Pronunciation:

KAL-see-um OX-i-bate, mag-NEE-zee-um OX-i-bate, poe-TAS-ee-um OX-i-bate, SOE-dee-um OX-i-bate

Brand Names:

• Xywav

Dosage Forms:

• Solution

Warnings:

Central Nervous System DepressionCalcium oxybate/magnesium oxybate/potassium oxybate/sodium oxybate is a CNS depressant. Clinically significant respiratory depression and obtundation may occur in patients treated with calcium oxybate/magnesium oxybate/potassium oxybate/sodium oxybate at recommended doses. Many patients who received calcium oxybate/magnesium oxybate/potassium oxybate/sodium oxybate during clinical trials in narcolepsy and idiopathic hypersomnia were receiving central nervous system stimulantsAbuse and MisuseThe active moiety of calcium oxybate/magnesium oxybate/potassium oxybate/sodium oxybate is oxybate or gamma hydroxybutyrate (GHB). Abuse or misuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death.Because of the risks of CNS depression and abuse and misuse, calcium oxybate/magnesium oxybate/potassium oxybate/sodium oxybate is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Xywav and Xyrem REMS .

Classifications:

Therapeutic—

Central Nervous System Agent

Uses of This Medicine:

Calcium oxybate, magnesium oxybate, potassium oxybate, and sodium oxybate combination is used to treat cataplexy (weak or paralyzed muscles) or excessive daytime sleepiness (EDS) in patients with narcolepsy. Narcolepsy is an uncontrollable desire for sleep or a sudden attack of deep sleep. This medicine is also used to treat idiopathic hypersomnia (IH).

This medicine is available only under a restricted distribution program called Xywav® and Xyrem® REMS (Risk Evaluation and Mitigation Strategy) Program. You can only get it from one central pharmacy.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of calcium oxybate, magnesium oxybate, potassium oxybate, and sodium oxybate combination to treat idiopathic hypersomnia in children and to treat cataplexy or excessive daytime sleepiness in children younger than 7 years of age. Safety and efficacy have not been established.

Older adults—

Appropriate studies on the relationship of age to the effects of sodium oxybate have not been performed in the geriatric population. However, elderly patients are more likely to have unwanted effects (eg, headache) or age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving this medicine.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Carbinoxamine
• Chloral Hydrate
• Diphenhydramine
• Doxylamine
• Eszopiclone
• Ethchlorvynol
• Hydroxyzine
• Promethazine
• Ramelteon
• Zaleplon
• Zolpidem
• Zopiclone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acepromazine
• Alfentanil
• Alprazolam
• Amobarbital
• Anileridine
• Aprobarbital
• Aripiprazole
• Asenapine
• Baclofen
• Benperidol
• Benzhydrocodone
• Bromazepam
• Buprenorphine
• Buspirone
• Butabarbital
• Butalbital
• Butorphanol
• Cannabidiol
• Cannabis
• Carisoprodol
• Carphenazine
• Cetirizine
• Chlordiazepoxide
• Chlorpromazine
• Chlorzoxazone
• Clobazam
• Clonazepam
• Clorazepate
• Clozapine
• Codeine
• Cyclobenzaprine
• Dantrolene
• Daridorexant
• Dexmedetomidine
• Diacetylmorphine
• Diazepam
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diphenoxylate
• Droperidol
• Enflurane
• Esketamine
• Estazolam
• Ethopropazine
• Ethylmorphine
• Fentanyl
• Flibanserin
• Flunitrazepam
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fospropofol
• Gabapentin
• Gabapentin Enacarbil
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Isoflurane
• Ketamine
• Ketazolam
• Ketobemidone
• Lacosamide
• Lemborexant
• Levocetirizine
• Levorphanol
• Lofexidine
• Lorazepam
• Lormetazepam
• Loxapine
• Meclizine
• Medazepam
• Melperone
• Meperidine
• Mephenesin
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Metoclopramide
• Midazolam
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Nicomorphine
• Nitrazepam
• Nitrous Oxide
• Olanzapine
• Oliceridine
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxycodone
• Oxymorphone
• Papaveretum
• Paregoric
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenobarbital
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Prazepam
• Pregabalin
• Primidone
• Prochlorperazine
• Promazine
• Propofol
• Quazepam
• Quetiapine
• Remifentanil
• Remimazolam
• Remoxipride
• Ropeginterferon Alfa-2b-njft
• Scopolamine
• Secobarbital
• Sertindole
• Sufentanil
• Sulpiride
• Suvorexant
• Tapentadol
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Tramadol
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Valproic Acid
• Zotepine
• Zuranolone

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is not recommended. Your doctor may decide not to treat you with this medication, change some of the other medicines you take, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, history of or
• Drug abuse or dependence, history of—Dependence may be more likely to develop.

• Breathing or lung problems (eg, hypopnea or sleep apnea) or
• Depression, history of—Use with caution. May make these conditions worse.

• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Obesity—Use with caution. May increase risk for sleep-related breathing problems.

• Succinic semialdehyde dehydrogenase deficiency (rare inborn metabolism disorder)—Should not be used in patients with this condition.

Proper Use of This Medicine:

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. If too much is taken, it may become habit-forming. If you think this medicine is not working properly after you have taken it for several weeks, check with your doctor first and do not increase the dose.

It is very important that you understand the requirements of the Xywav® and Xyrem® REMS program, and become familiar with the Xywav® Medication Guide and patient instructions. Ask your doctor if you have any questions.

This medicine can be taken as a single dose (for idiopathic hypersomnia) or divided into 2 nightly doses. The first nightly dose should be taken at least 2 hours after you eat.

This medicine can make you sleep very quickly (within 5 to 15 minutes) without feeling drowsy. It is best to take the medicine only at bedtime or when you are ready to fall asleep. Take it only at bedtime and while in bed.

Measure your dose with the marked plastic syringe that comes with the medicine. Mix it with 1/4 cup of water. Mix both doses before you go to bed. Store the second dose close to your bed in a child, out of the reach of children.

Take the second dose 2 1/2 to 4 hours after you take the first dose. You may need to set an alarm clock to wake you up so you can take the second dose on time. Remain on your bed after taking the first and second doses of this medicine.

Use the medicine within 24 hours after it has been mixed with water.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (solution):
  • For cataplexy or excessive daytime sleepiness:
    • Adults—At first, 2.25 grams (g) taken at bedtime (first dose), then 2.25 g taken 2.5 to 4 hours later (second dose). Your doctor may adjust your dose as needed and tolerated. However, the dose is usually not more than 9 g per night.
    • Children 7 years of age and older—Dose is based on body weight and must be determined by your doctor:
      • Weighing 45 kilograms (kg) or more—At first, 2.25 g or less given at bedtime and repeated one time during the night. The first dose should be taken at bedtime and the second dose taken 2.5 to 4 hours later. Your doctor may adjust your dose as needed and tolerated. However, the dose is usually not more than 4.5 g per night.
      • Weighing 30 kg to less than 45 kg—At first, 1.5 g or less given at bedtime and repeated one time during the night. The first dose should be taken at bedtime and the second dose taken 2.5 to 4 hours later. Your doctor may adjust your dose as needed. However, the dose is usually not more than 3.75 g per night.
      • Weighing 20 to less than 30 kg—At first, 1.0 g or less given at bedtime and repeated one time during the night. The first dose should be taken at bedtime and the second dose taken 2.5 to 4 hours later. Your doctor may adjust your dose as needed. However, the dose is usually not more than 3 g per night.
    • Children younger than 7 years of age or weighing less than 20 kg—Use and dose must be determined by your doctor.
  • For idiopathic hypersomnia:
    • Once a night dosing:
      • Adults—At first, 3 grams (g) or less taken at bedtime. Your doctor may adjust your dose as needed and tolerated. However, the dose is usually not more than 6 g per night.
      • Children—Use and dose must be determined by your doctor.
    • Two times a night dosing:
      • Adults—At first, 4.5 grams (g) or less taken at bedtime, divided into two doses (eg, 2.25 g each). Your doctor may adjust your dose as needed and tolerated. However, the dose is usually not more 9 g per night.
      • Children—Use and dose must be determined by your doctor.

Missed dose—

If you miss a dose of this medicine, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss the second dose, skip that dose and do not take any more medicine until the next night. Do not use extra medicine to make up for a missed dose.

Storage—

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Pour any unused medicine down the sink drain after 24 hours. Use a marker to cross out the label on the bottle, then throw it in the trash.

Precautions While Using This Medicine:

It is very important that your doctor check your or your child's progress at regular visits to make sure the medicine is working properly and to check for any unwanted effects.

Do not use this medicine if you are also taking another sedative or hypnotic medicine (eg, Ambien®, Phenergan®, Seconal®). Also, do not drink alcohol while you are using this medicine. Doing so may increase the risk for serious unwanted effects.

It is against the law and dangerous for anyone else to use your medicine. Keep your unused medicine in a safe and secure place. People who are addicted to drugs might want to steal this medicine.

Check with your doctor before using this medicine with alcohol or other medicines that affect the central nervous system (CNS). The use of alcohol or other medicines that affect the CNS with Xywav® may worsen the side effects of this medicine, such as dizziness, poor concentration, drowsiness, unusual dreams, and trouble with sleeping. Some examples of medicines that affect the CNS are antihistamines or medicine for allergies or colds, sedatives, tranquilizers, or sleeping medicines, medicine for depression, medicine for anxiety, prescription pain medicine or narcotics, medicine for attention deficit and hyperactivity disorder, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics.

This medicine may make you dizzy, drowsy, or less alert than you are normally. Do not drive or do anything else that could be dangerous for at least 6 hours after taking this medicine.

Do not use more of this medicine or take it more often than your doctor tells you to. This can be life-threatening. Symptoms of an overdose include: extreme dizziness or weakness, slow heartbeat or breathing, seizures, trouble breathing, or cold, clammy skin. Call your doctor right away if you notice these symptoms.

This medicine may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. Make sure the doctor knows if you have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. Also tell the doctor if you have sudden or strong feelings, such as feeling nervous, angry, restless, violent, or scared. If you or your caregiver notice any of these side effects, tell your doctor right away.

This medicine may cause unusual behavior while you are sleeping. Other people living in your house should monitor you for the possibility of sleep-related problems, including sleepwalking, sleep talking, sleep eating, or bedwetting. Tell your doctor if any of these occur.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or non-prescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Bedwetting

sleepiness or unusual drowsiness

sleepwalking

Less common

Anxiety

burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings

confusion about identity, place, and time

discouragement

feeling sad or empty

irritability

lack of appetite

loss of interest or pleasure

pain in the arm or leg

seeing, feeling, or hearing things that are not there

sleep paralysis

thoughts of killing oneself

tremor

trouble breathing

trouble concentrating

trouble sleeping

unusual tiredness or weakness

Incidence not known

Being forgetful

blurred vision

chest tightness

decrease in the amount of urine

dizziness

falls

fever

headache

hives, itching, skin rash

hoarseness

increased urge to urinate during the night

irritation

joint pain, stiffness, or swelling

nervousness

noisy, rattling breathing

pounding in the ears

redness of the skin

swelling of the face, fingers, hands, feet, or lower legs

trouble swallowing

waking to urinate at night

weight gain

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

Agitation

chest pain or discomfort

clumsiness

drowsiness

lightheadedness, dizziness, or fainting

loss of consciousness

loss of strength or energy

low body temperature

muscle pain or weakness

seizures

shakiness and unsteady walk

shivering

slow or irregular heartbeat

unsteadiness, trembling, or other problems with muscle control or coordination

unusual weak feeling

weak or feeble pulse

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Decreased weight

diarrhea

dry mouth

increased sweating

nausea

vomiting

Less common

Clenching, gnashing, or grinding teeth

feeling drunk

snoring

Incidence not known

Difficulty in moving

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.