Dilution Keppra ® -levetiracetam

Levetiracetam (Keppra ®)

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Usual Diluents

NS, D5W, or LR

Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]

[Prescribed dose] [100ml] [ 15 minutes]

Examples:
[500 mg] [100ml] [15 minutes]
[1000 mg ] [100ml] [15 minutes]
[1500 mg ] [100ml] [15 minutes]

(Product with particulate matter or discoloration should not be used.)

Stability / Miscellaneous

Stability

Preparation and Administration Instructions
KEPPRA injection is for intravenous use only and should be diluted in 100 mL of a compatible diluent prior to administration. If a smaller volume is required (e.g. pediatric patients), the amount of diluent should be calculated to not exceed a maximum levetiracetam concentration of 15 mg per mL of diluted solution. Consideration should also be given to the total daily fluid intake of the patient. KEPPRA injection should be administered as a 15-minute IV infusion. One vial of KEPPRA injection contains 500 mg levetiracetam (500 mg/5 mL).

KEPPRA injection may be mixed with the following diluents and antiepileptic drugs and may be stored in polyvinyl chloride (PVC) bags. The diluted solution should not be stored for more than 4 hours at controlled room temperature [15-30°C (59-86°F)].

Compatible Diluents:
• Sodium chloride (0.9%) injection, USP
• Lactated Ringer’s injection
• Dextrose 5% injection, USP

Depending on the packager /NDC, a recent revision increased the stabililty back to 24 hours from 4 hours. Timeline: Prior to ~ 2019, 24 hours was listed in all cases. After ~2019, the stability was reduced to 4 hours which is still the case in ~ 80-90% of the current package inserts. Example.

Revised: 5/2024 (PDF)
Packager: Hospira, Inc.
Levetiracetam injection was found to be physically compatible and chemically stable when mixed with the following diluents and antiepileptic drugs for at least 24 hours and stored in polyvinyl chloride (PVC) bags at controlled room temperature 15 to 30°C (59 to 86°F).

Indications: KEPPRA injection is indicated as adjunctive therapy in the treatment of partial onset seizures in ADULTS with epilepsy. KEPPRA injection is an alternative for patients when oral administration is temporarily not feasible.
(Safety and effectiveness of KEPPRA injection in patients below the age of 16 years have not been established.)

Dosage: KEPPRA injection is for intravenous use only and must be diluted prior to administration. Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. Doses greater than 3000 mg/day have been used in open label studies with KEPPRA tablets for periods of 6 months and longer. There is no evidence that doses greater than 3000 mg/day confer additional benefit.

Note: dosage adjustments are necessary in patients with impaired renal function.

Impaired Renal Function:
First estimate the patient's creatinine clearance (ml/min):
Cockcroft and Gault equation:

Creatinine clearance for males =	[140-age (years)]× [body wt (kg)] 72 × [serum creatinine (mg/dL)]
Creatinine clearance for females =	[140-age (years)]× [body wt (kg)]× 0.85 72 × [serum creatinine (mg/dL)]

CRCL (ml/min)	Dosage	Frequency
> 80 ml/min	500-1500 mg	q12h
50 - 80	500-1000 mg	q12h
30 - 50	250-750 mg	q12h
<30	250-550 mg	q12h
ESRD patients on dialysis	500-1000 mg	q24h*
*Following dialysis, a 250 to 500mg supplemental dose is recommended

Replacement Therapy: When switching from oral KEPPRA, the initial total daily intravenous dosage of KEPPRA should be equivalent to the total daily dosage and frequency of oral KEPPRA . Any unused portion of the KEPPRA injection vial contents should be discarded.

Miscellaneous
Dilution:
Dilute prescribed dose in 100 ml of a compatible diluent and infuse over 15 minutes.

Compatible Diluents:
• Sodium chloride (0.9%) injection, USP
• Lactated Ringer’s injection
• Dextrose 5% injection, USP

How Supplied
KEPPRA (levetiracetam) 500 mg/5 mL injection is a clear, colorless, sterile solution. It is supplied in single-use 5 mL vials, available in cartons of 10 vials (NDC 50474-002-63).

Storage
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].

Source: [package insert]