SARENIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SARENIN (SARENIN).

How it works

SARENIN is a novel small molecule inhibitor of the NLRP3 inflammasome, blocking its assembly and subsequent IL-1β and IL-18 release. This reduces sterile inflammation in autoimmune and autoinflammatory diseases.

What the body does with it

Metabolism	Not extensively metabolized; primarily excreted unchanged in urine (70-80%). Minor hepatic metabolism via CYP3A4 to inactive metabolites.
Excretion	Primarily renal excretion (70-80% unchanged), with 15-20% biliary/fecal elimination; total clearance correlates with creatinine clearance.
Half-life	12-15 hours in healthy adults; prolonged to 24-30 hours in moderate renal impairment (CrCl 30-50 mL/min) and up to 48 hours in ESRD requiring dose adjustment.
Protein binding	99% bound to albumin and alpha-1 acid glycoprotein.
Volume of Distribution	0.3-0.5 L/kg, indicating distribution into plasma and extracellular fluid with limited tissue penetration.
Bioavailability	Oral: 60-75% (first-pass metabolism 20-30%); food reduces absorption by 20%; IV: 100%.
Onset of Action	Oral: 1-2 hours; intravenous: 5-10 minutes; peak effect by 4-6 hours (oral) and 1-2 hours (IV).
Duration of Action	12-24 hours based on once-daily dosing; therapeutic effect persists for 24 hours in steady state; longer duration in renal impairment.

Classification & Brands

Dosing & administration

Intravenous: 10 mg loading dose over 30 minutes, followed by 2 mg/hour continuous infusion. Adjust infusion rate based on blood pressure response. Oral: 25 mg twice daily.

Dosage form	INJECTABLE
Renal impairment	GFR 30-59 mL/min: Reduce oral dose by 50%. GFR 15-29 mL/min: Reduce oral dose by 75%. GFR <15 mL/min: Not recommended. For IV dosing, no adjustment needed for single dose, but infusion rate should be reduced by 50% for GFR <60 mL/min.
Liver impairment	Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce oral dose by 50%; IV loading dose same, infusion rate reduced by 50%. Child-Pugh Class C: Contraindicated.
Pediatric use	Weight ≤20 kg: 0.2 mg/kg IV loading dose over 30 minutes, followed by 0.02 mg/kg/hour continuous infusion. Weight >20 kg: Same as adult dosing.
Geriatric use	Start with 50% of adult dose (oral 12.5 mg twice daily; IV loading dose 5 mg over 30 minutes, infusion rate 1 mg/hour). Titrate slowly to avoid hypotension.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SARENIN (SARENIN).

Breastfeeding	Present in human milk; M/P ratio unknown. Not recommended during breastfeeding due to potential adverse effects (e.g., bradycardia, hypotension).
Teratogenic Risk	First trimester: Limited human data; animal studies show embryotoxicity at supratherapeutic doses. Second trimester: Suggested increased risk of intrauterine growth restriction. Third trimester: Risk of fetal bradycardia and hypoglycemia due to placental transfer.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Black Box Warning: Increased risk of severe infections including tuberculosis (TB), invasive fungal infections, and other opportunistic pathogens. Perform TB screening prior to initiation; monitor for infections during therapy.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to SARENIN or any excipient; concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole); severe hepatic impairment (Child-Pugh C); active serious infection (including TB), untreated latent TB; live vaccination during therapy.

Clinical Precautions

Precautions

Hypersensitivity reactions (including anaphylaxis); avoid live vaccines; hematologic effects (neutropenia, thrombocytopenia); hepatotoxicity; pregnancy/lactation; increased infection risk; prior to starting, screen for TB and test for latent infections.

Clinical Tips & Counseling

Drug interactions

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SARENIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SARENIN (SARENIN).

How it works

What the body does with it

Metabolism	Not extensively metabolized; primarily excreted unchanged in urine (70-80%). Minor hepatic metabolism via CYP3A4 to inactive metabolites.
Excretion	Primarily renal excretion (70-80% unchanged), with 15-20% biliary/fecal elimination; total clearance correlates with creatinine clearance.
Half-life	12-15 hours in healthy adults; prolonged to 24-30 hours in moderate renal impairment (CrCl 30-50 mL/min) and up to 48 hours in ESRD requiring dose adjustment.
Protein binding	99% bound to albumin and alpha-1 acid glycoprotein.
Volume of Distribution	0.3-0.5 L/kg, indicating distribution into plasma and extracellular fluid with limited tissue penetration.
Bioavailability	Oral: 60-75% (first-pass metabolism 20-30%); food reduces absorption by 20%; IV: 100%.
Onset of Action	Oral: 1-2 hours; intravenous: 5-10 minutes; peak effect by 4-6 hours (oral) and 1-2 hours (IV).
Duration of Action	12-24 hours based on once-daily dosing; therapeutic effect persists for 24 hours in steady state; longer duration in renal impairment.

Classification & Brands

Dosing & administration

Intravenous: 10 mg loading dose over 30 minutes, followed by 2 mg/hour continuous infusion. Adjust infusion rate based on blood pressure response. Oral: 25 mg twice daily.

Dosage form	INJECTABLE
Renal impairment	GFR 30-59 mL/min: Reduce oral dose by 50%. GFR 15-29 mL/min: Reduce oral dose by 75%. GFR <15 mL/min: Not recommended. For IV dosing, no adjustment needed for single dose, but infusion rate should be reduced by 50% for GFR <60 mL/min.
Liver impairment	Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce oral dose by 50%; IV loading dose same, infusion rate reduced by 50%. Child-Pugh Class C: Contraindicated.
Pediatric use	Weight ≤20 kg: 0.2 mg/kg IV loading dose over 30 minutes, followed by 0.02 mg/kg/hour continuous infusion. Weight >20 kg: Same as adult dosing.
Geriatric use	Start with 50% of adult dose (oral 12.5 mg twice daily; IV loading dose 5 mg over 30 minutes, infusion rate 1 mg/hour). Titrate slowly to avoid hypotension.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SARENIN (SARENIN).

Breastfeeding	Present in human milk; M/P ratio unknown. Not recommended during breastfeeding due to potential adverse effects (e.g., bradycardia, hypotension).
Teratogenic Risk	First trimester: Limited human data; animal studies show embryotoxicity at supratherapeutic doses. Second trimester: Suggested increased risk of intrauterine growth restriction. Third trimester: Risk of fetal bradycardia and hypoglycemia due to placental transfer.
Fetal Monitoring