Oxybate Salts (Calcium, Magnesium, Potassium, and Sodium)

Medically reviewed by Drugs.com. Last updated on Nov 28, 2023.

Pronunciation

(OX i bate salts, KAL see um, mag NEE zee um, poe TAS ee um, & SOE dee um)

Index Terms

Calcium oxybate, magnesium oxybate, potassium oxybate, and sodium oxybate
Calcium, magnesium, potassium, and sodium oxybates
Xywav

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Oral:

Xywav: 500 mg/mL (180 mL) [barley free, gluten free, rye free, wheat free]

Brand Names: U.S.

Xywav

Pharmacologic Category

Central Nervous System Depressant

Pharmacology

The active moiety of oxybate salts (calcium, magnesium, potassium, and sodium) is oxybate or gamma-hydroxybutyrate (GHB). The therapeutic effects of GHB, a metabolite of GABA, are hypothesized to be mediated by GABA_B receptor activity at noradrenergic, dopaminergic, and thalamocortical neurons.

Distribution

V_d: 190 to 384 mL/kg.

Metabolism

Primarily via the Krebs cycle to form water and carbon dioxide; secondarily via beta oxidation; no active metabolites.

Excretion

Primarily via biotransformation to carbon dioxide and expiration; Urine: <5% as unchanged drug.

Onset of Action

Rapid (≤5 to 15 minutes).

Time to Peak

~1.3 hours.

Half-Life Elimination

~0.66 hours.

Protein Binding

<1%.

Special Populations: Hepatic Function Impairment

AUC is doubled, elimination half-life is longer, and oral clearance is reduced in cirrhotic patients (Child-Pugh class A and C).

Use: Labeled Indications

Narcolepsy: Treatment of cataplexy or excessive daytime sleepiness in patients ≥7 years of age with narcolepsy.

Contraindications

Concomitant use with sedative hypnotics or alcohol; succinic semialdehyde dehydrogenase deficiency.

Dosing: Adult

Narcolepsy: Oral: Initial: 2.25 g at bedtime after the patient is in bed, and 2.25 g taken 2.5 to 4 hours later (4.5 g/night). May increase nightly dose by 1.5 g (0.75 g at bedtime and 0.75 g 2.5 to 4 hours later) at weekly intervals based on efficacy and tolerability; usual effective dosage range: 6 to 9 g/night. Maximum dose: 9 g/night.

Missed second dose: Skip dose and resume usual dosing schedule the next day. Do not administer 2 doses at the same time.

Conversion from sodium oxybate to oxybate salts (calcium, magnesium, potassium, and sodium): On the first night of dosing with oxybate salts (calcium, magnesium, potassium, and sodium), initiate treatment at the same dose (gram for gram) and regimen as sodium oxybate.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing; use with caution.

Dosing: Pediatric

Narcolepsy (excessive daytime sleepiness/cataplexy): Note: Nightly, 2 doses are administered; some patients may require unequal doses to achieve optimal response. Dosing is presented as grams of oxybate.

Children ≥7 years and Adolescents:

<20 kg: Oral: There are no specific dosage recommendations in the manufacturer's labeling due to insufficient data; however, a lower initial starting dose and lower maximum dosages are recommended.

20 to <30 kg: Oral: Initial: ≤1 g at bedtime after the patient is in bed, then 2.5 to 4 hours later, administer second dose of ≤1 g. After 1 week, titrate dose based on efficacy and tolerability at weekly intervals; increase dose in ≤0.5 g/dose (≤1 g/night) increments per week; maximum single dose: 3 g/dose; maximum daily dose: 6 g/night.

30 to <45 kg: Oral: Initial: ≤1.5 g at bedtime after the patient is in bed, then 2.5 to 4 hours later, administer second dose of ≤1.5 g. After 1 week, titrate dose based on efficacy and tolerability at weekly intervals; increase dose in ≤0.5 g/dose (≤1 g/night) increments per week; maximum single dose: 3.75 g/dose; maximum daily dose: 7.5 g/ night.

≥45 kg: Oral: Initial: ≤2.25 g at bedtime after the patient is in bed, then 2.5 to 4 hours later, administer second dose of ≤2.25 g . After 1 week, titrate dose based on efficacy and tolerability at weekly intervals; increase dose in ≤0.75 g/dose (≤1.5 g/night) increments per week; maximum single dose: 4.5 g/dose; maximum daily dose: 9 g/night.

Converting from sodium oxybate (Xyrem) to oxybate salts (calcium, magnesium, potassium, and sodium oxybate) (Xywav): Discontinue sodium oxybate (Xyrem) and initiate oxybate salts (calcium, magnesium, potassium, and sodium) (Xywav) at the same dose (gram per gram); titrate as needed based on efficacy and tolerability.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Administration

Oral: Administer on an empty stomach, ≥2 hours after eating. Administer first dose at bedtime. Administer second nightly dose 2.5 to 4 hours after the first dose; an alarm clock may need to be set for the second dose. Prepare both doses prior to bedtime. Prior to ingestion, dilute each dose with approximately ¼ cup water in provided empty pharmacy containers. Administer both doses while patient is in bed; patient should lie down immediately after dose and remain in bed.

Storage

Store between 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Dispense in tight containers. Diluted solution should be consumed within 24 hours.

Drug Interactions

Alcohol (Ethyl): May enhance the CNS depressant effect of Oxybate Salt Products. Avoid combination

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Benzodiazepines: May enhance the CNS depressant effect of Oxybate Salt Products. Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Consider therapy modification

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Consider therapy modification

Hypnotics (Nonbenzodiazepine): May enhance the CNS depressant effect of Oxybate Salt Products. Avoid combination

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Rilmenidine: Oxybate Salt Products may enhance the CNS depressant effect of Rilmenidine. Avoid combination

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Valproate Products: May increase the serum concentration of Oxybate Salt Products. Management: Decrease the dose of the oxybate salt product by at least 20% when initiating therapy with valproate products. When initiating oxybate salt products in patients taking valproate products, use a lower starting dose of the oxybate salt. Consider therapy modification

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Gastrointestinal: Nausea (13%)

Nervous system: Headache (20%)

1% to 10%:

Dermatologic: Diaphoresis (including night sweats; 6%)

Gastrointestinal: Decreased appetite (8%), diarrhea (6%), vomiting (5%), xerostomia (4%)

Genitourinary: Urinary incontinence (4%)

Nervous system: Anxiety (including agitation, panic attack, and tension; 5%), confusion (1%), depressed mood (4%), depression (3%), dizziness (10%), drowsiness (2%), fatigue (4%; including asthenia), irritability (3%), parasomnias (including abnormal dreams, night terrors, sleep paralysis, sleep talking, and somnambulism; 6%), paresthesia (3%)

Neuromuscular & skeletal: Muscle spasm (2%), tremor (3%)

<1%: Nervous system: Hallucination

Frequency not defined:

Nervous system: Central nervous system depression

Respiratory: Respiratory depression

ALERT: U.S. Boxed Warning

Central nervous system depression

Oxybate salts (calcium, magnesium, potassium, and sodium) are CNS depressants. Clinically significant respiratory depression and obtundation may occur in patients treated with oxybate salts (calcium, magnesium, potassium, and sodium) at recommended doses. Many patients who received oxybate salts (calcium, magnesium, potassium, and sodium) during clinical trials in narcolepsy were receiving CNS stimulants.

Abuse and misuse

The active moiety of oxybate salts (calcium, magnesium, potassium, and sodium) is oxybate or 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 the level of consciousness, coma, and death.

Restricted access

Because of the risks of CNS depression and abuse and misuse, oxybate salts (calcium, magnesium, potassium, and sodium) is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the XYWAV and XYREM REMS.

Warnings/Precautions

Concerns related to adverse effects:

• Behavioral and psychiatric effects: Use of oxybate salts (calcium, magnesium, potassium, and sodium) and sodium oxybate, which has the same active moiety, has been associated with aggression, agitation, amnesia, anxiety, confusion, depression, psychosis, suicidality, and visual hallucinations.

• CNS depression: Oxybate salts (calcium, magnesium, potassium, and sodium) may impair physical or mental abilities. Patients must be instructed not to engage in hazardous activities requiring mental alertness or motor coordination for at least 6 hours after taking oxybate salts (calcium, magnesium, potassium, and sodium).

• Parasomnias: Parasomnias, including sleepwalking, may occur with use. Evaluate episodes of sleep walking and implement appropriate interventions.

• Respiratory depression: [US Boxed Warning]: At recommended doses, obtundation and clinically significant respiratory depression may occur. Many patients who received oxybate salts (calcium, magnesium, potassium, and sodium) during clinical trials in narcolepsy were receiving CNS stimulants. Use with caution in patients with compromised respiratory function. Concurrent use with other CNS depressants may increase the risk of respiratory depression, hypotension, profound sedation, syncope, and death. Use is contraindicated with alcohol and sedative hypnotics; concomitant CNS depressant use should generally be avoided; however, if concomitant use is required, dosage adjustments or discontinuation of 1 or more CNS depressant agent (including oxybate salts [calcium, magnesium, potassium, and sodium]) should be considered. If short-term opioid use is required, consider temporarily discontinuing oxybate salts (calcium, magnesium, potassium, and sodium).

Disease-related concerns:

• Hepatic insufficiency: Use with caution in patients with preexisting liver impairment.

• Sleep-related breathing disorders: Sleep-related breathing disorders (eg, sleep apnea, reduced oxygenation) may occur; may be more common in patients with narcolepsy, or that are obese, male, or postmenopausal (not on hormone-replacement therapy).

Other warnings/precautions:

• Abuse/misuse/diversion: [US Boxed Warning]: Oxybate salts (calcium, magnesium, potassium, and sodium; the salts of gamma hydroxybutyrate [GHB]) are CNS depressant controlled substances with abuse potential. Seizures, respiratory depression, decreases in level of consciousness, coma, and death have been reported when GHB, either alone or in combination with other CNS depressants, has been abused. Health care providers should be alert to problems of abuse, misuse, and diversion. Patients should be evaluated for a history of drug abuse and should be monitored for signs of misuse, abuse, and addiction.

• Restricted access: [US Boxed Warning]: Oxybate salts (calcium, magnesium, potassium, and sodium) are available only through a restricted distribution program to prescribers and patients enrolled in the Xywav and Xyrem REMS Program and dispensed to the patient only by the central pharmacy that is specially certified (1-866-997-3688 or www.xywavxyremrems.com).

• Tolerance/withdrawal: Tolerance to oxybate salts (calcium, magnesium, potassium, and sodium), or withdrawal following its discontinuation, has not been clearly defined in controlled clinical trials, but has been reported at larger doses used for illicit purposes.

Monitoring Parameters

Emergent or worsening depression, suicidal ideation, emergence or increase in the occurrence of behavioral or psychiatric events; impaired motor/cognitive function; drug abuse/misuse.

Pregnancy Considerations

The active moiety of oxybate salts, gamma-hydroxybutyrate, crosses the placenta. The injection formulation of sodium oxybate, when used as an anesthetic during labor and delivery, was shown to cause a slight decrease in Apgar scores due to sleepiness in the neonate.

Patient Education

What is this drug used for?

• It is used to treat sudden loss of muscle tone (cataplexy) in patients with narcolepsy.

• It is used to treat a lot of sleepiness during the day in patients with narcolepsy.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Diarrhea, upset stomach, or throwing up

• Bedwetting

• Headache

• Sweating a lot

• Abnormal dreams, sleep talking, or other abnormal effects during sleep

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Depression like thoughts of suicide, nervousness, emotional ups and downs, thinking that is not normal, anxiety, or lack of interest in life

• Hallucinations (seeing or hearing things that are not there)

• Feeling confused, not able to focus, or change in behavior

• A change in weight without trying

• Feeling more or less hungry

• Sleepwalking

• Trouble breathing, slow breathing, or shallow breathing

• Breathing problems during sleep (sleep apnea)

• Very bad dizziness or passing out

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.