VIGABATRIN ZYDUS PHARMACEUTICALS UK

Vigabatrin oral solution treatment may only be initiated by a specialist in epileptology, neurology or paediatric neurology. Follow-up should be arranged under supervision of a specialist in epileptology, neurology or paediatric neurology.

Posology Vigabatrin oral solution is for oral administration once or twice daily and may be taken before or after meals. If the control of epilepsy is not clinically significantly improved after an adequate trial, vigabatrin treatment should not be continued.

Vigabatrin should be gradually withdrawn under close medical supervision. Adults Maximal efficacy is usually seen in the 2-3 g/day range. A starting dose of 1 g daily should be added to the patient's current antiepileptic medicinal product regimen.

5 g increments at weekly intervals depending on clinical response and tolerability. The highest recommended dose is 3 g/day. No direct correlation exists between the plasma concentration and the efficacy. 2). Paediatric population Resistant partial epilepsy The recommended starting dose in neonates, children and adolescents is 40 mg/kg/day.

5-3 g/day Bodyweight: >50 kg: 2-3 g/day The maximum recommended dose in each of these categories should not be exceeded. Monotherapy for infantile spasms (West's Syndrome) The recommended starting dose is 50 mg/kg/day. This may be titrated over a period of one week if necessary.

Doses of up to 150 mg/kg/day have been used with good tolerability. Older people and patients with renal impairment Since vigabatrin is eliminated via the kidney, caution should be exercised when administering the drug to the older people and more particularly in patients with creatinine clearance less than 60 ml/min.

Adjustment of dose or frequency of administration should be considered. Such patients may respond to a lower maintenance dose. 8).

Summary of the safety profile Visual field defects ranging from mild to severe have been reported frequently in patients receiving vigabatrin. Severe cases are potentially disabling. The onset is usually after months to years of vigabatrin therapy.

4). Approximately 50% of patients in controlled clinical studies have experienced undesirable effects during vigabatrin treatment. In adults, these were mostly central nervous system related such as sedation, drowsiness, fatigue and impaired concentration.

However, in children excitation or agitation is frequent. The incidence of these undesirable effects is generally higher at the beginning of treatment and decreases with time. As with other antiepileptic drugs, some patients may experience an increase in seizure frequency, including status epilepticus with vigabatrin.

Patients with myoclonic seizures may be particularly liable to this effect. New onset myoclonus and exacerbation of existing myoclonus may occur in rare cases. Tabulated list of adverse reactions Undesirable effects ranked under headings of frequency are listed below, using the following convention: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

3). 4). Eye disorders visual field defect vision blurred, diplopia, nystagmus retinal disorder (mainly peripheral) optic atrophy Reduced visual acuity Gastrointestinal disorders nausea, vomiting, abdominal pain Hepato-biliary disorders hepatitis Skin and subcutaneous tissue disorders alopecia rash angioedema, urticaria Musculoskeletal and connective tissue disorders arthralgia General disorders and administration site conditions fatigue oedema, irritability Investigations*** weight increased *Psychiatric reactions have been reported during vigabatrin therapy.

4). Depression was a common psychiatric reaction in clinical trials but seldom required discontinuation of vigabatrin. **Rare reports of encephalopathic symptoms such as marked sedation, stupor and confusion in association with non-specific slow wave activity on electroencephalogram have been described soon after the initiation of vigabatrin treatment.

4). ***Laboratory data indicate that vigabatrin treatment does not lead to renal toxicity. Decreases in ALT and AST, which are considered to be a result of inhibition of these aminotransferases by vigabatrin, have been observed. Paediatric population Psychiatric disorders Very common: excitation, agitation Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Except for the treatment of infantile spasms, Vigabatrin oral solution should not be initiated as monotherapy. Visual field defects (VFD) have been reported in patients receiving vigabatrin with a high prevalence (about 1/3 of patients).

1. The onset is usually after months to years of vigabatrin therapy. The degree of visual field restriction may be severe. Most of the patients with perimetry-confirmed defects have been asymptomatic. Hence, this undesirable effect can only be reliably detected by systematic perimetry which is usually possible only in patients with a developmental age of more than 9 years.

A specifically developed method based on field specific Visual Evoked Potentials (VEP) is available from the company on request to test the presence of peripheral vision in children aged 3 years and above. At present this method has not been validated in the detection of vigabatrin attributed visual field defects.

Electroretinography may be useful but should be used only in adults who are unable to cooperate with perimetry or in the very young (see Visual Field Defects). Available data suggests that visual field defects are irreversible even after discontinuation of vigabatrin.

A deterioration of VFD after the treatment is discontinued cannot be excluded. Therefore, vigabatrin should only be used after a careful assessment of the balance of benefits and risk compared with alternatives. Vigabatrin is not recommended for use in patients with any pre-existing clinically significant visual field defect.

Patients should undergo systematic screening examination when starting vigabatrin and at regular intervals for detection of visual field defects and reduced visual acuity. Visual field testing and assessment of visual acuity should continue at 6 month intervals for the whole duration of treatment (see Visual Field Defects and Visual Acuity).

Visual Field Defects (VFD) Based on available data, the usual pattern is a concentric constriction of the visual field of both eyes, which is generally more marked nasally than temporally. In the central visual field (within 30 degree of eccentricity), frequently an annular nasal defect is seen.

However, the VFDs reported in patients receiving vigabatrin have ranged from mild to severe. Severe cases may be characterized by tunnel vision. Blindness was also reported in severe cases. Most patients with perimetry-confirmed defects had not previously spontaneously noticed any symptoms, even in cases where a severe defect was observed in perimetry.

Available evidence suggests that the VFD is irreversible even after discontinuation of vigabatrin. A deterioration of VFD after the treatment is discontinued cannot be excluded. Pooled data from prevalence surveys suggest that as many as 1/3 of patients receiving vigabatrin therapy have VFDs.

Males may be at greater risk than females. 1. A possible association between the risk of visual field defects and the extent of vigabatrin exposure, both in terms of daily dose (from 1 gram to more than 3 grams) and in terms of duration of treatment (maximum during the first three years) has been shown in this study.

All patients should have ophthalmological consultation with visual field examination before the initiation of vigabatrin treatment. Appropriate visual field testing (perimetry) by using a standardised static perimetry (Humphrey or Octopus) or kinetic perimetry (Goldmann) must be performed before treatment initiation and at six-month intervals for the whole duration of treatment.

Static perimetry is the preferred method for detecting vigabatrin associated visual field defect. Electroretinography may be useful but should only be used in adults who are unable to cooperate with perimetry. Based on the available data the first oscillatory potential and 30 Hz flicker responses of the electroretinogram appear to be correlated with a vigabatrin associated VFD.

These responses are delayed and reduced beyond the normal limits. Such changes have not been seen in vigabatrin treated patients without a VFD. The patient and/or caregiver must be given a thorough description of the frequency and implications of the development of VFD during vigabatrin treatment.

Patients should be instructed to report any new visual problems and symptoms which may be associated with visual field constriction. If visual symptoms develop, the patient should be referred to an ophthalmologist. If a visual field constriction is observed during follow-up, consideration should be given to gradual discontinuation of vigabatrin.

If the decision to continue treatment is made, consideration should be given to more frequent follow-up (perimetry) in order to detect progression or sight threatening defects. Vigabatrin should not be used concomitantly with other retinotoxic drugs.

Paediatric population Perimetry is seldom possible in children less than 9 years of developmental age. The risks of treatment must be very carefully weighed against possible benefit in children. Currently, there is no established method to diagnose or exclude visual field defects in children in whom a standardised perimetry cannot be performed.

A specifically developed method based on field specific Visual Evoked Potentials (VEP) is available from the company on request to test the presence of peripheral vision in children aged 3 years and above. At present this method has not been validated in the detection of vigabatrin attributed visual field defects.

If the method reveals normal central visual field response but an absent peripheral response, benefit-risk of vigabatrin must be reviewed and consideration given to gradual discontinuation. The presence of peripheral vision does not exclude the possibility of developing VFD.

Electroretinography may be useful but should be used only in children less than 3 years of age. Visual acuity The […]

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