sodium oxybate (Rx)

Brand and Other Names:Xyrem, oxybate sodium, more...GHB (synonym)
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

oral solution, Schedule III

  • 500mg/mL
more...

Narcolepsy

Indicated for cataplexy or excessive daytime sleepiness (EDS) in patients with narcolepsy

Initial: 4.5 g per night PO divided in 2 doses; take 2.25 g HS and 2.25 g taken 2.5-4 hr later

Increase dose by 1.5 g/night at weekly intervals (additional 0.75 g at bedtime and 0.75 g taken 2.5-4 hr later) to the effective dose range of 6-9 g/night PO; not to exceed 9 g/night

Recommended dose regimens

  • 4.5 g/night: 2.25 g HS and 2.25 g 2.5-4 hr later
  • 6 g/night: 3 g HS and 3 g 2.5-4 hr later
  • 7.5 g/night: 3.75 g HS and 3.75 g 2.5-4 hr later
  • 9 g/night: 4.5 g HS and 4.5 g 2.5-4 hr later

Dosage Modifications

Renal impairment: No dose adjustment necessary

Hepatic impairment

  • Reduce initial dosage by one-half of the original dosage per night, divided into 2 doses

Coadministration with divalproex sodium

  • Patients already stabilized on sodium oxybate: When adding divalproex sodium, reduce initial nightly sodium oxybate dose by ≥20%
  • Patients already taking divalproex sodium: Initiate sodium oxybate at a lower starting dose; monitor response and adjust dose accordingly

Dosage Forms & Strengths

oral solution, Schedule III

  • 500mg/mL
more...

Narcolepsy

Indicated for cataplexy or excessive daytime sleepiness (EDS) in patients aged ≥7 years with narcolepsy

<7 years: Safety and efficacy not established

≥7 years

  • <20 kg: Consider a lower starting dosage, maximum weekly dosage increases, and total maximum nightly dosage; unequal dosages may be required for some patients to achieve optimal treatment
  • 20 to <30 kg: Initiate at ≤1 g HS and ≤1 g; may increase at weekly intervals up to 0.5-g/dose; not to exceed 3 g/dose
  • 30 to <45 kg: Initiate at ≤1.5 gram HS and ≤1.5 g; may increase at weekly intervals up to 0.5-g/dose; not to exceed 3.75 g/dose
  • ≥45 kg: Initiate at ≤2.25 g HS and ≤2.25 g; may increase at weekly intervals up to 0.75-g/dose; not to exceed 4.5 g/dose

Dosage Modifications

Renal impairment: No dose adjustment necessary

Hepatic impairment

  • Reduce initial dosage by one-half of the original dosage per night, divided into 2 doses

Coadministration with divalproex sodium

  • Patients already stabilized on sodium oxybate: When adding divalproex sodium, reduce initial nightly sodium oxybate dose by ≥20%
  • Patients already taking divalproex sodium: Initiate sodium oxybate at a lower starting dose; monitor response and adjust dose accordingly
Next:

Interactions

Interaction Checker

and sodium oxybate

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Headache (20-25%)

            Nausea (8-20%)

            Dizziness (4-15%)

            Pharyngitis (10-19%)

            Infection (10-19%)

            Vomiting (2-11%)

            Pediatric patients

            • Enuresis (18%)
            • Nausea (17%)
            • Headache (16%)
            • Vomiting (16%)
            • Weight decreased (12%)

            1-10%

            Somnolence (1-8%)

            Enuresis (3-7%)

            Diarrhea (2-4%)

            Disturbance in attention (1-4%)

            Sleep walking (3%)

            Upper abdominal pain (2-3%)

            Pain (<3%)

            Feeling drunk (<3%)

            Peripheral edema (1-3%)

            Disorientation (1-3%)

            Sleep paralysis (1-3%)

            Pain in extremity (1-3%)

            Irritability (<3%)

            Paresthesia (2-3%)

            Cataplexy (1-2%)

            Anxiety (1-2%)

            Dry mouth (1-2%)

            Muscle spasms (<2%)

            Pediatric patients

            • Decreased appetite (8%)
            • Dizziness (6%)

            <1%

            Psychosis

            Paranoia

            Hallucinations

            Agitation

            Postmarketing Reports

            Arthralgia

            Decreased appetite

            Fall

            Fluid retention

            Hangover

            Hypersensitivity

            Hypertension

            Memory impairment

            Nocturia

            Panic attack

            Vision blurred

            Weight decreased

            Aggression

            Previous
            Next:

            Warnings

            Black Box Warnings

            Central nervous system (CNS)

            • Sodium oxybate is a CNS depressant
            • In clinical trials at recommended doses, obtundation and clinically significant respiratory depression occurred in adults
            • During clinical trials in narcolepsy, many patients were also receiving CNS stimulants

            Abuse and misuse

            • Sodium oxybate is the sodium salt of gamma-hydroxybutyrate (GHB)
            • Abuse or misuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in level of consciousness, coma, and death

            Risk Evaluation and Mitigation Strategy program

            • Owing to the risks of CNS depression and abuse and misuse, available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Xyrem REMS Program
            • Requirements of the Xyrem REMS Program include the following:
              • Prescribing healthcare providers are specially certified
              • Dispensing pharmacies are specially certified
              • Drug will be dispensed and shipped only to patients who are enrolled in the Xyrem REMS Program with documentation of safe use
              • Further information is available at www.XYREMREMS.com or 1-866-XYREM88® (1-866-997- 3688)

            Contraindications

            Hypersensitivity

            Concomitant sedative-hypnotic drugs or other drugs used for insomnia

            Coadministration with alcohol

            Succinic semialdehyde dehydrogenase deficiency

            Cautions

            Xyrem is a Schedule III controlled substance; sodium oxybate or gamma-hydroxybutyrate (GHB), the active ingredient, is a Schedule I controlled substance

            Abuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death

            Illicit use and abuse of GHB reported, carefully evaluate for a history of drug abuse and closely monitor for signs of misuse or abuse of GHB (see Contraindications)

            Risks of: depression, respiratory depression, confusion, neuropsychiatric events including hallucinations, paranoia, psychosis, aggression, and agitation; use caution when considering concurrent use of sodium oxybate with other CNS depressants; monitor patients for emergent or increased depression and suicidality

            Only take at bedtime; monitor for impaired motor/cognitive function; caution patients against hazardous activities requiring complete mental alertness or motor coordination within the first 6 hr of dosing or after first initiating treatment until certain that sodium oxybate does not affect them adversely; do not operate machinery for at least 6 hr after dose

            Use with caution in patients with sleep apnea

            Evaluate episodes of parasomnias, including sleepwalking

            Do not drink alcoholic beverages (see Contraindications)

            Sodium intake

            • Product has high salt content; caution in patients who are sensitive to salt intake (eg, heart failure, renal impairment, hypertension)
            • Approximate sodium content per total nightly dose
              • 3 gram/night: 550 mg of sodium
              • 4.5 gram/night: 820 mg of sodium
              • 6 gram/night: 1100 mg of sodium
              • 7.5 gram/night: 1400 mg of sodium
              • 9 gram/night: 1640 mg of sodium

            Drug interactions overview

            • Coadministration with divalproex sodium resulted in a 25% mean increase in systemic exposure to sodium oxybate and greater impairment on some tests of attention and working memory
            • CNS depressants
              • Concurrent use with other CNS depressants (eg, opioid analgesics, benzodiazepines, sedating antidepressants or antipsychotics, sedating antiepileptic drugs, general anesthetics, muscle relaxants, illicit CNS depressants) may increase the risk of respiratory depression, hypotension, profound sedation, syncope, and death
              • If sodium oxybate must be combined with these CNS depressants, consider reducing dose or discontinuation of one or more CNS depressants (including sodium oxybate)
              • If short-term use opioid use required (eg, postoperative, perioperative), consider interrupting sodium oxybate treatment
            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            There are no adequate data on the developmental risk associated with use in pregnant women

            Clinical considerations

            • Not studied in labor and delivery
            • Placental transfer is rapid and GHB detected in newborns at delivery after IV administration of GHB to mother

            Animal data

            • Oral administration to pregnant rats or rabbits throughout organogenesis produced no clear evidence of developmental toxicity; however, oral administration to rats throughout pregnancy and lactation resulted in increased stillbirths and decreased offspring postnatal viability and growth, at a clinically relevant dose

            Lactation

            GHB is excreted in human milk after oral administration of sodium oxybate

            There is insufficient information on risk to a breastfed infant, and there is insufficient information on milk production in nursing mothers

            Consider developmental and health benefits of breastfeeding along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from drug or from underlying maternal condition

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

            more...
            Previous
            Next:

            Pharmacology

            Mechanism of Action

            CNS depressant; sodium oxybate is the sodium salt of gamma hydroxybutyrate, an endogenous compound and metabolite of the neurotransmitter GABA

            It is hypothesized that the therapeutic effects on cataplexy and excessive daytime sleepiness are mediated through GABAB actions at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons

            Absorption

            Bioavailability: 88% (fasting)

            Peak plasma time: 0.5-1.25 hr (fasting); 0.75-2 hr (high fat meal)

            Food delays absorption and a reduction in peak plasma concentration by a mean of 59% and of systemic exposure (AUC) by 37%

            Distribution

            Protein bound: <1%

            Vd: 190-384 mL/kg

            Metabolism

            Major elimination pathway is by producing carbon dioxide and water via the tricarboxylic acid (Krebs) cycle and secondarily by beta-oxidation

            Primary pathway involves a cytosolic NADP+-linked enzyme, GHB dehydrogenase that catalyzes the conversion of sodium oxybate to succinic semialdehyde, which is then biotransformed to succinic acid by succinic semialdehyde dehydrogenase

            Succinic acid enters the Krebs cycle where it is metabolized to carbon dioxide and water

            Elimination

            Half-life: 0.5-1 hr

            Clearance is almost entirely by biotransformation to CO2, which is then eliminated by expiration

            Excretion: Mostly lung (expiration of CO2); <5% urine

            Previous
            Next:

            Administration

            Oral Administration

            Administer first dose at least 2 hr after eating

            Prepare both doses prior to bedtime

            Prior to ingestion, dilute each dose of with ~2 oz (~60 mL) of water in the provided empty pharmacy containers

            Administer both doses while in bed and lie down immediately after dosing

            Patients should remain in bed following ingestion of the first and second doses; do not take the second dose until 2.5-4 hr after first dose

            If second dose is missed, skip dose and do not administer again until the following night

            Do not both doses at one time

            Storage

            Undiluted oral solution: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)

            Diluted oral solution: Use within 24 hr once diluted

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.