Sodium Oxybate

Some medicines are not suitable for people with certain conditions, and sometimes a medicine may only be used if extra care is taken. For these reasons, before you start taking sodium oxybate it is important that your doctor or pharmacist knows:

• If you are pregnant, trying for a baby or breast-feeding.
• If you have epilepsy.
• If you have any problems with your heart or your breathing, or if you have high blood pressure.
• If you have problems with your liver or kidneys.
• If you are on a 'low sodium' diet for medical reasons.
• If you have ever had a depressive illness.
• If you have porphyria, a rare inherited blood disorder.
• If you have ever had a drug addiction problem.
• If you are taking any other medicines. This includes any medicines you are taking which are available to buy without a prescription, as well as herbal and complementary medicines.
• If you have ever had an allergic reaction to a medicine.

• Keep your regular appointments with your doctor. This is so your progress can be monitored.
• Treatment with sodium oxybate is usually long-term. Continue to take the medicine unless you are advised otherwise. Stopping suddenly can cause problems and your doctor may want you to reduce your dose gradually if this is necessary.
• Sodium oxybate will make you sleepy, so do not drive within six hours of taking a dose. You may also continue to feel sleepy during the following day, so do not drive and do not use tools or machines if this happens, as you may put yourself and others at risk.
• You should not drink alcohol while you are on sodium oxybate.
• If you buy any medicines, check with a pharmacist that they are suitable for you to take with sodium oxybate. Some strong painkillers should not be taken with this medicine.
• If you are having an operation or dental treatment, tell the person carrying out the treatment that you are taking this medicine.
• Sodium oxybate is known to cause dependence, particularly where more than the recommended doses are taken. If you are concerned about this, you should discuss it with your doctor.

Dosage Forms And Strengths

Xyrem is a clear to slightly opalescent oral solution, in a concentration of 0.5 g per mL.

Storage And Handling

Xyrem is a clear to slightly opalescent oral solution. Each prescription includes a carton containing one bottle of Xyrem, a press-in-bottle-adaptor, an oral measuring device (plastic syringe), and a Medication Guide. The pharmacy provides two empty vials with child-resistant caps with each Xyrem shipment.

Each amber bottle contains Xyrem oral solution at a concentration of 0.5 g per mL and has a child-resistant cap.

Carton containing one 180 mL bottle NDC 68727-100-01

Storage

Keep out of reach of children.

Xyrem should be stored at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) (see USP Controlled Room Temperature).

Dispense in tight containers.

Solutions prepared following dilution should be consumed within 24 hours.

Handling And Disposal

Xyrem is a Schedule III drug under the Controlled Substances Act. Xyrem should be handled according to state and federal regulations. It is safe to dispose of Xyrem down the sanitary sewer.

Distributed By: Jazz Pharmaceuticals, Inc. Palo Alto, CA 94304. Revised: April 2014

Do not drink alcohol. Dangerous side effects or death can occur when alcohol is combined with sodium oxybate. Check your food and medicine labels to be sure these products do not contain alcohol.

Sodium oxybate must not be taken with other drugs that are used for sleep or sedation.

Sodium oxybate will cause drowsiness and can impair your thinking or reactions. You may still feel sleepy the morning after taking this medicine. Wait at least 6 hours or until you are fully awake before you drive, operate machinery, pilot an airplane, or do anything that requires you to be awake and alert.

Sodium oxybate is a prescription medicine used for the treatment of narcolepsy, to:

• reduce daytime sleepiness
• reduce cataplexy (weak or paralyzed muscles) attacks

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your doctor about all of the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take medicines to help you sleep (sedatives) or if you use alcohol. See FDA Warning.

It is not known if sodium oxybate crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using sodium oxybate.

General

• Restricted distribution program (Xyrem Success Program) in effect due to abuse potential and risk of adverse CNS and respiratory effects.1 (See Boxed Warning.)

Administration

Oral Administration

Administer orally in 2 equally divided doses daily.1 Administer at least 2 hours after eating.1

Dilute each dose with approximately 60 mL of water in the child-resistant vial provided by pharmacy.1 Prepare both doses before bedtime.1

Take first dose at bedtime and second dose 2.5–4 hours later (while sitting in bed).1

May need to set alarm clock to awaken for second dose; place second dose in close proximity to bed.1

Lie down and remain in bed after each dose.1

Dosage

Adults

Initially, 4.5 g nightly in 2 doses of 2.25 g each.1 Increase dosage in increments of 1.5 g daily (0.75 g per dose) at 1-week intervals to a maximum dosage of 9 g daily.1

Prescribing Limits

Adults

Maximum 9 g daily.1

Special Populations

Hepatic Impairment

Initially, 2.25 g nightly in 2 doses of approximately 1.13 g each.1

Renal Impairment

Specific dosage recommendation not available.1

Geriatric Patients

Select dosage with caution, usually starting at lower end of dosage range, because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

• It is used to treat sudden loss of muscle tone (cataplexy) in patients with narcolepsy.
• It is used to treat a lot of sleepiness during the day in patients with narcolepsy.

• Central Nervous System Depressant

Oral: Administer on an empty stomach; separate last meal (or food) and first dose by ≥2 hours; try to take at similar time each day. Doses should be administered while in bed; patient should lie down immediately after dose and should remain in bed. Both doses should be prepared prior to bedtime. The first dose is taken at bedtime and the second dose is taken 2.5 to 4 hours later; an alarm clock may need to be set for the second dose. Patients typically fall asleep within 5-15 minutes; patients may take up to 2 hours to fall asleep (rare).

Contains a high sodium content; limit dietary intake of sodium.

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

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

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

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

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

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

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

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

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

CNS Depressants: Sodium Oxybate may enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

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

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

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

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

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

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

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

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

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

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

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

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

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

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

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

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

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

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

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

Rilmenidine: May enhance the CNS depressant effect of Sodium Oxybate. Avoid combination

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

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

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

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

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

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

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

Valproate Products: May increase the serum concentration of Sodium Oxybate. Management: Consider a sodium oxybate dose reduction of at least 20% if combined with valproic acid. Consider therapy modification

Sodium oxybate is a CNS depressant. In clinical trials at recommended doses, obtundation and clinically significant respiratory depression occurred in sodium oxybate–treated patients. Almost all of the patients who received sodium oxybate during clinical trials in narcolepsy were receiving CNS stimulants.

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

Because of the risks of CNS depression, abuse, and misuse, sodium oxybate is only available through a restricted distribution program called the Xyrem REMS Program, using the central pharmacy that is specially certified. Prescribers and patients must enroll in the program. For further information go to http://www.xyremrems.com or call 1-866-997-3688.

Adverse effects have been reported with maternal use. The injection formulation, when used as an anesthetic during labor and delivery, was shown to cross the placenta in concentrations ≤25% of maternal levels; a slight decrease in Apgar scores due to sleepiness in the neonate was observed. Sodium oxybate was not detected in infant blood 30 minutes after delivery.

Use is not recommended. US FDA pregnancy category: C

Animal studies have shown no evidence of teratogenicity but embryolethality was reported. Data from a limited number of pregnant women exposed in the first trimester indicate a possible increased risk of spontaneous abortions. Limited data from pregnant patients during second and third trimesters indicate no malformative nor feto/neonatal toxicity of this drug. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.