Vigabatrin

Use has been associated with decreased hemoglobin and hematocrit; cases of significantly reduced hemoglobin (• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Peripheral edema and edema independent of hypertension, heart failure, weight gain, renal or hepatic dysfunction has been reported.

Patients must be closely monitored for potential neurotoxicity (observed in animal models but not established in adults).

Peripheral neuropathy manifesting as numbness or tingling in the toes or feet, reduced distal lower limb vibration or position sensation, or progressive loss of reflexes, starting at the ankles, has been reported in adult patients.

Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify healthcare provider immediately if symptoms occur.

Vigabatrin causes permanent vision loss in infants, children, and adults. Due to the risk of vision loss and because vigabatrin, provides an observable symptomatic benefit when it is effective, the patient who fails to show substantial clinical benefit within a short period of time after initiation of treatment (2 to 4 weeks for infantile spasms; 30% of patients ranging in severity from mild to severe, including tunnel vision to within 10 degrees of visual fixation, and can result in disability. In some cases, vigabatrin can damage the central retina and may decrease visual acuity. Symptoms of vision loss are unlikely to be recognized by the patient or caregiver before loss is severe. Vision loss of milder severity, although potentially unrecognized by the patient or caregiver, may still adversely affect function. Vision should be assessed to the extent possible at baseline (no later than 4 weeks after initiation), at least every 3 months during therapy and at 3 to 6 months after discontinuation. Once detected, vision loss is not reversible; even with frequent monitoring, it is expected that some patients will develop severe vision loss. In patients who cannot be tested, treatment may continue according to clinical judgement, with appropriate patient counseling. Vigabatrin should not be used in patients with, or at high risk of, other types of irreversible vision loss unless the benefits of treatment clearly outweigh the risks. The interaction of other types of irreversible v

Use has been associated with an average weight gain of 3.5 kg in adults and ≥7% of baseline body weight in pediatric patients. Disease-related concerns:

Use with caution in patients with a history of psychosis (psychotic/agitated reactions may occur more frequently), depression, or behavioral problems.

Use with caution in patients with renal impairment; modify dose in children (≥10 years) and adults with renal impairment (CrCl • Seizures: May cause an increase in seizure frequency in some patients; use with particular caution in patients with myoclonic seizures, which may be more prone to this effect. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Use with caution in the elderly as moderate to severe sedation and confusion have been reported; consider dose and/or frequency adjustments as renal clearance may be decreased. Other warnings/precautions:

Vigabatrin is not indicated as a first-line agent for complex partial seizures.

Abnormal MRI changes have been reported in some infants. Resolution of MRI changes usually occurs with discontinuation of therapy. MRI changes were not seen in older children and adult patients.

Because of the risk of permanent vision loss, vigabatrin is only available through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) program. Under the Vigabatrin REMS program, only prescribers and pharmacies registered with the program are able to prescribe and distribute vigabatrin. Vigabatrin may only be dispensed to patients who are enrolled in and meet all conditions of the Vigabatrin REMS program. Call 866-244-8175 or visit http://www.vigabatrinREMS.com for further information.

Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.