KERLEDEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for KERLEDEX (KERLEDEX).

How it works

Kerledex is a selective serotonin reuptake inhibitor (SSRI) that potentiates serotonergic activity in the CNS by inhibiting the reuptake of serotonin at the presynaptic neuronal membrane.

What the body does with it

Metabolism	Extensively metabolized in the liver primarily by CYP2D6 and CYP3A4; also metabolized by CYP2C9 and CYP2C19. The major metabolite is desmethylkerledex, which is pharmacologically active.
Excretion	Renal: 70% unchanged; fecal/biliary: 20% as metabolites; 10% as minor metabolites. Total renal clearance 180 mL/min, active tubular secretion accounts for 60% of renal elimination.
Half-life	Terminal half-life 12 hours (range 10–14) in normal renal function; extended to 30–50 hours in severe renal impairment (CrCl <30 mL/min); 6–8 hours in hepatic cirrhosis.
Protein binding	95% bound (primarily to albumin; minor binding to alpha-1-acid glycoprotein). Unbound fraction increases to 10% in hypoalbuminemia (albumin <2.5 g/dL).
Volume of Distribution	0.3 L/kg (central compartment 0.12 L/kg, peripheral 0.18 L/kg). Suggests limited tissue distribution; does not cross blood-brain barrier significantly.
Bioavailability	Oral: 80% (range 70–90%); IM: 95% (extensive first-pass metabolism reduces bioavailability compared to IV).
Onset of Action	Oral: 0.5–1 hour; IV: 2–5 minutes; IM: 15–30 minutes. Time to peak effect: oral 2–4 hours; IV 1 hour.
Duration of Action	Oral: 6–8 hours; IV: 4–6 hours; IM: 6–8 hours. Duration increases by 2–3 hours with food intake due to delayed gastric emptying.

Classification & Brands

Dosing & administration

Intravenous: 500 mg every 6 hours; Oral: 250 mg every 8 hours.

Dosage form	TABLET
Renal impairment	CrCl > 50 mL/min: no adjustment; CrCl 10-50 mL/min: extend interval to every 12 hours; CrCl < 10 mL/min: extend interval to every 24 hours.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated.
Pediatric use	Intravenous: 10 mg/kg every 6 hours; Oral: 5 mg/kg every 8 hours; maximum 500 mg/dose.
Geriatric use	Initiate at lowest dose; monitor renal function and adjust per renal guidelines; increased risk of CNS adverse effects.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for KERLEDEX (KERLEDEX).

Breastfeeding	Contraindicated during breastfeeding. KERLEDEX is excreted in human milk with an M/P ratio of 1.8; potential for serious adverse reactions in nursing infants.
Teratogenic Risk	First trimester: Known teratogen; associated with major congenital malformations including cardiovascular and neural tube defects. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and preterm birth. Avoid in pregnancy unless no alternative.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS - Kerledex may increase the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. Monitor closely for clinical worsening, suicidality, or unusual changes in behavior.

Side Effect Profile

Serious Effects

Absolute Contraindications

Concomitant use with MAOIs or within 14 days of discontinuing an MAOI, concomitant use with pimozide, known hypersensitivity to kerledex or any excipients, and use in patients with severe hepatic impairment.

Clinical Precautions

Precautions

Serotonin syndrome, discontinuation syndrome, activation of mania/hypomania, seizures, angle-closure glaucoma, hyponatremia, abnormal bleeding, sexual dysfunction, weight changes, and potential for QT interval prolongation.

Clinical Tips & Counseling

Drug interactions

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KERLEDEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for KERLEDEX (KERLEDEX).

How it works

Kerledex is a selective serotonin reuptake inhibitor (SSRI) that potentiates serotonergic activity in the CNS by inhibiting the reuptake of serotonin at the presynaptic neuronal membrane.

What the body does with it

Metabolism	Extensively metabolized in the liver primarily by CYP2D6 and CYP3A4; also metabolized by CYP2C9 and CYP2C19. The major metabolite is desmethylkerledex, which is pharmacologically active.
Excretion	Renal: 70% unchanged; fecal/biliary: 20% as metabolites; 10% as minor metabolites. Total renal clearance 180 mL/min, active tubular secretion accounts for 60% of renal elimination.
Half-life	Terminal half-life 12 hours (range 10–14) in normal renal function; extended to 30–50 hours in severe renal impairment (CrCl <30 mL/min); 6–8 hours in hepatic cirrhosis.
Protein binding	95% bound (primarily to albumin; minor binding to alpha-1-acid glycoprotein). Unbound fraction increases to 10% in hypoalbuminemia (albumin <2.5 g/dL).
Volume of Distribution	0.3 L/kg (central compartment 0.12 L/kg, peripheral 0.18 L/kg). Suggests limited tissue distribution; does not cross blood-brain barrier significantly.
Bioavailability	Oral: 80% (range 70–90%); IM: 95% (extensive first-pass metabolism reduces bioavailability compared to IV).
Onset of Action	Oral: 0.5–1 hour; IV: 2–5 minutes; IM: 15–30 minutes. Time to peak effect: oral 2–4 hours; IV 1 hour.
Duration of Action	Oral: 6–8 hours; IV: 4–6 hours; IM: 6–8 hours. Duration increases by 2–3 hours with food intake due to delayed gastric emptying.

Classification & Brands

Dosing & administration

Intravenous: 500 mg every 6 hours; Oral: 250 mg every 8 hours.

Dosage form	TABLET
Renal impairment	CrCl > 50 mL/min: no adjustment; CrCl 10-50 mL/min: extend interval to every 12 hours; CrCl < 10 mL/min: extend interval to every 24 hours.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated.
Pediatric use	Intravenous: 10 mg/kg every 6 hours; Oral: 5 mg/kg every 8 hours; maximum 500 mg/dose.
Geriatric use	Initiate at lowest dose; monitor renal function and adjust per renal guidelines; increased risk of CNS adverse effects.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for KERLEDEX (KERLEDEX).

Breastfeeding	Contraindicated during breastfeeding. KERLEDEX is excreted in human milk with an M/P ratio of 1.8; potential for serious adverse reactions in nursing infants.
Teratogenic Risk	First trimester: Known teratogen; associated with major congenital malformations including cardiovascular and neural tube defects. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and preterm birth. Avoid in pregnancy unless no alternative.
Fetal Monitoring