DailyMed Label: sodium oxybate

DailyMed Label: sodium oxybate

2023

DailyMed Prescription

sodium oxybate

sodium oxybate

Amneal Pharmaceuticals NY LLC

NDC: 69238-2391

NDC: 69238-2391

NDC: 69238-2391

NDC: 69238-2391

NDC: 69238-2391

Sodium oxybate, a CNS depressant, is the active ingredient in Sodium Oxybate Oral Solution. The chemical name for sodium oxybate is sodium 4‑hydroxybutyrate. The molecular formula is C 4 H 7 NaO 3 , and the molecular weight is 126.09 g/mole. The chemical structure is: Sodium oxybate is a white to off-white, crystalline powder that is very soluble in aqueous solutions. Each mL of Sodium Oxybate Oral Solution contains 0.5 g of sodium oxybate (equivalent to 0.413 g/mL of oxybate) in USP Purified Water, neutralized to pH 7.5 with malic acid.

Sodium Oxybate Oral Solution is indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy.

Dosage for Adult Patients • Initiate dosage at 4.5 g per night orally, divided into two doses ( 2.1 ). • Titrate to effect in increments of 1.5 g per night at weekly intervals (0.75 g at bedtime and 0.75 g taken 2.5 to 4 hours later) ( 2.1 ). • Recommended dosage range: 6 g to 9 g per night orally ( 2.1 ). Total Nightly Dose Take at Bedtime Take 2.5 to 4 Hours Later 4.5 g per night 2.25 g 2.25 g 6 g per night 3 g 3 g 7.5 g per night 3.75 g 3.75 g 9 g per night 4.5 g 4.5 g Dosage for Pediatric Patients (7 years of Age and Older) • The recommended starting dosage, titration regimen, and maximum total nightly dosage are based on body weight ( 2.2 ). Important Administration Information • Prepare both doses prior to bedtime; dilute each dose with approximately ¼ cup of water in pharmacy-provided containers ( 2.3 ). • Allow 2 hours after eating before dosing ( 2.3 ). • Take each dose while in bed and lie down after dosing ( 2.3 ). Patients with Hepatic Impairment Recommended starting dosage is one-half of the original dosage per night administered orally, divided into two doses ( 2.4 ).

Sodium Oxybate Oral Solution is a clear to slightly opalescent oral solution, in a concentration of 0.5 g per mL (0.5 g/mL of sodium oxybate equivalent to 0.413 g/mL of oxybate).

Sodium Oxybate Oral Solution is contraindicated for use in: • combination with sedative hypnotics [see Warnings and Precautions ( 5.1 )] . • combination with alcohol [see Warnings and Precautions ( 5.1 )] . • patients with succinic semialdehyde dehydrogenase deficiency [see Clinical Pharmacology ( 12.3 )] .

• CNS depression: Use caution when considering the concurrent use of Sodium Oxybate Oral Solution with other CNS depressants ( 5.1 ). • Caution patients against hazardous activities requiring complete mental alertness or motor coordination within the first 6 hours of dosing or after first initiating treatment until certain that Sodium Oxybate Oral Solution does not affect them adversely ( 5.1 ). • Depression and suicidality: Monitor patients for emergent or increased depression and suicidality ( 5.5 ). • Confusion/Anxiety: Monitor for impaired motor/cognitive function ( 5.6 ). • Parasomnias: Evaluate episodes of sleepwalking ( 5.7 ). • High sodium content in Sodium Oxybate Oral Solution: Monitor patients with heart failure, hypertension, or impaired renal function ( 5.8 ).

The following clinically significant adverse reactions appear in other sections of the labeling:

• Concomitant use with divalproex sodium: An initial reduction in Sodium Oxybate Oral Solution dose of at least 20% is recommended ( 2.5 , 7.2 ).

• Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ). • Geriatric patients: Monitor for impaired motor and/or cognitive function when taking Sodium Oxybate Oral Solution ( 8.5 ).

Sodium Oxybate Oral Solution is a clear to slightly opalescent oral solution. Each prescription includes one bottle of Sodium Oxybate Oral Solution with attached press in bottle adaptor, an oral measuring device (plastic syringe), and a Medication Guide. The pharmacy provides two empty containers with child-resistant caps with each Sodium Oxybate Oral Solution shipment. Each amber bottle contains Sodium Oxybate Oral Solution at a concentration of 0.5 g per mL (0.5 g/mL of sodium oxybate equivalent to 0.413 g/mL of oxybate) and has a child-resistant cap. One 180 mL bottle                                       NDC 69238-2391-1

Sodium Oxybate Oral Solution is a CNS depressant. The mechanism of action of Sodium Oxybate Oral Solution in the treatment of narcolepsy is unknown. Sodium oxybate is the sodium salt of gamma-hydroxybutyrate (GHB), an endogenous compound and metabolite of the neurotransmitter GABA. It is hypothesized that the therapeutic effects of Sodium Oxybate Oral Solution on cataplexy and excessive daytime sleepiness are mediated through GABA B actions at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons.

Carcinogenesis Administration of sodium oxybate to rats at oral doses of up to 1,000 mg/kg/day for 83 (males) or 104 (females) weeks resulted in no increase in tumors. Plasma exposure (AUC) at the highest dose tested was 2 times that in humans at the maximum recommended human dose (MRHD) of 9 g per night. The results of 2-year carcinogenicity studies in mouse and rat with gamma-butyrolactone, a compound that is metabolized to sodium oxybate in vivo , showed no clear evidence of carcinogenic activity. The plasma AUCs of sodium oxybate achieved at the highest doses tested in these studies were less than that in humans at the MRHD. Mutagenesis Sodium oxybate was negative in the in vitro bacterial gene mutation assay, an in vitro chromosomal aberration assay in mammalian cells, and in an in vivo rat micronucleus assay. Impairment of Fertility Oral administration of sodium oxybate (150, 350, or 1,000 mg/kg/day) to male and female rats prior to and throughout mating and continuing in females through early gestation resulted in no adverse effects on fertility. The highest dose tested is approximately equal to the MRHD on a mg/m 2 basis.

The efficacy of Sodium Oxybate Oral Solution for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy has been established in the following adequate and well-controlled trials: • Cataplexy in adult narcolepsy in Trials N1 and N2 [see Clinical Studies ( 14.1 )] • Excessive Daytime Sleepiness (EDS) in adult narcolepsy in Trials N3 and N4 [see Clinical Studies ( 14.2 )] • Cataplexy and EDS in pediatric narcolepsy in Trial N5 [see Clinical Studies ( 14.3 )]