Sabril (vigabatrin)

Since there is no direct correlation between plasma vigabatrin concentrations and efficacy, therapeutic drug monitoring of vigabatrin is not useful.

The manufacturer states that the lowest dosage and shortest duration of therapy with vigabatrin consistent with clinical objectives should be used.

The dosage regimen of vigabatrin depends on the indication, age group, weight, and dosage form (tablets or powder for oral solution).

If therapy is to be discontinued, vigabatrin should be withdrawn gradually.

Vigabatrin is available orally as tablets, a powder for oral solution with a final concentration of 50 mg/mL, and a concentrated 100 mg/mL oral solution that does not require reconstitution or dilution prior to administration. Vigabatrin is administered orally and may be given without regard to meals.

When using the powder for oral solution, clinicians should review and discuss the medication guide and instructions on proper reconstitution, administration, and dosing procedures with the patient or caregiver(s) and confirm their understanding. When using the concentrated 100 mg/mL oral solution, verify the strength and dose of the product before prescribing, dispensing, and administering the product.

Vigabatrin powder for oral solution should be prepared and administered according to the manufacturer's directions. The manufacturer states that only water should be used to dissolve the powder.

To prepare the oral solution, the entire contents of the appropriate number of packets of vigabatrin powder for oral solution (500 mg/packet) should be emptied into a clean cup and dissolved with 10 mL of cold or room-temperature water per packet; resultant solutions have a final concentration of 50 mg/mL. For doses between 0 and 500 mg, 1 packet of vigabatrin powder should be dissolved with 10 mL of water; for doses between 501 mg and 1 g, 2 packets of vigabatrin powder should be dissolved with 20 mL of water; and for doses between 1 and 1.5 g, 3 packets of vigabatrin powder should be dissolved with 30 mL of water. The solution should be mixed thoroughly with a small spoon or other clean utensil until the powder has completely dissolved and the solution is clear. The resulting solution should be discarded if it is not clear (or free of particles) and colorless. Each dose of vigabatrin oral solution should be administered immediately following preparation.

Depending on the dose to be administered, a 3-mL or 10-mL oral syringe supplied by the pharmacy should be used to withdraw the specific volume of solution that will provide the appropriate dose and any remaining solution should be discarded. A calibrated measuring device should be used to measure and deliver the dose of vigabatrin powder for oral solution or oral solution; a household teaspoon or tablespoon is not an appropriate measuring device.

Store vigabatrin tablets and powder for oral solution at 20-25degreesC.

Store unopened bottles of vigabatrin 100 mg/mL oral solution between 20-25degreesC (excursions permitted to 15-30degreesC). After opening vigabatrin 100 mg/mL oral solution, store at room temperature or in a refrigerator, between 2-30degreesC; discard any unused medication within 90 days after first opening.

Vigabatrin is not extensively metabolized by hepatic cytochrome P450 (CYP) isoenzymes. Vigabatrin induces CYP2C9, but does not appear to induce other hepatic CYP isoenzymes.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*None.

There are no contraindication contraindications for this drug.

• Chronic kidney disease stage 2 (mild) GFR 60-89 ml/min
• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Pregnancy
• Reduced visual acuity
• Suicidal ideation
• Visual field defect

• Anemia
• Edema
• Peripheral neuropathy
• Weight gain

Vigabatrin causes permanent damage to vision in a high percentage of patients.

The most common adverse effects reported (incidence >=5% over placebo) in adolescents and adults >=16 years of age with refractory CPS included blurred vision, somnolence, dizziness, abnormal coordination, tremor, and fatigue.

In controlled clinical studies in pediatric patients 3 to 16 years of age with refractory CPS receiving vigabatrin, adverse effects occurring at an incidence >=5% over placebo included weight gain.

In a placebo-controlled study in pediatric patients with IS, adverse effects occurring in >5% of vigabatrin-treated patients and more frequently than in placebo recipients included somnolence, bronchitis, ear infection, and acute otitis media.

More Frequent

• Vision impairment
• Visual field defect

Less Frequent

• Anemia
• Chest pain
• Influenza

Rare or Very Rare

• Accidental fall
• Acquired dystonia
• Acute respiratory failure
• Angioedema
• Cholestasis
• Drug-induced psychosis
• Dyskinesia
• Encephalopathy
• Gastrointestinal hemorrhage
• Hearing loss
• Hypomania
• Intramyelinic edema
• Laryngeal edema
• Malignant hyperthermia
• Multiple organ failure
• Myoclonus
• Optic neuritis
• Peripheral motor neuropathy
• Pulmonary thromboembolism
• Stevens-johnson syndrome
• Suicidal
• Suicidal ideation
• Toxic epidermal necrolysis

More Frequent

• Acute bacterial otitis media
• Acute cognitive impairment
• Arthralgia
• Ataxia
• Blurred vision
• Depression
• Diarrhea
• Diplopia
• Disturbance of attention
• Dizziness
• Drowsy
• Fatigue
• Headache disorder
• Insomnia
• Irritability
• Memory impairment
• Nausea
• Nystagmus
• Tremor
• Upper respiratory infection
• Weight gain

Less Frequent

• Abdominal distension
• Acute abdominal pain
• Asthenopia
• Back pain
• Bronchitis
• Dyspepsia
• Edema
• Fever
• Hyporeflexia
• Lethargy
• Muscle fasciculation
• Myalgia
• Ocular pain
• Peripheral sensory neuropathy
• Pharyngitis
• Urinary tract infection
• Vertigo

Rare or Very Rare

• Acne vulgaris
• Aggressive behavior
• Alopecia
• Cough
• Delirium
• Dysmenorrhea
• Erectile dysfunction
• Esophagitis
• Facial edema
• Hypertonia
• Hypoesthesia
• Hypotonia
• Indifference
• Maculopapular rash
• Muscle spasm
• Pruritus of skin
• Skin rash
• Stridor
• Tinnitus

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Safety and efficacy of vigabatrin tablets and powder for oral solution, as adjunctive therapy for refractory CPS in pediatric patients 2 to 16 years of age have been established. The drug is indicated as adjunctive therapy for refractory CPS in pediatric patients 2 years of age and older who have not responded adequately to several alternative treatments. The dosage recommendation in this population depends on the age group and is based on weight . Adverse effects in this pediatric population are similar to those observed in adults.

Safety and efficacy of vigabatrin have not been established in pediatric patients younger than 2 years with refractory CPS.

Safety and efficacy of vigabatrin (all formulations) as monotherapy for IS have been established in pediatric patients 1 month to 2 years of age, and the drug is indicated in such patients when the potential benefits of vigabatrin therapy outweigh the potential risk of developing permanent vision loss. Safety and efficacy of the drug have not been established in patients with IS outside this age group.

Abnormal MRI signal changes and IME have been observed in infants and young children treated with vigabatrin.

The elimination half-life of vigabatrin is approximately 5.7 hours in infants (5 months to 2 years of age) , 6.8 hours for children (3 to 9 years of age), 9.5 hours in children and adolescents 10 to 16 years of age, and 10.5 hours in adults.

There are no adequate data on the developmental risk associated with use of vigabatrin in pregnant patients. Limited data from case reports and cohort studies in pregnant patients have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, animal data suggest use of vigabatrin in pregnancy may result in fetal harm.

Vigabatrin produced developmental toxicity, including teratogenic, neurobehavioral, and neurohistopathologic effects, when administered to pregnant animals in clinically relevant dosages. Developmental neurotoxicity was observed in animals given vigabatrin during a period of postnatal development corresponding to the third trimester of human pregnancy.

The North American Antiepileptic Drug (NAAED) Pregnancy Registry may be contacted at 888-233-2334 (for patients); NAAED registry information also is available on the website https://www.aedpregnancyregistry.org.

Vigabatrin distributes into milk; the effects on the breast-fed infant and on milk production are not known Because of the potential for serious adverse reactions to vigabatrin in nursing infants , the manufacturer recommends against breast-feeding while taking vigabatrin. In the event that a decision is made to continue breastfeeding during vigabatrin therapy, the nursing infant should be monitored for potential adverse effects.

Because of the possibility of decreased renal function in geriatric patients, careful dosage selection is recommended. Adjusting the dosage or frequency of administration should be considered in geriatric patients; such patients may respond to a lower maintenance dosage.

Vigabatrin 100 mg/mL oral solution is not approved for use in adults.

Clinical studies of vigabatrin did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adults.

Vigabatrin is known to be substantially excreted by the kidney, and the risk of toxic reactions to the drug may be greater in patients with impaired renal function. Because geriatric patients are more likely to have reduced renal function, careful dosage selection is advised and renal function monitoring may be useful.

Administration of single oral doses of vigabatrin to 5 patients older than 65 years of age with reduced renal function (creatinine clearance (ClCr) less than 50 mL/minute) resulted in moderate to severe sedation and confusion in 4 out of 5 patients lasting up to 5 days.

Renal clearance of vigabatrin is reduced by 36% in healthy individuals 65 years of age or older compared with healthy younger individuals; an adjustment in vigabatrin dosage or frequency of administration should be considered in patients in this age group.

Other reported clinical experience has not identified differences in responses to vigabatrin between geriatric and younger patients.