostimulation (RNS)
• Deep brain stimulation (DBS)
• Ketogenic diet
• Epilepsy surgery

Are these alternatives as effective as Felbatol? The effectiveness of these treatments can vary widely depending on the individual and the specific type of epilepsy. In some cases, they may provide comparable or even superior seizure control with fewer risks than Felbatol.

Emerging Therapies and Research

Ongoing research in epilepsy treatment is exploring several promising avenues:

• Gene therapy for specific genetic epilepsies
• Precision medicine approaches tailored to individual genetic profiles
• Novel drug delivery methods to improve efficacy and reduce side effects
• Neuromodulation techniques using advanced brain-computer interfaces
• Cannabidiol (CBD) and other cannabis-derived compounds

While these emerging therapies offer hope for improved epilepsy management in the future, it’s important to note that many are still in experimental stages and may not be widely available or approved for general use.

In conclusion, while Felbatol remains an important option for some patients with severe, treatment-resistant epilepsy, its use must be carefully considered and closely monitored due to the potential for serious side effects. As research continues to advance our understanding of epilepsy and its treatment, new and potentially safer options may become available, offering hope for improved seizure control and quality of life for individuals living with this challenging condition.

Felbatol Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Warnings:

Severe (sometimes fatal) blood/bone marrow problems (such as low red/white blood cells and platelets) and liver problems have occurred with felbamate. Felbamate should be used only by people with severe seizures (epilepsy) that cannot be controlled with other medications. Do not use this drug if you have liver problems. Discuss the risks and benefits with your doctor before starting felbamate.

Tell your doctor right away if you have signs of infection (such as sore throat that doesn’t go away, fever, chills), signs of anemia (such as unusual tiredness), easy bruising/bleeding, or signs of liver problems (such as nausea/vomiting that doesn’t stop, stomach/abdominal pain, yellowing eyes/skin, dark urine). Usually, people who have liver problems while taking this drug should not start taking it again.

Your doctor will check certain blood tests (liver function, complete blood count) and may have you see a doctor who treats blood/bone marrow problems before you start felbamate and while you use this drug. Blood/bone marrow problems may also occur after you stop taking the drug. Blood tests may be needed for some time after you stop taking felbamate. Keep all medical and lab appointments.

Warnings:

Severe (sometimes fatal) blood/bone marrow problems (such as low red/white blood cells and platelets) and liver problems have occurred with felbamate. Felbamate should be used only by people with severe seizures (epilepsy) that cannot be controlled with other medications. Do not use this drug if you have liver problems. Discuss the risks and benefits with your doctor before starting felbamate.

Tell your doctor right away if you have signs of infection (such as sore throat that doesn’t go away, fever, chills), signs of anemia (such as unusual tiredness), easy bruising/bleeding, or signs of liver problems (such as nausea/vomiting that doesn’t stop, stomach/abdominal pain, yellowing eyes/skin, dark urine). Usually, people who have liver problems while taking this drug should not start taking it again.

Your doctor will check certain blood tests (liver function, complete blood count) and may have you see a doctor who treats blood/bone marrow problems before you start felbamate and while you use this drug. Blood/bone marrow problems may also occur after you stop taking the drug. Blood tests may be needed for some time after you stop taking felbamate. Keep all medical and lab appointments.

… Show More

Uses

Felbamate is used to treat severe seizures. This medication should be used only when you cannot take other medications or when other medications have not been able to control your seizures. Felbamate is known as an anticonvulsant or anti-epileptic drug.

How to use Felbatol

Read and sign the Informed Consent form provided by your doctor. Read the Medication Guide provided by your pharmacist before you start taking felbamate and each time you get a refill. If you have any questions, ask your doctor or pharmacist before starting felbamate.

Take this medication by mouth with or without food as directed by your doctor, usually 3 to 4 times a day. Take with food or milk if stomach upset occurs.

If you are using the liquid form of this medication, shake the bottle well before each dose. Carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose.

The dosage is based on your medical condition and response to treatment. For children, the dosage is also based on weight. To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose.

Take this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.

Do not stop taking this medication without consulting your doctor. Seizures may become worse when this drug is suddenly stopped. Your dose may need to be gradually decreased.

If you are already taking other anti-seizure medications, carefully follow your doctor’s directions for adjusting the dose of these other medications when you start taking felbamate.

Tell your doctor if your seizures get worse.

Side Effects

See also Warning section.

Drowsiness, dizziness, nausea, vomiting, diarrhea, constipation, trouble sleeping, loss of coordination, headache, blurred/double vision, hiccups, or loss of appetite may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: fainting.

A small number of people who take anticonvulsants for any condition (such as seizure, bipolar disorder, pain) may experience depression, suicidal thoughts/attempts, or other mental/mood problems. Tell your doctor right away if you or your family/caregiver notice any unusual/sudden changes in your mood, thoughts, or behavior such as signs of depression, suicidal thoughts/attempts, thoughts about harming yourself.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US – Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before taking felbamate, tell your doctor or pharmacist if you are allergic to it; or to meprobamate; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: blood/bone marrow disorders (such as anemia, bleeding problems, low white blood cell count), liver disease, kidney disease, mental/mood disorders (such as depression, suicidal thoughts).

This drug may make you dizzy or drowsy or blur your vision. It may also cause double vision. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Older adults may be more sensitive to the side effects of this drug, especially dizziness, loss of coordination, or fainting. These side effects can increase the risk of falling.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This medication passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Some products that may interact with this drug include: clopidogrel, orlistat.

This medication may decrease the effectiveness of hormonal birth control such as pills, patch, or ring. This could cause pregnancy. Discuss with your doctor or pharmacist if you should use reliable backup birth control methods while using this medication. Also tell your doctor if you have any new spotting or breakthrough bleeding, because these may be signs that your birth control is not working well.

Tell your doctor or pharmacist if you are taking other products that cause drowsiness including alcohol, marijuana (cannabis), antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), and opioid pain relievers (such as codeine, hydrocodone).

Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

Does Felbatol interact with other drugs you are taking?

Enter your medication into the WebMD interaction checker

Overdose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

Do not share this medication with others.

Lab and/or medical tests (such as complete blood count, kidney/liver tests) should be done before, during, and after treatment with this medication. See also Warning section.

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

Images

Felbatol 600 mg/5 mL oral suspension

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Felbatol 600 mg tablet

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Felbatol 600 mg/5 mL oral suspension

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Felbatol 400 mg tablet

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CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

Felbamate – StatPearls – NCBI Bookshelf

Brian Hanrahan; Robert P. Carson.

Author Information and Affiliations

Last Update: August 22, 2022.

Continuing Education Activity

Felbamate is an anti-epileptic drug that was approved by the Food and Drug Administration for the management of focal seizures and Lennox-Gastaut syndrome. It should be a consideration for patients with drug-resistant epilepsy where the benefit of seizure control outweighs the risk of severe idiosyncratic reactions. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, monitoring, and toxicity of felbamate so that providers can direct patient therapy to optimal outcomes.

Objectives:

• Describe the mechanism of action of felbamate that leads to its anti-seizure characteristics.

• Outline the various approved and other indications for felbamate.

• Identify the potential adverse events associated with felbamate therapy.

• Review interprofessional team strategies for improving care coordination and communication to advance felbamate therapy and improve outcomes.

Access free multiple choice questions on this topic.

Indications

Felbamate is an anti-epileptic drug (AED) approved by the Food and Drug Administration (FDA) in 1993 to manage focal seizures and Lennox-Gastaut syndrome. Several small class III studies have suggested felbamate may be an effective treatment for absence seizures, juvenile myoclonic epilepsy, and infantile spasms.[1]

Felbamate’s approval for focal seizures had its basis in trials which showed it was an effective monotherapy and add-on therapy to phenytoin and carbamazepine for patients with uncontrolled focal epilepsy[2][3]

A major multicenter trial in children with Lennox-Gastaut syndrome (LGS) led to its approval for LGS.[4] This double-blinded, randomized control study found that treatment with felbamate led to an increased quality of life and a statistically significant reduction in the frequency of the various types of seizures associated with LGS. It seemed particularly effective in the treatment of atonic seizures. Since atonic seizures are particularly debilitating in this patient population, the use of felbamate was anticipated to be commonplace in the management of LGS at the time of its FDA approval.

Roughly 4000 patients had exposure to felbamate prior to approval.[5] At its peak, over 100000 people had exposure to the medication. Unfortunately, post-approval use revealed a previously unknown risk of life-threatening adverse events (aplastic anemia, hepatic failure) not seen in pre-approval studies. This lead to a dramatic reduction in its use. Currently, it should be a consideration for patients with drug-resistant epilepsy where the benefit of seizure control outweighs the risk of severe idiosyncratic reactions.

Mechanism of Action

The mechanism of action of felbamate (2-phenyl-1,3-propanediol dicarbamate) is not well understood, but researchers believe there may be several. The primary antiepileptic activity is thought to be the modulation of the N-Methyl–aspartate (NMDA) receptor, reducing glutamatergic transmission. [5] Other actions include weak inhibition of GABA-receptor binding and inhibition of voltage-gated sodium channels as well as calcium channels.

Administration

Felbamate is available as conventional tablets and as an oral suspension. Available tablet formulations are in 400mg and 600 mg doses. The oral suspension is available in a 600 mg/5 ml suspension.

Felbamate has good bioavailability (greater than 90%) via the GI tract and reaches peak plasma concentration in 3 to 5 hours. It is minimally bound to serum protein (20 to 25%) and is primarily eliminated by renal excretion. The half-life of the drug is usually 14 to 23 hours, and serum concentrations are linearly related to the dose.[6] Interestingly, its clearance is 40 to 50% higher in children than adults.

If used as a monotherapy for partial seizures in adults, the recommendation is that felbamate is initiated at 1200mg/day in 3 to 4 divided doses. Dosing can be increased by 600 mg increments every two weeks up to 3600mg/day. If added as adjunctive therapy, titration can be more aggressive; 1200 mg increments every week up to 3600 mg/day.[7] Adolescents over 14 years of age receive the same dose as adults.

Lennox-Gastaut syndrome is the most common reason for using this medication in the pediatric population. Children (2 to 14 years of age) should initiate therapy at an initial dose of 15 mg/kg/day in 3 to 4 divided doses. Titration should be 15mg/kg/day per week up to  45 mg/kg/day or 3600 mg/day, whichever is less.[7]

Felbamate should be used cautiously in patients with impaired renal function, with a 50% reduction in both initial and maintenance doses.

Felbamate has several drug interactions with commonly used AEDs. Enzyme-inducing AEDs, such as carbamazepine and phenytoin, will increase the clearance of felbamate. Gabapentin and valproic acid will decrease felbamate clearance. Lastly, felbamate can increase levels of phenytoin, phenobarbital, and valproic acid and reduce levels of carbamazepine. [6]

Adverse Effects

Initial studies showed that felbamate carried relatively little systemic toxicity and less CNS depression when compared to the older generation AEDs. Common side effects include drowsiness, insomnia, anorexia, nausea, dizziness, and headache.[8] Anorexia and other side effects are more likely to occur with higher serum levels.[9]

A rapid titration schedule can increase the risk of neurologic side effects. Decreasing the titration rate may reduce this risk. Somnolence is more likely to occur in the first 4 weeks of treatment and decreases with continued therapy.

Contraindications

Felbamate should not be given to patients with a history of hepatic dysfunction or any form of blood dyscrasia. Patients with known hypersensitivity to felbamate or other carbamates should avoid felbamate.

Monitoring

The target serum concentrations for felbamate are between 30 to 60 mg/L.[6]

Due to the increased risk of idiosyncratic reactions in the first 6 to 12 months after initiating therapy, clinical and laboratory monitoring is essential; this includes a comprehensive metabolic panel, blood counts, and hepatic function panel. Serum studies should be completed before, during, and after the completion of felbamate therapy. Blood work can be performed biweekly or less for the first 3 months of therapy and then every 6 to 12 months thereafter.

Toxicity

Felbamate use is limited by severe, life-threatening, and idiosyncratic reactions (aplastic anemia and hepatic failure). Both reactions can carry a mortality rate above 30%. These reactions are usually seen during the first 6 to 12 months of therapy but can occur later. Aplastic anemia can lead to symptoms of bleeding, bruising, and pale skin color. The first symptoms of hepatic dysfunction include lethargy, nausea, and vomiting. If hepatic enzymes (AST, ALT) increase two or more times, the upper limit of normal felbamate should be discontinued.

Aplastic anemia: There were 34 reported cases of felbamate-related aplastic anemia in the first six years of FDA approval.[5] None of these cases occurred in children below the age of 13. Patients who developed aplastic anemia tended to be older (above 17 years of age) and have a history of AED allergies/toxicity, cytopenia, and/or immune disease. [5] Researchers estimated that patients on felbamate were at a more than 100 fold greater risk for developing aplastic anemia (27 to 207/million) than the general population (2 to 2.5/million).[10] There is no known way to reduce the risk of occurrence. Early signs of aplastic anemia include declining reticulocyte counts and thrombocytopenia. Patients with any symptoms of easy bruising, bleeding, and/or lethargy should seek immediate medical care.

Hepatic Failure: In the first six years after FDA approval, there were 18 cases of hepatic failure in patients taking felbamate.[5] The risk for developing hepatotoxicity and liver failure is higher than the general population, approximately 1 in 30000, but less than the risk of aplastic anemia. Cases have occurred in children as young as 5 years old. The mean time of hepatic failure after the initiation of therapy ranged between 25 to 939 days.[5] Patients with symptoms of jaundice, fatigue, and/or GI complaints should seek immediate medical care.

Enhancing Healthcare Team Outcomes

Felbamate therapy is best accomplished using an interprofessional healthcare team that includes clinicians, specialists, nurses, and pharmacists. The monitoring for idiosyncratic reactions from felbamate falls upon the responsibilities of neurologists and primary care clinicians. The pharmacist should thoroughly educate the patient and caregiver about medication compliance and the need for regular follow-up. Close monitoring is vital because the drug has correlations with severe adverse reactions; this requires interprofessional communication between the two specialties to ensure no issues arise. Nursing is often the first point of contact the patient has with the healthcare team. They need to be prepared to offer counsel, answer questions, and alert appropriate team members if intervention is warranted. As noted above, clinical and laboratory monitoring is essential following drug initiation, though it may be spaced out after the first 3 months of therapy. If there is a concern for aplastic anemia or hepatic dysfunction in any patients on felbamate, they should be evaluated in an emergency care setting. With an interprofessional approach, monitoring for adverse events and verifying therapeutic efficacy can result in optimal patient outcomes with felbamate. [Level 5]

Review Questions

• Access free multiple choice questions on this topic.

• Comment on this article.

References

1.

French J, Smith M, Faught E, Brown L. Practice advisory: The use of felbamate in the treatment of patients with intractable epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 1999 May 12;52(8):1540-5. [PubMed: 10331676]

2.

Shi LL, Dong J, Ni H, Geng J, Wu T. Felbamate as an add-on therapy for refractory partial epilepsy. Cochrane Database Syst Rev. 2017 Jul 18;7(7):CD008295. [PMC free article: PMC6483495] [PubMed: 28718506]

3.

Leppik IE, Dreifuss FE, Pledger GW, Graves NM, Santilli N, Drury I, Tsay JY, Jacobs MP, Bertram E, Cereghino JJ. Felbamate for partial seizures: results of a controlled clinical trial. Neurology. 1991 Nov;41(11):1785-9. [PubMed: 1944909]

4.

Felbamate Study Group in Lennox-Gastaut Syndrome. Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). N Engl J Med. 1993 Jan 07;328(1):29-33. [PubMed: 8347179]

5.

Pellock JM. Felbamate. Epilepsia. 1999;40 Suppl 5:S57-62. [PubMed: 10530695]

6.

Johannessen SI, Battino D, Berry DJ, Bialer M, Krämer G, Tomson T, Patsalos PN. Therapeutic drug monitoring of the newer antiepileptic drugs. Ther Drug Monit. 2003 Jun;25(3):347-63. [PubMed: 12766564]

7.

Thakkar K, Billa G, Rane J, Chudasama H, Goswami S, Shah R. The rise and fall of felbamate as a treatment for partial epilepsy–aplastic anemia and hepatic failure to blame? Expert Rev Neurother. 2015;15(12):1373-5. [PubMed: 26566191]

8.

Heyman E, Levin N, Lahat E, Epstein O, Gandelman-Marton R. Efficacy and safety of felbamate in children with refractory epilepsy. Eur J Paediatr Neurol. 2014 Nov;18(6):658-62. [PubMed: 24906615]

9.

Harden CL, Trifiletti R, Kutt H. Felbamate levels in patients with epilepsy. Epilepsia. 1996 Mar;37(3):280-3. [PubMed: 8598188]

10.

Pellock JM, Brodie MJ. Felbamate: 1997 update. Epilepsia. 1997 Dec;38(12):1261-4. [PubMed: 9578519]

Disclosure: Brian Hanrahan declares no relevant financial relationships with ineligible companies.

Disclosure: Robert Carson declares no relevant financial relationships with ineligible companies.

HOW TO GET RID OF CHLOROPHENOLS | Ural Branch of the Russian Academy of Sciences

A new approach to the determination of traces of substituted phenols and anilines in aqueous media has been developed at the Institute of Biology, Komi Scientific Center. New techniques were applied, in particular, to reveal the mechanisms of formation of phenolic compounds in natural and drinking waters. We talked about these studies with the leading researcher of the ecoanalytical laboratory of the IB Komi Scientific Center of the Ural Branch of the Russian Academy of Sciences, Doctor of Chemical Sciences Ivan Vladimirovich Gruzdev.

— How do phenols, anilines and their derivatives get into the water?

— These substances are commonly found in wastewater from the woodworking, pharmaceutical, organic synthesis and petrochemical industries, where they are used as basic and intermediate components or as by-products of production. Their contact with chlorine in any technological process leads to the formation of even more toxic chlorine-containing products. Chlorine-substituted phenols and anilines are also formed during the disinfection of drinking water with various chlorinating agents. Under natural conditions, compounds of these classes are produced during the destruction of soil organic matter, as well as widely used antiseptics and pesticides, such as chlorhexidine, triclosan, linuron, aminocarb, etc.

— What is their danger?

– Phenolic compounds are very toxic, they are the third largest environmental hazard after heavy metals and petroleum products. Their presence in water significantly impairs its taste and smell. By taste and smell, phenol is found in drinking water already at a concentration of ~50 µg/dm ³ . When disinfecting water with chlorine, this effect is greatly enhanced. According to the requirements for the quality of drinking water, the concentration of chlorophenols should not exceed 0.5 µg/dm ³ .

A particular danger of the presence of chlorophenols in drinking water is that they are direct precursors of polychlorinated dibenzo-p-dioxins, the formation of which can occur as a result of the chemical interaction of any two molecules of chlorinated phenols. And dioxins are global ecotoxicants with powerful mutagenic, immunosuppressive, carcinogenic and embryotoxic effects.

Recently, due to the widespread use of polymeric materials, much attention has been paid to bis-phenol and alkylphenols (octyl- and nonylphenols). Alkylphenols are actively used as hardeners and stabilizers for various plastic materials. Bis-phenol is used in the manufacture of polycarbonate plastics, which are used in various construction materials, cookware, food and water storage containers. Every day, each of us encounters bis-phenol when picking up a check in a store – it is also used in the production of thermal paper for cash registers. Due to the spatial similarity of the molecules of alkylphenols and bis-phenol with some hormones, in particular, with the female sex hormone estradiol, these substances can be recognized by the body as hormones and disrupt the normal functioning of the reproductive and endocrine systems.

— How are phenolic compounds formed in natural conditions?

— The natural waters of the rivers and lakes of the northern territories of Europe, used for water treatment, are characterized by high color, which in turn is due to the presence of humic substances entering aquatic ecosystems from soils, peatlands and swamps. During the biochemical and hydrolytic decomposition of aqueous humus, a number of low molecular weight organic substances are formed, including phenol and its derivatives.

— What methods did you use to determine phenols and anilines in aqueous media?

– Quantitative chemical analysis of water samples was based on a whole range of chromatographic techniques for both individual and simultaneous determination of variously substituted chlorophenols, chloranilines, alkylphenols, methylanilines, nitroanilines and nitrophenols – more than 50 compounds in total.

All methods were developed on the basis of our ecoanalytical laboratory and are based on a new approach to the chemical modification of phenols and anilines – both in terms of functional groups and aromatic nucleus. The fundamental difference of this approach is the halogenation of phenols and anilines directly in water (the introduction of halogen atoms into an organic molecule). Previously, this approach could not be implemented due to the high oxidative activity of halogens in water—the studied phenols and anilines are easily oxidized in such media, and the already formed halogen derivatives of these compounds are also oxidized.

To obtain halogen derivatives of phenols and anilines directly in water, we proposed new halogenation systems containing substances that reversibly react with halogens (amino acids, bromide anions, ammonia, etc.). This makes it possible to significantly reduce the oxidative activity of halogens and practically eliminate the oxidation of halogenated analytes in the presence of halogen in aqueous solutions.

For each of the six classes of investigated substances (chlorine-, nitro- and alkylphenols, chlorine-, methyl- and nitroanilines) we have developed brominating systems and obtained bromo derivatives of 45 compounds.

For the first time in analytical practice, iodination was proposed for the determination of phenols and anilines in aqueous media. Iodizing systems were developed for three classes of the studied substances (chlorine and alkylphenols, methylanilines), and iodinated forms of 32 compounds were obtained directly in water.

Since the functional groups of phenols and anilines are not affected by halogenation, it becomes possible to correct their analytical properties by additional derivatization in an organic extract using the most available acylating and silylating agents.

Due to the two-stage chemical modification of phenols and anilines, their highly efficient extraction from aqueous media, reliable identification and highly sensitive detection at the level of 0.002-0.01 μg/dm ³ are achieved.

— What did you find out about the mechanisms of formation of phenols and their derivatives in water?

– As our studies have shown, the rate of degradation of humic acids increases significantly with an increase in temperature and an increase in the pH value of water. Thus, when natural water is alkalized to pH 11–13, the phenol content increases 3–5 times in 72 hours. The same effect is achieved by boiling natural water for 15 minutes.

Boiling tap water from centralized water supply increases the concentration of not only phenol, but also chlorophenols. So, with 15-minute boiling, the concentration of phenol in water increases on average 3.5 times, 2-chlorophenol – 2 times, 2,6-dichlorophenol – 1.5 times.

– What is the reason for this?

— Traditionally, chlorophenols in drinking water are thought to result from the direct chlorination of phenol. In our opinion, the main source of chlorophenols in drinking water is chlorinated humic acids. The formation of chlorine-substituted humic acids occurs at the stage of disinfection of drinking water with active chlorine, and their subsequent destruction is accompanied by the formation of various low-molecular organochlorine compounds, including chlorophenols.

To reveal the mechanism of formation of chlorophenols in Syktyvkar tap water, we conducted a series of experiments on phenol chlorination in model solutions prepared on the basis of distilled water.

According to our data, the source water of the Vychegda River contains phenol at a concentration of 5 to 15 µg/dm ³ . The necessary dose of chlorine for disinfection is determined experimentally on the basis of the chlorine absorption of water and at a contact time of water and chlorine of 30 minutes usually does not exceed 3 mg / dm ³ . Similar conditions were chosen for chlorination of phenol in model solutions: phenol concentration 10 µg/dm ³ , molecular chlorine 3 mg/dm ³ , contact time 30 min. We have shown that practically no chlorophenols are formed under these conditions. It is possible to obtain chlorine derivatives of phenol at the level of maximum permissible concentrations (~0.5 μg/dm3) only by increasing the concentration of phenol to 100 μg/dm ³ and chlorine to 30 mg/dm ³ , i.e. ten times.

Based on these data, the following conclusion can be drawn. The reaction rate of phenol chlorination under real water treatment conditions is very low due to the low initial concentration of both phenol and chlorine, and chlorophenols are practically not formed during direct phenol chlorination. Consequently, the main source of chlorophenols in drinking water is humic acids, which are not completely removed from water during water treatment. During the disinfection of drinking water with molecular chlorine, they are chlorinated, followed by destruction, as a result of which various chlorine-substituted phenols are released.

Thus, in order to exclude the presence of chlorophenols in drinking water, it is necessary to completely remove high-molecular organic impurities during water treatment or use artesian water for this, which, due to natural filtration, does not contain high-molecular organic impurities.

Prepared by

E. Ponizovkina

I.V. Gruzdev in ecoanalytical laboratory

Year:

2018

Month:

October

Issue number:

19

Absolute number:

1182

instructions for use, price, analogues, composition, indications

Transparent red liquid with cherry/phenol odor.

Active ingredient: phenol 1.4% (14 mg/ml).
Excipients: glycerol, sodium saccharin, cherry flavor, FD&C Red No. 40 (E129), purified water.

Medicines for the treatment of diseases of the larynx and pharynx. Antiseptics.
ATC code: R02AA19

Phenol solutions have a strong bactericidal activity against vegetative forms of microorganisms. In addition, these solutions have an anesthetic effect.
Pharmacokinetics
Phenol, which is part of the composition, is excreted by mucus with further excretion through the gastrointestinal tract. The passage of the drug through the liver and excretion by the kidneys is more likely in cases of overdose.

Pain reliever and antiseptic.
For the temporary relief of minor irritation and soreness in the mouth and throat.

Use in children under 3 years of age is possible only on prescription, in children under 12 years of age only under adult supervision.
Spray the spray in the appropriate dosage on the inflamed area of ​​the mucous membrane, hold the applied solution for 15 seconds, then spit out the remaining solution.
Dose
One spray is 0.7 ml and corresponds to a content of 9.8 mg of phenol.
The dose of the drug varies for different categories of patients. If the doctor has not prescribed otherwise, in order to relieve sore throat, it is recommended: adults and children over 12 years of age – 3-5 clicks on the spray bottle (corresponding to the content of 29.4 mg and 49 mg of phenol, respectively) on the affected area of ​​the mucous membrane every 2 hours ; children from 3 to 12 years old – up to 3 clicks on the spray bottle (corresponds to the content of 29. 4 mg of phenol) on the affected area of ​​the mucous membrane every 2 hours; children under 3 years old – the need to use the spray and its dosage regimen is determined by the attending physician.

In some cases, allergic reactions may occur (skin rash, skin redness, itching, rash, angioedema). Possible reactions at the site of application (local swelling of the mucous membrane of the oral cavity or pharynx). The concentration of phenol in the preparation is considered safe from the point of view of potential toxic or carcinogenic properties. Oracept does not have a damaging effect on tooth enamel.

Children under 3 years of age.
Hypersensitivity to any ingredients of the drug.
Serious violations of the liver and kidneys.
Inflammation of the epiglottis.
Inflammatory diseases with lesions of the mucous membranes due to increased absorption of the drug and an increased risk of systemic toxic effects.

An overdose of phenol can cause mucosal lesions, nausea, vomiting, increased sweating and diarrhoea. Dizziness and weakness may occur. Patients may experience agitation followed by loss of consciousness. There may also be depression of the central nervous system with oppression of blood circulation and respiration. In severe cases, pulmonary edema, liver or kidney damage may develop. A lethal dose of 1-15 g of phenol (when taken orally) can lead to death due to respiratory failure. If an overdose is suspected, it is recommended to take activated charcoal and gastric lavage.

Phenol solution should not be applied to large areas of skin, mucous membranes or large wounds, as systemic toxic effects may develop due to absorption.
It is forbidden to exceed the doses recommended by the instructions and apply to children under 3 years of age without an appropriate doctor’s prescription.
Avoid getting the drug in the eyes. In case of accidental contact with eyes, rinse with plenty of water. Avoid inhalation of phenol solution.
Severe or persistent sore throat, or accompanied by high fever, headache, nausea and/or vomiting, may indicate a serious illness. You should immediately consult a doctor and do not use Oracept before consulting a doctor.
The drug is intended for short-term use. Patients should immediately stop taking the drug and consult a doctor if the symptoms of the disease do not subside within 7 days of using the drug for lesions of the oral cavity and within 2 days of use for lesions of the pharynx; if irritation, pain and redness of the mucous membrane do not subside or worsen; if the body temperature rises, a local swelling or rash appears.

There are no data on the use of the drug during pregnancy and breastfeeding. Oracept is not recommended for use during these periods.

The drug does not affect the ability to drive a car and work with mechanisms.

Data on the effect of the drug on the action of other drugs are not available.
The drug is prescribed in the complex therapy of inflammatory diseases of the oral cavity and throat along with sulfonamides, antibiotics, vitamins. Without consulting a doctor, the drug should not be used simultaneously with drugs for the treatment of myasthenia gravis; drugs that depress the central nervous system, disinfectant solutions, which contain heavy metals; MAO inhibitors; blockers of neuromuscular transmission; opioids; vasoconstrictors.