Vigabatrin increases the levels of inhibitory compound GABA in the brain. It is used as an antiepileptic medicine. [select-faq faq_id='7209']

Indications of Vigabatrin include:

• Infantile spasms:

  • Is used as a monotherapy for infantile spasms in babies 1 month to 2 years of age only in those where the potential benefits outweigh the potential risk of vision loss.

• Refractory complex partial seizures:

  • Used as adjunctive therapy in refractory complex partial seizures for adults and pediatric patients 10 years and older, who have partial or no response to several alternative treatments and only in those where the potential benefits outweigh the risk of vision loss.

Vigabatrin Dose in Adults

Dose in the treatment of Refractory complex partial seizures:

• • 500 mg orally 2 times/day initially.
  • The dose can be increased daily by 500 mg at weekly intervals on the basis on response and tolerability to a maximum dose of 1.5 gms 2 times/day.

Note: Withdraw slowly at the rate of 1g/day on a weekly basis if there is no substantial clinical benefit observed within three months of treatment initiation.

Vigabatrin Dose in Childrens

Note: Use the lowest effective and shortest exposure consistent with therapeutic objectives.

Dose in the treatment of Infantile spasms:

• Infants and Children 1 month to 2 years of age:
  • Powder for oral solution: 50 mg/kg/day orally divided 2 times/day initially
  • The dose may be titrated based on response and tolerability upwards by 25 - 50 mg/kg/day increments every 3 days to the maximum daily dose of 150 mg/kg/day divided in 2 times/day

Note:

• To taper, the dose should be decreased by 25 - 50 mg/kg/day every 3 - 4 days.
• If a substantial clinical benefit is not observed then withdraw therapy in 2 - 4 weeks or discontinue treatment if evidence of treatment failure becomes obvious earlier than 2 to 4 weeks.

Dose in the adjunctive treatment of Refractory complex partial seizures:

Note:

• The dose is dependent upon the weight and/or age.
• Withdraw slowly at the rate of 1g/day on a weekly basis if there is no substantial clinical benefit observed within 3 months of treatment initiation.
• Discontinue treatment if there is no response earlier than 3 months.

  ---

• Fixed dosing:

  • Children older than 10 years and Adolescents:
    • Patient weight 25 - 60 kg and age 10 - 16 years:
      • 250 mg orally 2 times/day initially
      • Increase the daily dose in 500 mg increments every week based on response and tolerability.
      • The recommended maintenance dose is 1,000 mg 2 times/day
      • To taper, decrease daily dose by one-third every week for 3 weeks.
    • Patient weight above 60 kg (regardless of age), or age above 16 years (regardless of weight):
      • 500 mg orally 2 times/day initially
      • Increase the daily dose in 500 mg increments every week based on response and tolerability.
      • The recommended dose is 1,500 mg 2 times/day.
      • To taper, decrease dose by 1,000 mg/day on a weekly basis.
  • Weight-band dosing:
    • Children ≥2 years and weighing ≥10 kg and Adolescents ≤16 years:
      • 40 mg/kg/day orally divided twice dailyinitially
      • The maintenance dosages are based on the patient's weight
      • Maintenance:
        • 10 to 15 kg: 500 to 1,000 mg/day orally divided 2 times/day.
        • 16 to 30 kg: 1,000 to 1,500 mg/day orally divided 2 times/day.
        • 31 to 50 kg: 1,500 to 3,000 mg/day orally divided 2 times/day.
        • >50 kg: 2,000 to 3,000 mg/day orally divided 2 times/day.

Pregnancy Risk Factor: C

• Studies on animals have shown that there are adverse reactions.
• Vigabatrin crosses a placental barrier in humans.
• Reports of birth defects have been made following pregnancy. These include male genital malformations and cardiac defects.
• It is not possible to report the duration of exposure and maternal dose.

Vigabatrin use during breastfeeding:

• Breast milk is present in very small quantities (=4% weight-adjusted maternal dosage).
• Breastfeeding mothers should not use the drug. Therefore, it is important to decide whether to stop breastfeeding or discontinue using the drug.

Vigabatrin dose in Renal disease:

Note: Cockcroft-Gault formula may be used to estimate renal function:

• CrCl >50 to 80 mL/minute:
  • Dose reduction by 25%
• CrCl >30 to 50 mL/minute:
  • Dose reduction by 50%
• CrCl >10 to 30 mL/minute:
  • Dose reduction by 75%

Vigabatrin Dose in Liver Disease:

There is no dose adjustment required/not been studied. 

Common Side Effects of Vigabatrin Include:

• Central Nervous System:
  • Drowsiness
  • Fatigue
  • Headache
  • Dizziness
  • Irritability
  • Sedated State
  • Insomnia
• Dermatologic:
  • Skin Rash
• Endocrine & Metabolic:
  • Weight Gain
• Gastrointestinal:
  • Vomiting
  • Diarrhea
  • Constipation
• Infection:
  • Viral Infection
• Neuromuscular & Skeletal:
  • Tremor
• Ophthalmic:
  • Visual Field Loss
  • Blurred Vision
  • Nystagmus Disorder
• Otic:
  • Otitis Media
  • Otic Infection
• Respiratory:
  • Upper Respiratory Tract Infection
  • Bronchitis
  • Nasopharyngitis
  • Pneumonia
  • Nasal Congestion
• Miscellaneous:
  • Fever

Less Common Side Effects of Vigabatrin Include:

• Cardiovascular:
  • Peripheral Edema
  • Edema
• Central Nervous System:
  • Disturbance In Attention
  • Ataxia
  • Memory Impairment
  • Paresthesia
  • Lethargy
  • Seizure
  • Depression
  • Hypotonia
  • Status Epilepticus
  • Abnormal Sensory Symptoms
  • Anxiety
  • Confusion
  • Hyperreflexia
  • Hypoesthesia
  • Hyporeflexia
  • Abnormal Behavior
  • Abnormality In Thinking
  • Dysarthria
  • Impaired Consciousness
  • Vertigo
  • Peripheral Neuropathy
• Endocrine & Metabolic:
  • Increased Thirst
• Gastrointestinal:
  • Nausea
  • Decreased Appetite
  • Viral Gastroenteritis
  • Upper Abdominal Pain
  • Dyspepsia
  • Stomach Discomfort
  • Abdominal Pain
  • Abdominal Distention
• Genitourinary:
  • Dysmenorrhea
  • Urinary Tract Infection
• Hematologic & Oncologic:
  • Anemia
  • Bruise
  • Decreased Hemoglobin
• Infection:
  • Candidiasis
  • Influenza
• Neuromuscular & Skeletal:
  • Arthralgia
  • Limb Pain
  • Asthenia
  • Back Pain
  • Muscle Spasm
  • Myalgia
• Ophthalmic:
  • Diplopia
  • Strabismus
  • Conjunctivitis
  • Asthenopia
• Otic:
  • Tinnitus
• Respiratory:
  • Sinusitis
  • Cough
  • Pharyngolaryngeal Pain
  • Sinus Headache
  • Croup

Frequency Not Defined:

• Central Nervous System:
  • Suicidal Ideation
  • Suicidal Tendencies
• Ophthalmic:
  • Decreased Visual Acuity
  • Permanent Vision Loss
  • Tunnel Vision
  • Visual Field Defect

Contraindication to Vigabatrin Include:

• Allergy reactions to vigabatrin and any component of this formulation
• Breastfeeding
• Pregnancy

Warnings and Precautions

• Anemia:
  • There have been cases of hemoglobin levels that were significantly lower than 8 g/dL and/or hematocrits that were less than 24 %.
• CNS depression:
  • CNS depression can lead to impairment of mental or physical abilities.
  • Patients should be cautious about tasks that require mental alertness, such as driving or operating machinery.
• Edema
  • Peripheral edema has been reported in cases that are not related to hypertension, heart disease, weight gain, renal dysfunction, or hypertension.
• Neurotoxicity:
  • Infants have experienced rare cases of intramyelinic swelling. 
  • Potential neurotoxicity must be monitored closely in infants. This has been observed in animal models, but not in adults.
• Peripheral neuropathy:
  • Adult patients have reported numbness or tingling in their feet or toes.
• Suicidal ideation:
  • Suicidal thoughts/behaviors may increase.
  • Watch out for any changes in behavior or thoughts that could indicate depression or suicidal thoughts.
  • Notify your healthcare provider immediately if you notice these symptoms.
• Vision loss: [US Boxed Warning]:
  • Vigabatrin can cause permanent visual impairment in children and adults.
  • Vigabatrin is associated with the risk of vision impairment and provides a measurable symptomatic benefit when effective.
  • Patients who fail to demonstrate substantial clinical benefit in a short time period after initiating treatment (i.e., infantile spasms or refractory complex partial seizures) should be removed from therapy.
  • Vigabatrin should not be used if the prescribing physician has identified evidence of treatment failure earlier than expected.
  • It is important to periodically assess the patient's response and ongoing need for treatment.
  • Vision loss can happen at any time, including weeks after treatment has begun.
  • While vision loss is more likely with increased doses and cumulative exposure, there are no known doses or exposures that are completely safe.
  • It is possible for vision loss to worsen even after discontinuation.
  • Children's vision loss can be difficult to assess. Infants and children have poor visual acuity.
  • The majority of data is available for adult patients.
  • Vigabatrin can cause permanent bilateral concentric visual field constriction. It is a medication that causes severe and permanent blindness in up to 30% of patients.
  • Vigabatrin may cause damage to the central retina in some cases and decrease visual acuity.
  • The caregiver or patient will not be able to recognize symptoms of vision loss before it is too severe.
  • Even though vision loss of milder severity may not be recognized by the caregiver or patient, it can still negatively affect one's ability to function.
  • It is important to evaluate the vision as soon as possible after initiation (not later than 4 weeks), every 3 to 6 months during therapy, and whenever discontinuation occurs.
  • Vision loss cannot be reversed once it is detected.
  • It is possible for some patients to develop severe vision loss even with regular monitoring.
  • Patients who are unable to be tested may continue treatment according to their clinical judgement, and with appropriate patient counseling.
  • Patients with irreversible vision loss or patients at high risk should not use Vigabatrin unless the benefits clearly outweigh any risks.
  • Although not well understood, it is possible that vigabatrin can cause irreversible damage to the eyes.
  • If the benefits outweigh any potential adverse effects, Vigabatrin should never be taken with other drugs such as glaucoma or retinopathy.
  • It is important to use the lowest dose and the shortest exposure possible, consistent with clinical goals.
  • It is possible that vision loss caused by vigabatrin could be more common in children and infants than in adults.
• Weight loss
  • The average weight gain associated with the use of this medication is 3.5kg in adults, and >7% in children.
• Psychiatric behavior
  • Patients with a history psychosis (psychotic/agitated responses may occur more often), depression, or other behavioral problems should be cautious.
• Renal impairment
  • Patients with impaired renal function should be cautious
  • Children and adults with impaired renal function (CrCl 80 mg/minute) can be modified to adjust the dose.
• Seizures:
  • Some patients may experience an increase in seizures frequency. Patients with myoclonic seizure disorder should be cautious.

Vigabatrin: Drug Interaction

Monitor:

• 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 to 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, preferably by automated threshold visual field testing.
• Observe patient for excessive sedation, especially when instituting or increasing therapy
• Hemoglobin and hematocrit
• Suicidality (eg, suicidal thoughts, depression, behavioral changes)
• Weight gain
• Edema

How to administer Vigabatrin?

• Administer without regard to meals.

Oral solution:

• Mix with water immediately prior to administration.
• Administer using an oral syringe provided by the manufacturer. 

Mechanism of action of Vigabatrin:

• The brain's levels of the inhibitory compound Gamma Amino Butyric Acid (GABA), increase by irreversibly inhibiting gamma-aminobutyric acids transaminase. 
• The rate at which GABA-T is resynthesis determines the duration of the effect.

Notice:It has not been proven that serum concentrations correlate with efficacy.

TimeRate of GABA-T Resynthesis Dependent: Variable (not directly correlated with serum concentrations).

Absorption is rapid and complete

Protein binding: It does not bind to plasma proteins.

Metabolism: Insignificant

Bioavailability: Tablet and oral solution are bioequivalent.

Half-life elimination:

• Renal Impairment prolongs half-life.
• Infants (5 months to 2 years):
  • ~5.7 hours
• Children (4 to 14 years):
  • ~5.5 hours
• Children (10 to 16 years):
  • 9.5 hours;
• Adults:
  • 10.5 hours

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)

Excretion: 80% of the drug is excreted via urine in unchanged form.

International Brands of Vigabatrin:

• Loxxovigin
• Pudida
• Sabril
• Sabrilan
• Sabrilex
• Sabrivatrin

Vigabatrin Brands in Pakistan: