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Vigabatrin

Pronunciation

(vye GA ba trin)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Packet, Oral:

Sabril: 500 mg (50 ea)

Tablet, Oral:

Sabril: 500 mg [scored]

Brand Names: U.S.

  • Sabril

Pharmacologic Category

  • Anticonvulsant, Miscellaneous

Pharmacology

Irreversibly inhibits gamma-aminobutyric acid transaminase (GABA-T), increasing the levels of the inhibitory compound gamma amino butyric acid (GABA) within the brain. Duration of effect is dependent upon rate of GABA-T resynthesis.

Absorption

Rapid, complete

Distribution

Vd: 1.1 L/kg

Metabolism

Insignificant

Excretion

Urine (80% as unchanged drug)

Clearance: Infants: 2.4 ± 0.8 L/hour; Children: 5.7 ± 2.5 L/hour; Adults: 7 L/hour

Time to Peak

Infants (5 months to 2 years): 2.5 hours; Children (10 to 16 years) and Adults: 1 hour (2 hours with food)

Duration of Action

Resynthesis of GABA-T dependent: Variable (not strictly correlated to serum concentrations)

Half-Life Elimination

Prolonged in renal impairment

Infants (5 months to 2 years): ~5.7 hours; Children (4 to 14 years): ~5.5 hours (Sabril Canadian product monograph 2015); Children (10 to16 years): 9.5 hours; Adults: 10.5 hours

Special Populations: Renal Function Impairment

AUC increased 30% and half-life increased 55% in patients with mild renal impairment (CrCl >50 to 80 mL/minute). AUC and half-life increased twofold in patients with moderate renal impairment (CrCl >30 to 50 mL/minute). In patients with severe renal impairment (CrCl >10 to 30 mL/minute), AUC increased 4.5-fold and half-life increased 3.5-fold.

Special Populations: Elderly

Renal clearance was 36% lower in elderly patients compared with younger patients.

Special Populations: Children

The clearance was 2.4 and 5.8 L/hour in infants (5 months to 2 years) and children (10 to 16 years), respectively, compared with 7 L/hour in adults.

Special Populations: Race

Renal clearance was 25% lower in Japanese patients compared with white patients.

Use: Labeled Indications

US labeling:

Infantile spasms: As monotherapy for pediatric patients 1 month to 2 years of age with infantile spasms for whom the potential benefits outweigh the potential risk of vision loss.

Refractory complex partial seizures: As adjunctive therapy for adults and pediatric patients 10 years and older with refractory complex partial seizures who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss.

Canadian labeling:

Infantile spasms: As monotherapy for pediatric patients 2 months to 2 years of age with infantile spasms for whom the potential benefits outweigh the risk of ophthalmologic abnormalities.

Partial seizures with or without secondary generalization: As adjunctive therapy for adults and pediatric patients ≥2 years and older with partial seizures with or without secondary generalization who have inadequately responded to other antiepileptic drug therapy and for whom the potential benefits outweigh the risk of ophthalmologic abnormalities.

Contraindications

There are no contraindications listed in the manufacturer’s labeling.

Canadian labeling: Hypersensitivity to vigabatrin or any component of the formulation; pregnancy; breast-feeding

Dosing: Adult

US labeling:

Refractory complex partial seizures: Oral: Initial: 500 mg twice daily; increase daily dose by 500 mg increments at weekly intervals based on response and tolerability. Recommended dose: 1.5 g twice daily. Note: To taper, decrease dose by 1 g daily on a weekly basis.

Canadian labeling:

Partial seizures with or without secondary generalization (adjunctive treatment): Oral: Initial: 1 g/day in 1 or 2 divided doses (initial doses up to 2 g/day may be necessary for severe seizure activity); titrate daily dose in 0.5 g increments per tolerability and response; optimal range: 2 to 3 g/day (maximum dose: 3 g/day; higher doses are not associated with increased efficacy and may increase risk of adverse reactions). Note: To taper, decrease dose by1 g/day once a week. Discontinue therapy if clinically meaningful improvement in seizure control is not observed within 3 months.

Dosing: Geriatric

Refractory complex partial seizures: Refer to adult dosing. Initiate at low end of dosage range; monitor closely for sedation and confusion.

Dosing: Pediatric

US labeling:

Infantile spasms: Infants and Children 1 month to 2 years: Oral: Initial dosing: 50 mg/kg/day divided twice daily; may titrate upwards by 25 to 50 mg/kg/day increments every 3 days to a maximum of 150 mg/kg/day divided twice daily. Note: To taper, decrease dose by 25 to 50 mg/kg/day increments every 3 to 4 days.

Refractory complex partial seizures:

Children and Adolescents 10 to <17 years and 25 to 60 kg: Initial: 250 mg twice daily; increase daily dose by 500 mg increments at weekly intervals based on response and tolerability. Recommended dose: 1,000 mg twice daily. Note: To taper, decrease daily dose by one-third every week for 3 weeks.

Children ≥10 years and >60 kg and Adolescents ≥17 years: Refer to adult dosing.

Canadian labeling:

Infantile spasms: Infants and Children 2 months to 2 years: Oral solution: Initial dosing: 50 mg/kg/day divided twice daily; may titrate upwards by 25 to 50 mg/kg/day increments every 3 days to a maximum of 150 mg/kg/day. Note: To taper, decrease dose by 25 to 50 mg/kg/day increments every 3 to 4 days. Discontinue therapy if clinically meaningful improvement in seizure control is not observed within 4 weeks.

Partial seizures with or without secondary generalization (adjunctive treatment):

Children ≥2 years and Adolescents ≤16 years: Oral: Initial: 40 mg/kg/day divided twice daily; maintenance dosages based on patient weight:

10 to 15 kg: 500 to 1,000 mg daily divided twice daily

16 to 30 kg: 1,000 to 1,500 mg daily divided twice daily

31 to 50 kg: 1,500 to 3,000 mg daily divided twice daily

>50 kg: 2,000 to 3,000 mg daily divided twice daily

Adolescents ≥17 years: Refer to adult dosing.

Dosing: Renal Impairment

US labeling: Note: Renal function may be estimated using the Schwartz equation (children 10 to <12 years) and the Cockcroft-Gault formula (children ≥12 years, adolescents, and adults):

Children (≥10 years), Adolescents, and Adults:

CrCl >50 to 80 mL/minute: Decrease dose by 25%

CrCl >30 to 50 mL/minute: Decrease dose by 50%

CrCl >10 to 30 mL/minute: Decrease dose by 75%

Canadian labeling: Note: Renal function may be estimated using the Cockcroft-Gault formula:

CrCl >50 to 80 mL/minute: Decrease dose by 25%

CrCl >30 to 50 mL/minute: Decrease dose by 50%

CrCl >10 to 30 mL/minute: Decrease dose by 75%

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; has not been studied. However, does not undergo appreciable hepatic metabolism.

Reconstitution

Powder for oral solution: Dissolve each 500 mg powder packet in 10 mL of cold or room temperature water to make a 50 mg/mL solution. The Canadian labeling indicates that the powder may be dissolved with 10 mL of cold or room temperature water, fruit juice, milk, or infant formula. After reconstitution, use immediately; discard any unused portion or if the resulting solution is not free of particles or colorless.

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

Administration

Administer without regard to meals.

Oral solution: Administer using an oral syringe (provided).

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

Storage

Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

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

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

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

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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

ClonazePAM: Vigabatrin may enhance the CNS depressant effect of ClonazePAM. Vigabatrin may increase the serum concentration of ClonazePAM. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

Fosphenytoin: Vigabatrin may decrease the serum concentration of Fosphenytoin. Monitor therapy

Hydrocodone: CNS Depressants may enhance the CNS depressant effect of Hydrocodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

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

Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. 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 adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

Metyrosine: CNS Depressants may enhance the sedative effect of Metyrosine. Monitor therapy

Mianserin: May diminish the therapeutic effect of Anticonvulsants. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Orlistat: May decrease the serum concentration of Anticonvulsants. Monitor therapy

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

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification

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

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Phenytoin: Vigabatrin may decrease the serum concentration of Phenytoin. Monitor therapy

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

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

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

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

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

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. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Test Interactions

Vigabatrin has been reported to decrease AST and ALT activity in the plasma in up to 90% of patients, causing the enzymes to become undetectable in some patients; this may preclude use of AST and ALT as markers for hepatic injury. Vigabatrin may increase amino acids in the urine leading to false-positive tests for rare genetic metabolic disorders

Adverse Reactions

Note: Adult and pediatric information presented combined unless significantly different.

>10%:

Central nervous system: Somnolence (adults 22% to 24%; infants 17% to 45%), headache (33%), fever (adults 4% to 5%; infants 19% to 29%), fatigue (23% to 28%), dizziness (21% to 24%), irritability (adults 10%; infants 16% to 23%), sedation (adults 2% to 4%; infants 17% to 19%), insomnia (infants 10% to 12%)

Dermatologic: Rash (infants 8% to 11%)

Gastrointestinal: Vomiting (adults 7%; infants 14% to 20%), constipation (adults 6% to 8%; infants 12% to 14%), diarrhea (10% to 13%)

Neuromuscular & skeletal: Tremor (14% to 15%)

Ocular: Visual field constriction (≥30%), nystagmus (13% to 15%), blurred vision (11% to 13%)

Otic: Otitis media (infants 10% to 44%)

Respiratory: Upper respiratory tract infection (adults 7% to 9%; infants 46% to 51%), bronchitis (infants 30%), pharyngitis (13% to 14%), pneumonia (infants 11% to 13%), nasal congestion (infants 4% to 13%)

Miscellaneous: Viral infection (infants 19% to 20%)

1% to 10%:

Cardiovascular: Peripheral edema (2% to 5%), edema (1%)

Central nervous system: Memory impairment (7% to 10%), coordination impaired (7% to 9%), disturbance in attention (5% to 9%), depression (4% to 7%), lethargy (4% to 7%), seizure (infants 4% to 7%), confusion (4% to 6%), hypotonia (infants 4% to 6%), status epilepticus (2% to 6%), sensory disturbance (4% to 5%), anxiety (4%), hypoesthesia (3% to 4%), abnormal behavior (3%), abnormal thinking (3%), aggression (2%), postictal state (2%), vertigo (2%)

Dermatologic: Contusion (3% to 4%)

Endocrine & metabolic: Dysmenorrhea (7% to 9%), fluid retention (2%)

Gastrointestinal: Nausea (9% to 10%), appetite decreased (infants 7% to 9%), weight gain (6% to 8%), viral gastroenteritis (infants 5% to 6%), abdominal pain (3% to 5%), dyspepsia (4%), abdominal distention (2%), appetite increased (2%), hemorrhoidal symptoms (2%)

Genitourinary: Urinary tract infection (4% to 6%)

Neuromuscular & skeletal: Arthralgia (8% to 10%), pain in extremity (5% to 6%), back pain (4% to 6%), hyporeflexia (4% to 5%), paresthesia (5%), weakness (5%), hyper-reflexia (4%), myalgia (3%), muscle spasms (2% to 3%), dysarthria (2%), joint swelling (2%), shoulder pain (2%)

Ocular: Diplopia (3% to 7%), strabismus (5%), conjunctivitis (2% to 5%), eye strain (2%)

Otic: Tinnitus (2%)

Respiratory: Pharyngolaryngeal pain (7% to 9%), sinusitis (infants 5% to 9%), cough (2% to 8%), sinus headache (4% to 6%), dyspnea (2%)

Miscellaneous: Candidiasis (infants 3% to 8%), influenza (3% to 5%), croup (infants 1% to 5%), thirst (2%)

<1% (Limited to important or life-threatening): Acute psychosis, angioedema, cholestasis, deafness, delayed puberty, delirium, encephalopathy, facial edema, gastrointestinal hemorrhage, hypomania, laryngoedema, malignant hyperthermia, multiorgan failure, optic neuritis, pruritus, psychotic disorder, pulmonary embolism, respiratory failure, Stevens-Johnson syndrome, toxic epidermal necrolysis

ALERT: U.S. Boxed Warning

Vision loss:

Vigabatrin causes permanent bilateral concentric visual field constriction. Because assessing vision loss is difficult in infants and children, the frequency and extent of vision loss is poorly characterized in these patients. For this reason, the risk described below is primarily based on the adult experience.

In adults, 30% or more of patient scan be affected, ranging in severity from mild to severe, including tunnel vision to within 10 degrees of visual fixation, and can result in disability. In some cases, vigabatrin also can damage the central retina and may decrease visual acuity.

The onset of vision loss from vigabatrin is unpredictable and can occur within weeks of starting treatment or sooner, or at any time during treatment, even after months or years.

Symptoms of vision loss from vigabatrin are unlikely to be recognized by the patients or caregivers before vision loss is severe. Vision loss of milder severity, while often unrecognized by the patient or caregiver, can still adversely affect function.

The risk of vision loss increases with increasing dose and cumulative exposure, but there is no dose or exposure known to be free of risk of vision loss.

Unless a patient is formally exempted from periodic ophthalmologic assessment as documented in the SHARE program, assess vision to the extent possible at baseline (no later than 4 weeks after starting vigabatrin) and at least every 3 months during therapy. Vision assessment is also required about 3 to 6 months after the discontinuation of vigabatrin therapy. Once detected, vision loss caused by vigabatrin is not reversible. It is expected that, even with frequent monitoring, some patients will develop severe vision loss.

Consider drug discontinuation, balancing benefit and risk, if visual loss is documented.

It is possible that vision loss can worsen despite discontinuing vigabatrin.

Because of the risk of vision loss, withdraw vigabatrin from patients who do not show substantial clinical benefit within 3 months of initiation for patients with refractory complex partial seizures and within 2 to 4 weeks of initiation for patients with infantile spasms, or sooner if treatment failure becomes obvious. Periodically reassess patient response to and continued need for vigabatrin.

Do not use vigabatrin in patients with, or at high risk of, other types of irreversible vision loss unless the benefits of treatment clearly outweigh the risks. The interaction of other types of irreversible vision damage with vision damage from vigabatrin has not been well characterized, but is likely adverse.

Do not use vigabatrin with other drugs associated with serious adverse ophthalmic effects such as retinopathy or glaucoma unless the benefits clearly outweigh the risks.

Use the lowest dose and shortest exposure to vigabatrin that is consistent with clinical objectives.

The possibility that vision loss from vigabatrin may be more common, more severe, or have more severe functional consequences in infants and children than in adults cannot be excluded.

Because of the risk of permanent vision loss, vigabatrin is available only through a special restricted program under a risk evaluation and mitigation strategy (REMS) called the SHARE program. Further information is available at http://www.sabril.net or by calling 1-888-457-4273.

Warnings/Precautions

Concerns related to adverse effects:

• Anemia: Use has been associated with decreased hemoglobin and hematocrit; cases of significantly reduced hemoglobin (<8 g/dL) and/or hematocrit (<24%) have been reported.

• CNS effect: Somnolence and fatigue can occur with use; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Edema: Peripheral edema and edema independent of hypertension, heart failure, weight gain, renal or hepatic dysfunction has been reported.

• Neurotoxicity: Patients must be closely monitored for potential neurotoxicity (observed in animal models but not established in adults).

• Peripheral neuropathy: Peripheral neuropathy manifesting as numbness or tingling in the toes or feet, reduced distal lower limb vibration or position sensation, or progressive loss of reflexes, starting at the ankles, has been reported in adult patients.

• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (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 healthcare provider immediately if symptoms occur.

• Vision loss: [US Boxed Warning]: Vigabatrin causes permanent vision loss in infants, children, and adults. Due to the risk of vision loss and because vigabatrin, provides an observable symptomatic benefit when it is effective, the patient who fails to show substantial clinical benefit within a short period of time after initiation of treatment (2-4 weeks for infantile spasms; <3 months for refractory complex partial seizures), should be withdrawn from therapy. If in the clinical judgment of the prescriber evidence of treatment failure becomes obvious earlier in treatment, vigabatrin should be discontinued at that time. Patient response to and continued need for treatment should be periodically assessed. The onset of vision loss is unpredictable, and can occur within weeks of starting treatment or sooner, or at any time during treatment, even after months or years. The risk of vision loss increases with increasing dose and cumulative exposure, but there is no dose or exposure known to be free of risk of vision loss. It is possible that vision loss can worsen despite discontinuation. Assessment of vision loss is difficult in children and the frequency and extent of vision loss in infants and children is poorly characterized. Most data are available in adult patients. Vigabatrin causes permanent bilateral concentric visual field constriction in >30% of patients ranging in severity from mild to severe, including tunnel vision to within 10 degrees of visual fixation, and can result in disability. In some cases, vigabatrin can damage the central retina and may decrease visual acuity. In infants and children, symptoms of vision loss are unlikely to be recognized by the parent or caregiver before loss is severe. Vision loss of milder severity, although potentially unrecognized by the parent or caregiver, may still adversely affect function. Vision should be assessed to the extent possible at baseline (no later than 4 weeks after initiation), at least every 3 months during therapy and at 3-6 months after discontinuation. Once detected, vision loss is not reversible; even with frequent monitoring, it is expected that some patients will develop severe vision loss. Vigabatrin should not be used in patients with, or at high risk of, other types of irreversible vision loss unless the benefits of treatment clearly outweigh the risks. The interaction of other types of irreversible vision damage with vision damage from vigabatrin has not been well-characterized, but is likely adverse. Vigabatrin should not be used with other drugs associated with serious adverse ophthalmic effects such as retinopathy or glaucoma unless the benefits clearly outweigh the risks. The lowest dose and shortest exposure should be used that is consistent with clinical objectives. The possibility that vision loss from vigabatrin may be more common, more severe or have more severe functional consequences in infants and children than in adults cannot be excluded.

• Weight gain: Use has been associated with an average weight gain of 3.5 kg in adults and ≥7% of baseline body weight in pediatric patients.

Disease-related concerns:

• Psychiatric behavior: Use with caution in patients with a history of psychosis (psychotic/agitated reactions may occur more frequently), depression, or behavioral problems.

• Renal impairment: Use with caution in patients with renal impairment; modify dose in children (≥10 years) and adults with renal impairment (CrCl <80 mL/minute).

• Seizures: May cause an increase in seizure frequency in some patients; use with particular caution in patients with myoclonic seizures, which may be more prone to this effect.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Sedatives: Effects with other sedative drugs or ethanol may be potentiated.

Special populations:

• Elderly: Use with caution in the elderly as severe sedation and confusion have been reported; consider dose and/or frequency adjustments as renal clearance may be decreased.

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

Other warnings/precautions:

• Appropriate use: Vigabatrin is not indicated as a first-line agent for complex partial seizures.

• MRI abnormalities: Abnormal MRI changes have been reported in some infants. Resolution of MRI changes usually occurs with discontinuation of therapy. MRI changes were not seen in older children and adult patients.

• SHARE program: [US Boxed Warning]: Because of the risk of permanent vision loss, vigabatrin is only available through a restricted distribution program (SHARE) under a Risk Evaluation and Mitigation Strategy (REMS) program. Under the SHARE program, only prescribers and pharmacies registered with the program are able to prescribe and distribute vigabatrin. Vigabatrin may only be dispensed to patients who are enrolled in and meet all conditions of SHARE. Call 888-45-SHARE or visit http://sabril.net/ for further information.

• Withdrawal: Anticonvulsants 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.

Monitoring Parameters

Ophthalmologic examination by an ophthalmic professional with expertise in visual field interpretation and the ability to perform dilated indirect ophthalmoscopy of the retina at baseline (no later than 4 weeks after therapy initiation), periodically during therapy (every 3 months), and 3-6 months after discontinuation of therapy; assessment should include visual acuity and visual field whenever possible including mydriatic peripheral fundus examination and visual field perimetry. Due to the difficulty in performing perimetry in young children the Canadian labeling suggests that Visual Evoked Potentials may be used. Observe patient for excessive sedation, especially when instituting or increasing therapy; hemoglobin and hematocrit; suicidality (eg, suicidal thoughts, depression, behavioral changes); weight gain/edema

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Vigabatrin crosses the placenta in humans (Tran, 1998). Birth defects have been reported following use in pregnancy and include: cardiac defects, limb defects, male genital malformations, fetal anticonvulsant syndrome, renal and ear abnormalities. Time of exposure or maternal dosage was not reported and information is not available relating to the incidence or types of these outcomes in comparison to the general epilepsy population. Visual field examinations have been conducted following in utero exposure in a limited number of children tested at ≥6 years of age; no visual field loss was observed in 4 children and results were inconclusive in 2 others (Lawthorn 2009; Sorri 2005). Use during pregnancy is contraindicated in Canadian product labeling.

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

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, constipation, abdominal pain, cough, pharyngitis, rhinitis, headache, insomnia, joint pain, diarrhea, nausea, vomiting, tooth pain, back pain, or twitching. Have patient report immediately to prescriber burning or numbness feeling, angina, change in balance, tremors, severe dizziness, passing out, confusion, chills, loss of strength and energy, vision changes, blindness, involuntary eye movements, severe muscle pain, severe muscle weakness, edema, pain with urination, polyuria, excessive weight gain, memory impairment, abnormal gait, or signs of depression (suicidal ideation, anxiety, emotional instability, or illogical thinking) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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