KIGABEQ: Uses, Dosage & Side Effects

What Is KIGABEQ and What Is It Used For?

KIGABEQ contains the active substance vigabatrin, a well-established antiepileptic drug that has been used in clinical practice since the late 1980s. Vigabatrin is classified as a fatty acid derivative antiepileptic agent (ATC code N03AG04). KIGABEQ represents a paediatric-adapted formulation of vigabatrin, developed specifically to address the dosing challenges encountered when treating very young children. While vigabatrin has been available for many years as granules for oral solution under the brand name Sabril, KIGABEQ provides a distinct advantage: its scored soluble tablets in 100 mg and 500 mg strengths allow for more precise, weight-based dose adjustments that are critical in the rapidly changing physiology of growing infants and young children.

KIGABEQ was classified as a "hybrid medicine" by the European Medicines Agency (EMA), meaning it is related to an existing reference medicine (Sabril) but offers a different pharmaceutical form better suited to its target population. The EMA granted marketing authorisation for KIGABEQ in September 2018, recognising the important clinical need for an age-appropriate vigabatrin formulation in paediatric epilepsy care. The marketing authorisation holder is ORPHELIA Pharma SAS, based in Paris, France. KIGABEQ is not currently approved by the U.S. Food and Drug Administration (FDA); in the United States, vigabatrin is available as Sabril.

Vigabatrin works through a unique pharmacological mechanism among antiepileptic drugs. It is a selective, irreversible inhibitor of GABA transaminase (GABA-T), the enzyme responsible for the breakdown (catabolism) of gamma-aminobutyric acid (GABA) in the brain. GABA is the most important inhibitory neurotransmitter in the central nervous system, playing a fundamental role in regulating neuronal excitability. When neurons become excessively excitable and fire in uncontrolled patterns, seizures occur. By permanently inactivating GABA-T, vigabatrin prevents the degradation of GABA, causing its concentration in the brain to rise significantly. This elevated GABA level enhances inhibitory neurotransmission, effectively dampening the excessive electrical activity that underlies seizures.

The irreversible nature of vigabatrin's enzyme inhibition is pharmacologically noteworthy. Unlike many drugs whose effects cease when the drug is cleared from the body, vigabatrin's anticonvulsant effect persists until the body synthesises new GABA-T enzyme molecules, a process that takes several days. This means the clinical duration of action is determined by the rate of enzyme resynthesis rather than by the plasma half-life of the drug itself (which is approximately 5–8 hours). This pharmacokinetic-pharmacodynamic dissociation is an important concept for clinicians and caregivers to understand when managing dose timing and treatment discontinuation.

KIGABEQ is indicated for two specific clinical conditions in children aged 1 month to under 7 years:

• Infantile spasms (West syndrome) – as monotherapy: Infantile spasms are a severe form of epilepsy that typically presents between 3 and 12 months of age. The condition is characterised by clusters of sudden, brief involuntary movements (spasms) often involving flexion or extension of the trunk, limbs, and neck. West syndrome classically includes a triad of infantile spasms, a specific electroencephalographic (EEG) pattern called hypsarrhythmia, and developmental regression. International guidelines, including those from the International League Against Epilepsy (ILAE) and the National Institute for Health and Care Excellence (NICE), recognise vigabatrin as a first-line treatment for infantile spasms, particularly when tuberous sclerosis complex (TSC) is the underlying cause, where response rates exceed 90%.
• Resistant partial epilepsy (focal onset seizures) – as add-on therapy: KIGABEQ is also indicated as adjunctive (add-on) treatment in children with partial epilepsy (also known as focal seizures) with or without secondary generalisation, when all other appropriate drug combinations have proved inadequate or have not been tolerated. This means KIGABEQ is reserved for cases where standard first-line and second-line antiepileptic medications have failed to achieve adequate seizure control.

What Should You Know Before Taking KIGABEQ?

Contraindications

KIGABEQ must not be used in the following situations:

• Hypersensitivity: Do not use KIGABEQ if the child has a known allergy to vigabatrin or to any of the excipients in the formulation (crospovidone type B, mannitol, or sodium stearyl fumarate). Allergic reactions to vigabatrin are uncommon but can include rash, urticaria (hives), and in rare cases, angioedema (swelling of the face, lips, tongue, or throat).
• Pre-existing visual field defects: KIGABEQ is absolutely contraindicated in patients with any clinically significant visual field defect that has been identified prior to treatment. Since vigabatrin carries a substantial risk of causing further visual field constriction, administering the drug to a patient with existing visual impairment would be clinically inappropriate and potentially dangerous.

Warnings and Precautions

Before and during treatment with KIGABEQ, the following precautions must be observed:

• Visual field monitoring: A baseline ophthalmological examination should be performed within 4 weeks of starting KIGABEQ. Systematic perimetry (visual field testing) should be repeated every 6 months. For children under 9 years of age who cannot reliably perform standard perimetry, electroretinography (ERG) is recommended as an alternative monitoring tool. If visual field defects are detected, the risks and benefits of continuing treatment must be carefully reassessed. Monitoring must continue for 6–12 months after vigabatrin is discontinued.
• Suicidal ideation and behaviour: An increased risk of suicidal thoughts and behaviour has been reported with antiepileptic drugs, including vigabatrin. Patients (and their caregivers) should be monitored for signs of depression, behavioural changes, or suicidal ideation, and medical advice should be sought immediately if such symptoms emerge.
• Encephalopathic symptoms: In rare cases, vigabatrin can cause encephalopathy-like symptoms, including marked sedation, stupor, and confusion. Risk factors include using a higher-than-recommended starting dose, rapid dose escalation, and renal impairment. If encephalopathic symptoms develop, the dose should be reduced or the drug discontinued.
• MRI abnormalities: Magnetic resonance imaging (MRI) studies have shown T2-weighted hyperintensities and restricted diffusion in certain brain regions (particularly the thalamus, basal ganglia, brainstem, and cerebellum) in approximately 22% of vigabatrin-treated infants, compared with only 4% receiving other therapies. These abnormalities are generally reversible upon discontinuation of vigabatrin, but their long-term clinical significance is not fully understood.
• Movement disorders: Cases of dystonia, dyskinesia, and hypertonia have been reported in patients taking vigabatrin. If involuntary movements develop, the prescribing physician should assess whether the benefits of continued treatment outweigh the risks.
• Abrupt withdrawal: KIGABEQ should never be stopped abruptly, as this may trigger rebound seizures. The dose should be gradually reduced over a period of 2–4 weeks under medical supervision.
• Psychiatric effects: Agitation, depression, paranoid reactions, and psychosis have been reported. These are more common in adults but should be monitored in paediatric patients as well.
• Laboratory test interference: Vigabatrin suppresses alanine aminotransferase (ALT) enzyme activity by 30–100%, which may interfere with liver function tests and lead to falsely normal ALT results. Additionally, vigabatrin may cause false positive results on urinary amino acid screening tests.

Pregnancy and Breastfeeding

KIGABEQ is a paediatric-specific formulation intended for children aged 1 month to under 7 years and is therefore not intended for use in women of childbearing potential or in breastfeeding mothers. The relevant safety considerations regarding vigabatrin use during pregnancy and breastfeeding apply to the reference medicine Sabril, which is available in formulations used by adults. Animal studies with vigabatrin have not shown adverse effects on male or female fertility. For comprehensive information about vigabatrin use in pregnancy or breastfeeding, healthcare providers should consult the Sabril Summary of Product Characteristics.

Renal Impairment

Because vigabatrin is eliminated unchanged by the kidneys, patients with renal impairment (creatinine clearance less than 60 ml/min) require dose adjustment and particularly close monitoring for adverse effects, especially sedation, confusion, and encephalopathic symptoms. The prescribing physician should consider reducing the dose and monitoring serum drug levels where possible. Vigabatrin is not significantly removed by haemodialysis.

How Does KIGABEQ Interact with Other Drugs?

One of the pharmacological advantages of vigabatrin is its remarkably low potential for drug interactions. Unlike many antiepileptic drugs that are extensively metabolised by hepatic cytochrome P450 (CYP) enzymes and bound to plasma proteins – creating numerous opportunities for pharmacokinetic interactions – vigabatrin follows a simple pharmacokinetic pathway. It is rapidly absorbed after oral administration, is not bound to plasma proteins, is not metabolised by the liver, and is eliminated almost entirely unchanged through renal excretion. This pharmacokinetic profile means that vigabatrin neither affects the metabolism of other drugs nor is its own clearance significantly altered by other medications.

Vigabatrin does not induce or inhibit hepatic CYP enzymes, meaning it will not accelerate or slow the metabolism of other medicines that are processed through the liver. This is particularly relevant in the paediatric epilepsy setting, where children are frequently treated with multiple antiepileptic drugs simultaneously and where drug interactions can complicate treatment and increase the risk of adverse effects.

Despite this generally favourable interaction profile, there are several specific interactions and precautions to be aware of:

Laboratory Test Interactions

An important non-drug interaction that clinicians and caregivers should be aware of is vigabatrin's effect on certain laboratory tests. Vigabatrin suppresses alanine aminotransferase (ALT) enzyme activity by 30–100%. This means that standard liver function tests may show falsely normal ALT values in patients taking vigabatrin, potentially masking liver disease. If liver function monitoring is needed, clinicians should rely on alternative markers such as aspartate aminotransferase (AST) or gamma-glutamyl transferase (GGT), and should inform the laboratory that the patient is receiving vigabatrin.

Additionally, vigabatrin increases the amount of amino acids excreted in the urine, which may produce false positive results on standard newborn screening tests for amino acid disorders or other urinary amino acid analyses. This is important to communicate to neonatal screening programmes and laboratory staff to avoid unnecessary follow-up investigations.

What Is the Correct Dosage of KIGABEQ?

KIGABEQ dosing is weight-based and must be carefully individualised for each child. The tablets are dissolved in 5–10 ml of cold or room temperature water before administration. The solution, which appears whitish and slightly cloudy, should be taken immediately after preparation – it must not be stored for later use. Both the 100 mg and 500 mg tablets have a score line that allows them to be divided into equal halves for more precise dosing. KIGABEQ can be given with or without food, and it can be administered orally or through a gastric (nasogastric) tube.

Infantile Spasms (West Syndrome) – Monotherapy

The recommended starting dose for infantile spasms is 50 mg/kg/day, divided into two daily administrations. If spasms persist after the initial 3-day period, the dose may be increased by 25 mg/kg/day at intervals of 3 days until spasm cessation is achieved or the maximum dose of 150 mg/kg/day is reached. Clinical trials and post-marketing experience have shown that vigabatrin is particularly effective for infantile spasms caused by tuberous sclerosis complex (TSC), where response rates of over 90% have been observed. For infantile spasms of other aetiologies, response rates are approximately 50–70%.

If there is no meaningful clinical benefit after 2–4 weeks at the maximum tolerated dose, the prescribing physician should consider gradually discontinuing KIGABEQ. Continued treatment should only be maintained if the benefits clearly outweigh the risks, particularly the risk of irreversible visual field defects. The decision to continue vigabatrin therapy should be regularly reassessed at each clinical visit.

Resistant Partial Epilepsy – Add-on Therapy

For resistant partial epilepsy, KIGABEQ is always used as add-on therapy alongside the child's existing antiepileptic regimen. The initial dose is 40 mg/kg/day, divided into two daily doses. The maintenance dose depends on the child's body weight and clinical response, with the treating physician adjusting the dose to achieve optimal seizure control while minimising side effects. Treatment should only be initiated after adequate trials of appropriate first-line and second-line antiepileptic drugs have failed to provide adequate seizure control or have been poorly tolerated.

Missed Dose

If a dose of KIGABEQ is missed, it should be given as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped and the regular dosing schedule resumed. The caregiver should never give a double dose to make up for a missed one, as this increases the risk of side effects, particularly sedation and drowsiness. If multiple doses are missed or if there is uncertainty about how to proceed, the treating physician or pharmacist should be consulted.

Overdose

Cases of vigabatrin overdose have been reported, with doses ranging from 3 g to 90 g. Symptoms of overdose typically include drowsiness (somnolence), decreased consciousness or coma, vertigo, headache, psychomotor agitation, respiratory depression, apnoea (particularly in young infants), bradycardia, and hypotension. There is no specific antidote for vigabatrin overdose. Standard supportive measures should be employed, including gastric lavage or administration of activated charcoal if the ingestion is recent. Haemodialysis is not expected to be effective because vigabatrin is not significantly removed by dialysis. In the event of suspected overdose, caregivers should seek immediate emergency medical attention.

What Are the Side Effects of KIGABEQ?

Like all medicines, KIGABEQ can cause side effects, although not everybody gets them. It is important for caregivers to understand the range of possible adverse effects, from common and usually manageable symptoms to rare but potentially serious complications. The frequency categories used below follow the standard European classification: very common (affects more than 1 in 10 patients), common (1 in 10 to 1 in 100), uncommon (1 in 100 to 1 in 1,000), rare (1 in 1,000 to 1 in 10,000), and very rare (fewer than 1 in 10,000).

The most clinically significant side effect of vigabatrin is the development of visual field defects, which is discussed in detail in the warnings section above. Beyond visual effects, vigabatrin has a well-characterised safety profile that has been established through decades of clinical use and extensive post-marketing surveillance. Many side effects are dose-related and may improve with dose reduction.

Many of the neuropsychiatric side effects (somnolence, agitation, insomnia) tend to occur early in treatment and may diminish over time as the child adjusts to the medication. If a child experiences unusual behavioural changes, excessive drowsiness, new onset movement abnormalities, or any visual concerns, caregivers should contact the treating physician promptly. It is important to never adjust the dose or discontinue the medication without medical supervision.

The risk of visual field defects is related to both the cumulative dose and the duration of treatment. Current guidelines recommend using the lowest effective dose for the shortest duration necessary to control seizures, and regularly reassessing the need for continued therapy. For infantile spasms specifically, treatment courses are often relatively short (weeks to months), which may limit the extent of visual field damage compared with longer-term use in resistant partial epilepsy.

How Should You Store KIGABEQ?

KIGABEQ soluble tablets should be stored at room temperature with no special temperature requirements. The tablets should be kept in the original container to protect them from moisture and light degradation. The shelf life of unopened KIGABEQ is 4 years from the date of manufacture, as indicated on the packaging.

Once the bottle is first opened, the tablets must be used within 100 days. Caregivers are advised to write the date of first opening on the bottle label to ensure this time limit is observed. Any tablets remaining after 100 days should be discarded, even if they appear unchanged, as their quality can no longer be guaranteed.

After dissolving a tablet in water (5–10 ml), the resulting solution must be administered immediately. The prepared solution should not be stored, refrigerated, or saved for later use. Any unused solution should be discarded.

• Keep KIGABEQ out of the sight and reach of children
• Do not use after the expiry date stated on the carton and bottle label
• Do not throw away any medicines via household waste or wastewater – return unused medicines to your pharmacist for safe disposal

What Does KIGABEQ Contain?

Each KIGABEQ tablet contains a precisely measured quantity of vigabatrin as the active pharmaceutical ingredient. Vigabatrin is a synthetic amino acid analogue that is structurally related to GABA (gamma-aminobutyric acid). Its chemical name is 4-amino-5-hexenoic acid, and it is available as a racemic mixture of its S(+) and R(-) enantiomers. Only the S(+)-enantiomer is pharmacologically active, while the R(-)-enantiomer has no known therapeutic effect and is eliminated unchanged.

The 100 mg tablets are white, oval-shaped, scored, and measure approximately 9.4 mm × 5.3 mm. The 500 mg tablets are also white, oval-shaped, scored, and measure approximately 16.0 mm × 9.0 mm. Both tablet strengths can be divided into equal halves along the score line, allowing for more precise dose adjustments. The tablets dissolve in water in less than one minute, producing a whitish, slightly cloudy solution with no objectionable taste, which is an important consideration for paediatric acceptability.

KIGABEQ is essentially sodium-free, containing less than 1 mmol (23 mg) of sodium per tablet, making it suitable for patients on a sodium-restricted diet. The formulation does not contain lactose, gluten, or any animal-derived ingredients.