ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Felbamate: Pediatric drug information

Felbamate: Pediatric drug information
(For additional information see "Felbamate: Drug information" and see "Felbamate: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Aplastic anemia:

The use of felbamate is associated with a marked increase in the incidence of aplastic anemia. Accordingly, felbamate should only be used in patients whose epilepsy is so severe that the risk of aplastic anemia is deemed acceptable in light of the benefits conferred by its use. Ordinarily, a patient should not be placed on and/or continued on felbamate without consideration of appropriate expert hematologic consultation.

Among felbamate-treated patients, aplastic anemia (pancytopenia in the presence of a bone marrow largely depleted of hematopoietic precursors) occurs at an incidence that may be more than a 100-fold greater than that seen in the untreated population (ie, 2 to 5 per million persons per year). The risk of death in patients with aplastic anemia generally varies as a function of its severity and etiology; current estimates of the overall case fatality rate are in the range of 20% to 30%, but rates as high as 70% have been reported in the past.

There are too few felbamate-associated cases, and too little known about them to provide a reliable estimate of the syndrome's incidence or its case fatality rate or to identify the factors, if any, that might conceivably be used to predict who is at greater or lesser risk.

In managing patients on felbamate, the clinical manifestation of aplastic anemia may not be seen until after a patient has been taking felbamate for several months (eg, onset of aplastic anemia among felbamate-exposed patients for whom data are available has ranged from 5 to 30 weeks). However, the injury to bone marrow stem cells that is held to be ultimately responsible for the anemia may occur weeks to months earlier. Accordingly, patients who are discontinued from felbamate remain at risk for developing anemia for a variable, and unknown, period afterwards.

It is not known whether the risk of developing aplastic anemia changes with duration of exposure. Consequently, it is not safe to assume that a patient who has been on felbamate without signs of hematologic abnormality for long periods of time is without risk.

It is not known whether the dose of felbamate affects the incidence of aplastic anemia.

It is not known whether concomitant use of antiseizure drugs and/or other drugs affects the incidence of aplastic anemia.

Aplastic anemia typically develops without premonitory clinical or laboratory signs; the full blown syndrome presents with signs of infection, bleeding, or anemia. Accordingly, routine blood testing cannot be reliably used to reduce the incidence of aplastic anemia, but, it will, in some cases, allow the detection of the hematologic changes before the syndrome declares itself clinically. Discontinue felbamate if any evidence of bone marrow depression occurs.

Hepatic failure:

Evaluation of postmarketing experience suggests that acute liver failure is associated with the use of felbamate. The reported rate in the United States has been approximately 6 cases of liver failure leading to death or transplant per 75,000 patient-years of use. This rate is an underestimate because of underreporting, and the true rate could be considerably greater than this. For example, if the reporting rate is 10%, the true rate would be 1 case per 1,250 patient-years of use.

Of the cases reported, approximately 67% resulted in death or liver transplantation, usually within 5 weeks of the onset of signs and symptoms of liver failure. The earliest onset of severe hepatic dysfunction followed subsequently by liver failure was 3 weeks after initiation of felbamate. Although some reports described dark urine and nonspecific prodromal symptoms (eg, anorexia, malaise, GI symptoms), in other reports it was not clear if any prodromal symptoms preceded the onset of jaundice.

It is not known whether the risk of developing hepatic failure changes with duration of exposure.

It is not known whether the dosage of felbamate affects the incidence of hepatic failure.

It is not known whether concomitant use of other AEDs and/or other drugs affects the incidence of hepatic failure.

Felbamate should not be prescribed for anyone with a history of hepatic dysfunction.

Treatment with felbamate should be initiated only in individuals without active liver disease and with normal baseline serum transaminases. It has not been proved that periodic serum transaminase testing will prevent serious injury, but it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspected drug enhances the likelihood for recovery. There is no information available that documents how rapidly patients can progress from normal liver function to liver failure, but other drugs known to be hepatotoxins can cause liver failure rapidly (eg, from normal enzymes to liver failure in 2 to 4 weeks). Accordingly, monitoring of serum transaminase levels (AST and ALT) is recommended at baseline and periodically thereafter. While more frequent monitoring increases the chances of early detection, the precise schedule for monitoring is a matter of clinical judgment.

Discontinue felbamate if serum AST or serum ALT levels become increased at least 2 times the upper limit of normal, or if clinical signs and symptoms suggest liver failure. Patients who develop evidence of hepatocellular injury while taking felbamate and are withdrawn from the drug for any reason should be presumed to be at increased risk for liver injury if felbamate is reintroduced. Accordingly, such patients should not be considered for re-treatment.

Brand Names: US
  • Felbatol
Therapeutic Category
  • Antiseizure Agent, Miscellaneous
Dosing: Pediatric

Note: Not recommended for first-line therapy; reserve for refractory clinical situations (failed other therapies) and where benefits exceed hematologic (aplastic anemia) and hepatotoxicity risks (AAN/AES [French 1999]).

Lennox-Gastaut syndrome; adjunctive therapy

Lennox-Gastaut syndrome; adjunctive therapy: Children and Adolescents 2 to 14 years: Oral: Initial: 15 mg/kg/day in 3 or 4 divided doses; increase dose by 15 mg/kg/day increments at weekly intervals; maximum daily dose: 45 mg/kg/day or 3,600 mg/day whichever is less. Note: At initiation of felbamate, decrease dose of concomitant carbamazepine, phenytoin, phenobarbital, or valproic acid by 20% to 33%. Further dosage reductions may be necessary as dose of felbamate is increased.

Partial seizures, adjunctive therapy

Partial seizures, adjunctive therapy: Adolescents ≥14 years: Oral: Initial: 1,200 mg/day in 3 or 4 divided doses; increase dose in 1,200 mg/day increments at weekly intervals; maximum daily dose: 3,600 mg/day. Note: At initiation of felbamate, decrease dose of concomitant carbamazepine, phenytoin, phenobarbital, or valproic acid by 20%. Further dosage reductions may be necessary as dose of felbamate is increased.

Partial seizures, monotherapy

Partial seizures, monotherapy:

Adolescents ≥14 years: Oral:

Initial: 1,200 mg/day in divided doses 3 or 4 times daily; titrate previously untreated patients under close clinical supervision, increasing the dose in 600 mg/day increments every 2 weeks to 2,400 mg/day based on clinical response and thereafter to 3,600 mg/day if clinically indicated.

Conversion to monotherapy: Initial: 1,200 mg/day in divided doses 3 or 4 times daily, reduce the dosage of the concomitant antiseizure medication(s) by 33% at the initiation of felbamate therapy; at week 2, increase felbamate daily dose to 2,400 mg/day in divided doses while reducing the dosage of the other antiseizure medication(s) up to an additional 33% of their original dose; at week 3, increase the felbamate dosage up to a maximum daily dose: 3,600 mg/day and continue to reduce the dosage of the other antiseizure medication(s) as clinically indicated.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment for toxicity: Any signs/symptoms of aplastic anemia (infection, anemia, bleeding): Discontinue therapy.

Dosing: Kidney Impairment: Pediatric

Children ≥2 years and Adolescents: Oral: Reduce initial and maintenance doses by 50%; adjunctive therapy with medications that affect felbamate plasma concentrations, especially antiseizure medications, may warrant further reductions in felbamate daily doses in patients with renal dysfunction.

Dosing: Hepatic Impairment: Pediatric

Children ≥2 years and Adolescents:

Baseline: Use is contraindicated in patients with hepatic impairment.

Hepatotoxicity during therapy: If AST or ALT ≥2 × ULN or signs and symptoms of liver dysfunction (failure): Discontinue therapy.

Dosing: Adult

(For additional information see "Felbamate: Drug information")

Note: Not for use as first-line therapy; use only in patients with severe epilepsy and/or inadequate response to alternative treatment due to risk of aplastic anemia and/or liver failure.

Focal onset seizures, adjunctive therapy

Focal (partial) onset seizures, adjunctive therapy: Oral: Initial: 1.2 g/day in 3 to 4 divided doses; may increase in increments of 1.2 g/day at weekly intervals based on response and tolerability to a maximum of 3.6 g/day in divided doses (Shi 2019; manufacturer's labeling).

Focal onset seizures, monotherapy

Focal (partial) onset seizures, monotherapy: Oral: Initial: 1.2 g/day in 3 to 4 divided doses; may increase in increments of 600 mg/day at 2-week intervals to 2.4 g/day based on response and tolerability; may further increase as needed to a maximum of 3.6 g/day in divided doses (Abou-Khalil 2016; manufacturer's labeling).

Conversion to monotherapy: Oral: Initiate at 1.2 g/day in 3 to 4 divided doses; reduce the dosage of the concomitant antiseizure medication(s) by 33% at the initiation of felbamate therapy; at week 2, increase the felbamate dosage to 2.4 g/day while reducing the dosage of the other antiseizure medication(s) up to an additional 33% of their original dosage; at week 3, increase the felbamate dosage up to 3.6 g/day and continue to reduce the dosage of the other antiseizure medication(s) as clinically indicated.

Discontinuation of therapy: In chronic therapy, unless safety concerns require more rapid withdrawal, withdraw gradually (eg, increments of 300 to 600 mg every week) to minimize the potential of increased seizure frequency or status epilepticus (Pellock 2006).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Adjunctive therapy with medications that affect felbamate plasma concentrations, especially antiseizure drugs, may warrant further reductions in felbamate daily doses in patients with kidney dysfunction.

Altered kidney function (Glue 1997; expert opinion; manufacturer's labeling):

CrCl >50 mL/minute: No dosage adjustment necessary.

CrCl 10 to 50 mL/minute: Initial and maintenance doses: Administer 50% to 75% of usual indication-specific dose.

CrCl <10 mL/minute: Initial and maintenance doses: Administer 50% of usual indication-specific dose.

Hemodialysis, intermittent (thrice weekly): Likely to be significantly removed by hemodialysis (low protein binding, small Vd) (expert opinion): Dose as for CrCl <10 mL/minute (expert opinion).

Peritoneal dialysis: Dose as for CrCl <10 mL/minute (expert opinion).

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, seizure control) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, CNS effects) due to drug accumulation is important.

Some degree of removal is likely based on pharmacokinetic characteristics (has not been studied). Reduce initial dose to 50% of usual indication-specific dose; titrate cautiously based on patient response and tolerability (expert opinion).

PIRRT (eg, sustained, low-efficiency diafiltration):

Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, seizure control) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, CNS effects) due to drug accumulation is important.

Some degree of removal is likely based on pharmacokinetic characteristics (has not been studied). Reduce initial doses by 50% of usual indication-specific dose; titrate cautiously based on patient response and tolerability (expert opinion).

Dosing: Hepatic Impairment: Adult

Use is contraindicated in patients with a history of hepatic dysfunction.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children and adults unless otherwise indicated.

1% to 10%:

Cardiovascular: Palpitations (≥1%), tachycardia (≥1%)

Dermatologic: Acne vulgaris (adults: 3%), bullous rash (≤1%), pruritus (≥1%), skin rash (adults: 3%), urticaria (≤1%)

Endocrine & metabolic: Hypokalemia (≤1%), hyponatremia (≤1%), hypophosphatemia (adults: 3%), increased lactate dehydrogenase (≤1%), intermenstrual bleeding (adults: 3%), weight gain (≥1%), weight loss (adults: 3%)

Gastrointestinal: Constipation (adults: 7%), diarrhea (adults: 5%), dyspepsia (adults: 9%), esophagitis (≤1%), increased appetite (≤1%), vomiting (9%)

Genitourinary: Urinary tract infection (adults: 3%)

Hematologic & oncologic: Granulocytopenia (≤1%), leukocytosis (≤1%), leukopenia (≤1%), lymphadenopathy (≤1%), thrombocytopenia (≤1%)

Hepatic: Increased serum alanine aminotransferase (adults: 5%), increased serum alkaline phosphatase (≤1%), increased serum aspartate aminotransferase (≥1%)

Hypersensitivity: Facial edema (adults: 3%)

Nervous system: Aggressive behavior (≥1%), agitation (≥1%), anxiety (adults: 5%), asthenia (≥1%), euphoria (≤1%), fatigue (adults: 7%), hallucination (≤1%), headache (adults: 7%), insomnia (adults: 9%), malaise (≥1%), migraine (≤1%), psychological disorder (≥1%), suicidal tendencies (≤1%)

Neuromuscular & skeletal: Dystonia (≤1%)

Ophthalmic: Diplopia (adults: 3%)

Respiratory: Flu-like symptoms (≥1%), rhinitis (adults: 7%), upper respiratory infection (adults: 9%)

<1%:

Cardiovascular: Substernal pain, supraventricular tachycardia

Dermatologic: Skin photosensitivity, Stevens-Johnson syndrome

Gastrointestinal: Buccal mucous membrane swelling

Hematologic & oncologic: Agranulocytosis, platelet disorder, positive ANA titer

Hepatic: Increased gamma-glutamyl transferase

Hypersensitivity: Nonimmune anaphylaxis

Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen

Frequency not defined: Gastrointestinal: Anorexia, nausea

Postmarketing (may include combination therapy):

Cardiovascular: Atrial arrhythmia, atrial fibrillation, bradycardia, edema, flushing, heart failure, hypertension, hypotension, ischemic changes (necrosis), limb embolism, livedo reticularis, peripheral ischemia, thrombophlebitis, torsades de pointes

Dermatologic: Alopecia, body odor, diaphoresis, gangrene of skin and/or subcutaneous tissues, lichen planus, toxic epidermal necrolysis

Endocrine & metabolic: Dehydration, hyperammonemia, hyperglycemia, hypernatremia, hypocalcemia, hypoglycemia, hypomagnesemia, menstrual disease, SIADH

Gastrointestinal: Aphthous stomatitis, dysphagia, enteritis, flatulence, gastric dilation, gastric ulcer, gastritis, gastroesophageal reflux disease, gastrointestinal hemorrhage, gingival hemorrhage, glossitis, hematemesis, intestinal obstruction, non-Hirschsprung megacolon, pancreatitis, rectal hemorrhage

Genitourinary: Dysuria, hematuria, urinary retention, urolithiasis (Sparagana 2001), vaginal hemorrhage

Hematologic & oncologic: Anemia, aplastic anemia, decreased prothrombin time, disorder of hemostatic components of blood, disseminated intravascular coagulation, eosinophilia, hemolytic anemia, hemolytic-uremic syndrome, Henoch-Schönlein purpura, hypochromic anemia, leukemia (including myeloid leukemia), lymphoproliferative disorders (T cell and B cell), malignant lymphoma, neoplasm, pancytopenia, prolonged prothrombin time

Hepatic: Hepatic failure, hepatitis, hepatorenal syndrome, jaundice

Infection: Sepsis

Nervous system: Apathy, brain edema, cerebrovascular disease, choreoathetosis, coma, confusion, delusions, dysarthria, encephalopathy, extrapyramidal reaction, hypothermia, lack of concentration, manic reaction, myasthenia, neuritis (mononeuritis), paralysis, paranoid ideation, psychosis, rigors, status epilepticus

Neuromuscular & skeletal: Arthralgia, dyskinesia, Lambert-Eaton syndrome, muscle spasm, rhabdomyolysis

Ophthalmic: Conjunctivitis, hemianopia, nystagmus disorder

Otic: Hearing loss

Renal: Acute kidney injury, nephrosis

Respiratory: Asthma, dyspnea, epistaxis, hypoxia, pleural effusion, pneumonia, pneumonitis, pulmonary hemorrhage, respiratory depression

Miscellaneous: Hyperpyrexia

Contraindications

Hypersensitivity to felbamate, carbamates, or any component of the formulation; history of any blood dyscrasia or hepatic dysfunction

Warnings/Precautions

Concerns related to adverse effects:

• Aplastic anemia: Felbamate is associated with a significant increased risk of aplastic anemia. Risk may be more than 100-fold greater than in untreated population. Current estimates of fatality are 20% to 30%, but higher rates (up to 70%) have been reported in the past. Aplastic anemia can develop at any point during therapy and for an unknown period of time after discontinuation of therapy. It is not known if dose, duration of therapy, or concomitant medication use affects risk. Routine blood monitoring may be helpful in detecting hematologic changes before any clinical onset of signs/symptoms of the disease; however, aplastic anemia often develops without any prior indication or warnings. Discontinue use if any evidence of bone-marrow suppression occurs.

• Hepatic failure: Felbamate has been associated with rare cases of hepatic failure (estimated >6 cases per 75,000 patients per year). Of the cases reported in the literature, 67% have resulted in fatality or liver transplant. Onset may or may not be preceded by prodromal symptoms. It is not known whether dose, duration of therapy, or concomitant medication use affects risk. Monitoring of serum transaminases has not been demonstrated to prevent serious hepatic injury, however, early diagnosis and drug withdrawal may improve the likelihood of recovery. Obtain baseline transaminase levels and periodically thereafter; discontinue use if transaminase levels increase to ≥2 times the ULN or with signs/symptoms suggesting hepatic failure. Therapy should not be initiated or reintroduced in patients with evidence of hepatic damage or who discontinue use for any reason.

• Suicidal ideation: Pooled analysis of trials involving various antiseizure medications (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify health care provider immediately if symptoms occur.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment; half-life is increased.

Concurrent drug therapy issues:

• Sedatives: CNS effects may be potentiated when used with other sedative drugs or ethanol.

Other warnings/precautions:

• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Suspension, Oral:

Felbatol: 600 mg/5 mL (237 mL [DSC], 946 mL [DSC])

Generic: 600 mg/5 mL (5 mL [DSC], 237 mL, 240 mL, 473 mL, 946 mL)

Tablet, Oral:

Felbatol: 400 mg, 600 mg [scored]

Generic: 400 mg, 600 mg

Generic Equivalent Available: US

Yes

Pricing: US

Suspension (Felbamate Oral)

600 mg/5 mL (per mL): $0.63 - $2.71

Tablets (Felbamate Oral)

400 mg (per each): $2.95 - $9.23

600 mg (per each): $3.83 - $10.57

Tablets (Felbatol Oral)

400 mg (per each): $17.64

600 mg (per each): $20.22

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Prescribing and Access Restrictions

A patient “informed consent” form should be completed and signed by the patient and physician. Copies are available from MEDA Pharmaceuticals by calling 800-526-3840.

Administration: Pediatric

Oral: May be administered without regard to meals; shake suspension well before use

Administration: Adult

Administer with or without food. Shake suspension prior to use.

Storage/Stability

Store in tightly closed container at controlled room temperature of 20°C to 25°C (68°F to 77°F).

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/UCM263034.pdf, must be dispensed with this medication.

Use

Monotherapy or adjunctive therapy in patients with partial seizures with and without secondary generalization (FDA approved in ages ≥14 years and adults); adjunctive therapy in children who have partial and generalized seizures associated with Lennox-Gastaut syndrome (FDA approved in ages 2 to 14 years). Note: Not recommended for first-line therapy; reserve for refractory clinical situations (failed other therapies) and where benefits exceed hematologic (aplastic anemia) and hepatotoxicity risks (AAN/AES [French 1999]).

Metabolism/Transport Effects

Substrate of CYP2E1 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C19 (weak)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

CarBAMazepine: Felbamate may increase serum concentrations of the active metabolite(s) of CarBAMazepine. Specifically, concentrations of the carbamazepine epoxide metabolite may be increased. CarBAMazepine may decrease the serum concentration of Felbamate. Felbamate may decrease the serum concentration of CarBAMazepine. Management: Initiate felbamate at typical doses (1,200 mg/day in 3 or 4 divided doses for adults and children 14 years of age or older; 15 mg/kg/day in 3 or 4 divided doses in children 2 to 14 years of age) while reducing the carbamazepine dose by 20%. Risk D: Consider therapy modification

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

CloBAZam: CYP2C19 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of CloBAZam. CYP2C19 Inhibitors (Weak) may increase the serum concentration of CloBAZam. Risk C: Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Felbamate. Risk C: Monitor therapy

Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy

DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

Fosphenytoin: May decrease the serum concentration of Felbamate. Felbamate may increase the serum concentration of Fosphenytoin. Management: Initiate felbamate at typical doses (1,200 mg/day in 3 or 4 divided doses for adults and children 14 years of age or older; 15 mg/kg/day in 3 or 4 divided doses in children 2 to 14 years of age) while reducing the fosphenytoin dose by 20%. Risk D: Consider therapy modification

Hormonal Contraceptives: Felbamate may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing felbamate to ensure contraceptive reliability. Risk D: Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification

Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mavacamten: CYP2C19 Inhibitors (Weak) may increase the serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a weak CYP2C19 inhibitor. For those stable on mavacamten who are initiating a weak CYP2C19 inhibitor, reduce mavacamten dose by one dose level. Risk D: Consider therapy modification

Mefloquine: May diminish the therapeutic effect of Antiseizure Agents. Mefloquine may decrease the serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyraPONE: Antiseizure Agents may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Mianserin: May diminish the therapeutic effect of Antiseizure Agents. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Orlistat: May decrease the serum concentration of Antiseizure Agents. Risk C: Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

PHENobarbital: May decrease the serum concentration of Felbamate. Felbamate may increase the serum concentration of PHENobarbital. Management: Initiate felbamate at typical doses (1,200 mg/day in 3 or 4 divided doses for adults and children 14 years of age or older; 15 mg/kg/day in 3 or 4 divided doses in children 2 to 14 years of age) while reducing the phenobarbital dose by 20%. Risk D: Consider therapy modification

Phenytoin: Felbamate may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Felbamate. Management: Initiate felbamate at typical doses (1,200 mg/day in 3 or 4 divided doses for adults and children 14 years of age or older; 15 mg/kg/day in 3 or 4 divided doses in children 2 to 14 years of age) while reducing the phenytoin dose by 20%. Risk D: Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Primidone: Felbamate may increase serum concentrations of the active metabolite(s) of Primidone. Specifically, phenobarbital concentrations may increase. Primidone may decrease the serum concentration of Felbamate. Management: Initiate felbamate at typical doses (1,200 mg/day in 3 or 4 divided doses for adults and children 14 years of age or older; 15 mg/kg/day in 3 or 4 divided doses in children 2 to 14 years of age) while reducing the primidone dose by 20%. Risk D: Consider therapy modification

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Ulipristal: Felbamate may decrease the serum concentration of Ulipristal. Risk X: Avoid combination

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Valproate Products: Felbamate may increase the serum concentration of Valproate Products. Management: Initiate felbamate at typical doses (1,200 mg/day in 3 or 4 divided doses for adults and children 14 years of age or older; 15 mg/kg/day in 3 or 4 divided doses in children 2 to 14 years of age) while reducing the valproate product dose by 20%. Risk D: Consider therapy modification

Vasopressin: Drugs Suspected of Causing SIADH may enhance the therapeutic effect of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification

Food Interactions

Tablet: Food does not affect absorption. Management: Administer without regard to meals.

Pregnancy Considerations

Postmarketing case reports in humans include fetal death, genital malformation, anencephaly, encephalocele, and placental disorder.

Patients exposed to felbamate during pregnancy are encouraged to enroll themselves into the North American Antiepileptic Drug (AED) Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.

Monitoring Parameters

CBC with differential, reticulocyte count, and platelet count (baseline, periodic during therapy, and after discontinuation [for significant period]); liver function tests (including bilirubin) (baseline, periodic during therapy); signs and symptoms of suicidality (eg, anxiety, depression, behavior changes).

Mechanism of Action

While not entirely known, felbamate likely possesses multiple mechanisms of action, including NMDA antagonism, calcium and sodium channel inhibition, and potentiation of GABA response (Abou-Khalil 2016; White 1999; manufacturer’s labeling).

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Rapid and almost complete; food has no effect upon the tablet's absorption (Patsalos 2018; manufacturer’s labeling).

Distribution: Vd: 0.7 to 0.91 L/kg (Patsalos 2018).

Protein binding: 22% to 48 % (Patsalos 2017), primarily to albumin.

Half-life elimination: 20 to 23 hours (average); prolonged by 9 to 15 hours in patients with renal impairment.

Bioavailability: >90% (Patsalos 2018).

Time to peak, serum: 2 to 6 hours (Patsalos 2018).

Excretion: Urine (40% to 50% as unchanged drug, 40% as inactive metabolites).

Clearance: Decreased in renal impairment (40% to 50%). Clearance faster in children than adults (20% to 65%) (Perucca 2006), particularly younger children (Carmant 1994).

Children 2 to 9 years: 61.3 ± 8.2 mL/kg/hour.

Children 10 to 12 years: 34.3 ± 4.3 mL/kg/hour.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Felbamyl;
  • (AT) Austria: Taloxa;
  • (BE) Belgium: Taloxa;
  • (CH) Switzerland: Taloxa;
  • (CO) Colombia: Taloxa;
  • (CZ) Czech Republic: Taloxa;
  • (DE) Germany: Taloxa;
  • (ES) Spain: Taloxa;
  • (FR) France: Taloxa;
  • (GB) United Kingdom: Taloxa;
  • (HU) Hungary: Taloxa;
  • (IE) Ireland: Felbatol;
  • (IT) Italy: Taloxa;
  • (LT) Lithuania: Taloxa;
  • (LU) Luxembourg: Taloxa;
  • (NL) Netherlands: Taloxa;
  • (NO) Norway: Taloxa;
  • (NZ) New Zealand: Taloxa;
  • (PL) Poland: Taloxa;
  • (PR) Puerto Rico: Felbatol;
  • (SE) Sweden: Taloxa;
  • (SK) Slovakia: Taloxa;
  • (UY) Uruguay: Felbamyl;
  • (ZA) South Africa: Taloxa
  1. Abou-Khalil BW. Antiepileptic drugs. Continuum (Minneap Minn). 2016;22(1):132-156. doi:10.1212/CON.0000000000000289 [PubMed 26844734]
  2. Bar-Oz B, Nulman I, Koren G, Ito S. Anticonvulsants and breast feeding: a critical review. Paediatr Drugs. 2000;2(2):113-126. [PubMed 10937463]
  3. Carmant L, Holmes GL, Sawyer S, et al. Efficacy of felbamate in therapy for partial epilepsy in children. J Pediatr. 1994;125(3):481-486. [PubMed 8071763]
  4. Felbamate [prescribing information]. Branchburg, NJ: Amneal Pharmaceuticals; February 2015.
  5. Felbatol tablet, suspension (felbamate) [prescribing information]. Somerset, NJ: MEDA Pharmaceuticals Inc; February 2018. [PubMed 8243374 ]
  6. French J, Smith M, Faught E, et al, “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,” Epilepsia, 1999, 40(6):803-8.
  7. Glue P, Sulowicz W, Colucci R, et al. Single-dose pharmacokinetics of felbamate in patients with renal dysfunction. Br J Clin Pharmacol. 1997;44(1):91-93. doi:10.1046/j.1365-2125.1997.00619.x [PubMed 9241102]
  8. Hägg S, Spigset O. Anticonvulsant use during lactation. Drug Saf. 2000;22(6):425-440. [PubMed 10877037]
  9. Patsalos PN, Spencer EP, Berry DJ. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: a 2018 update. Ther Drug Monit. 2018;40(5):526-548. doi:10.1097/FTD.0000000000000546 [PubMed 29957667]
  10. Patsalos PN, Zugman M, Lake C, et al. Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: a comparison of free non-protein-bound concentrations. Epilepsia. 2017;58:1234–1243. DOI:10.1111/epi.13802 [PubMed 28542801]
  11. Pellock JM, Faught E, Leppik IE, Shinnar S, Zupanc ML. Felbamate: consensus of current clinical experience. Epilepsy Res. 2006;71(2-3):89-101. doi:10.1016/j.eplepsyres.2006.06.020 [PubMed 16889941]
  12. Perucca E. Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age.Clin Pharmacokinet. 2006;45(4):351-363. [PubMed 16584283]
  13. Shi LL, Bresnahan R, Martin-McGill KJ, Dong J, Ni H, Geng J. Felbamate add-on therapy for drug-resistant focal epilepsy. Cochrane Database Syst Rev. 2019;8(8):CD008295. doi:10.1002/14651858.CD008295.pub5 [PubMed 31425617]
  14. Sparagana SP, Strand WR, Adams RC. Felbamate urolithiasis. Epilepsia. 2001;42(5):682-685. doi:10.1046/j.1528-1157.2001.32500.x [PubMed 11380578]
  15. White HS. Comparative anticonvulsant and mechanistic profile of the established and newer antiepileptic drugs. Epilepsia. 1999;40(suppl 5):S2-S10. doi:10.1111/j.1528-1157.1999.tb00913.x [PubMed 10530688]
Topic 13297 Version 390.0

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟