vigabatrin

vye-GAH-bat-rin

Therapeutic Classification: anticonvulsants

REMS

Refractory complex partial seizures in patients who have responded inadequately to several alternative treatments (and where potential benefits outweigh the risk of vision loss) (as adjunctive therapy).
Infantile spasms in patients in whom potential benefits outweigh the risk of vision loss.

Acts an irreversible inhibitor of γ-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the metabolism of the inhibitory neurotransmitter GABA. This action results in increased levels of GABA in the central nervous system.

Therapeutic effects:

Decreased incidence and severity of refractory complex partial seizures.
Decreased incidence of spasms in infants.

Absorption: Completely absorbed following oral administration.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Minimal metabolism, mostly eliminated unchanged in urine.

Half-Life: 7.5 hr.

(anticonvulsant effect)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1 hr‡	12 hr‡

‡blood level.

‡clinical benefit should be seen in 2–4 wk for IS or within 3 mo for complex partial seizures.

Contraindicated in:

History or high risk of other types of irreversible vision loss unless benefits of treatment clearly outweigh risks;
Lactation: Lactation.

Use Cautiously in:

Renal impairment (↓ dose if CCr <50 mL/min);
History of suicidal ideation;
OB: Use during pregnancy only if the potential maternal benefit justifies the potential fetal risk;
Pedi: Abnormal MRI signal changes have been seen in infants;
Geri: Consider age-related in renal function ( risk of sedation/confusion).

CV: edema

Derm: STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

EENT: blurred vision, nystagmus, vision loss, tunnel vision

Hemat: anemia

Metab: weight gain

MS: arthralgia

Neuro: abnormal coordination, confusion, drowsiness, fatigue, memory impairment, tremor, INTRAMYELINIC EDEMA, peripheral neuropathy, SUICIDAL THOUGHTS

Drug-drug:

Should not be used concurrently with other drugs having adverse ocular effects; ↑ risk of additive toxicity.
May ↓ phenytoin levels and effectiveness.

Either tablets or powder for oral solution can be used for refractory complex partial seizures; only powder for oral solution or oral solution should be used for infantile spasms.

Refractory Complex Partial Seizures

PO (Adults and Children ≥17 yr): 500 mg twice daily initially; may ↑ in 500-mg increments every 7 days, depending on response, up to 1500 mg twice daily.
PO (Children 2–16 yr and >60 kg): 500 mg twice daily initially; may ↑ in 500-mg increments every 7 days, depending on response, up to 1500 mg twice daily.
PO (Children 2–16 yr and 26–60 kg): 250 mg twice daily initially; may ↑ every 7 days, depending on response, up to 1000 mg twice daily.
PO (Children 2–16 yr and 21–25 kg): 250 mg twice daily initially; may ↑ every 7 days, depending on response, up to 750 mg twice daily.
PO (Children 2–16 yr and 16–20 kg): 225 mg twice daily initially; may ↑ every 7 days, depending on response, up to 650 mg twice daily.
PO (Children 2–16 yr and 10–15 kg): 175 mg twice daily initially; may ↑ every 7 days, depending on response, up to 525 mg twice daily.

Renal Impairment

PO (Adults and Children ≥2 yr and ≥10 kg): CCr >50–80 mL/min: ↓dose by 25%; CCr >30–50 mL/min: ↓dose by 50%; CCr >10–30 mL/min: ↓dose by 75%.

Infantile Spasms

PO (Children 1 mo–2 yr): 25 mg/kg twice daily initially; may be ↑ by 25–50 mg/kg/day increments every 3 days up to a maximum of 150 mg/kg/day (75 mg/kg twice daily); dosage adjustments are necessary for renal impairment.

(Generic available)

Tablets (Sabril): 500 mg
Oral solution (Vigafyde): 100 mg/mL
Powder for oral solution (Sabril, Vigadrone, Vigpoder): 500 mg/pkt

Assess location, duration, and characteristics of seizure activity. Institute seizure precautions. Assess response to and continued need for vigabatrin periodically during therapy.
Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
Test vision at baseline (no later than 4 wk after starting), at least every 3 mo during, and 3–6 mo after discontinuation of therapy. Vision loss is irreversible and may not be noticed by patient or caregiver until severe; consider discontinuation of vigabatrin if vision loss occurs. Vision loss may continue after discontinuation of therapy. Risk of vision loss ↑ with dose and cumulative exposure.
Assess for signs and symptoms of peripheral neuropathy (numbness or tingling or toes or feet, reduced lower limb vibration or position sensation, progressive loss of reflexes starting at ankles).
Assess for rash periodically during therapy. May cause SJS or TEN. Discontinue vigabatrin if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, or eosinophilia.

Lab Test Considerations:

Monitor CBC periodically during therapy. May cause anemia.
- May ↓ AST and ALT levels. Monitor for hepatic injury.
- May ↑ amino acids in urine causing false positive results of genetic metabolic diseases.

Do not confuse vigabatrin with dabigatran.
Available only through Vigabatrin REMS program of restricted distribution. Only prescribers and pharmacies registered in the program and patients enrolled in the program have access. Patients receive vigabatrin from a specialty pharmacy. Further information is available at www.vigabatrinREMS.com, or call 1-866-244-8175.
PO: Administer twice daily without regard to food.
- Mix each 500 mg packet of oral solution with 10 mL of water for a concentration of 50 mg/mL; may be administered cold or at room temperature. Solution is clear and colorless; do not administer solutions that are discolored or contain particulate matter. Administer resulting solution using the 3-mL or 10-mL oral syringe provided by the pharmacy. Oral solution may be administered at the same time as food but should only be mixed with water.

Enroll patient in Vigabatrin REMS program.
Explain purpose and side effects of medication to patient. Advise patient/caregiver to read Patient Information before starting therapy. Instruct patient to take as directed, around the clock. Discuss with health care professional what to do if a dose is missed. Medication should be gradually discontinued to prevent seizures.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications. Patient should avoid taking alcohol or other CNS depressants.
Inform patient of the risk of permanent vision loss, particularly loss of peripheral vision, and that vision loss may not be detected before it is severe and is irreversible. Emphasize the importance of monitoring vision every 3 mo. Advise patient to notify health care professional immediately if changes in vision (not seeing as well as before starting therapy, tripping, bumping into things, more clumsy than usual, surprised by people or things coming in front of you that seem to come out of nowhere) or changes in infant's vision are suspected.
May cause drowsiness, ataxia, fatigue, and confusion. Caution patient to avoid driving or other activities requiring alertness until response to medication is known. Tell patient not to resume driving until physician gives clearance based on control of seizure disorder.
Inform patient and caregivers of risk of suicidal thoughts and behavior and advise that behavioral changes, emergency or worsening signs and symptoms of depression, unusual changes in mood, or emergence of suicidal thoughts, behavior, or thoughts of self-harm or rash should be reported to health care professional immediately.
Advise patient to notify health care professional if an ↑ in seizures, weight gain, or edema occurs or if sleepiness, ear infection, or irritability occurs in an infant.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Encourage pregnant patients to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling 1-888-233-2334; information is available at www.aedpregnancyregistry.org.

Decreased incidence and severity of refractory complex partial seizures.
Decreased incidence of spasms in infants.

Sabril, Vigadrone, Vigafyde, Vigpoder

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Action ⬆ ⬇

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Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆