Vision Loss, Skin and Subcutaneous Tissue Disorders

Vision Loss

• SABRIL causes permanent bilateral concentric visual field constriction. Because assessing vision may be difficult in infants and children, the frequency and extent of vision loss is poorly characterized in these patients. For this reason, the risk described below is primarily based on the adult experience.
• Based upon adult studies, 30 percent or more of patients can be affected, 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, SABRIL also can damage the central retina and may decrease visual acuity.
• The onset of vision loss from SABRIL is unpredictable, and can occur within weeks of starting treatment or sooner, or at any time after starting treatment, even after months or years.
• Symptoms of vision loss from SABRIL are unlikely to be recognized by patients or caregivers before vision loss is severe.Vision loss of milder severity, while often unrecognized by the patient or caregiver, can still adversely affect function.
• The risk of vision loss increases with increasing dose and cumulative exposure, but there is no dose or exposure known to be free of risk of vision loss.
• Unless a patient is formally exempted from periodic ophthalmologic assessment as documented in the SHARE program, vision should be assessed to the extent possible at baseline (no later than 4 weeks after starting SABRIL) and at least every 3 months during therapy.Vision assessment is also required about 3 to 6 months after the discontinuation of SABRIL therapy.
• Once detected, vision loss due to SABRIL is not reversible. It is expected that, even with frequent monitoring, some patients will develop severe vision loss.
• Drug discontinuation should be considered, balancing benefit and risk, if visual loss is documented.
• It is possible that vision loss can worsen despite discontinuation of SABRIL.
• Because of the risk of visual loss, SABRIL should be withdrawn from patients with refractory complex partial seizures who fail to show substantial clinical benefit within 3 months of initiation and within 2-4 weeks of initiation for patients with infantile spasms, or sooner if treatment failure becomes obvious. Patient response to and continued need for SABRIL should be periodically reassessed.
• SABRIL 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 vision damage with vision damage from SABRIL has not been well-characterized, but is likely adverse.
• SABRIL should not be used with other drugs associated with serious adverse ophthalmic effects such as retinopathy or glaucoma unless the benefits clearly outweigh the risks.
• The possibility that vision loss from SABRIL may be more common, more severe or have more severe functional consequences in infants and children than in adults cannot be excluded.
• The lowest dose and shortest exposure to SABRIL consistent with clinical objectives should be used.

Because of the risk of permanent vision loss, SABRIL is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the SHARE Program [see Warnings and Precautions (5.2)]. Further information is available at [www.sabril.net or 1-888-45-SHARE1-888-45-SHARE FREE].

Skin and Subcutaneous Tissue Disorders

• Angioedema, maculo-papular rash, pruritus, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), alopecia