CRENESSITY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CRENESSITY (CRENESSITY).

How it works

CRENESSITY is a selective antagonist of the C-C chemokine receptor type 5 (CCR5), blocking HIV-1 entry into cells by binding to CCR5 and preventing gp120 interaction.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4 and CYP3A5; minor contribution from CYP2C9 and CYP2C19.
Excretion	Primarily hepatobiliary excretion into feces; less than 5% excreted renally as unchanged drug.
Half-life	Terminal elimination half-life approximately 20 hours, supporting once-daily dosing.
Protein binding	99.9% bound to plasma proteins, predominantly albumin.
Volume of Distribution	12 L/kg, indicating extensive extravascular distribution.
Bioavailability	Oral bioavailability approximately 30%.
Onset of Action	Oral: Clinical effects on lipid parameters observed within 2 weeks of initiation.
Duration of Action	Duration of action: 24 hours, consistent with once-daily administration.

Classification & Brands

Dosing & administration

300 mg orally once daily with food.

Dosage form	CAPSULE
Renal impairment	No dosage adjustment required for GFR ≥30 mL/min; not studied in GFR <30 mL/min or dialysis.
Liver impairment	Child-Pugh A and B: no adjustment; Child-Pugh C: not recommended.
Pediatric use	Not approved in pediatric patients; safety and efficacy not established.
Geriatric use	No specific dose adjustment; use caution due to increased frequency of comorbidities and 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 CRENESSITY (CRENESSITY).

Breastfeeding	No human data on excretion in breast milk. Animal studies indicate transfer into milk. M/P ratio unknown. Risk of infant toxicity cannot be excluded. Recommend discontinue breastfeeding or avoid drug.
Teratogenic Risk	First trimester: Based on animal studies, there is a risk of fetal malformations including cardiac and neural tube defects. Second trimester: Potential for fetal growth restriction. Third trimester: Risk of premature labor and low birth weight. Avoid use unless benefit outweighs risks.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

Coadministration with strong CYP3A inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) due to decreased CRENESSITY exposure.

Clinical Precautions

Precautions

Hepatotoxicity: monitor liver enzymes; severe skin and hypersensitivity reactions; risk of treatment failure with CXCR4-tropic virus; embryo-fetal toxicity (use effective contraception).

Clinical Tips & Counseling

Drug interactions

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CRENESSITY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CRENESSITY (CRENESSITY).

How it works

CRENESSITY is a selective antagonist of the C-C chemokine receptor type 5 (CCR5), blocking HIV-1 entry into cells by binding to CCR5 and preventing gp120 interaction.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4 and CYP3A5; minor contribution from CYP2C9 and CYP2C19.
Excretion	Primarily hepatobiliary excretion into feces; less than 5% excreted renally as unchanged drug.
Half-life	Terminal elimination half-life approximately 20 hours, supporting once-daily dosing.
Protein binding	99.9% bound to plasma proteins, predominantly albumin.
Volume of Distribution	12 L/kg, indicating extensive extravascular distribution.
Bioavailability	Oral bioavailability approximately 30%.
Onset of Action	Oral: Clinical effects on lipid parameters observed within 2 weeks of initiation.
Duration of Action	Duration of action: 24 hours, consistent with once-daily administration.

Classification & Brands

Dosing & administration

300 mg orally once daily with food.

Dosage form	CAPSULE
Renal impairment	No dosage adjustment required for GFR ≥30 mL/min; not studied in GFR <30 mL/min or dialysis.
Liver impairment	Child-Pugh A and B: no adjustment; Child-Pugh C: not recommended.
Pediatric use	Not approved in pediatric patients; safety and efficacy not established.
Geriatric use	No specific dose adjustment; use caution due to increased frequency of comorbidities and 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 CRENESSITY (CRENESSITY).

Breastfeeding	No human data on excretion in breast milk. Animal studies indicate transfer into milk. M/P ratio unknown. Risk of infant toxicity cannot be excluded. Recommend discontinue breastfeeding or avoid drug.
Teratogenic Risk	First trimester: Based on animal studies, there is a risk of fetal malformations including cardiac and neural tube defects. Second trimester: Potential for fetal growth restriction. Third trimester: Risk of premature labor and low birth weight. Avoid use unless benefit outweighs risks.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

Coadministration with strong CYP3A inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) due to decreased CRENESSITY exposure.

Clinical Precautions

Precautions

Hepatotoxicity: monitor liver enzymes; severe skin and hypersensitivity reactions; risk of treatment failure with CXCR4-tropic virus; embryo-fetal toxicity (use effective contraception).

Clinical Tips & Counseling

Drug interactions

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