Brivaracetam (brivaracetam)
Anticonvulsants Intravenous Vial (Ml); Oral Solution, Oral; Oral Tablet
Last reviewed · Source: First Databank (FDB) drug data
Overview
Brivaracetam, a pyrrolidine derivative, is an anticonvulsant.
Brivaracetam, a pyrrolidine derivative, is an anticonvulsant. The drug is structurally and chemically related to levetiracetam. The exact mechanism of action by which brivaracetam exerts its anticonvulsant effects has not been fully elucidated, but may be related to its potent and selective binding affinity for synaptic vesicle protein 2A (SV2A).
SV2A is a transmembrane glycoprotein that is widely distributed in the CNS; although its precise role in neurotransmission is not fully understood, it is thought to modulate synaptic vesicle exocytosis and neurotransmitter release. Reduced expression of SV2A has been demonstrated in patients with epilepsy, which correlates with data from animal models suggesting that SV2A deficiency increases seizure vulnerability. The anticonvulsant potency of selective SV2A ligands has been shown to be strongly correlated with their in-vitro binding affinity.
Brivaracetam demonstrates 15- to 30-fold higher affinity for SV2A than levetiracetam.
Brivaracetam does not appear to have effects on other known targets potentially involved in epilepsy, including voltage-gated potassium or calcium channels, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), gamma-aminobutyric acid A (GABAA), glycine, or N-methyl-D-aspartate (NMDA) receptors at therapeutic concentrations. Although brivaracetam has demonstrated inhibitory effects on voltage-gated sodium channels, this effect appears to be unrelated to the drug's anticonvulsant activity.
Brivaracetam exhibits dose-proportional pharmacokinetics over a dose range of 10-600 mg. The drug is rapidly and almost completely absorbed following oral administration; peak plasma concentrations are attained at a median of 1 hour (range: 0.25-3 hours) under fasting conditions. Administration with a high-fat meal slows the rate but not extent of absorption.
Following IV administration of a single 100-mg dose, plasma brivaracetam concentrations were initially higher within the first hour of dosing than with oral administration of the 50- and 100-mg tablets, but the dosage forms were bioequivalent in terms of overall exposure. Bioequivalence also has been demonstrated between the tablet and oral solution formulations of the drug. Brivaracetam distributes readily and rapidly into the CNS; in vitro and animal studies indicate that the drug crosses the blood-brain barrier faster and to a greater extent than levetiracetam, likely due to its increased lipophilicity.
Metabolism of brivaracetam occurs primarily via hydrolysis of the amide moiety by hepatic and extrahepatic amidase to form the carboxylic acid metabolite; a secondary pathway involves hydroxylation (mediated principally by CYP2C19) to form the hydroxy metabolite. An additional hydroxy acid metabolite is created by further biotransformation of these metabolites. None of the identified metabolites are pharmacologically active.
Brivaracetam and its metabolites are eliminated principally by renal excretion. Over 95% of a dose is excreted in the urine within 72 hours, with less than 10% as unchanged brivaracetam; fecal excretion accounts for less than 1% of the dose. The elimination half-life of brivaracetam is approximately 9 hours.
The drug is weakly bound (no more than 20%) to plasma proteins.
USES: Brivaracetam is used to treat seizures.
Generic name: brivaracetam
Pronunciation: (BRIV-a-RA-se-tam)
Drug class: Anticonvulsants
Therapeutic class: Central Nervous System Agents
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Brivaracetam
Indications
The following indications are listed for Brivaracetam:
- Focal Epilepsy
Also known as: Cortical Epilepsy, Focal Seizures, Local Epilepsy, Partial Epilepsy, Partial Onset Seizures, Partial Seizures.
Dosing
No dosing information is available for this tab.
Brivaracetam is administered orally (as tablets or oral solution). The drug also may be administered IV when oral administration is temporarily not feasible; the manufacturer states that clinical experience with IV brivaracetam is limited to 4 consecutive days of treatment.
Commercially available brivaracetam tablets and oral solution are bioequivalent, and the bioavailability of the tablets is similar to that of the injection formulation. All dosage forms can be used interchangeably without dosage adjustment.
Brivaracetam tablets and oral solution are administered orally twice daily without regard to food. The tablets should be swallowed whole with liquid, and not chewed or crushed. The oral solution is administered without dilution; if necessary, the solution may be administered through a nasogastric or gastric feeding tube. When using the brivaracetam oral solution, a calibrated measuring device should be used to measure and administer the prescribed dose; a household teaspoon or tablespoon is not an adequate measuring device. Unused portions of the oral solution should be discarded 5 months after the container is first opened.
Brivaracetam injection is administered twice daily by direct (''bolus'') IV injection or infusion over 2-15 minutes; the drug may be administered IV without further dilution or may be diluted with 0.9% sodium chloride, lactated Ringer's, or 5% dextrose injection. Diluted solutions of brivaracetam may be stored for up to 4 hours in polyvinyl chloride (PVC) bags at room temperature. Brivaracetam injection should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit; the drug should not be administered if discoloration or particulate matter is observed. Commercially available brivaracetam injection contains no preservatives and is intended for single use; any partially used vials should be discarded.
When discontinuing therapy, brivaracetam should be withdrawn gradually to minimize the potential for increased seizure frequency and status epilepticus in patients with seizure disorders. (See Discontinuance of Therapy under Cautions: Warnings/Precautions.)
Patients currently receiving or beginning therapy with brivaracetam and/or any other anticonvulsant for any indication should be closely monitored for the emergence or worsening of depression, suicidal thoughts or behavior (suicidality), and/or any unusual changes in mood or behavior. (See Suicidality Risk under Cautions: Warnings/Precautions.)
| Drug label | Dosing type | Instructions |
|---|---|---|
| Brivaracetam 10 Mg/Ml Oral Sol | Maintenance | Take 5 milliliters (50 mg) by oral route 2 times per day. |
| Brivaracetam 10 Mg Tablet | Maintenance | Take 1 tablet (10 mg) by oral route 2 times per day. |
| Brivaracetam 25 Mg Tablet | Maintenance | Take 1 tablet (25 mg) by oral route 2 times per day. |
| Brivaracetam 50 Mg Tablet | Maintenance | Take 1 tablet (50 mg) by oral route 2 times per day. |
| Brivaracetam 75 Mg Tablet | Maintenance | Take 1 tablet (75 mg) by oral route 2 times per day. |
| Brivaracetam 100 Mg Tablet | Maintenance | Take 1 tablet (100 mg) by oral route 2 times per day. |
| Brivaracetam 50 Mg/5 Ml Vial | Maintenance | Inject 5 milliliters (50 mg) over 2-15 minute(s) by intravenous route2 times per day. |
| Drug label | Dosing type | Instructions |
|---|---|---|
| Brivaracetam 10 Mg/Ml Oral Sol | Maintenance | Take 5 milliliters (50 mg) by oral route 2 times per day. |
| Brivaracetam 50 Mg/5 Ml Vial | Maintenance | Inject 5 milliliters (50 mg) over 2-15 minute(s) by intravenous route2 times per day. |
| Brivaracetam 10 Mg Tablet | Maintenance | Take 1 tablet (10 mg) by oral route 2 times per day. |
| Brivaracetam 25 Mg Tablet | Maintenance | Take 1 tablet (25 mg) by oral route 2 times per day. |
| Brivaracetam 50 Mg Tablet | Maintenance | Take 1 tablet (50 mg) by oral route 2 times per day. |
| Brivaracetam 75 Mg Tablet | Maintenance | Take 1 tablet (75 mg) by oral route 2 times per day. |
| Brivaracetam 100 Mg Tablet | Maintenance | Take 1 tablet (100 mg) by oral route 2 times per day. |
Drug interactions
Brivaracetam is metabolized to some extent by cytochrome P-450 (CYP) isoenzyme 2C19; additional biotransformation of the metabolites is mediated by CYP2C9. (See Description.)
Brivaracetam is a weak inhibitor of CYP2C19; however, this inhibition is not expected to be clinically important. The drug inhibits epoxide hydrolase in vitro. Brivaracetam does not inhibit CYP1A2, 2A6, 2B6, 2C8, 2C9, 2D6, or 3A4, nor induce CYP1A2, 2B6, 2C9, 2C19, 3A4, or epoxide hydrolase.
Brivaracetam is not a substrate of the efflux transporters P-glycoprotein (P-gp) or multidrug resistance proteins (MRP) 1 and MRP2. The drug does not inhibit P-gp, breast cancer resistance protein (BCRP), bile salt export pump (BSEP), multidrug and toxin extrusion transporters (MATE) 1 and MATE2/K, MRP2, organic anion transporters (OAT) 1 and OAT3, organic cation transporters (OCT) 1 and OCT2, or organic anion transport proteins (OATP) 1B1 and OATP1B3.
Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
Cyp3a4 Inducers/Lumateperone
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Lumateperone is a substrate of CYP3A4. Inducers of CYP3A4 may induce the metabolism of lumateperone.(1)
CLINICAL EFFECTS: The concurrent administration of a CYP3A4 inducer may decrease the exposure to lumateperone.(1)
PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.
PATIENT MANAGEMENT: The manufacturer of lumateperone states that concurrent use with CYP3A4 inducers should be avoided.(1)
DISCUSSION: Coadministration of lumateperone with rifampin, a strong CYP3A4 inducer, resulted in a 98% reduction in area-under-curve (AUC) and a 90% reduction in concentration maximum (Cmax).(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(2,3) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, efavirenz, elagolix, etravirine, fexinidazole, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, repotrectinib, rifabutin, telotristat, thioridazine, and tovorafenib.(2,3) Weak inducers of CYP3A4 include: amprenavir, armodafinil, aumolertinib, bexarotene, brivaracetam, clobazam, danshen, darolutamide, dexamethasone, dicloxacillin, echinacea, eslicarbazepine, garlic, genistein, gingko, ginseng, glycyrrhizin, nevirapine, omaveloxolone, oxcarbazepine, pioglitazone, quercetin, rufinamide, sotorasib, sulfinpyrazone, sunvozertinib, tecovirimat, terbinafine, ticlopidine, troglitazone, vemurafenib, and vinblastine.(2,3)
Cyp3a4 Inducers/Zuranolone
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Inducers of CYP3A4 may induce the metabolism of zuranolone.(1)
CLINICAL EFFECTS: Concurrent use of a CYP3A4 inducer may result in a loss of zuranolone efficacy.(1)
PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.
PATIENT MANAGEMENT: Avoid the concurrent use of zuranolone with CYP3A4 inducers.(1)
DISCUSSION: Coadministration of zuranolone with rifampin decreased the maximum concentration (Cmax) by 0.31-fold and area-under-curve (AUC) by 0.15-fold.(1) Strong CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort. Moderate CYP3A4 inducers linked to this monograph include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, fexinidazole, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib. Weak CYP3A4 inducers linked to this monograph include: armodafinil, aumolertinib, bexarotene, brigatinib, brivaracetam, clobazam, danshen, darolutamide, dexamethasone, dicloxacillin, echinacea, eslicarbazepine, flucloxacillin, garlic, genistein, ginseng, glycyrrhizin, methylprednisolone, mobocertinib, nevirapine, omaveloxolone, oritavancin, oxcarbazepine, pioglitazone, pitolisant, quercetin, relugolix, rufinamide, sarilumab, sulfinpyrazone, sunvozertinib, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vemurafenib, vinblastine, and zanubrutinib.(2,3)
Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
Brivaracetam; Lamotrigine; Perampanel/Rifampin; Rifapentine
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Rifampin and rifapentine may induce the metabolism of brivaracetam by CYP2C19(1) and lamotrigine(2,3) and perampanel(4) by CYP3A4.
CLINICAL EFFECTS: The concurrent use of rifampin or rifapentine with brivaracetam,(1) lamotrigine,(2,3) or perampanel(4) may result in decreased levels and clinical effectiveness of the anticonvulsant.
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Patients receiving rifampin or rifapentine concurrently with brivaracetam, lamotrigine, or perampanel should be observed for decreased anticonvulsant levels and clinical effectiveness. The dose of the anticonvulsant may need to be adjusted if the rifamycin is added to or removed from therapy. Refer to the current anticonvulsant prescribing information for information on dosage adjustments.
DISCUSSION: Concurrent rifampin decreases brivaracetam levels by 45%.(1) A study in 10 healthy subjects examined the effects of rifampin (600 mg daily for five days) on a single dose of lamotrigine (25 mg). Pretreatment with rifampin decreased the lamotrigine area-under-curve (AUC) and half-life (T1/2) by 43.7% and 40.8%, respectively. Lamotrigine clearance over bioavailability increased 98.3%. The amount of lamotrigine excreted as the glucuronide metabolite increased 36%.(2) A study in 10 healthy subjects examining the effects of rifampin (600 mg daily for 5 days) on a single dose of lamotrigine (25 mg) showed that rifampin increased the apparent clearance of lamotrigine by approximately 2-fold and decreased the AUC by 40%.(3) Rifampin and rifapentine are expected to decrease perampanel concentrations.(4)
Cyp3a4 Inducers/Erlotinib
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Inducers of CYP3A4 may induce the metabolism of erlotinib.(1)
CLINICAL EFFECTS: Concurrent or recent use of a CYP3A4 inducer may result in decreased levels and effectiveness of erlotinib.(1)
PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.
PATIENT MANAGEMENT: Avoid the concurrent use of CYP3A4 inducers in patients receiving therapy with erlotinib. Consider the use of alternative agents with less enzyme induction potential.(1) Consider increasing the dosage of erlotinib by 50 mg increments as tolerated at two week intervals (to a maximum of 450 mg) while closely monitoring the patient. The highest dosage studied with concurrent rifampin is 450 mg. If the dosage of erlotinib is increased, it will need to be decreased when the inducer is discontinued.(1)
DISCUSSION: Pretreatment and concurrent therapy with rifampin increased erlotinib clearance by 3-fold and decreased the erlotinib area-under-curve (AUC) by 66% to 80%. This is equivalent to a dose of about 30 mg to 50 mg in NSCLC.(1) In a study, pretreatment with rifampin for 11 days decreased the AUC of a single 450 mg dose of erlotinib to 57.6% of the AUC observed with a single 150 mg dose of erlotinib.(1) In a case report, coadministration of phenytoin (180mg daily) and erlotinib (150mg daily) increased the phenytoin concentration from 8.2mcg/ml to 24.2mcg/ml and decreased the erlotinib concentration 12-fold (from 1.77mcg/ml to 0.15mcg/ml) and increased the erlotinib clearance by 10-fold (from 3.53 L/h to 41.7 L/h).(2) In a study, concurrent use of sorafenib (400 mg twice daily) and erlotinib (150 mg daily) decreased the concentration minimum (Cmin), concentration maximum (Cmax), and AUC of erlotinib.(3) In an animal study, concurrent use of dexamethasone and erlotinib decreased the AUC of erlotinib by 0.6-fold.(4) Strong inducers of CYP3A4 include: barbiturates, encorafenib, enzalutamide, fosphenytoin, ivosidenib, mitotane, phenobarbital, phenytoin, primidone, rifampin, and rifapentine.(5,6) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, fexinidazole, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, sotorasib, telotristat, thioridazine, and tovorafenib.(5,6) Weak inducers of CYP3A4 include: amprenavir, armodafinil, aumolertinib, bexarotene, brigatinib, brivaracetam, clobazam, danshen, darolutamide, dicloxacillin, echinacea, eslicarbazepine, flucloxacillin, garlic, genistein, ginkgo, ginseng, glycyrrhizin, mobocertinib, nevirapine, omaveloxolone, oritavancin, oxcarbazepine, pioglitazone, pitolisant, quercetin, relugolix, rufinamide, sarilumab, sulfinpyrazone, sunvozertinib, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vemurafenib, vinblastine, and zanubrutinib.(5,6)
Moderate Interaction: Assess the risk to the patient and take action as needed.
Moderate And Weak Cyp3a4 Inducers/Tacrolimus
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: Moderate or weak CYP3A4 inducers may accelerate the metabolism of tacrolimus.(1)
CLINICAL EFFECTS: Concurrent use of a moderate or weak CYP3A4 inducer may result in decreased levels and effectiveness of tacrolimus.(1)
PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.
PATIENT MANAGEMENT: The manufacturer of tacrolimus recommends monitoring tacrolimus whole blood trough concentrations and adjusting tacrolimus dose if needed. Monitor clinical response closely.(1)
DISCUSSION: A 13-year-old cystic fibrosis patient with a history of liver transplant on stable doses of tacrolimus underwent 2 separate courses of nafcillin therapy (a moderate CYP3A4 inducer). During the 1st course of nafcillin, his tacrolimus levels started to fall 3 days after starting nafcillin, became undetectable at day 8, and recovered to therapeutic levels without a change in tacrolimus dose 5 days after discontinuation of nafcillin. During the 2nd course of nafcillin, tacrolimus level became undetectable 4 days after starting nafcillin and recovered 3 days after stopping nafcillin.(2) Moderate inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 50-80% and include: belzutifan, bosentan, cenobamate, dabrafenib, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, modafinil, nafcillin, repotrectinib, telotristat, and tovorafenib.(3,4) Weak inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 20-50% and include: armodafinil, bexarotene, brigatinib, brivaracetam, clobazam, danshen, darolutamide, dexamethasone, dicloxacillin, echinacea, elafibranor, enasidenib, eslicarbazepine, floxacillin, garlic, genistein, ginseng, glycyrrhizin, meropenem-vaborbactam, nevirapine, oritavancin, omaveloxolone, oxcarbazepine, pioglitazone, relugolix, rufinamide, sulfinpyrazone, sunvozertinib, suzetrigine, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vinblastine, and zanubrutinib.(3,4)
Moderate And Weak Cyp3a4 Inducers/Ubrogepant
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: Moderate or weak CYP3A4 inducers may induce the metabolism of ubrogepant.(1)
CLINICAL EFFECTS: Concurrent use of a moderate or weak CYP3A4 inducer may result in decreased levels and effectiveness of ubrogepant.(1)
PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.
PATIENT MANAGEMENT: The manufacturer recommends a dosage adjustment of ubrogepant when coadministered with moderate or weak CYP3A4 inducers. Initial dose of ubrogepant should be 100 mg. If a second dose is needed, the dose of ubrogepant should be 100 mg.(1)
DISCUSSION: Coadministration of ubrogepant with rifampin, a strong CYP3A4 inducer, resulted in an 80% reduction in ubrogepant exposure. No dedicated drug interaction studies were conducted to assess concomitant use with moderate or weak CYP3A4 inducers. Dose adjustment for concomitant use of ubrogepant with moderate or weak CYP3A4 inducers is recommended based on a conservative prediction of 50% reduction in exposure of ubrogepant.(1) Moderate inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 50-80% and include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, fexinidazole, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pexidartinib, rifabutin, telotristat, thioridazine, and tovorafenib.(2,3) Weak inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 20-50% and include: armodafinil, bexarotene, brigatinib, brivaracetam, clobazam, danshen, dexamethasone, dicloxacillin, echinacea, elafibranor, eslicarbazepine, floxacillin, garlic, genistein, ginseng, glycyrrhizin, meropenem-vaborbactam, methylprednisolone, nevirapine, omaveloxolone, oritavancin, oxcarbazepine, pioglitazone, pitolisant, relugolix, repotrectinib, rufinamide, sarilumab, sulfinpyrazone, sunvozertinib, suzetrigine, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vemurafenib, vinblastine, and zanubrutinib.(2,3)
Selected Moderate-Weak Cyp3a4 Inducers/Exemestane
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: CYP3A4 inducers may induce the metabolism of exemestane.(1)
CLINICAL EFFECTS: Concurrent use of a CYP3A4 inducer may result in decreased levels and effectiveness of exemestane.(1)
PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.
PATIENT MANAGEMENT: The US manufacturer of exemestane recommends that patients receiving concurrent therapy with a strong CYP3A4 inducer receive 50 mg of exemestane daily after a meal.(1) It may be prudent to consider a dosage increase for patients receiving weaker CYP3A4 inducers.
DISCUSSION: In a study in 10 healthy postmenopausal subjects, pretreatment with rifampin (a strong CYP3A4 inducer, 600 mg daily for 14 days) decreased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of exemestane (25 mg) by 54% and 41%, respectively.(1) Strong inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 80% or more and include: carbamazepine, enzalutamide, mitotane, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort.(1-3) Moderate inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 50-80% and include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, fexinidazole, lesinurad, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) Weak inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 20-50% and include: armodafinil, aumolertinib, bexarotene, brigatinib, brivaracetam, clobazam, danshen, darolutamide, dexamethasone, dicloxacillin, echinacea, elafibranor, enasidenib, eslicarbazepine, floxacillin, garlic, gingko, ginseng, glycyrrhizin, lorlatinib, meropenem-vaborbactam, methylprednisolone, nevirapine, omaveloxolone, oritavancin, oxcarbazepine, pioglitazone, pitolisant, quercetin, relugolix, rufinamide, sarilumab, sulfinpyrazone, sunvozertinib, suzetrigine, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vemurafenib, vinblastine, and zanubrutinib.(2,3)
Weak Cyp3a4 Inducers/Atogepant
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: Weak CYP3A4 inducers may increase the metabolism of atogepant by CYP3A4.(1)
CLINICAL EFFECTS: The concurrent use of weak CYP3A4 inducers with atogepant may result in decreased levels and clinical effectiveness of atogepant.(1)
PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.
PATIENT MANAGEMENT: The manufacturer of atogepant recommends that patients on concomitant weak CYP3A4 inducers receive atogepant 30 mg or 60 mg once daily for prevention of episodic migraines and receive atogepant 60 mg once daily for prevention of chronic migraines.(1) Patients receiving concurrent therapy with CYP3A4 inducers and atogepant should be observed for decreased clinical effectiveness.
DISCUSSION: In a study of healthy subjects, rifampin, a strong CYP3A4 inducer, decreased the area-under-curve (AUC) and maximum concentration (Cmax) of atogepant by 60% and 30%, respectively. Topiramate, a weak CYP3A4 inducer, decreased atogepant AUC and Cmax by 25% and 24%, respectively.(1) Weak CYP3A4 inducers linked to this monograph include: armodafinil, aumolertinib, bexarotene, brigatinib, brivaracetam, clobazam, danshen, darolutamide, dexamethasone, dicloxacillin, echinacea, eslicarbazepine, floxacillin, garlic, genistein, ginseng, glycyrrhizin, methylprednisolone, mobocertinib, nevirapine, omaveloxolone, oritavancin, oxcarbazepine, pioglitazone, pitolisant, quercetin, relugolix, rufinamide, sarilumab, sulfinpyrazone, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vemurafenib, vinblastine, and zanubrutinib.(1,2)
Contraindications
Known hypersensitivity to brivaracetam or any ingredients in the formulation. (See Sensitivity Reactions under Cautions: Warnings/Precautions.)
There are no contraindication contraindications for this drug.
- Child-pugh class A hepatic impairment
- Child-pugh class B hepatic impairment
- Child-pugh class C hepatic impairment
- Depression
- Disease of liver
- Suicidal ideation
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in at least 5% of patients with partial-onset seizures receiving brivaracetam in controlled clinical trials and at least 2% more frequently than with placebo include somnolence/sedation, dizziness, fatigue, nausea/vomiting, diarrhea, headache, insomnia, and nasopharyngitis.
Less Frequent
- Drug-induced psychosis
Rare or Very Rare
- Accidental fall
- Angioedema
- Bronchospastic pulmonary disease
- Leukopenia
- Neutropenic disorder
- Stevens-johnson syndrome
- Suicidal
- Suicidal ideation
- Toxic epidermal necrolysis
More Frequent
- Dizziness
- Drowsy
- Fatigue
- Nausea
- Sedation
- Symptoms of anxiety
- Vomiting
Less Frequent
- Aggressive behavior
- Agitation
- Ataxia
- Behavioral disorders
- Constipation
- Depression
- Dysgeusia
- Euphoria
- Gait abnormality
- Injection site sequelae
- Irritability
- Mood changes
- Nervousness
- Nystagmus
- Vertigo
Rare or Very Rare
- Indifference
Precautions
No enhanced messaging available.
Safety and efficacy of brivaracetam have not been established in pediatric patients younger than 16 years of age.
Category C. (See Users Guide.)
The North American Antiepileptic Drug (NAAED) Pregnancy Registry may be contacted at 888-233-2334 (for patients); NAAED registry information also is available on the website http://www.aedpregnancyregistry.org.
Brivaracetam produced developmental toxicity (e.g., decreased fetal weight gain, delayed sexual maturation, long-term neurobehavioral changes) and some evidence of embryolethality when administered orally to pregnant animals at exposure levels higher than those associated with the maximum recommended human dose.
It is not known whether brivaracetam is distributed into human milk; however, the drug is distributed into milk in rats. Because many drugs are distributed into human milk, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
Experience with brivaracetam in patients 65 years of age and older is insufficient to establish efficacy in this age group. The manufacturer recommends cautious dosage selection in geriatric patients, taking into consideration the greater frequency of decreased hepatic, renal, and/or cardiac function, and other concomitant medical conditions and drug therapy in this population.
In a study evaluating the pharmacokinetics of brivaracetam (200 mg twice daily) in geriatric individuals 65-79 years of age with creatinine clearance of 53-98 mL/minute per 1.73 m2, plasma half-life of the drug was 7.9 hours in individuals 65-75 years of age and 9.3 hours in those over 75 years of age; brivaracetam clearance was slightly lower in these geriatric individuals compared with healthy younger adults.
ICD codes
| Code | Type | Description |
|---|---|---|
| Focal epilepsy | ||
| G40.0 | ICD10CM | Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset |
| G40.00 | ICD10CM | Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, not intractable |
| G40.009 | ICD10CM | Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, not intractable, without status epilepticus |
| G40.01 | ICD10CM | Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, intractable |
| G40.019 | ICD10CM | Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, intractable, without status epilepticus |
| G40.1 | ICD10CM | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures |
| G40.10 | ICD10CM | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, not intractable |
| G40.109 | ICD10CM | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, not intractable, without status epilepticus |
| G40.11 | ICD10CM | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, intractable |
| G40.119 | ICD10CM | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, intractable, without status epilepticus |
| G40.2 | ICD10CM | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures |
| G40.20 | ICD10CM | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, not intractable |
| G40.209 | ICD10CM | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, not intractable, without status epilepticus |
| G40.21 | ICD10CM | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, intractable |
| G40.219 | ICD10CM | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, intractable, without status epilepticus |
| G40.C | ICD10CM | Lafora progressive myoclonus epilepsy |
| G40.C0 | ICD10CM | Lafora progressive myoclonus epilepsy, not intractable |
| G40.C01 | ICD10CM | Lafora progressive myoclonus epilepsy, not intractable, with status epilepticus |
| G40.C09 | ICD10CM | Lafora progressive myoclonus epilepsy, not intractable, without status epilepticus |
| G40.C1 | ICD10CM | Lafora progressive myoclonus epilepsy, intractable |
| G40.C11 | ICD10CM | Lafora progressive myoclonus epilepsy, intractable, with status epilepticus |
| G40.C19 | ICD10CM | Lafora progressive myoclonus epilepsy, intractable, without status epilepticus |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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