Professional Drug Information > Sabril

Vigabatrin (Systemic)

VA CLASSIFICATION
Primary: CN400

Commonly used brand name(s): Sabril.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

^*Not commercially available in the U.S.

Category:


Anticonvulsant —

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

[Epilepsy (treatment adjunct)]—Vigabatrin is indicated for the adjunctive management of epilepsy that is not satisfactorily controlled by conventional therapy.^{01}

[Infantile spasms (treatment)]—Vigabatrin is indicated as initial monotherapy for the management of infantile spasms (West syndrome).^{01}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    129.16^{01}

pKa—
    4.02^{01}

Solubility
    Freely soluble in water, sparingly soluble in methanol, slightly soluble in ethanol, and in soluble in chloroform, hexane, and toluene.^{01}


pH
    20% aqueous solution: 6.8^{01}

Mechanism of action/Effect:

Vigabatrin indirectly increases the levels of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, by inhibiting the enzyme responsible for regulating GABA levels, gamma-aminobutyric acid transaminase (GABA-T).^{01}

Absorption:

Vigabatrin is rapidly absorbed following oral administration. The presence of food may slightly decrease the rate, but not the extent, of absorption.

Distribution:

The volume of distribution is slightly greater than that of total body water.^{01}

Elimination

Young adults: 5–8 hours^{01}

Elderly:12–13 hours^{01}

Renal Impairment: Prolonged; rate is directly related to renal clearance of creatinine^{01}

Time to peak concentration:

2 hours^{01}

Elimination:
    Renal: 70% is excreted as unchanged drug within the first 24 hours post-dose^{01}
    In dialysis: 40 to 60% reductions in vigabatrin plasma concentrations have been reported in patients with renal failure receiving hemodialysis.^{01}


Precautions to Consider

Carcinogenicity

No carcinogenic effects were observed in mice or rats that received doses of vigabatrin as high as 150 mg per kg of body weight per day for up to 24 months.^{01}

Mutagenicity

No evidence demonstrating a connection between vigabatrin administration and genotoxicity was found following studies involving in vitroand in vivosystems, eukaryotic and prokaryotic cells, and tests for both gene mutations and chromosome aberrations.^{01}

Pregnancy/Reproduction

Pregnancy—
Vigabatrin is not recommended during pregnancy. Risk-benefit must be carefully considered.

Studies in animals have shown that vigabatrin may cause serious neurotoxicity in the fetus.

Breast-feeding

It is not known whether vigabatrin is distributed into breast milk. However, the manufacturer states that vigabatrin therapy is contraindicated during lactation.^{01}

Pediatrics

Appropriate studies performed to date have not demonstrated pediatrics-specific problems that would limit the usefulness of vigabatrin in children greater than 2 months of age. However, because of the risks of ophthalmological abnormalities and the difficulty in assessing visual fields in infants and young children, vigabatrin should be used in these patients only if clearly indicated. The need for continued vigabatrin therapy for all infants and young children should be reassessed periodically, and frequent examination by a pediatric ophthalmologist is recommended.


Geriatrics


Although appropriate studies on the relationship of age to the effects of vigabatrin have not been performed in the geriatric population, no geriatrics-specific problems have been documented to date. However, elderly patients are more likely to have age-related renal function impairment, which may require adjustment of dosage in patients receiving vigabatrin.^{01}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Vigabatrin does not appear to induce the hepatic cytochrome P450 system.^{01}
Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Phenobarbital or
Phenytoin    (mean decreases in phenytoin (16–33%) and phenobarbital (9–21%) levels have been reported following concurrent vigabatrin administration; clinical relevance is unknown)

^{01}

Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT])
Aspartate aminotransferase (AST [SGOT]) and
Hemoglobin    (chronic treatment with vigabatrin may lead to slightly decreased levels. ^{01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Aggression or
» Psychotic tendencies    (patients with a history of these behavioral disturbances may be more likely to have an episode following vigabatrin therapy; patients should begin therapy at a lower dose and be monitored closely)

^{01}
Hypersensitivity to vigabatrin
» Myoclonic seizures    (seizure frequency may increase)

^{01}
» Renal impairment    (caution is warranted when creatinine clearance is < 60 mL/min; starting dose should be lowered and the patient closely monitored for adverse effects^{01})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Ophthalmic assessments, including expert mydriatic peripheral fundus examinations and visual field perimetry    (recommended prior to initiation of therapy and at periodic intervals [approximately every 3 months] during vigabatrin treatment)




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Amnesia^{01}
    
ophthalmological abnormalities, including bilateral optic disc pallor^{01} (decreased vision)
    
diplopia^{01} (double vision ; seeing double)
    
nystagmus^{01} (uncontrolled back-and-forth and/or rolling eye movements)
    
optic atrophy ^{01}(blindness; blurred vision; decreased vision; eye pain)
    
peripheral retinal atrophy (decreased vision)
    
and visual field constriction^{01} (decrease in vision or other change in vision)
^{01}    
seizures, increased^{01}

Note: Ophthalmological abnormalities reportedly occur from six months to more than 6 years following initiation of vigabatrin therapy; however, preliminary data shows that they occur most frequently in the 1st year of treatment with vigabatrin.


Incidence rare
    
Optic neuritis ^{01}( blue-yellow color blindness )



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Abdominal pain^{01}
    
agitation^{01}
    
anxiety^{01}
    
arthralgia^{01} (joint pain)
    
ataxia^{01} (shakiness and unsteady walk ; clumsiness, ; unsteadiness, ; trembling, ; or other problems with muscle control or coordination)
    
confusion^{01}
    
constipation^{01}
    
coordination abnormal^{01}
    
depression^{01}
    
dizziness^{01}
    
drowsiness^{01}
    
diarrhea^{01}
    
fatigue^{01}
    
hyperkinesia^{01} ( hyperactivity ; increased movement)— effect seen primarily in pediatric populations
    
paresthesia^{01} (tingling,; burning,; prickly sensations)
    
somnolence^{01} (sleepiness or unusual drowsiness)
    
tremor^{01}

Incidence less frequent
    
Aggression^{01} —effect seen primarily in pediatric populations
    
concentration impaired ^{01}
    
emotional lability^{01}
    
headache^{01}
    
hyporeflexia^{01}
    
hypotonia^{01} ( muscle weakness)—effect seen primarily in pediatric populations
    
increased saliva^{01} —effect seen primarily in pediatric populations
    
insomnia^{01}
    
nausea^{01}
    
speech disorder^{01}
    
thinking abnormal^{01}
    
urinary tract infection^{01}
    
vomiting^{01}
    
weight gain^{01}





Overdose
For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
    
Abnormal behavior
    
agitation
    
apnea ( bluish lips or skin ; difficulty in breathing)
    
bradycardia (slow or irregular heartbeat (less than 50 beats per minute) ; light-headedness ; dizziness or fainting ; unusual tiredness)
    
coma
    
confusion
    
hypotension (low blood pressure)
    
irritability
    
loss of consciousness
    
psychosis (mood or mental changes )
    
respiratory depression
    
speech disorder
    
vertigo ( dizziness or light-headedness ; feeling of constant movement of self or surroundings ; sensation of spinning)


Treatment of overdose


To enhance elimination :
Plasma concentrations have been reduced (40–60%) by hemodialysis within renal failure populations^{01}. However, the role of hemodialysis in the treatment of vigabatrin overdose is unknown.



Specific treatment:
There is no specific antidote. Treatment should be symptomatic and supportive.^{01}

+



Supportive care:
Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Vigabatrin (systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to vigabatrin or any of its components

Pregnancy— Contraindicated for use during pregnancy





Breast-feeding—Contraindicated for use during breast feeding





Use in the elderly—Due to the fact that vigabatrin is eliminated by the kidney, caution should be used when administering the drug to elderly patients
Other medical problems, especially a history of aggression, myoclonic seizures, psychotic tendencies, or renal impairment

Proper administration
For powder (sachet) dosage form—Mixing contents in 10 mL of water, fruit juice, milk, or infant formula immediately before use, and then administering the appropriate aliquot with an oral syringe

» Proper dosing
Taking as soon as possible; not taking if almost time for next scheduled dose; not doubling doses

Proper storage

Precautions while using this medication
Regular visits to physician to check progress

» Eye examinations every 3 months to help avoid potential reactions

» Caution when driving, using machines, or doing other jobs requiring alertness

» Checking with physician before discontinuing medication; gradual dosage reduction usually needed to maintain seizure control


Side/adverse effects
Signs of potential side effects, especially amnesia, ophthalmological effects, or increased seizure frequency


For oral dosing forms:
Vigabatrin may be taken with or without food

Abrupt discontinuation of vigabatrin treatments may cause an increase in epileptic episodes. The dose should be gradually reduced over a 2 to 4 week period.

Entire contents of packet (sachet) should be dissolved in cold or room temperature water, juice, or milk immediately prior to oral administration.^{01}


Oral Dosage Forms

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

VIGABATRIN FOR ORAL SOLUTION

Usual Adult Dose
[Antiepileptic ]
Oral, initially 1 gram per day; increasing by increments of 500 mg to between 2 grams and 4 grams per day depending on clinical response and tolerability. ^{01}


Note: Lower doses should be used to initiate vigabatrin treatment in elderly patients or in patients with a creatinine clearance < 60 mL per minute. These patients should be observed closely for adverse effects, such as sedation and confusion.^{01}


Usual adult prescribing limits
4 grams per day. Doses higher than 4 grams per day do not result in improved efficacy.^{01}

Usual Pediatric Dose
[Antiepileptic ]
Oral, initially 40 mg per kg of body weight (mg/kg) per day; increasing to 80 to 100 mg/kg per day in two divided doses^{01}. Therapy may be started at 500 mg per day and increased by increments of 500 mg per day at weekly intervals, depending on response.^{01}

For patients weighing 10 to 15 kg: 0.5 to 1 gram per day

For patients weighing 16 to 30 kg: 1 to 1.5 grams per day

For patients weighing 31 to 50 kg: 1.5 to 3 grams per day

For patients weighing over 50 kg: 2 to 4 grams per day

[Infantile spasm treatment ]
Oral, 50 to 100 mg per kg per day in two divided doses, depending on spasm severity Dosage may be titrated upward over 1 week. Daily doses of up to 150 mg/kg/day have been used with good tolerability^{01}


Usual pediatric prescribing limits

Usual Geriatric Dose
See Usual adult dose.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


0.5 grams (500 mg) (Rx) [Sabril ( film-coated)]

Packaging and storage:
Store between 15 and 30 °C (room temperature), in a tight container. Protect from moisture.^{01}

Preparation of dosage form:
Dissolve contents of the packet (sachet) in 10 mL of cold or room temperature water, juice, or milk, immediately before administration. For an infant, the contents also may be dissolved in 10 mL of infant formula, and the appropriate dose drawn up and administered with an oral syringe.^{01}

Auxiliary labeling:
   • May cause drowsiness^{01}.
   • May cause dizziness^{01}.

Additional information:
May be taken with or without food.^{01}


VIGABATRIN TABLETS

Usual adult dose
See Vigabatrin for Oral Solution

Usual adult prescribing limits
See Vigabatrin for Oral Solution

Usual pediatric dose
See Vigabatrin for Oral Solution

Usual geriatric prescribing limits
See Vigabatrin for Oral Solution

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


500 mg (Rx) [Sabril]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), in a tight container. Protect from moisture.^{01}

Auxiliary labeling:
   • May cause drowsiness^{01}.
   • May cause dizziness^{01}.

Developed: 03/05/2001

References

1. Product Information: Sabril®, vigabatrin. Aventis Pharma Inc., Laval, Quebec (PI revised 09/2000) reviewed 01/2001.
   

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