Drug information of Sodium Oxybate

Sodium Oxybate


Sodium oxybate  is a central nervous system depressant used for the treatment of cataplexy and extreme daytime sleepiness (EDS) associated with narcolepsy.

Mechanism of effect

The exact mechanism of action is unknown. It is the sodium salt of the endogenous compound gamma hydroxybutyrate which is a metabolite of the GABA neurotransmitter and it's thought that it's therapeutic effects are mediated via GABA B actions at noradrenergic, dopaminergic and thalamocortical neurons.

Pharmacokinetics

Bioavailability: 88% (fasting)

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

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

Protein bound: <1%

Vd: 190-384 mL/kg

Metabolism

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

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

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

Half-life: 0.5-1 hr

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

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

Drug indications

For the treatment of cataplexy in narcolepsy and excessive daytime sleepiness (EDS) in narcolepsy.

Dosage

Adult

Narcolepsy

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

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

Recommended dose regimens

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

Pediatric

Narcolepsy

<7 years: Safety and efficacy not established

≥7 years

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

Drug contraindications

Hypersensitivity

Concomitant sedative-hypnotic drugs or other drugs used for insomnia

Coadministration with alcohol

Succinic semialdehyde dehydrogenase deficiency

Side effects

Anxiety, Cataplexy, Diarrhea , Disorientation, Disturbance in attention, Dizziness , Dry mouth, Enuresis, Feeling drunk, Headache , Infection , Irritability, Muscle spasms, Nausea , Pain, Pain in extremity, Paresthesia, Peripheral edema, Pharyngitis , Sleep paralysis, Sleep walking , Somnolence , Upper abdominal pain, Vomiting

Pediatric patients

Enuresis , Nausea , Headache , Vomiting , Weight decreased , Decreased appetite , Dizziness

Interactions

Aripiprazole , Alprazolam , Amitriptyline , Ethosuximide , Etomidate , Oxazepam , Olanzapine , Imipramine , Belladonna , Papaverine , perphenazine , Propofol , Promethazine , Primidone , Pimozide , Trazodone , Tramadol , Trifluoperazine , Trimipramine , Topiramate , Thiothixene , Thioridazine , Desipramine , Doxepin , Risperidone , Zolpidem , Sevoflurane , Cinnarizine , Flurazepam , Fluphenazine , Phenobarbital , Phenytoin , Lorazepam , Maprotiline , Methadone , Methocarbamol , Nortriptyline , Haloperidol , Hydroxyzine , Chlorpromazine , Chlordiaze poxide , Chlorpheniramine , Clemastine , Clozapine , Clomipramine , Clonazepam , Clonidine , Azelastine , Cyclobenzaprine , Quetiapine , Buprenorphine , Oxecarbazepin , Expectorant , Baclofen , Terazosin , Atropine/ diphenoxylate( Lomotil® ) , Dimenhydrinate , stiripentol , dexmedetomidine , Tolcapone , Estazolam , Clorazepate , Cariprazine , Opium , entacapone , Perampanel , Paliperidone , Paraldehyde , Butorphanol , Butabarbital , Acetaminophen and benzhydrocodone , Phenindamine , Molindone , Triprolidine , Tripelennamine , Trimeprazine , Asenapine , Carbinoxamine , Flavoxate , Doxylamine , Dexchlorpheniramine , chlorcyclizine + pseudoephedrine , chlorcyclizine + phenylephrine , Chloral hydrate , Chlorzoxazone , Orphenadrine , Meclizine , Trimethobenzamide , Azatadine , Tapentadol , Pergolide , Droperidol , Cyclizine , Promazine , Ropinirole , Sibutramine , Cyproheptadine , Melatonin , Midazolam , Cabergoline , Ketamine , Desflurane , Prochlorperazine , Amoxapine , Pentobarbital , Amobarbital , Levorphanol , Oxycodone , Ziprasidone , protriptyline , morphine , meperidine , codeine , Pentazocine , Mirtazapine , Dantrolene , Apomorphine , marijuana , Diphenoxylate , Valproic acid , Sufentanil , Alfentanil , Sertindole , Carisoprodol , Hydrocodone , Zaleplon , Meprobamate , Loxapine , Butalbital and Acetaminophen , Triazolam , Terfenadine , feverfew , Amisulpride , Dipipanone , Iloperidone , Ramelteon , Rotigotine , Secobarbital , Metaxalone , Temazepam , Papaveretum , Quazepam , Brompheniramine , Oxymorphone , Mianserin , lofexidine , eszopiclone , hydromorphone , nalbuphine , lofepramine

Alerts

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

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

Use with caution in patients with sleep apnea

Evaluate episodes of parasomnias, including sleepwalking

Do not drink alcoholic beverages

Sodium intake

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

Drug interactions overview

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

Black Box Warnings

Central nervous system (CNS)

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

Abuse and misuse

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

Points of recommendation

Use the medicine exactly as directed.

Sodium oxybate may be habit-forming. Never share sodium oxybate with another person, especially someone with a history of drug abuse or addiction. Misuse of this medicine can cause breathing problems, seizure, loss of consciousness, or death. Selling or giving away sodium oxybate is against the law.

Do not allow anyone else to use your medication.

Take sodium oxybate on an empty stomach at least 2 hours after a meal. It is important to take sodium oxybate at the same time each night.

Sodium oxybate must be taken at bedtime and again two and a half to four hours later. This medicine works very fast and should be taken while you are sitting in bed ready for sleep. Prepare both doses while you are getting ready for bed. Place the second dose next to your bed so you can take it without getting up. You will most likely need to set an alarm to awaken for the second dose.

Each dose of sodium oxybate must be mixed with two ounces (one quarter cup) of water. Both doses must be used within the same night. Throw away any sodium oxybate dose that has been mixed with water but not used within 24 hours of mixing.

Do not stop using sodium oxybate suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using sodium oxybate.

Your doctor will need to check your progress every 3 months. If you need surgery, tell the surgeon ahead of time that you are using sodium oxybate.

Store at room temperature away from moisture and heat.

Pregnancy level

C

Related drugs

Chloral hydrate


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