Drugs List

Therapeutic Indications

Uses

Epilepsy-partial seizures with/without secondary generalisation-adjunctive
Monotherapy for infantile spasms (West's syndrome)

Monotherapy treatment of infantile spasms (West's syndrome).
Adjunctive treatment of resistant partial epilepsy with or without secondary generalised seizures not controlled adequately by conventional therapy or has not been tolerated.

Administration

Soluble tablets, tablets and granules for oral solution are for oral administration.

Granules for oral solution may be placed in a beverage (e.g. water, fruit juice or milk) immediately before oral administration.

Granules for oral solution may be dissolved in water and administered via the unlicensed route of rectum, following the same dosing schedule as the established oral dose for Resistant Partial Epilepsy.

Soluble tablets should be dissolved in water before oral administration.

Gastric administration of soluble tablets can be used for children who cannot swallow, but can be fed by enteral route.

Contraindications

Visual field defects
Breastfeeding

Precautions and Warnings

Children under 9 years
Elderly
History of psychiatric disorder
Pregnancy
Renal impairment - creatinine clearance below 60ml/minute
Renal impairment in children - eGFR < 60ml/minute/1.73m sq

Reduce dose and/or alter dose interval in patients with renal impairment
Advise patient ability to drive or operate machinery may be impaired
Folic acid 5mg daily required pre-conception to end of 1st trimester
Not all available brands are licensed for all age groups
Treatment to be initiated and supervised by a specialist
Monitor visual field status before and during treatment
Monitor for signs of suicide ideation or behaviour
Monitor neurological function
Monitor visual acuity during and after treatment
Refer women considering pregnancy for specialist advice and monitoring
Advise patient to report new visual problems and symptoms
Consider discontinuing if visual function deteriorates unexpectedly
Increased risk of irreversible visual field defects
May affect results of some laboratory tests
Avoid abrupt withdrawal
To discontinue, reduce dose gradually for last 2-4 weeks of therapy
Consider dose reduction or discontinuation if movement disorders occur
Reduce dose and/or alter dose interval in elderly patients
Advise patient not to take St John's wort concurrently
Advise patient to seek medical advice if treatment is ineffective
Advise patient/carers to report signs of suicide ideation or behaviour

Some patients may experience an increase in seizure frequency or the onset of new types of seizure. Abrupt withdrawal may also lead to rebound seizures.

Encephalopathic symptoms may be noticed soon after the initiation of vigabatrin treatment. Higher than recommended starting dose, faster dose escalation at higher steps than recommended, and renal failure may increase the risk of neurological adverse reactions. These events may be reversible following dose reduction or discontinuation of vigabatrin.

Abnormalities on Magnetic Resonance Imagine (MRI) scans have been observed during vigabatrin treatment for infantile spasms. Resolution usually occurs with discontinuation of treatment, however some lesions may be resolved despite continued use.

Some patients may experience visual field defects (VFD), featuring a higher risk for males than females. Data suggests one third of patients receiving vigabatrin develop visual field defects which may cause permanent vision loss. VFD onset usually occurs after months to years of therapy, and the degree of visual field restriction may be severe, VFD may persist after vigabatrin discontinuation, and further deterioration after discontinuation cannot be excluded. The usual pattern is a concentric constriction of the visual field of both eyes, which is generally more marked nasally than temporally.

VFD may not be detected until it is severe and child integrity may be affected by undetected moderate defects. Therefore, a vision assessment is required at baseline (no later than 4 weeks after starting treatment) and every 6 months while on therapy. This must be continued 6 to 12 months after the discontinuation of therapy. VFD may only be reliably detected by systematic perimetry which is only possible in patients with a developmental age of more than 9 years. Consequently, the risk of VFD due to vigabatrin treatment should be considered against the benefits when providing vigabatrin therapy in children under 9 years. There is currently no method to diagnose VFD in children under 9 years of age, frequency and severity have only been indirectly characterised in this population via the presence of electroretinogram or visual evoked potential anomalies.

Available data suggests that visual field defects are irreversible, so vigabatrin should only be used after a careful assessment of the risks and benefits compared to alternatives. Patients may be asymptomatic but have severe visual field defects confirmed during perimetry. Patients and caregivers should be given a thorough description of the frequency and implications of visual field defect development during vigabatrin treatment and advised to report any new visual problems and symptoms. If a visual field constriction is observed during follow-up, consideration should be given to gradual discontinuation of vigabatrin. If treatment continues, consideration should be given to more frequent perimetry in order to detect progression or sight threatening defects.

Visual acuity may be reduced in some patients, its prevalence is unknown. Some manufacturers recommend assessment of visual acuity during ophthalmological consultations, before initiation of treatment and every 6 months during treatment.

Pregnancy and Lactation

Pregnancy

Use vigabatrin with caution during pregnancy.

Manufacturers do not recommend using vigabatrin during pregnancy unless the women's clinical condition requires treatment.

Animal studies have shown reproductive toxicity. Available information regarding human studies have also shown reports of malformations including cleft lip, cardiovascular malformations and neural tube defects when treated with vigabatrin. Congenital abnormalities and spontaneous abortion were reported in infants of mothers taking vigabatrin, however, limited data available means it is not clear if vigabatrin produces an increased risk of malformation. Monotherapy should be practised when possible. There is limited data on the connection with visual field defects in children exposed to vigabatrin in utero.
In addition to the above risks, the impact to maternal health if treatment is changed or discontinued must also be considered. Treatment must not be discontinued abruptly and ongoing management should be discussed with an appropriate specialist

Schaefer (2015) suggests that the use of vigabatrin during the first trimester is not an indication for the termination of pregnancy. However, an increased risk of birth defects should be anticipated. A follow-up sonography should be performed to ascertain the normal development of the foetus.

Lactation

Vigabatrin is contraindicated during breastfeeding.

Manufacturers advises that the patient either discontinues vigabatrin or discontinues breastfeeding. Available data indicates vigabatrin is expressed in human breast milk, however, effects on exposed infants are unknown.

Side Effects

Abdominal pain
Abnormal thoughts
Aggression
Agitation
Anaemia
Angioedema
Arthralgia
Ataxia
Attention disturbances
Blurred vision
Confusion
Depression
Diplopia
Dizziness
Drowsiness
Dyskinesia
Dystonia
EEG changes
Encephalopathy
Excitation
Fatigue
Haemoglobin decrease
Hallucinations
Headache
Hepatitis
Hypertonia
Hypomania
Impaired concentration
Impaired memory
Impairment of mental skills
Involuntary movement disorders
Irritability
Mania
Minor psychiatric disturbances
Myoclonus
Nausea
Nervousness
Nystagmus
Oedema
Optic atrophy
Optic neuritis
Paraesthesia
Paranoia
Precipitation of status epilepticus
Psychosis
Rash
Reduced visual acuity
Retinal disturbances
Sedation
Seizure frequency increased
Somnolence
Speech disturbances
Stupor
Suicidal tendencies
Transaminases abnormal
Tremor
Urticaria
Visual field defects
Vomiting
Weight gain

Presentation

Oral formulations of vigabatrin.

Drugs List

Therapeutic Indications

Uses

Epilepsy-partial seizures with/without secondary generalisation-adjunctive
Monotherapy for infantile spasms (West's syndrome)

Monotherapy treatment of infantile spasms (West's syndrome).
Adjunctive treatment of resistant partial epilepsy with or without secondary generalised seizures not controlled adequately by conventional therapy or has not been tolerated.

Dosage

Tablets and granules for oral solution are administered once or twice daily.

Soluble tablets are for oral or gastric administration twice daily.

Adults

Children

Neonates

Administration

Soluble tablets, tablets and granules for oral solution are for oral administration.

Granules for oral solution may be placed in a beverage (e.g. water, fruit juice or milk) immediately before oral administration.

Granules for oral solution may be dissolved in water and administered via the unlicensed route of rectum, following the same dosing schedule as the established oral dose for Resistant Partial Epilepsy.

Soluble tablets should be dissolved in water before oral administration.

Gastric administration of soluble tablets can be used for children who cannot swallow, but can be fed by enteral route.

Contraindications

Visual field defects
Breastfeeding

Precautions and Warnings

Children under 9 years
Elderly
History of psychiatric disorder
Pregnancy
Renal impairment - creatinine clearance below 60ml/minute
Renal impairment in children - eGFR < 60ml/minute/1.73m sq

Reduce dose and/or alter dose interval in patients with renal impairment
Advise patient ability to drive or operate machinery may be impaired
Folic acid 5mg daily required pre-conception to end of 1st trimester
Not all available brands are licensed for all age groups
Treatment to be initiated and supervised by a specialist
Monitor visual field status before and during treatment
Monitor for signs of suicide ideation or behaviour
Monitor neurological function
Monitor visual acuity during and after treatment
Refer women considering pregnancy for specialist advice and monitoring
Advise patient to report new visual problems and symptoms
Consider discontinuing if visual function deteriorates unexpectedly
Increased risk of irreversible visual field defects
May affect results of some laboratory tests
Avoid abrupt withdrawal
To discontinue, reduce dose gradually for last 2-4 weeks of therapy
Consider dose reduction or discontinuation if movement disorders occur
Reduce dose and/or alter dose interval in elderly patients
Advise patient not to take St John's wort concurrently
Advise patient to seek medical advice if treatment is ineffective
Advise patient/carers to report signs of suicide ideation or behaviour

Some patients may experience an increase in seizure frequency or the onset of new types of seizure. Abrupt withdrawal may also lead to rebound seizures.

Encephalopathic symptoms may be noticed soon after the initiation of vigabatrin treatment. Higher than recommended starting dose, faster dose escalation at higher steps than recommended, and renal failure may increase the risk of neurological adverse reactions. These events may be reversible following dose reduction or discontinuation of vigabatrin.

Abnormalities on Magnetic Resonance Imagine (MRI) scans have been observed during vigabatrin treatment for infantile spasms. Resolution usually occurs with discontinuation of treatment, however some lesions may be resolved despite continued use.

Some patients may experience visual field defects (VFD), featuring a higher risk for males than females. Data suggests one third of patients receiving vigabatrin develop visual field defects which may cause permanent vision loss. VFD onset usually occurs after months to years of therapy, and the degree of visual field restriction may be severe, VFD may persist after vigabatrin discontinuation, and further deterioration after discontinuation cannot be excluded. The usual pattern is a concentric constriction of the visual field of both eyes, which is generally more marked nasally than temporally.

VFD may not be detected until it is severe and child integrity may be affected by undetected moderate defects. Therefore, a vision assessment is required at baseline (no later than 4 weeks after starting treatment) and every 6 months while on therapy. This must be continued 6 to 12 months after the discontinuation of therapy. VFD may only be reliably detected by systematic perimetry which is only possible in patients with a developmental age of more than 9 years. Consequently, the risk of VFD due to vigabatrin treatment should be considered against the benefits when providing vigabatrin therapy in children under 9 years. There is currently no method to diagnose VFD in children under 9 years of age, frequency and severity have only been indirectly characterised in this population via the presence of electroretinogram or visual evoked potential anomalies.

Available data suggests that visual field defects are irreversible, so vigabatrin should only be used after a careful assessment of the risks and benefits compared to alternatives. Patients may be asymptomatic but have severe visual field defects confirmed during perimetry. Patients and caregivers should be given a thorough description of the frequency and implications of visual field defect development during vigabatrin treatment and advised to report any new visual problems and symptoms. If a visual field constriction is observed during follow-up, consideration should be given to gradual discontinuation of vigabatrin. If treatment continues, consideration should be given to more frequent perimetry in order to detect progression or sight threatening defects.

Visual acuity may be reduced in some patients, its prevalence is unknown. Some manufacturers recommend assessment of visual acuity during ophthalmological consultations, before initiation of treatment and every 6 months during treatment.

Pregnancy and Lactation

Pregnancy

Use vigabatrin with caution during pregnancy.

Manufacturers do not recommend using vigabatrin during pregnancy unless the women's clinical condition requires treatment.

Animal studies have shown reproductive toxicity. Available information regarding human studies have also shown reports of malformations including cleft lip, cardiovascular malformations and neural tube defects when treated with vigabatrin. Congenital abnormalities and spontaneous abortion were reported in infants of mothers taking vigabatrin, however, limited data available means it is not clear if vigabatrin produces an increased risk of malformation. Monotherapy should be practised when possible. There is limited data on the connection with visual field defects in children exposed to vigabatrin in utero.
In addition to the above risks, the impact to maternal health if treatment is changed or discontinued must also be considered. Treatment must not be discontinued abruptly and ongoing management should be discussed with an appropriate specialist

Schaefer (2015) suggests that the use of vigabatrin during the first trimester is not an indication for the termination of pregnancy. However, an increased risk of birth defects should be anticipated. A follow-up sonography should be performed to ascertain the normal development of the foetus.

Lactation

Vigabatrin is contraindicated during breastfeeding.

Manufacturers advises that the patient either discontinues vigabatrin or discontinues breastfeeding. Available data indicates vigabatrin is expressed in human breast milk, however, effects on exposed infants are unknown.

Side Effects

Abdominal pain
Abnormal thoughts
Aggression
Agitation
Anaemia
Angioedema
Arthralgia
Ataxia
Attention disturbances
Blurred vision
Confusion
Depression
Diplopia
Dizziness
Drowsiness
Dyskinesia
Dystonia
EEG changes
Encephalopathy
Excitation
Fatigue
Haemoglobin decrease
Hallucinations
Headache
Hepatitis
Hypertonia
Hypomania
Impaired concentration
Impaired memory
Impairment of mental skills
Involuntary movement disorders
Irritability
Mania
Minor psychiatric disturbances
Myoclonus
Nausea
Nervousness
Nystagmus
Oedema
Optic atrophy
Optic neuritis
Paraesthesia
Paranoia
Precipitation of status epilepticus
Psychosis
Rash
Reduced visual acuity
Retinal disturbances
Sedation
Seizure frequency increased
Somnolence
Speech disturbances
Stupor
Suicidal tendencies
Transaminases abnormal
Tremor
Urticaria
Visual field defects
Vomiting
Weight gain

Effects on Laboratory Tests

Vigabatrin may increase the amount of amino acids in the urine possibly leading to a false positive test for certain rare genetic metabolic disorders (e.g. alpha aminoadipic aciduria).

Vigabatrin may also lead to a decrease in measured plasma activity of alanine aminotransferase (ALT) and to a lesser extent, aspartate aminotransferase (AST). The magnitude of suppression for ALT has been reported to vary between 30% and 100%. Therefore, these liver tests may be quantitatively unreliable in patients taking vigabatrin.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111.

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: July 2020

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Products Characteristics: Kigabeq 500mg soluble tablets. Veriton Pharma Ltd. Revised December 2019.

Summary of Products Characteristics: Kigabeq 100mg soluble tablets. Veriton Pharma Ltd. Revised December 2019.

Summary of Products Characteristics: Sabril 500mg film-coated tablets. SANOFI. Revised March 2020.

Summary of Products Characteristics: Sabril 500mg granules for oral solution. SANOFI. Revised March 2020.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 13 May 2020