Sodium oxybate is the sodium salt of gamma hydroxybutyric acid (GHB), a naturally occurring central nervous system transmitter with sedative and anesthetic properties. In Europe, sodium oxybate has been used for various medical purposes including narcolepsy, intravenous anesthesia, alcohol dependence, and opiate dependence. In the U.S., sodium oxybate is used for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients with narcolepsy. Sodium oxybate differs from modafinil and other stimulant treatments for narcolepsy in that it significantly decreases cataplexy episodes in addition to EDS; the drug is frequently prescribed along with stimulant therapies for narcolepsy. A median decrease in the total number of weekly cataplexy episodes of nearly 70% has been reported in clinical trials in adults with narcolepsy receiving a dose of 9 grams/night. Historically, GHB was commonly used as a dietary supplement for enhancing athletic performance and as a sleep aid. As a result of serious adverse events associated with GHB use as a dietary supplement, the FDA prohibited the marketing of GHB in 1991. Commonly known by slang terms such as Liquid Ecstasy or Liquid E, GHB can produce euphoria, making it a popular but dangerous party drug of abuse. GHB has not been approved for any medical use and has gained notoriety as a date rape drug due to its sedative and amnestic properties.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral solution (Xyrem):
-See the manufacturer's "Instructions for Use" in the product label.
-Prepare both doses prior to the patient's bedtime.
-Dilute each dose with approximately 60 mL (one-fourth cup) of water in the empty child-resistant containers provided. Ensure the second dose is kept in a safe place until given, close to the patient's bed. Ensure the cap is applied and locked into the child-resistant position to prevent access to the medication by children.
-The patient should consume each dose while in bed and should lie down immediately after each dose as they may fall asleep abruptly without first feeling drowsy.
-Patients should remain in bed after each dose.
-First dose: Administer at bedtime, at least 2 hours after eating.
-Second dose: Administer the second dose 2.5 to 4 hours after the first dose. Patients and/or caregivers may need to set an alarm to awaken for the second dose.
-If the second dose is missed, the patient should skip the missed dose and do not take again until the next night. Never take both doses at once.
-Storage: Discard any diluted solution that is not used within 24 hours. May discard down the sink drain or flush down the toilet.
Oral suspension (Lumryz):
-See the manufacturer's "Instructions for Use" in the product label.
-Prepare the dose prior to the patient's bedtime.
-Prior to ingestion, the medication should be suspended in approximately 80 mL (one-third cup) of water in the mixing cup provided. Do not use hot water.
-After mixing, have the patient consume the medication within 30 minutes. Patients should take sodium oxybate at least 2 hours after eating.
-The patient should take the medication while in bed and lie down immediately after dosing as they may fall asleep abruptly without first feeling drowsy. Patients will often fall asleep within 5 minutes of taking the medication and will usually fall asleep within 15 minutes, though the time it takes an individual patient to fall asleep may vary from night to night.
-Patients should remain in bed following ingestion of sodium oxybate.
-Storage: Discard any unused, diluted suspension. May discard down the sink drain or flush down the toilet.
Sodium oxybate is a central nervous system (CNS) depressant. Obtundation has occurred at recommended doses. Sodium oxybate may cause patients to fall asleep abruptly without first feeling drowsy; patients often fall asleep within 5 to 15 minutes of administration. The sudden onset of sleep has resulted in falls complicated by injuries, in some cases requiring hospitalization. Patients should remain in bed during and after a dose and must refrain from engaging in activities requiring mental alertness and motor coordination for at least 6 hours after a dose. During adult clinical trials of immediate-release sodium oxybate, dizziness (9% to 15%), drowsiness (1% to 8%), tremor (5% or less), paresthesias (1% to 3%), disturbance in attention (4% or less), parasomnias (complex sleep-related behaviors) including somnambulism (sleepwalking) (3% or less), and sleep paralysis (3% or less) were reported as side effects at incidences greater than with placebo. A dose-response relationship was observed for paresthesias, disturbance in attention, and sleepwalking. Overall, sleepwalking was reported in 6% of adult patients during clinical trials of immediate-release sodium oxybate, with potential or significant injury in some instances. In adult clinical trials of an extended-release formulation of sodium oxybate, side effects were similar to those noted in immediate-release studies, with the most common CNS effects reported as dizziness (4% to 6%) and headache (7% or less). Drowsiness (up to 4%) and somnambulism (up to 2%) were also reported in adults receiving the extended-release formulation. Headache (17%), dizziness (8%), and sleepwalking (6%) were among the most common adverse reactions reported during a pediatric trial; headache was among the adverse effects which led to discontinuation of treatment. Complex sleep-related behaviors have been reported with postmarketing use in both adult and pediatric patients. Hangover, headache, fall, memory impairment have also been reported with postmarketing use. Coadministration of sodium oxybate with other CNS depressants may increase the risk of depressed respiration, low blood pressure, profound sedation, fainting, and death. If concurrent use is required, consider dose reduction or discontinuation of one or more CNS depressant (including sodium oxybate). Consider sodium oxybate interruption if the short-term use of an opioid is required.
In adult clinical trials, there were 2 suicides and 2 attempted suicides in patients treated with immediate-release sodium oxybate, including 3 patients with a history of depressive psychiatric disorder. One pediatric patient experienced suicidal ideation and two reported depression while receiving sodium oxybate during a clinical trial for narcolepsy. In adult clinical trials of an extended-release formulation, there were no suicide attempts, but 1 patient developed suicidal ideation at the 9 gram/night dose. The emergence or increase of behavioral changes or psychiatric events requires careful and immediate evaluation. Monitor patients carefully with a history of depression or suicidal ideation or attempt, or if other behavioral or psychiatric changes occur during treatment in any treated individual. Depression (7%), confusion (3%), anxiety (5.8%), hallucinations, paranoia, psychosis, aggression, and agitation have been reported during adult clinical trials and postmarketing use of sodium oxybate immediate release solution; depression or confusion led to treatment discontinuation in less than 1% of patients treated. In a controlled trial of immediate-release sodium oxybate in adults, the incidence of depression was 1.7%, 1.5%, 3.2%, and 3.6% for placebo, 4.5 grams, 6 grams, and 9 grams/night doses, respectively. Depression also occurred and appeared to be dose-related, with incidences reported as 0% at 4.5 grams/night, 1% at 6 grams/night, 1.1% at 7.5 grams/night, and 1.3% at 9 grams/night. Confusion also appears to be dose-related; 17% of patients receiving 9 grams/night in a fixed-dose trial with the immediate-release product experienced confusion; resolution of the confusion occurred either soon after treatment termination or with continued treatment. Disorientation (1% to 3%), anxiety (1% to 2%), irritability (3% or less), and feeling drunk (impaired cognition, 3% or less) were reported more often than with placebo. A dose-response relationship was observed for disorientation, irritability, and concentration impairment (feeling drunk). In a pediatric clinical trial for narcolepsy, tactile hallucinations, suicidal ideation, affect lability (emotional lability), anger, anxiety, and depression were among the adverse effects which led to discontinuation of treatment. Panic attack has been reported during postmarketing use of immediate release sodium oxybate solution. In adult trials of extended-release sodium oxybate suspension, 7.5% of patients experienced anxiety. Depression also occurred and appeared to be dose-related, with incidences reported as 0% at 4.5 grams/night, 1% at 6 grams/night, 1.1% at 7.5 grams/night, and 1.3% at 9 grams/night.
Sodium oxybate is a central nervous system (CNS) depressant. Sodium oxybate may impair respiratory drive, especially in patients with compromised respiratory function. Life-threatening respiratory depression has been reported in overdoses. Central apnea and clinically relevant desaturation events have been observed in both pediatric and adult patients. In a pediatric clinical trial for narcolepsy, sleep apnea syndrome was among the adverse effects which led to discontinuation of treatment. Coadministration of sodium oxybate with other CNS depressants may increase the risk of respiratory depression, low blood pressure, profound sedation, fainting, and death. If concurrent use is required, consider dose reduction or discontinuation of one or more CNS depressants (including sodium oxybate). Consider sodium oxybate interruption if the short-term use of an opioid is required.
Nausea (8% to 20%), vomiting (2% to 11%), diarrhea (3% to 4%), upper abdominal pain (1% to 3%), and xerostomia (1% to 2%) were reported more often than placebo during adult clinical trials of immediate release sodium oxybate. A dose-response relationship was observed for nausea and vomiting. Nausea (2.8%) was the most common adverse effect leading to treatment discontinuation in adults. Nausea (20%), vomiting (18%), weight loss (13%), and anorexia (9%) were among the most common adverse reactions reported during a pediatric trial for narcolepsy; weight loss was among the adverse effects which led to discontinuation of treatment. Anorexia and weight loss have also been reported during postmarketing use. These effects were also noted in adult clinical trials of an extended-release formulation of sodium oxybate, with nausea (1% to 8%), vomiting (3% to 6%), anorexia (3% to 4%), and weight loss (up to 4% of patients) reported.
Unspecified pain (3% or less), pain in extremity (1% to 3%), cataplexy (1% to 2%), and muscle cramps (2% or less) were reported more often than placebo during adult clinical trials of immediate-release sodium oxybate. Arthralgia has been reported with postmarketing use of the immediate-release formulation; however, the frequency is unknown, and causality has not been established.
Peripheral edema (3% or less), urinary incontinence (enuresis) (3% to 7%), and hyperhidrosis (1% to 3%) were reported more often than placebo during adult clinical trials of immediate-release sodium oxybate. Enuresis was also reported in clinical trials of adults taking extended-release sodium oxybate, with 2% to 9% of patients affected in a dose-related manner. Enuresis was reported in 19% of patients during a pediatric trial for narcolepsy. Hypertension, edema, blurred vision, nocturia, and unspecified hypersensitivity have been reported during postmarketing use; however, the frequencies are unknown, and causality has not been established. Sodium oxybate has a high salt content. In patients sensitive to salt intake (e.g., those with heart failure, hypertension, renal impairment) consider the amount of sodium intake per dose of sodium oxybate.
Doses of gamma hydroxybutyrate (GHB) exceeding 50 mg/kg may produce symptoms of anesthesia and serious toxicity. Toxic effects of sodium oxybate, the sodium salt of GHB, become apparent within 15 minutes of oral ingestion due to the rapid absorption of the drug. Signs and symptoms of sodium oxybate intoxication include agitation, ataxia, sinus bradycardia, Cheyne-Stokes respiration, coma, confusion, delirium, dizziness, hallucinations, hypersalivation, hypertension, hypothermia, hypotonia, hypoxia, myoclonia, nausea/vomiting, nystagmus, respiratory depression, seizures, sinus tachycardia, and visual impairment. Death has occurred in association with sodium oxybate (GHB) toxicity. In clinical trials with sodium oxybate, two overdoses were reported. In the first case, an estimated dose of 150 grams, more than 15 times the maximum recommended dose, caused a patient to be unresponsive with brief periods of apnea, urinary incontinence, and fecal incontinence. This individual recovered without sequelae. In the second case, death was reported following a multiple drug overdose consisting of sodium oxybate and numerous other drugs.
Sodium oxybate, the sodium salt of gamma hydroxybutyrate (GHB), is a psychoactive drug that produces a wide range of pharmacological effects. It is a sedative-hypnotic that produces dose and concentration dependent CNS effects in humans. The onset of effect is rapid, enhancing its desirability as a drug of abuse or misuse. The drug is purported to produce euphoria and libido increase in illicit use. The rapid onset of sedation, coupled with the amnestic features of sodium oxybate, particularly when combined with alcohol, has proven to be dangerous. The abuse of GHB is associated with psychological dependence and tolerance. Physiological dependence has been reported after illicit use of GHB at frequent repeated doses (18 to 250 grams/day), in excess of the therapeutic dose range for accepted medical use. In these cases, the signs and symptoms of abrupt discontinuation included a withdrawal syndrome consisting of insomnia, restlessness, anxiety, psychosis, lethargy, nausea, tremor, sweating, muscular cramps, tachycardia, headache, dizziness, rebound fatigue and sleepiness, confusion, and in severe cases, visual hallucinations, agitation, and delirious state. These symptoms generally abated in 3 to 14 days. The discontinuation effects of sodium oxybate have not been systematically evaluated in controlled clinical trials. Although the clinical trial experience with sodium oxybate in narcolepsy/cataplexy patients at therapeutic doses does not show clear evidence of a withdrawal syndrome, two patients reported anxiety and one reported insomnia following abrupt discontinuation; in the two patients with anxiety, the frequency of cataplexy had increased markedly at the same time.
In an ISMP safety report, sodium oxybate was noted as 1 of the 19 drugs having the strongest signals for serotonin syndrome with 10 cases reported over 1 year to the FDA Adverse Event Reporting System (FAERS). Serotonin syndrome rarely happens with single drug therapy, and more commonly is reported with interactions between multiple serotonergic drugs or accidental or intentional drug overdoses. The mechanism by which sodium oxybate might promote serotonergic excess is not clear. The manufacturer has not reported serotonin syndrome as an adverse reaction postmarketing.
Sodium oxybate is contraindicated in patients with succinic semialdehyde dehydrogenase deficiency. This rare disorder is an inborn error of metabolism variably characterized by mental retardation, hypotonia, and ataxia.
Depression, and suicidal ideation and behavior, can occur in patients treated with sodium oxybate, and behavioral changes were reported in both pediatric and adult populations treated with sodium oxybate during clinical evaluations. Some events, such as confusion, generally increased in incidence as the dosage increased. Carefully monitor for the emergence or increase in the occurrence of a behavioral or psychiatric event in adult and pediatric patients taking sodium oxybate. The emergence of depression requires careful and immediate evaluation. Patients with a previous history of a depressive illness and/or suicide attempt should be monitored carefully for the emergence of depressive symptoms while taking sodium oxybate.
Complex sleep-related behaviors (parasomnias) including sleepwalking have been reported in both adult and pediatric patients taking sodium oxybate. In clinical trials, several instances of sleepwalking resulted in significant injury. Advise patients to report any unusual sleep-related behaviors to their provider. Fully evaluate episodes of sleepwalking and consider appropriate interventions.
Sodium oxybate causes CNS depression. Obtundation and clinically significant respiratory depression have occurred in patients treated with sodium oxybate at recommended doses; many of the patients in clinical trials for narcolepsy were also receiving CNS stimulants. Coadministration with alcohol and sedative-hypnotics is contraindicated; warn patients against ethanol ingestion and do not use in patients with active alcoholism. Coadministration with other CNS depressants may increase the risk of respiratory depression, hypotension, profound sedation, syncope, and death. If concurrent use is required, consider dose reduction or discontinuation of one or more of the CNS depressants. Consider sodium oxybate dosing interruption if the short-term use of an opioid (e.g., during or after surgery) is required. Sodium oxybate may cause patients to fall asleep abruptly without first feeling drowsy and patients will often fall asleep within 5 to 15 minutes of dosing. Patients should remain in bed during and after a dose and must refrain from engaging in hazardous occupations or activities requiring mental alertness and motor coordination (e.g., driving or operating machinery, flying an airplane) for at least 6 hours after a dose.
Sodium oxybate is the sodium salt of gamma hydroxybutyrate (GHB), an illicit drug of abuse. Abuse or misuse of GHB, either alone or in combination with other CNS depressants, has been associated with adverse central nervous system reactions including seizure, respiratory depression, decreased levels of consciousness, coma, and death. The rapid onset of sedation and amnestic properties of sodium oxybate can be dangerous for voluntary and involuntary users. Carefully evaluate patients for a history of substance abuse and follow patients closely, observing them for signs of misuse and abuse of GHB (e.g., increase in the size or frequency of dosing, drug-seeking behavior, feigned cataplexy).
Sodium oxybate may impair respiratory drive, especially in patients with compromised respiratory function or preexisting respiratory insufficiency. Central apneas and clinically relevant desaturation events have been observed in both pediatric and adult patients. Use sodium oxybate with caution in patients with pulmonary disease, including sleep apnea, that places them at risk for respiratory depression or hypoxemia. Sleep-related breathing disorders tend to be more prevalent with obesity, in men, in postmenopausal women not on hormone replacement therapy, and among patients with narcolepsy.
Use sodium oxybate cautiously in patients with hepatic disease, since the drug is extensively metabolized in the liver. Patients with compromised liver function have an increased elimination half-life and systemic exposure to the drug. Initial dosage reduction of 50% of immediate-release sodium oxybate is recommended in patients with hepatic impairment. Due to a lack of availability of appropriate dosage options with extended-release sodium oxybate, patients with hepatic impairment should not be initiated on this formulation. However, patients who have been titrated to a maintenance dose of immediate-release sodium oxybate can be switched to the extended-release formulation if the appropriate dosage strength is available.
Sodium oxybate has a high sodium content. Consider the amount of daily sodium intake in patients sensitive to salt (e.g., those with heart failure, cardiac disease, hypertension, renal disease). The sodium content per total nightly dose of sodium oxybate is 550 mg for 3 grams; 820 mg for 4.5 grams; 1,100 mg for 6 grams; 1,400 mg for 7.5 grams; and 1,640 mg for 9 grams.
Clinical narcolepsy studies did not include sufficient numbers of geriatric subjects age 65 years of age and older to determine whether they respond differently to sodium oxybate than younger adults; use caution with initial dosage and dosage titrations. In other controlled trials of immediate-release sodium oxybate, 39 (5%) of 874 patients were 65 years or older. Discontinuations of treatment due to adverse reactions were increased in geriatric adults compared to younger adults (20.5% vs. 18.9%) and the frequency of headaches was markedly increased in the older adults. The most common adverse reactions were similar in both age categories.
There are no adequate data on the developmental risk associated with the use of sodium oxybate during human pregnancy. Animal studies produced no clear evidence of developmental/teratogenic toxicity; however, increased stillbirths and decreased postnatal viability and growth were seen at clinically relevant doses. Because there are no adequate and well-controlled studies in pregnant women, sodium oxybate should be used during pregnancy only if the benefits outweigh the potential risks to the fetus. In a case of illicit use of GHB during pregnancy, the woman delivered a healthy newborn with a good Apgar score; however, the quantity of GHB ingested and the duration of drug use were not reported. Monitor exposed neonates carefully. The subsequent effects of sodium oxybate on later growth, development, and maturation in humans are unknown. Sodium oxybate has not been adequately studied for use during labor or obstetric delivery. Uterine contractions diminished 20 minutes after injection of parenteral sodium oxybate during obstetric anesthesia and the neonates had stable cardiovascular and respiratory measures but were very sleepy, resulting in a slight decrease in Apgar scores.
Gamma hydroxy butyrate (GHB) is excreted in human milk after sodium oxybate administration. There is insufficient information on the risk to a breastfed infant and with regard to the effect on milk production in lactating individuals. The developmental and health benefits of breast-feeding should be considered along with the clinical need for sodium oxybate treatment and any potential adverse effects on the breastfed infant the drug or from the underlying maternal condition. An alternative medication may be preferred (or an alternate form of feeding), especially while nursing a newborn or premature infant. If sodium oxybate administration cannot be avoided, it is advisable to avoid breast-feeding for 4 to 5 hours after each dose to minimize infant exposure to the drug, and the nursing infant should be monitored for adverse drug effects such as sedation, respiratory depression, agitation, and vomiting. Data are limited to a few case reports which suggest no long term adverse effects to the breastfed infant within the usual maternal dosage limit of 9 grams/day orally. However, more data are needed in lactating and breast-feeding patients.
For the treatment of cataplexy and excessive daytime sleepiness in patients with narcolepsy:
Oral dosage (immediate release oral solution; e.g., Xyrem):
Adults: 4.5 grams/night PO initially, divided into 2 equal doses of 2.25 grams, the first given at bedtime and the second given 2.5 to 4 hours later. May increase dosage by 1.5 grams/night (0.75 grams/dose) at weekly intervals. Effective dosage range: 6 to 9 grams/night, in 2 divided doses. Max: 9 grams/night; higher dosages have not been studied and should not ordinarily be administered.
Children and Adolescents 7 to 17 years weighing 45 kg or more: 4.5 grams or less/night PO initially, divided into 2 equal doses, the first given at bedtime and the second given 2.5 to 4 hours later. May increase dosage by no more than 1.5 grams/night (0.75 grams/dose) at weekly intervals. Max: 9 grams/night. For patients who sleep more than 8 hours/night, the first dose can be given at bedtime or after an initial period of sleep. Unequal dosages may be required for some patients to achieve optimal treatment.
Children and Adolescents 7 to 17 years weighing 30 to 44 kg: 3 grams or less/night PO initially, divided into 2 equal doses, the first given at bedtime and the second given 2.5 to 4 hours later. May increase dosage by no more than 1 gram/night (0.5 gram/dose) at weekly intervals. Max: 7.5 grams/night. For patients who sleep more than 8 hours/night, the first dose can be given at bedtime or after an initial period of sleep. Unequal dosages may be required for some patients to achieve optimal treatment.
Children and Adolescents 7 to 17 years weighing 20 to 29 kg: 2 grams or less/night PO initially, divided into 2 equal doses, the first given at bedtime and the second given 2.5 to 4 hours later. May increase dosage by no more than 1 gram/night (0.5 gram/dose) at weekly intervals. Max: 6 grams/night. For patients who sleep more than 8 hours/night, the first dose can be given at bedtime or after an initial period of sleep. Unequal dosages may be required for some patients to achieve optimal treatment.
Children and Adolescents 7 to 17 years weighing less than 20 kg: Specific dosing recommendations are not available; consider lower starting dosage, weekly increases, and total maximum than those over 20 kg. [For patients weighing 20 to 29 kg, the initial dosage is 2 grams or less/night PO, divided into 2 equal doses, the first given at bedtime and the second given 2.5 to 4 hours later, with increases of no more than 1 gram/night (0.5 gram/dose) at weekly intervals. Max: 6 grams/night.] For patients who sleep more than 8 hours/night, the first dose can be given at bedtime or after an initial period of sleep. Unequal dosages may be required for some patients to achieve optimal treatment.
Oral dosage (extended-release oral suspension, i.e., Lumryz):
Adults: 4.5 grams PO once per night, initially. Titrate by increments of 1.5 grams per night at weekly intervals to effect. Recommended dosage range: 6 to 9 grams PO once per night. Max: 9 grams/night. SWITCHING FROM IMMEDIATE-RELEASE: May switch to the extended-release (ER) suspension at the nearest equivalent total nightly dosage (e.g., a patient who takes 3.75 grams PO twice per night may switch to ER suspension at 7.5 grams PO once per night.)
Maximum Dosage Limits:
-Adults
9 grams/night PO.
-Geriatric
9 grams/night PO.
-Adolescents
Weighing 45 kg or more: 9 grams/night PO.
Weighing 30 to 44 kg: 7.5 grams/night PO.
Weighing 20 to 29 kg: 6 grams/night PO.
-Children
7 to 12 years weighing 45 kg or more: 9 grams/night PO.
7 to 12 years weighing 30 to 44 kg: 7.5 grams/night PO.
7 to 12 years weighing 20 to 29 kg: 6 grams/night PO.
7 to 12 years weighing less than 20 kg: Specific information not available; a maximum nightly dosage less than 6 grams/night PO should be considered.
1 to 6 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Oral solution: Reduce the recommended initial dosage by 50%.
Oral extended-release (ER) suspension: Patients with hepatic impairment should not initiate treatment with the oral ER suspension due to a lack of appropriate dosage strengths; however, a patient maintained on the immediate-release oral solution may be switched to an equivalent ER suspension dosage if the appropriate dosage strength is available.
Patients with Renal Impairment Dosing
No dosage adjustments are needed.
Intermittent hemodialysis
Due to the rapid metabolism of sodium oxybate, hemodialysis and other forms of extracorporeal drug removal are unlikely to impact drug clearance.
*non-FDA-approved indication
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Acetaminophen; Caffeine: (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Acetaminophen; Dextromethorphan; Doxylamine: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs.
Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Alfentanil: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Alprazolam: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Amobarbital: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Amphetamine: (Moderate) Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold such as the amphetamines. Note that CNS stimulants, including the amphetamines, are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
Amphetamine; Dextroamphetamine Salts: (Moderate) Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold such as the amphetamines. Note that CNS stimulants, including the amphetamines, are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
Amphetamine; Dextroamphetamine: (Moderate) Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold such as the amphetamines. Note that CNS stimulants, including the amphetamines, are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
Anxiolytics; Sedatives; and Hypnotics: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Aspirin, ASA; Butalbital; Caffeine: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate. (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Aspirin, ASA; Caffeine: (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Aspirin, ASA; Caffeine; Orphenadrine: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants. (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Atropine; Difenoxin: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. Concurrent administration of diphenoxylate/difenoxin with sodium oxybate can potentiate the CNS-depressant effects of diphenoxylate/difenoxin.
Baclofen: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
Barbiturates: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Belladonna; Opium: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Benzodiazepines: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Benzphetamine: (Moderate) Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold such as the amphetamines. Note that CNS stimulants, including the amphetamines, methylphenidate, and modafinil are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
Buprenorphine: (Major) Concomitant use of buprenorphine with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of buprenorphine with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Buprenorphine; Naloxone: (Major) Concomitant use of buprenorphine with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of buprenorphine with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Bupropion: (Major) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as sodium oxybate. The risk of seizures with bupropion is dose related and is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Consider these risks before initiating treatment If used together, use low initial doses of bupropion and increase the dose gradually.
Bupropion; Naltrexone: (Major) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as sodium oxybate. The risk of seizures with bupropion is dose related and is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Consider these risks before initiating treatment If used together, use low initial doses of bupropion and increase the dose gradually.
Buspirone: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs.
Butalbital; Acetaminophen: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Butalbital; Acetaminophen; Caffeine: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate. (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Butalbital; Acetaminophen; Caffeine; Codeine: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate. (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Butalbital; Aspirin; Caffeine; Codeine: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate. (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Caffeine: (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Caffeine; Sodium Benzoate: (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sodium oxybate. CNS depressants can potentiate the effects of cannabidiol.
Capsaicin; Metaxalone: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
Carbidopa; Levodopa; Entacapone: (Major) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including sodium oxybate, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Carisoprodol: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
Celecoxib; Tramadol: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and sodium oxybate. Concurrent use may result in additive CNS depression.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with sodium oxybate should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with sodium oxybate should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Chlordiazepoxide: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Chlordiazepoxide; Amitriptyline: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Chlordiazepoxide; Clidinium: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Chlorpromazine: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines.
Chlorzoxazone: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
Clobazam: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Clonazepam: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Clorazepate: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Cocaine: (Major) Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with drugs that are known to lower seizure threshold such as cocaine.
Codeine: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Codeine; Phenylephrine; Promethazine: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines. (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Codeine; Promethazine: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines. (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
COMT inhibitors: (Major) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including sodium oxybate, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Cyclobenzaprine: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
Dantrolene: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
Deutetrabenazine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as sodium oxybate, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
Dexmethylphenidate: (Moderate) The stimulant effects of methylphenidate derivatives can be additive when used concurrently with other psychostimulants, such as sodium oxybate. The combination may increase the incidence of side effects; if these combinations cannot be avoided the patient should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other stimulant-related problems. Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold. Note that CNS stimulants, including methylphenidate, are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
Dextroamphetamine: (Moderate) Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold such as the amphetamines. Note that CNS stimulants, including the amphetamines, are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
Dextromethorphan; Bupropion: (Major) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as sodium oxybate. The risk of seizures with bupropion is dose related and is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Consider these risks before initiating treatment If used together, use low initial doses of bupropion and increase the dose gradually.
Diazepam: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Diphenoxylate; Atropine: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. Concurrent administration of diphenoxylate/difenoxin with sodium oxybate can potentiate the CNS-depressant effects of diphenoxylate/difenoxin.
Doxylamine: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs.
Doxylamine; Pyridoxine: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs.
Dronabinol: (Moderate) Concomitant use of dronabinol with other CNS depressants like sodium oxybate can potentiate the effects of dronabinol on respiratory depression.
Droperidol: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs.
Entacapone: (Major) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including sodium oxybate, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Ergotamine; Caffeine: (Moderate) Caffeine should be avoided or used cautiously with oxybates. Monitor for potential side effects such as nervousness, irritability, insomnia, and/or cardiac arrhythmias.
Esketamine: (Major) Closely monitor patients receiving esketamine and sodium oxybate for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Estazolam: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Eszopiclone: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Ethanol: (Contraindicated) Alcohol is contraindicated in patients using sodium oxybate or other oxybates. Dangerous, additive CNS depressant effects are possible, including respiratory depression. Patients should be strongly warned against the use of any alcohol-containing beverages in conjunction with oxybates.
Ethiodized Oil: (Major) Sodium oxybate lowers seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Etomidate: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with general anesthetics.
Fenfluramine: (Moderate) Use fenfluramine and sodium oxybate with caution due to an increased risk of serotonin syndrome and additive CNS depression. Monitor for excessive sedation, somnolence, and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fentanyl: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Fluphenazine: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines.
Flurazepam: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions. (Moderate) Oxybates should be administered on an empty stomach. Patients should administer their first bedtime dose at least 2 hours after eating and take their bedtime dosages at a consistent time in relation to meals each night. Food significantly decreases the bioavailability of sodium oxybate and other oxybates.
Gabapentin: (Major) Concomitant use of sodium oxybate with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
General anesthetics: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with general anesthetics.
Green Tea: (Major) Some, but not all, green tea products contain caffeine. Additive CNS stimulant effects are likely to occur when caffeine is coadministered with other CNS stimulants or psychostimulants. Caffeine should be avoided or used cautiously with sodium oxybate.
Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hydrocodone: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hydromorphone: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hydroxyzine: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs.
Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Iodixanol: (Major) Sodium oxybate lowers seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iohexol: (Major) Sodium oxybate lowers seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iomeprol: (Major) Sodium oxybate lowers seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopamidol: (Major) Sodium oxybate lowers seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopromide: (Major) Sodium oxybate lowers seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ioversol: (Major) Sodium oxybate lowers seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Isocarboxazid: (Major) Avoid use within 2 weeks of each other. Data for an interaction with sodium oxybate and MAOIs are lacking, but use of other CNS depressants may potentiate the CNS-depressant effects of sodium oxybate.
Isoflurane: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with general anesthetics.
Isosulfan Blue: (Major) Sodium oxybate lowers seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ketamine: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with general anesthetics.
Lasmiditan: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and sodium oxybate. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Lemborexant: (Contraindicated) Coadministration of sodium oxybate with other sedative hypnotic drugs, such as lemborexant, is contraindicated. The concurrent use of sodium oxybate and other CNS depressants may increase the risk of respiratory depression, hypotension, profound sedation, syncope, and death.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with sodium oxybate should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Levorphanol: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Lisdexamfetamine: (Moderate) Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold such as the amphetamines. Note that CNS stimulants, including the amphetamines, methylphenidate, and modafinil are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
Lofexidine: (Moderate) Monitor for additive sedation during coadministration of lofexidine and sodium oxybate. Lofexidine can potentiate the effects of CNS depressants. Patients should be advised to avoid driving or performing any other tasks requiring mental alertness until the effects of the combination are known.
Lopinavir; Ritonavir: (Major) One case report describes a possible interaction between sodium oxybate and ritonavir and saquinavir, leading to repetitive, clonic contractions. The patient also experienced shallow respirations, a heart rate of 40 beats per min, and was responsive only to painful stimuli. The exact contribution of ritonavir and saquinavir to this reaction cannot be determined since several other compounds were detected through a urinary toxin screen.
Lorazepam: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and sodium oxybate. Concurrent use may result in additive CNS depression.
Meperidine: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Meprobamate: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Metaxalone: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
Methadone: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Methamphetamine: (Moderate) Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold such as the amphetamines. Note that CNS stimulants, including the amphetamines, methylphenidate, and modafinil are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
Methohexital: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Methylphenidate Derivatives: (Moderate) The stimulant effects of methylphenidate derivatives can be additive when used concurrently with other psychostimulants, such as sodium oxybate. The combination may increase the incidence of side effects; if these combinations cannot be avoided the patient should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other stimulant-related problems. Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold. Note that CNS stimulants, including methylphenidate, are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
Methylphenidate: (Moderate) The stimulant effects of methylphenidate derivatives can be additive when used concurrently with other psychostimulants, such as sodium oxybate. The combination may increase the incidence of side effects; if these combinations cannot be avoided the patient should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other stimulant-related problems. Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold. Note that CNS stimulants, including methylphenidate, are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
Midazolam: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Monoamine oxidase inhibitors: (Major) Avoid use within 2 weeks of each other. Data for an interaction with sodium oxybate and MAOIs are lacking, but use of other CNS depressants may potentiate the CNS-depressant effects of sodium oxybate.
Morphine: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Morphine; Naltrexone: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Nabilone: (Moderate) Concomitant use of nabilone with other CNS depressants like sodium oxybate can potentiate the effects of nabilone on respiratory depression.
Nirmatrelvir; Ritonavir: (Major) One case report describes a possible interaction between sodium oxybate and ritonavir and saquinavir, leading to repetitive, clonic contractions. The patient also experienced shallow respirations, a heart rate of 40 beats per min, and was responsive only to painful stimuli. The exact contribution of ritonavir and saquinavir to this reaction cannot be determined since several other compounds were detected through a urinary toxin screen.
Non-Ionic Contrast Media: (Major) Sodium oxybate lowers seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Oliceridine: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Opiate Agonists: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Opicapone: (Major) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including sodium oxybate, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Orphenadrine: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
Oxazepam: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Oxycodone: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Oxymorphone: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Ozanimod: (Major) Coadministration of ozanimod with sodium oxybate is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sodium oxybate has been associated with cases of serotonin syndrome. Excess serotonin may contribute to the development of hypertensive crisis.
Pentobarbital: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Perphenazine: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines.
Perphenazine; Amitriptyline: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines.
Phendimetrazine: (Contraindicated) Phendimetrazine is a phenylalkaline sympathomimetic agent. All sympathomimetics and psychostimulants, including other anorexiants, should be used cautiously or avoided in patients receiving phendimetrazine. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmia.
Phenelzine: (Major) Avoid use within 2 weeks of each other. Data for an interaction with sodium oxybate and MAOIs are lacking, but use of other CNS depressants may potentiate the CNS-depressant effects of sodium oxybate.
Phenobarbital: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Phenothiazines: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines.
Phentermine: (Contraindicated) Because phentermine is a sympathomimetic and anorexic agent, it should not be used in combination with other psychostimulants.
Phentermine; Topiramate: (Contraindicated) Because phentermine is a sympathomimetic and anorexic agent, it should not be used in combination with other psychostimulants.
Phenytoin: (Moderate) In primates, sodium oxybate blood levels were elevated with phenytoin pretreatment. The clinical relevance of these pharmacokinetic changes have not been evaluated.
Pregabalin: (Major) Concomitant use of sodium oxybate with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
Primidone: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Procarbazine: (Contraindicated) Although procarbazine appears to be less likely than other MAOIs to produce serious drug interactions, clinicians should minimize the use of sympathomimetics, such as sodium oxybate, in patients receiving procarbazine. Sympathomimetics should not be used within 14 days after the use of a MAOI.
Prochlorperazine: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines.
Promethazine: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines.
Promethazine; Dextromethorphan: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines.
Promethazine; Phenylephrine: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines.
Propofol: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with general anesthetics.
Quazepam: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Rasagiline: (Moderate) Although sympathomimetics and psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B (MAO-B) inhibition of rasagiline at manufacturer recommended doses.
Remifentanil: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Remimazolam: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Ritonavir: (Major) One case report describes a possible interaction between sodium oxybate and ritonavir and saquinavir, leading to repetitive, clonic contractions. The patient also experienced shallow respirations, a heart rate of 40 beats per min, and was responsive only to painful stimuli. The exact contribution of ritonavir and saquinavir to this reaction cannot be determined since several other compounds were detected through a urinary toxin screen.
Saquinavir: (Minor) One case report describes a possible interaction between sodium oxybate and ritonavir and saquinavir, leading to repetitive, clonic contractions. The patient also experienced shallow respirations, a heart rate of 40 beats per min, and was responsive only to painful stimuli. The exact contribution of ritonavir and saquinavir to this reaction cannot be determined since several other compounds were detected through a urinary toxin screen.
Secobarbital: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Selegiline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and sodium oxybate. Concurrent use may result in additive CNS depression.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) The stimulant effects of methylphenidate derivatives can be additive when used concurrently with other psychostimulants, such as sodium oxybate. The combination may increase the incidence of side effects; if these combinations cannot be avoided the patient should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other stimulant-related problems. Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold. Note that CNS stimulants, including methylphenidate, are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
Sevoflurane: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with general anesthetics.
Skeletal Muscle Relaxants: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
St. John's Wort, Hypericum perforatum: (Major) St. John's wort, Hypericum Perforatum may reduce the neuronal uptake of monoamines and should be used cautiously with sympathomimetics.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and sodium oxybate. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Tapentadol: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Temazepam: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Thioridazine: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines.
Tolcapone: (Major) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including sodium oxybate, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Tramadol: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Tramadol; Acetaminophen: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Tranylcypromine: (Major) Avoid use within 2 weeks of each other. Data for an interaction with sodium oxybate and MAOIs are lacking, but use of other CNS depressants may potentiate the CNS-depressant effects of sodium oxybate.
Triazolam: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Trifluoperazine: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines.
Trimethobenzamide: (Major) Sodium oxybate should not be used in combination with CNS depressants. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with drugs like trimethobenzamide.
Valproic Acid, Divalproex Sodium: (Major) Concomitant use of oxybates with valproic acid (or valproate or divalproex sodium) results in an increased systemic exposure to GHB, which may cause increased attention and working memory impairment. Reduce the total oxybates dosage at least 20% in patients starting valproic acid or a related derivative. When initiating oxybates in a patient already taking valproic acid or a related derivative, start the oxybates at a lower initial dosage. Subsequently, the oxybates dosage can be adjusted based on clinical response and tolerability.
Zaleplon: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Zolpidem: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.
Sodium oxybate is a CNS depressant. The mechanism of action of sodium oxybate 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 on cataplexy and excessive daytime sleepiness are mediated through GABA-beta actions during sleep at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons. Sodium oxybate has been shown to effectively reduce stage 1 sleep, decrease wake-after-sleep onset, decrease the number of awakenings, and increase slow-wave sleep.
Sodium oxybate is administered orally and is the sodium salt of . Pharmacokinetics of GHB are non-linear and increase more than dose proportionally, with blood levels increasing 3.7-fold as the dose is doubled from 4.5 to 9 grams; single doses more than 4.5 grams have not been studied clinically. The pharmacokinetics are not altered with repeat administration. GHB is a hydrophilic compound with an apparent volume of distribution averaging 190 to 384 mL/kg. At GHB concentrations ranging from 3 to 300 mcg/mL, less than 1% is bound to plasma proteins. Sodium oxybate readily crosses the blood-brain barrier and the placenta. Animal studies indicate that metabolism is the major elimination pathway for sodium oxybate, producing carbon dioxide and water via the Krebs cycle and secondarily via beta-oxidation. The primary pathway involves a cytosolic NADP+-linked enzyme, GHB dehydrogenase, which catalyzes the conversion of sodium oxybate to succinic semialdehyde, which is then transformed to succinic acid by succinic semialdehyde dehydrogenase. Succinic acid enters the Krebs cycle and is converted to carbon dioxide and water. A second mitochondrial oxidoreductase enzyme, a transhydrogenase, also contributes to the conversion to succinic semialdehyde in the presence of alpha-ketoglutarate. An alternate pathway of biotransformation involves beta-oxidation via 3,4-dihydroxybutyrate to carbon dioxide and water. Sodium oxybate is also metabolized in the central nervous system; however, the exact pathway has not been described. There are no active metabolites and the elimination of the drug appears to be capacity-limited. The clearance of GHB is almost entirely by biotransformation to carbon dioxide, which is then expired. On average, less than 5% of a dose is excreted renally as the parent compound within 6 to 8 hours of dosing. Fecal excretion is negligible. The drug is virtually undetectable in the urine after 12 hours. The elimination half-life of GHB is 0.5 to 1 hour. Although laboratory assays are not routinely available, GHB is detectable in plasma and urine using gas chromatographic-mass spectrometric (GC-MS).
Affected cytochrome P450 (CYP450) enzymes and drug transporters: None
In vitro studies indicate that sodium oxybate does not significantly inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A at a concentration that is significantly higher than plasma concentrations achieved with therapeutic doses.
-Route-Specific Pharmacokinetics
Oral Route
-Immediate-release suspension (Xyrem): Sodium oxybate is rapidly absorbed after oral administration, with an absolute bioavailability of 88%. The average time to peak plasma concentration (Tmax) ranges from 0.5 to 1.25 hours. Absorption is delayed and decreased (increase in average Tmax from 0.75 to 2 hours, 59% decrease in Cmax, 37% decrease in AUC) when the drug is administered with a high-fat meal. The average peak plasma concentrations (Cmax) after administration of each of the two 2.25 gram doses given under fasting conditions 4 hours apart are similar. Doses should be given at least 2 hours after eating. Sedation often occurs within 5 and usually within 15 minutes of dosing. The duration of action is typically 2 to 3 hours.
-Extended-release suspension (Lumryz): Following oral administration of extended-release sodium oxybate, the Cmax following administration of a single 6-gram dose was 66 mcg/mL and the Tmax was 1.5 hours. Plasma levels of GHB increased dose-proportionally for Cmax and more than dose-proportionally for AUC (2-fold and 2.3-fold increases as total daily dose is doubled from 4.5 grams to 9 grams, respectively). Administration immediately after a high-fat meal resulted in a mean reduction in Cmax and AUC of GHB by 33% and 14%, respectively; average Tmax increased from 0.5 hours to 1.5 hours. Doses should be given at least 2 hours after eating. Sedation often occurs within 5 and usually within 15 minutes of dosing.
-Special Populations
Hepatic Impairment
The pharmacokinetics of sodium oxybate in 16 cirrhotic patients, half without ascites (Child-Pugh Class A) and half with ascites (Child-Pugh Class C) were compared to healthy adults after a single oral dose of 25 mg/kg. AUC values were double in the cirrhotic patients, with noted reductions in clearance of roughly 50% versus healthy controls. The mean half-life is 59 minutes in cirrhotic patients with ascites and 32 minutes in cirrhotic patients without ascites versus 22 minutes in healthy controls.
Renal Impairment
Because the kidney does not have a significant role in the clearance and excretion of sodium oxybate, the presence of renal impairment is not expected to affect drug pharmacokinetics.
Pediatrics
The pharmacokinetic characteristics of immediate-release sodium oxybate oral solution are similar in adults and pediatric patients. Body weight is the major intrinsic factor affecting sodium oxybate pharmacokinetics.
Geriatric
The pharmacokinetic characteristics of immediate-release sodium oxybate are consistent among younger adults (48 to 64 years of age) and older adults (65 to 75 years of age; data with the oral extended-release suspension are limited in older adults.
Gender Differences
In a study of healthy volunteers, no pharmacokinetic differences based on sex were detected after a single 4.5 grams oral dose of immediate-release sodium oxybate.
Ethnic Differences
There are insufficient data to evaluate any pharmacokinetic differences among races.