Calcium, magnesium, potassium, and sodium oxybates is a mixture of oxybate salts. The product is a central nervous system depressant approved for the treatment of cataplexy or excessive daytime sleepiness (EDS) in adult and pediatric patients 7 years of age and older with narcolepsy. It is also approved for idiopathic hypersomnia in adults. The active moiety of the product is oxybate or gamma-hydroxybutyric acid (GHB), a naturally occurring central nervous system transmitter with sedative and anesthetic properties. 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 adult patients receiving a dose of 9 grams/night. The Xywav product differs from Xyrem, a sodium oxybate formulation, in that the oxybate electrolytes are balanced in the Xywav formulation, eliminating the need for monitoring in patient populations requiring a low sodium diet. Illicit GHB, commonly known by slang terms such as Liquid Ecstasy or Liquid E, can produce euphoria, making it a popular but dangerous party drug of abuse. GHB has also gained notoriety as a date rape drug due to its sedative and amnestic properties. Abuse or misuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with seizures, respiratory depression, decreased consciousness, coma, and death. Because of the potential for CNS depression, abuse, or misuse, Xywav is only available through a Risk Evaluation and Mitigation Strategy (REMS) program called the Xywav and Xyrem REMS.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Liquid Formulations
-Administer twice nightly for narcolepsy and once or twice nightly for idiopathic hypersomnia.
-Administer the dose at bedtime, at least 2 hours after eating. If dosing twice nightly, take the second dose 2.5 to 4 hours after the first dose.
-Prepare all nightly doses prior to bedtime.
-Before administration, dilute each dose with approximately one-fourth cup (about 60 mL) of water in the empty child-resistant pharmacy containers provided. Ensure the cap is applied and locked into the child-resistant position to prevent access to the medication by children.
-Have the patient take each dose while in bed and lie down immediately after dosing. Patients must remain in bed after ingestion of each dose. The medication may cause patients to fall asleep abruptly without first feeling drowsy.
-Patients will often fall asleep within 5 minutes of the first dose, and will usually fall asleep within 15 minutes, although the time it takes for any individual to fall asleep may vary from night to night.
-If dosing twice nightly, set an alarm to awaken the patient for the second dose. If the second dose is missed, skip that dose; the patient should not take the medication again until the next night. Patients should never take 2 doses at the same time.
-Storage: Consume any diluted solution within 24 hours. Dispose of any unused, diluted solution in the sink drain after that.
The calcium, magnesium, potassium, and sodium oxybates product is a central nervous system (CNS) depressant. Obtundation is possible at recommended doses. 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. Oxybates may cause patients to fall asleep abruptly without first feeling drowsy; patients often fall asleep within 5 to 15 minutes of administration. Sudden sleep onset, including while in a standing position or rising from bed, has led to falls, some of which have been complicated by injuries or hospitalizations. Headache (16% to 20%), insomnia (9%), dizziness (10% to 12%), complex sleep-related behaviors (parasomnias 5% to 6%), fatigue/asthenia (4% to 5%), paresthesias (3%), snoring (3%), teeth grinding (bruxism), tremor (3% to 5%), and somnolence/drowsiness/sedation (2% to 5%) were reported during adult clinical trials for calcium, magnesium, potassium, and sodium oxybates. Parasomnias or complex sleep-related behaviors may include confusional arousal, nightmares, hypnopompic hallucination, abnormal dreams, abnormal rapid eye movements, sleep paralysis, sleep-walking (somnambulism), sleep-talking, sleep terror, and sleep-related eating disorder. Sleep paralysis was observed during clinical trial evaluation of sodium oxybate and may be relevant for the calcium, magnesium, potassium, and sodium oxybates product. The adverse effect profile in pediatric patients is expected to be similar to that of adult patients receiving the calcium, magnesium, potassium, and sodium oxybates product and pediatric patients receiving sodium oxybate alone. In pediatric trials of sodium oxybate, the most common adverse CNS effects included headache (17%), dizziness (8%), and sleep-walking (6%). Falls and memory impairment have been reported during postmarketing use of sodium oxybate. Coadministration with other CNS depressants may increase the risk of respiratory depressive effects, hypotension, profound sedation, syncope, and death. If concurrent use is required, consider dose reduction or discontinuation of one or more CNS depressants, including the oxybates product. Consider dose interruption if the short-term use of an opioid is required.
Anxiety including nervousness and panic attack (5% to 16%), depressed mood (3% to 4%), irritability (3%), depression (1% to 3%), confusion (3%), and feeling drunk/impaired cognition (3%) were reported during adult clinical trials for calcium, magnesium, potassium, and sodium oxybates. One patient experienced visual hallucinations which lead to treatment discontinuation. Adverse effects observed during clinical trial evaluation of sodium oxybate alone which may be relevant for the calcium, magnesium, potassium, and sodium oxybates product include disturbance in attention, feeling drunk/impaired cognition (psychomotor impairment), and disorientation (confusion). The adverse effect profile in pediatric patients is expected to be similar to that of adult patients receiving the calcium, magnesium, potassium, and sodium oxybates product and pediatric patients receiving sodium oxybate alone. Neuropsychiatric reactions that were reported in pediatric trials of sodium oxybate alone for narcolepsy include acute psychosis, confusion, and anxiety. Five of 104 pediatric patients reported adverse reactions that led to withdrawal of sodium oxybate including tactile hallucinations, emotional lability, anger, anxiety, depression, and suicidal ideation. Hangover, hallucinations, paranoia, psychosis, aggression, and agitation have been reported during postmarketing use of sodium oxybate. The emergence or increase of behavioral changes or psychiatric events requires careful and immediate evaluation. Monitor patients with a history of depression or suicidal ideation carefully for the emergence of depressive symptoms.
Nausea (13% to 21%), anorexia (decreased appetite 8%), weight loss (3%), diarrhea (5% to 6%), vomiting (5% to 7%), and xerostomia (4% to 6%) were reported during adult clinical trials for calcium, magnesium, potassium, and sodium oxybates. The adverse effect profile in pediatric patients is expected to be similar to that of adult patients receiving the calcium, magnesium, potassium, and sodium oxybates product and pediatric patients receiving sodium oxybate alone. In pediatric trials of sodium oxybate, the most common adverse GI effects included nausea (20%), vomiting (18%), weight loss (13%), and decreased appetite (9%). Five of 104 pediatric patients reported adverse reactions that led to withdrawal including weight loss.
The calcium, magnesium, potassium, and sodium oxybates product may impair respiratory drive, especially in patients with compromised respiratory function. Life-threatening respiratory depression has been reported in overdoses of sodium oxybate. Central apnea and clinically relevant desaturation events have been observed in both pediatric and adult patients receiving sodium oxybate. The adverse effect profile of the calcium, magnesium, potassium, and sodium oxybates product in pediatric patients is expected to be similar to that of adult patients and that of pediatric patients receiving sodium oxybate alone. In pediatric clinical trials with sodium oxybate, 5 of 104 pediatric patients reported adverse reactions that led to withdrawal including sleep apnea syndrome.
Muscle cramps were reported in 2% to 3% of adults during the clinical trial evaluation of calcium, magnesium, potassium, and sodium oxybates. Adverse effects observed during clinical trial evaluation of sodium oxybate which may be relevant for the calcium, magnesium, potassium, and sodium oxybates product include pain, pain in extremity (musculoskeletal pain), and cataplexy. The adverse effect profile of the calcium, magnesium, potassium, and sodium oxybates product in pediatric patients is expected to be similar to that of adult patients and that of pediatric patients receiving sodium oxybate alone. Arthralgia has been reported during postmarketing use of sodium oxybate; however, the frequency is unknown and causality has not been established.
Hyperhidrosis/night sweats (6% to 8%) and urinary incontinence (enuresis 4%) were reported during adult clinical trial evaluation of calcium, magnesium, potassium, and sodium oxybates. The adverse effect profile in pediatric patients is expected to be similar to that of adult patients receiving the calcium, magnesium, potassium, and sodium oxybates product and pediatric patients receiving sodium oxybate alone. In pediatric trials of sodium oxybate, enuresis (19%) was among the most common adverse effects reported. Nocturia, edema, hypertension, hypersensitivity, and blurred vision have been reported during postmarketing use of sodium oxybate.
The active moiety of the calcium, magnesium, potassium, and sodium oxybates product is gamma-hydroxybutyrate (GHB), a psychoactive drug that produces a wide range of pharmacological effects. It is a sedative-hypnotic that produces dose and concentration-dependent CNS effects. 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 amnestic features, 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 effects of discontinuing the calcium, magnesium, potassium, and sodium oxybates product have not been systematically evaluated in controlled clinical trials, but are expected to be similar to sodium oxybate alone.
Balance disorder/ataxia (3%) and falls (3%) have been reported in adult clinical trials for calcium, magnesium, potassium, and sodium oxybates. Gamma-hydroxybutyrate (GHB) is the active moiety of the calcium, magnesium, potassium, and sodium oxybates (Xywav) and the sodium oxybate (Xyrem) products. Doses of GHB exceeding 50 mg/kg may produce symptoms of anesthesia and serious toxicity. Toxic effects of GHB become apparent within 15 minutes of oral ingestion due to the rapid absorption of the drug. Signs and symptoms of GHB 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 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.
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 manufacturers of the various oxybates products have not reported serotonin syndrome as an adverse reaction in their product labels.
Calcium, magnesium, potassium, sodium oxybates 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.
In some cases, the use of calcium, magnesium, potassium, sodium oxybates has been associated with confusion, depression, psychosis, paranoia, hallucinations, agitation, aggression, and suicidal ideation. The emergence or worsening of behavioral changes or a psychiatric event requires careful and immediate evaluation. Monitor patients with a history of depression and/or suicidal attempt carefully for the emergence of depressive symptoms.
Complex sleep-related behaviors (parasomnias) including sleepwalking have been reported in both adult and pediatric patients receiving sodium oxybate. Significant injury has occurred. Advise patients to report any unusual sleep-related behaviors to their provider while receiving calcium, magnesium, potassium, sodium oxybates. Fully evaluate episodes of sleepwalking and consider appropriate interventions.
Calcium, magnesium, potassium, sodium oxybates causes CNS depression. Obtundation and clinically significant respiratory depression have occurred in patients treated with sodium oxybate at recommended doses due to CNS depression; many of these patients 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 (e.g., opioid analgesics, benzodiazepines) 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 CNS depressants, including oxybates. Consider oxybates interruption if the short-term use of an opioid (e.g., during or after surgery) is required. Calcium, magnesium, potassium, sodium oxybates may cause patients to fall asleep abruptly without first feeling drowsy. Patients will often fall asleep within 5 to 15 minutes of administration. 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.
Calcium, magnesium, potassium, and sodium oxybates are salts 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 seizures, respiratory depressive effects, decreased levels of consciousness, coma, and death. The rapid onset of sedation and amnestic properties of oxybates 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).
Calcium, magnesium, potassium, sodium oxybates 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. Calcium, magnesium, potassium, sodium oxybates should be used with caution in patients with pulmonary disease, including sleep apnea, due to the risk for respiratory depression or hypoxemia. Sleep-related breathing disorders tend to be more prevalent with obesity, in men, and in postmenopausal women not on hormone replacement therapy, as well as among patients with narcolepsy.
Calcium, magnesium, potassium, sodium oxybates should be used cautiously in patients with hepatic disease, since oxybate is extensively metabolized in the liver. Patients with compromised liver function have an increased elimination half-life and systemic exposure to the drug. An initial dosage reduction is recommended in patients with hepatic impairment.
Clinical studies of calcium, magnesium, potassium, sodium oxybates did not include sufficient numbers of geriatric subjects age 65 years and older to determine whether they respond differently from younger subjects. In other clinical studies of sodium oxybate, 39 (5%) of 874 patients were 65 years or older. Discontinuation of treatment due to adverse reactions was higher in geriatric patients than younger adults (21% vs. 19%). Frequency of headaches was markedly increased in the elderly (39% vs. 19%). The most common adverse reactions were similar in both age categories. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
There are no adequate data on the developmental risks associated with the use of calcium, magnesium, potassium, sodium oxybates during human pregnancy. Calcium, magnesium, potassium, sodium oxybate products have not been specifically studied during labor or obstetric delivery. Uterine contractions diminished 20 minutes after injection of parenteral sodium oxybate during obstetric anesthesia. Neonates had stable cardiovascular and respiratory measures but were very sleepy, resulting in a slight decrease in Apgar scores. In a case of illicit use of GHB during pregnancy, the woman delivered a healthy newborn with a good Apgar score; however, the duration of use and quantity of GHB ingested were not reported. Exposed neonates should be monitored carefully. Subsequent effects of sodium oxybate on later growth, development, and maturation in humans are unknown. Animal studies produced no clear evidence of developmental toxicity; however, increased stillbirths and decreased postnatal viability and growth were seen at clinically relevant doses.
The developmental and health benefits of breast-feeding should be considered along with the need of the mother for calcium, magnesium, potassium, sodium oxybates and any potential adverse effects on the breast-fed infant from the drug product or from the underlying maternal condition. There is insufficient information regarding maternal use of sodium oxybate and the risk to a breastfed infant and on milk production in the breast-feeding mother. Oxybate, also known as gamma-hydroxybutyrate (GHB), is excreted in human milk. Because the available data are too limited to be conclusive, an alternate drug may be preferred (or an alternate form of feeding), especially while nursing a newborn or premature infant. If administration cannot be avoided during breast-feeding, 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. In one case report, a breast-feeding mother taking 4.5 grams of sodium oxybate twice daily had a peak drug value of 23.2 mg/L at 1 hour after the dose, decreasing to 3.1 mg/L at 4 hours after the dose and 1 mg/L at 5 hours after the dose, at which time the concentration was within the proposed endogenous breast milk reference range of 0.13 to 1.03 mg/L. No adverse infant effects were reported. In a separate case, a woman with narcolepsy took sodium oxybate 4 grams each night at 10 p.m. and 2 a.m. and breastfed her infant (or provided pumped breast milk) exclusively for 6 months except for 4 hours after the 10 p.m. dose and 4 hours after the 2 a.m. dose. According to evaluations of the infant from the Ages and Stages Questionnaires at 2, 4, and 6 months and the pediatrician's clinical impressions of growth and development, the measured parameters were within the normal range.
For the treatment of cataplexy and excessive daytime sleepiness associated with narcolepsy:
Calcium, Magnesium, Potassium, Sodium Oxybates has been designated an orphan drug for narcolepsy by the FDA.
Oral dosage:
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 gram/dose) at weekly intervals. Effective dosage range: 6 to 9 grams/night. Doses more than 9 grams/night have not been studied and should not ordinarily be administered. SWITCHING FROM XYREM: On the first night of dosing with Xywav, initiate treatment at the same dose (gram for gram) and regimen as Xyrem. Thereafter, titrate based on response and tolerability.
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 the dosage by no more than 1.5 grams/night (0.75 gram/dose) at weekly intervals. Max: 9 grams/night (administered as 2 doses of 4.5 grams each). 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. SWITCHING FROM XYREM: On the first night of dosing with Xywav, initiate treatment at the same dose (gram for gram) and regimen as Xyrem. Thereafter, titrate based on response and tolerability.
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 the dosage by no more than 1 gram/night (0.5 gram/dose) at weekly intervals. Max: 7.5 grams/night (given in 2 doses of 3.75 grams each). 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. SWITCHING FROM XYREM: On the first night of dosing with Xywav, initiate treatment at the same dose (gram for gram) and regimen as Xyrem. Thereafter, titrate based on response and tolerability.
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 the dosage by no more than 1 gram/night (0.5 gram/dose) at weekly intervals. Max: 6 grams/night (given in 2 doses of 3 grams each). 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. SWITCHING FROM XYREM: On the first night of dosing with Xywav, initiate treatment at the same dose (gram for gram) and regimen as Xyrem. Thereafter, titrate based on response and tolerability.
Children and Adolescents 7 to 17 years weighing less than 20 kg: There is insufficient evidence to provide dosing recommendations. Consider a lower starting dosage, lower weekly dosage increases, and lower total maximum dosage than for children weighing 20 kg to 29 kg. Max: Consider a max total dose of less than 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. SWITCHING FROM XYREM: On the first night of dosing with Xywav, initiate treatment at the same dose (gram for gram) and regimen as Xyrem. Thereafter, titrate based on response and tolerability.
For the treatment of idiopathic hypersomnia:
Calcium, Magnesium, Potassium, Sodium Oxybates has been designated an orphan drug for this indication by the FDA.
Oral dosage:
Adults: Individualize based on clinical presentation. May administer as once or twice nightly regimen; may change between once and twice nightly regimens during titration as needed, based on efficacy and tolerability. Titrate initial dose by no more than 1.5 grams/week. ONCE NIGHTLY REGIMEN: 3 grams or less daily at bedtime initially; Max: 6 grams/day. TWICE NIGHTLY REGIMEN: 4.5 grams or less per night, divided into 2 doses (equal or unequal) given at bedtime and then 2.5 to 4 hours later. Max: 9 grams/day.
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: Consider a maximum total dose of less than 6 grams/night PO.
1 to 6 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Reduce the initial starting dose by one-half (50%) of the original dosage per night, divided into 2 doses.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*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.
The exact mechanism of action of these products in the treatment of narcolepsy and idiopathic hypersomnia is unknown. The Xywav product is a mixture of calcium oxybate, magnesium oxybate, potassium oxybate, and sodium oxybate (gamma-hydroxybutyrate). Gamma-hydroxybutyrate (GHB) is an endogenous compound and metabolite of the neurotransmitter GABA. It is hypothesized that the therapeutic effects are mediated through GABA-beta actions during sleep at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons.
Calcium, magnesium, potassium, and sodium oxybates is administered orally. The pharmacokinetics of the components of this product are nonlinear and similar following single or repeat dosing. Protein binding is not significant (less than 1%). The active moiety is oxybate, also known as gamma-hydroxybutyrate (GHB). GHB is a hydrophilic compound. The primary metabolic pathway involves a cytosolic NADP-linked enzyme, GHB dehydrogenase, that catalyzes the conversion of semialdehyde dehydrogenase, which is then biotransformed to succinic acid by the enzyme succinic semialdehyde dehydrogenase. Succinic acid enters the Krebs cycle where it is metabolized to carbon dioxide and water. A second mitochondrial oxidoreductase enzyme, a transhydrogenase, also catalyzes 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. No active metabolites have been identified. GHB has a mean elimination half-life of 0.66 hours. The clearance of GHB occurs almost completely by biotransformation to carbon dioxide, which is then eliminated by expiration. An average of less than 5% of unchanged drug appears in human urine within 6 to 8 hours after dosing. Fecal excretion is negligible.
Affected cytochrome P450 (CYP450) enzymes and drug transporters: None
Studies in vitro with pooled human liver microsomes indicate that oxybate does not significantly inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A up to levels considerably higher than those achieved with recommended doses.
-Route-Specific Pharmacokinetics
Oral Route
Following oral administration, the average time to peak plasma concentration (Tmax) is about 1.3 hours in healthy adults in the fasted state. The plasma levels of the active moiety gamma-hydroxybutyrate (GHB) increased more than dose-proportionally, with Cmax increasing about 2-fold and exposure (AUC) increasing 2.9-fold as the dose was doubled from 2.25 grams to 4.5 grams. Administration of the drug immediately after a high-fat meal resulted in a mean reduction in Cmax of GHB by 33%, and a mean reduction in systemic exposure (AUC) by 16%. Therefore, it is recommended to wait at least 2 hours after eating before taking calcium, magnesium, potassium, and sodium oxybates.
-Special Populations
Hepatic Impairment
The pharmacokinetics of gamma-hydroxybutyrate (GHB) in 16 cirrhotic patients, one-half without ascites (Child-Pugh Class A) and one-half with ascites (Child-Pugh Class C), were compared to healthy adults after a single sodium oxybate oral dose of 25 mg/kg. The 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. Because of an increase in exposure to calcium, magnesium, potassium, and sodium oxybates in patients with hepatic impairment, the starting dose should be reduced by one-half in patients with hepatic impairment.
Renal Impairment
Studies of the calcium, magnesium, potassium, and sodium oxybates product have not been conducted in patients with renal impairment.
Pediatrics
The pharmacokinetics of calcium, magnesium, potassium, and sodium oxybates have not been studied directly in pediatric patients. The pharmacokinetic characteristics of sodium oxybate alone are similar in adults and pediatric patients. Bodyweight is the major intrinsic factor affecting sodium oxybate pharmacokinetics.
Geriatric
There is no experience with the calcium, magnesium, potassium, and sodium oxybates product in geriatric patients. There is limited experience with use of sodium oxybate alone in geriatric patients. Results from one study with sodium oxybate indicate that the pharmacokinetics of gamma-hydroxybutyrate (GHB) are consistent among younger adults (48 to 64 years) and older adults (65 to 75 years).
Gender Differences
There are no data related to pharmacokinetic differences of calcium, magnesium, potassium, and sodium oxybates based upon gender. Results of one small study indicate no gender differences in the pharmacokinetics of gamma-hydroxybutyrate following a single 4.5-gram dose of sodium oxybate alone.
Ethnic Differences
There are insufficient data with calcium, magnesium, potassium, and sodium oxybates to determine if there are pharmacokinetic differences based upon race.