Sabril
SABRIL- vigabatrin tablet, film coated
Lundbeck LLC
WARNING: VISION LOSS
- SABRIL causes permanent bilateral concentric visual field constriction in 30 percent or more of patients that ranges 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 during treatment, even after months or years
- 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 assessment at baseline (no later than 4 weeks after starting SABRIL) and at least every 3 months during therapy is required for adults on SABRIL. 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- Because of the risk of vision loss, SABRIL should be withdrawn from patients who fail to show substantial clinical benefit within 3 months of initiation, or sooner if treatment failure becomes obvious. Patient response to and continued need for SABRIL should be periodically reassessed.
- 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, can still adversely affect function.
- 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 lowest dose and shortest exposure to SABRIL should be used that is consistent with clinical objectives
Because of the risk of permanent vision loss, SABRIL is available only through a special restricted distribution program called SHARE, by calling 1-888-45-SHARE. Only prescribers and pharmacies registered with SHARE may prescribe and distribute SABRIL. In addition, SABRIL may be dispensed only to patients who are enrolled in and meet all conditions of SHARE [see WARNINGS AND PRECAUTIONS, Distribution Program for SABRIL (SHARE Program) (5.2)].
1 INDICATIONS AND USAGE
1.1 Refractory Complex Partial Seizures in Adults
SABRIL® is indicated as adjunctive therapy for adult patients with refractory complex partial seizures (CPS) who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss [see WARNINGS AND PRECAUTIONS, Vision Loss (5.1)]. SABRIL is not indicated as a first line agent for complex partial seizures.
2 DOSAGE AND ADMINISTRATION
2.1 Refractory Complex Partial Seizures in Adults
SABRIL 500 mg tablets should be given as twice daily oral administration with or without food. Therapy should be initiated at 1 g/day (500 mg twice daily). Total daily dose may be increased in 500 mg increments at weekly intervals depending on response. The recommended dose of SABRIL in adults is 3 g/day (1.5 g twice daily). A 6 g/day dose has not been shown to confer additional benefit compared to the 3 g/day dose and is associated with an increased incidence of adverse events.
2.2 Patients with Renal Impairment
SABRIL is primarily eliminated through the kidney. In patients with renal impairment, dose adjustments should be made as follows:
In patients with mild renal impairment (CLcr >50 to 80 mL/min), the dose should be decreased by 25%; in patients with moderate renal impairment (CLcr >30 to 50 mL/min), the dose should be decreased by 50%; and in patients with severe renal impairment (CLcr >10 to <30 mL/min), the dose should be decreased by 75%.
CLcr in mL/min may be estimated from a serum creatinine (mg/dL) determination using the following formula:
CLcr * = [140-age (years)]×weight (kg)/72×serum creatinine (mg/dL)]*[×0.85 for female patients ]
The effect of dialysis on SABRIL clearance has not been adequately studied.
[See CLINICAL PHARMACOLOGY, Pharmacokinetics, Renal Impairment (12.3) and USE IN SPECIFIC POPULATIONS, Renal Impairment (8.6)].
2.3 General Dosing Considerations
SABRIL should be withdrawn gradually. In controlled clinical studies in adults with CPS, vigabatrin was tapered by decreasing the daily dose 1 g/day on a weekly basis until discontinued [see WARNINGS AND PRECAUTIONS, Withdrawal of Antiepileptic Drugs (AEDs) (5.6)].
3 DOSAGE FORMS AND STRENGTHS
3.1 Tablet
500 mg Tablet.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Vision Loss (see BOXED WARNING)
Because of the risk of vision loss and because SABRIL, when it is effective, provides an observable symptomatic benefit, a patient who fails to show substantial clinical benefit within 3 months of initiation of treatment, should be withdrawn from SABRIL. If in the clinical judgment of the prescriber evidence of treatment failure becomes obvious earlier than 3 months, treatment with SABRIL should be discontinued at that time. Patient response to and continued need for treatment should be periodically assessed.
Monitoring of Vision
Monitoring of vision by an ophthalmic professional with expertise in visual field interpretation and the ability to perform dilated indirect ophthalmoscopy of the retina is required, unless a patient is formally exempted from periodic ophthalmologic assessment as documented in the Support, Help And Resources for Epilepsy (SHARE) program. For patients receiving SABRIL who are not exempted, vision assessment is required at baseline (no later than 4 weeks after starting SABRIL) and at least every 3 months while on therapy and about 3-6 months after the discontinuation of therapy.
The diagnostic approach should be individualized for the patient and clinical situation. For all patients, attempts to monitor vision periodically and/or formal exemptions must be documented under the SHARE program. Perimetry is recommended, preferably by automated threshold visual field testing. Additional testing may also include electrophysiology (e.g., electroretinography [ERG]), retinal imaging (e.g., optical coherence tomography [OCT]), and/or other methods appropriate for the patient, but this additional testing is not required. In patients exempted from vision testing, treatment may continue according to clinical judgment, with appropriate patient counseling and with documentation in the SHARE program of the exemption. Because of variability, results from ophthalmic monitoring must be interpreted with caution, and repeat assessment is recommended if results are abnormal or uninterpretable. Repeat assessment in the first few weeks of treatment is recommended to establish if, and to what degree, reproducible results can be obtained, and to guide selection of appropriate ongoing monitoring for the patient.
The onset and progression of vision loss from SABRIL is unpredictable, and it may occur or worsen precipitously between assessments. Once detected, vision loss due to SABRIL is not reversible. It is expected that even with frequent monitoring, some SABRIL patients will develop severe vision loss. Drug discontinuation should be considered, balancing benefit and risk, if visual loss is documented.
5.2 Distribution Program for SABRIL (SHARE Program)
SABRIL is available only under a special restricted distribution program called the SHARE program. Under the SHARE program, only prescribers and pharmacies registered with the program are able to prescribe and distribute SABRIL. In addition, SABRIL may be dispensed only to patients who are enrolled in and meet all conditions of SHARE. Contact the SHARE program at 1-888-45-SHARE.
To enroll in SHARE, prescribers must understand the risks of SABRIL and complete the SHARE Prescriber Enrollment and Agreement Form indicating agreement to:
- Enroll all patients in SHARE
- Review the SABRIL Medication Guide with every patient
- Educate patients on the risks of SABRIL, including the risk of vision loss [see BOXED WARNING: VISION LOSS]
- Order and review vision assessments at initiation of SABRIL treatment and every 3 months during therapy
- Remove patients from SABRIL therapy if the patients do not experience meaningful reduction in seizures
- Counsel patients who fail to comply with the program requirements
- Remove patients from SABRIL therapy who fail to comply with the program requirements after appropriate counseling
The prescriber may, with appropriate documentation and caregiver counseling, exempt certain patients from vision assessment, using the Ophthalmologic Assessment Form, if:
- The patient is blind (subsequent Ophthalmologic Forms do not need to be submitted to the REMS coordinating center)
- The patient's general neurological and/or mental condition permanently precludes the need for visual assessment (subsequent Ophthalmologic Forms do not need to be submitted to the REMS coordinating center)
- The patient's general neurological condition temporarily precludes the ability to assess visual function. The evaluation, however, may be performed at a later time as clinically appropriate.
- The patient's medical condition prevents visual assessment being performed safely
- For other reasons specified by the prescriber
