REXTOVY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for REXTOVY (REXTOVY).

How it works

REXTOVY is a selective serotonin reuptake inhibitor (SSRI) that potentiates serotonergic activity in the CNS by inhibiting the reuptake of serotonin at the presynaptic neuron, thereby increasing synaptic serotonin levels. It also weakly inhibits norepinephrine reuptake.

What the body does with it

Metabolism	Primarily hepatic via CYP2D6 and CYP2C9 isoenzymes; metabolite R-REXTOVY (active) and S-REXTOVY (inactive). Minor renal excretion of glucuronide conjugates.
Excretion	Renal: 75% as unchanged drug; fecal: 20% (biliary excretion of metabolites); <5% other routes.
Half-life	Terminal half-life: 12 hours (range 8–15 h) in healthy adults; prolonged to 24 h in moderate renal impairment (CrCl <50 mL/min).
Protein binding	95% bound to serum albumin; minor binding to α1-acid glycoprotein.
Volume of Distribution	0.8 L/kg (total Vd ~56 L in 70 kg adult); indicates extensive tissue distribution.
Bioavailability	Oral: 60% (range 45–75%) due to first-pass metabolism; Subcutaneous: 90%.
Onset of Action	Oral: 30–45 min (fasted state); Subcutaneous: 10–15 min.
Duration of Action	6–8 hours for oral dose; 8–12 hours for subcutaneous dose; dose-dependent, shorter with higher gastric pH.

Classification & Brands

Dosing & administration

10 mg orally once daily, increased to 20 mg once daily after 4 weeks if tolerated and needed.

Dosage form	SPRAY, METERED
Renal impairment	GFR ≥30 mL/min: no adjustment. GFR 15–29 mL/min: 10 mg once daily maximum. GFR <15 mL/min: not recommended.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: 10 mg once daily maximum. Child-Pugh C: not recommended.
Pediatric use	Not established for patients <18 years of age.
Geriatric use	Starting dose 10 mg once daily; titrate cautiously due to increased risk of hypotension and dizziness.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for REXTOVY (REXTOVY).

Breastfeeding	Unknown if excreted in human milk. Because of potential for serious adverse reactions in nursing infants (e.g., immunosuppression), breastfeeding is contraindicated. M/P ratio not determined.
Teratogenic Risk	Pregnancy Category X. First trimester: Major congenital malformations (neural tube defects, cardiovascular anomalies) reported in up to 25% of exposed fetuses. Second and third trimesters: Increased risk of spontaneous abortion, intrauterine growth restriction, and fetal death. Use is contraindicated in women of childbearing potential unless adequate contraception is used.

Warnings & precautions

■ FDA Black Box Warning

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to REXTOVY or any excipient; concomitant use with MAOIs or within 14 days of MAOI therapy; concomitant use with pimozide; use in patients with uncontrolled epilepsy; use in patients with known QT prolongation or concurrent use with drugs that prolong QT interval.

Clinical Precautions

Precautions

Clinical worsening and suicide risk; serotonin syndrome; discontinuation syndrome; activation of mania/hypomania; seizures; angle-closure glaucoma; hyponatremia; bleeding risk (especially with NSAIDs, aspirin); bone fractures; sexual dysfunction; weight changes; QT prolongation (dose-dependent); impaired platelet aggregation.

Clinical Tips & Counseling

Drug interactions

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REXTOVY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for REXTOVY (REXTOVY).

How it works

What the body does with it

Metabolism	Primarily hepatic via CYP2D6 and CYP2C9 isoenzymes; metabolite R-REXTOVY (active) and S-REXTOVY (inactive). Minor renal excretion of glucuronide conjugates.
Excretion	Renal: 75% as unchanged drug; fecal: 20% (biliary excretion of metabolites); <5% other routes.
Half-life	Terminal half-life: 12 hours (range 8–15 h) in healthy adults; prolonged to 24 h in moderate renal impairment (CrCl <50 mL/min).
Protein binding	95% bound to serum albumin; minor binding to α1-acid glycoprotein.
Volume of Distribution	0.8 L/kg (total Vd ~56 L in 70 kg adult); indicates extensive tissue distribution.
Bioavailability	Oral: 60% (range 45–75%) due to first-pass metabolism; Subcutaneous: 90%.
Onset of Action	Oral: 30–45 min (fasted state); Subcutaneous: 10–15 min.
Duration of Action	6–8 hours for oral dose; 8–12 hours for subcutaneous dose; dose-dependent, shorter with higher gastric pH.

Classification & Brands

Dosing & administration

10 mg orally once daily, increased to 20 mg once daily after 4 weeks if tolerated and needed.

Dosage form	SPRAY, METERED
Renal impairment	GFR ≥30 mL/min: no adjustment. GFR 15–29 mL/min: 10 mg once daily maximum. GFR <15 mL/min: not recommended.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: 10 mg once daily maximum. Child-Pugh C: not recommended.
Pediatric use	Not established for patients <18 years of age.
Geriatric use	Starting dose 10 mg once daily; titrate cautiously due to increased risk of hypotension and dizziness.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for REXTOVY (REXTOVY).

Breastfeeding	Unknown if excreted in human milk. Because of potential for serious adverse reactions in nursing infants (e.g., immunosuppression), breastfeeding is contraindicated. M/P ratio not determined.
Teratogenic Risk	Pregnancy Category X. First trimester: Major congenital malformations (neural tube defects, cardiovascular anomalies) reported in up to 25% of exposed fetuses. Second and third trimesters: Increased risk of spontaneous abortion, intrauterine growth restriction, and fetal death. Use is contraindicated in women of childbearing potential unless adequate contraception is used.

Warnings & precautions

■ FDA Black Box Warning

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.