SABRIL: Package Insert and Label Information

SABRIL- vigabatrin tablet, film coated
Lundbeck LLC

WARNING:​ PERMANENT VISION LOSS

  • SABRIL can cause permanent bilateral concentric visual field constriction, including tunnel vision that can result in disability. In some cases, SABRIL also can damage the central retina and may decrease visual acuity [see Warnings and Precautions (5.1)]
  • 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.
  • Vision assessment is recommended at baseline (no later than 4 weeks after starting SABRIL), at least every 3 months during therapy, and about 3 to 6 months after the discontinuation of 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.
  • Consider drug discontinuation, balancing benefit and risk, if visual loss is documented.
  • Risk of new or worsening vision loss continues as long as SABRIL is used. 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  • Because of the risk of vision loss, SABRIL should be withdrawn from patients with refractory complex partial seizures who fail to show substantial clinical benefit within 3 months of initiation and within 2-4 weeks of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.
  • 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.
  • Use the lowest dosage and shortest exposure to SABRIL consistent with clinical objectives [see Dosage and Administration (2.1)].

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 SABRIL REMS Program [see Warnings and Precautions (5.2)]. Further information is available at www.SabrilREMS.com or 1-888-457-4273.

1 INDICATIONS AND USAGE

1.1 Refractory Complex Partial Seizures (CPS)

SABRIL is indicated as adjunctive therapy for adults and pediatric patients 10 years of age and older with refractory complex partial seizures who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss [see Warnings and Precautions (5.1)]. SABRIL is not indicated as a first line agent for complex partial seizures.

1.2 Infantile Spasms (IS)

SABRIL is indicated as monotherapy for pediatric patients with infantile spasms 1 month to 2 years of age for whom the potential benefits outweigh the potential risk of vision loss [see Warnings and Precautions (5.1)].

2 DOSAGE AND ADMINISTRATION

2. 1 Important Dosing and Administration Instructions

Dosing

Use the lowest dosage and shortest exposure to SABRIL consistent with clinical objectives [see Warnings and Precautions (5.1)].

The SABRIL dosing regimen depends on the indication, age group, weight, and dosage form (tablets or powder for oral solution) [see Dosage and Administration (2.2, 2.3)]. Patients with impaired renal function require dose adjustment [see Dosage and Administration (2.4)].

SABRIL tablets and powder for oral solution are bioequivalent. Either tablet or powder can be used for CPS. Powder for oral solution should be used for IS; tablets should not be used for IS because of difficulty in the administration of tablets to infants and young children.

Monitoring of SABRIL plasma concentrations to optimize therapy is not helpful.

Administration

Sabril is given orally with or without food.

SABRIL powder for oral solution should be mixed with water prior to administration [see Dosage and Administration (2.5)].

If a decision is made to discontinue SABRIL, the dose should be gradually reduced [see Dosage and Administration (2.2, 2.3) and Warnings and Precautions (5.6)].

2. 2 Refractory Complex Partial Seizures

Adults (Patients 17 Years of Age and Older)
Treatment should be initiated at 1000 mg/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 3000 mg/day (1500 mg twice daily). A 6000 mg/day dose has not been shown to confer additional benefit compared to the 3000 mg/day dose and is associated with an increased incidence of adverse events.

In controlled clinical studies in adults with complex partial seizures, SABRIL was tapered by decreasing the daily dose 1000 mg/day on a weekly basis until discontinued [ s ee Warnings and Precautions (5.6)] .

Pediatric (Patients 10 to 16 Years of Age)Treatment is based on body weight as shown in Table 1. Treatment should be initiated at a total daily dose of 500 mg/day (250 mg twice daily) and may be increased weekly in 500 mg/day increments to a total maintenance dose of 2000 mg/day (1000 mg twice daily). Patients weighing more than 60 kg should be dosed according to adult recommendations.

Table 1. Pediatric CPS Dosing Recommendations
Body Weight[kg] Total Daily*Starting Dose [mg/day] Total Daily*Maintenance Dose [mg/day]
25 to 60†† 500 2000

*Administered in two divided doses.
†Maintenance dose is based on 3000 mg/day adult-equivalent dose†† Patients weighing more than 60 kg should be dosed according to adult recommendations

In patients with refractory complex partial seizures, SABRIL should be withdrawn if a substantial clinical benefit is not observed within 3 months of initiating treatment. If, in the clinical judgment of the prescriber, evidence of treatment failure becomes obvious earlier than 3 months, treatment should be discontinued at that time [see Warnings and Precautions (5.1)].

In a controlled study in pediatric patients with complex partial seizures, SABRIL was tapered by decreasing the daily dose by one third every week for three weeks [ s ee Warnings and Precautions (5.6)] .

2.3 Infantile Spasms

The initial daily dosing is 50 mg/kg/day given in two divided doses (25 mg/kg twice daily); subsequent dosing can be titrated by 25 mg/kg/day to 50 mg/kg/day increments every 3 days, up to a maximum of 150 mg/kg/day given in 2 divided doses (75 mg/kg twice daily) [ s ee Use in Specific Populations (8.4)].

Table 2 provides the volume of the 50 mg/mL dosing solution that should be administered as individual doses in infants of various weights.

Table 2 Infant Dosing Table
Weight[kg] Starting Dose50 mg/kg/day Maximum Dose150 mg/kg/day
3 1.5 mL twice daily 4.5 mL twice daily
4 2 mL twice daily 6 mL twice daily
5 2.5 mL twice daily 7.5 mL twice daily
6 3 mL twice daily 9 mL twice daily
7 3.5 mL twice daily 10.5 mL twice daily
8 4 mL twice daily 12 mL twice daily
9 4.5 mL twice daily 13.5 mL twice daily
10 5 mL twice daily 15 mL twice daily
11 5.5 mL twice daily 16.5 mL twice daily
12 6 mL twice daily 18 mL twice daily
13 6.5 mL twice daily 19.5 mL twice daily
14 7 mL twice daily 21 mL twice daily
15 7.5 mL twice daily 22.5 mL twice daily
16 8 mL twice daily 24 mL twice daily

In patients with infantile spasms, SABRIL should be withdrawn if a substantial clinical benefit is not observed within 2 to 4 weeks. If, in the clinical judgment of the prescriber, evidence of treatment failure becomes obvious earlier than 2 to 4 weeks, treatment should be discontinued at that time [see Warnings and Precautions (5.1)].

In a controlled clinical study in patients with infantile spasms, SABRIL was tapered by decreasing the daily dose at a rate of 25 mg/kg to 50 mg/kg every 3 to 4 days [see Warnings and Precautions (5.6)].

2. 4 Patients with Renal Impairment

SABRIL is primarily eliminated through the kidney.

Infants
Information about how to adjust the dose in infants with renal impairment is unavailable.

Adult and pediatric patients 10 years and older

  • Mild renal impairment (CLcr >50 to 80 mL/min): dose should be decreased by 25%
  • Moderate renal impairment (CLcr >30 to 50 mL/min): dose should be decreased by 50%
  • Severe renal impairment (CLcr >10 to 30 mL/min): dose should be decreased by 75%.

CLcr in mL/min may be estimated from serum creatinine (mg/dL) using the following formulas:

  • Patients 10 to <12 years old: CLcr (mL/min/1.73 m2) = (K × Ht) / Scr

height (Ht) in cm; serum creatinine (Scr) in mg/dL
K (proportionality constant): Female Child (<12 years): K=0.55; Male Child (<12 years): K=0.70

  • Adult and pediatric patients 12 years or older: CLcr (mL/min) = [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 (12.3) and Use in Specific Populations (8.6)].

2.5 Preparation and Administration Instructions for SABRIL Powder for Oral Solution

If using SABRIL powder for oral solution, physicians should review and discuss the Medication Guide and instructions for mixing and giving SABRIL with the patient or caregiver(s). Physicians should confirm that patients or caregiver(s) understand how to mix SABRIL powder with water and administer the correct daily dose.

Empty the entire contents of each 500 mg packet into a clean cup, and dissolve in 10 mL of cold or room temperature water per packet. Administer the resulting solution using the 10 mL oral syringe supplied with the medication. The concentration of the final solution is 50 mg/mL.

Table 3 below describes how many packets and how many milliliters (mL) of water will be needed to prepare each individual dose. The concentration after reconstitution is 50 mg/mL.

Table 3. Number of SABRIL Packets and mL of Water Needed for Each Individual Dose

Individual Dose [mg]

[Given Twice Daily]

Total Number of

Sabril Packets

Total mL of Water

Required for Dissolving

0 to 500 1 packet 10 mL
501 to 1000 2 packets 20 mL
1001 to 1500 3 packets 30 mL

Discard the resulting solution if it is not clear (or free of particles) and colorless. Each individual dose should be prepared and used immediately. Discard any unused portion of the solution after administering the correct dose.

3 DOSAGE FORMS AND STRENGTHS

Tablet: 500 mg: white, oval, film-coated, biconvex, scored on one side, and debossed with OV 111 on the other.

Powder for Oral Solution: 500 mg packets of a white to off-white granular powder.

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