LUMRYZ

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LUMRYZ (LUMRYZ).

How it works

Gamma-hydroxybutyrate (GHB) receptor agonist; modulates dopaminergic, noradrenergic, and opioid systems; induces slow-wave sleep.

What the body does with it

Metabolism	Primarily metabolized via the tricarboxylic acid (Krebs) cycle; minor metabolism via beta-oxidation and CYP450 enzymes (CYP2D6, CYP3A4).
Excretion	Primarily renal excretion of unchanged drug; approximately 80-90% of a dose is recovered in urine within 24 hours, with less than 2% in feces.
Half-life	Terminal elimination half-life is approximately 60 hours (range 50-70 hours) in healthy adults, supporting once-daily dosing.
Protein binding	Approximately 70-75% bound to serum albumin.
Volume of Distribution	Apparent volume of distribution is approximately 3-4 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral bioavailability is approximately 80-90% due to limited first-pass metabolism.
Onset of Action	Following oral administration, clinical effects are typically observed within 30-60 minutes.
Duration of Action	The duration of clinical effect is approximately 8-10 hours, although plasma concentrations remain above therapeutic threshold for up to 12 hours.

Classification & Brands

Dosing & administration

For narcolepsy: 4.5 g to 9 g orally once nightly at bedtime. Administer as a liquid suspension reconstituted from powder.

Dosage form	FOR SUSPENSION, EXTENDED RELEASE
Renal impairment	Contraindicated in patients with eGFR < 30 mL/min/1.73 m². For eGFR 30-60 mL/min/1.73 m², reduce dose to 4.5 g nightly. No adjustment for eGFR ≥ 60 mL/min/1.73 m².
Liver impairment	Contraindicated in Child-Pugh Class C. For Child-Pugh Class A or B, reduce dose to 4.5 g nightly.
Pediatric use	Not approved for use in pediatric patients (safety and efficacy not established). Clinical studies have not been conducted in children.
Geriatric use	No specific dose adjustment recommended, but monitor for increased sensitivity and risk of falls or cognitive impairment. Use lowest effective dose (4.5 g nightly) in patients ≥65 years due to potential renal impairment.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LUMRYZ (LUMRYZ).

Breastfeeding

Sodium oxybate is excreted in human milk. The milk-to-plasma ratio is approximately 0.5. The effects on the nursing infant are unknown. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during treatment with LUMRYZ.

Teratogenic Risk

LUMRYZ (sodium oxybate) is a CNS depressant. Animal studies have shown adverse effects on fetal development at clinically relevant doses. There are no adequate and well-controlled studies in pregnant women. The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. First trimester: potential risk of major malformations. Second and third trimesters: risk of fetal CNS depression, hypotonia, and respiratory depression.

Warnings & precautions

■ FDA Black Box Warning

Central nervous system (CNS) depression; concomitant use with alcohol or other CNS depressants may cause respiratory depression, hypotension, profound sedation, coma, or death. LUMRYZ is a Schedule III controlled substance with abuse potential; abuse may lead to dependence and withdrawal.

Side Effect Profile

Serious Effects

Absolute Contraindications

Concomitant use with alcohol or other CNS depressants; succinic semialdehyde dehydrogenase deficiency; history of drug abuse (relative); severe hepatic impairment.

Clinical Precautions

Precautions

CNS depression including respiratory depression; abuse and dependence; withdrawal symptoms; seizures; confusion/anxiety; depression/suicidality; nocturnal eating/driving; respiratory compromise; use in patients with compromised respiratory function; hypertension; and use with caution in hepatic impairment.

Clinical Tips & Counseling

Drug interactions

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LUMRYZ

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LUMRYZ (LUMRYZ).

How it works

Gamma-hydroxybutyrate (GHB) receptor agonist; modulates dopaminergic, noradrenergic, and opioid systems; induces slow-wave sleep.

What the body does with it

Metabolism	Primarily metabolized via the tricarboxylic acid (Krebs) cycle; minor metabolism via beta-oxidation and CYP450 enzymes (CYP2D6, CYP3A4).
Excretion	Primarily renal excretion of unchanged drug; approximately 80-90% of a dose is recovered in urine within 24 hours, with less than 2% in feces.
Half-life	Terminal elimination half-life is approximately 60 hours (range 50-70 hours) in healthy adults, supporting once-daily dosing.
Protein binding	Approximately 70-75% bound to serum albumin.
Volume of Distribution	Apparent volume of distribution is approximately 3-4 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral bioavailability is approximately 80-90% due to limited first-pass metabolism.
Onset of Action	Following oral administration, clinical effects are typically observed within 30-60 minutes.
Duration of Action	The duration of clinical effect is approximately 8-10 hours, although plasma concentrations remain above therapeutic threshold for up to 12 hours.

Classification & Brands

Dosing & administration

For narcolepsy: 4.5 g to 9 g orally once nightly at bedtime. Administer as a liquid suspension reconstituted from powder.

Dosage form	FOR SUSPENSION, EXTENDED RELEASE
Renal impairment	Contraindicated in patients with eGFR < 30 mL/min/1.73 m². For eGFR 30-60 mL/min/1.73 m², reduce dose to 4.5 g nightly. No adjustment for eGFR ≥ 60 mL/min/1.73 m².
Liver impairment	Contraindicated in Child-Pugh Class C. For Child-Pugh Class A or B, reduce dose to 4.5 g nightly.
Pediatric use	Not approved for use in pediatric patients (safety and efficacy not established). Clinical studies have not been conducted in children.
Geriatric use	No specific dose adjustment recommended, but monitor for increased sensitivity and risk of falls or cognitive impairment. Use lowest effective dose (4.5 g nightly) in patients ≥65 years due to potential renal impairment.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LUMRYZ (LUMRYZ).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Concomitant use with alcohol or other CNS depressants; succinic semialdehyde dehydrogenase deficiency; history of drug abuse (relative); severe hepatic impairment.