LUPKYNIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LUPKYNIS (LUPKYNIS).

How it works

Calcineurin inhibitor immunosuppressant that binds to cyclophilin A, inhibiting calcineurin activity, which prevents dephosphorylation and activation of nuclear factor of activated T-cells (NFAT), thereby reducing cytokine production and T-cell activation.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; minor contribution from CYP3A5.
Excretion	Primarily hepatic metabolism; <1% excreted unchanged in urine; approximately 66% of total radioactivity recovered in feces (mainly metabolites) and 22% in urine (mainly metabolites).
Half-life	Terminal elimination half-life approximately 30 hours; supports once-daily dosing; steady-state reached by day 4.
Protein binding	Greater than 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Apparent Vd/F ~24 L (approximately 0.34 L/kg assuming 70 kg); indicates distribution into tissues.
Bioavailability	Oral bioavailability approximately 35% (range 20–50%) under fasting conditions; high-fat meal reduces Cmax and AUC by about 50%.
Onset of Action	Oral: maximal urinary protein reduction observed within 4 weeks; initial decline in proteinuria as early as 2 weeks.
Duration of Action	Once-daily dosing maintains therapeutic effect; sustained reduction in proteinuria with continuous treatment; effect wanes after discontinuation.

Classification & Brands

Dosing & administration

23.7 mg orally twice daily with food.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for GFR ≥30 mL/min. Avoid use in severe renal impairment (GFR <30 mL/min) due to lack of data.
Liver impairment	Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose to 15.8 mg orally twice daily. Child-Pugh Class C: Not recommended.
Pediatric use	Safety and efficacy not established in pediatric patients; no approved dose.
Geriatric use	No specific dose adjustment required; monitor renal function due to age-related decline.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LUPKYNIS (LUPKYNIS).

Breastfeeding	It is unknown if voclosporin is excreted in human milk. In animal studies, voclosporin and its metabolites were detected in milk of lactating rats. No M/P ratio available for humans. Due to potential for serious adverse reactions in nursing infants, advise women not to breastfeed during treatment and for 4 weeks after last dose.
Teratogenic Risk	LUPKYNIS (voclosporin) is a calcineurin inhibitor. Based on animal studies, there is a risk of fetal harm in all trimesters. In rats and rabbits, voclosporin administration during organogenesis resulted in increased embryofetal mortality and reduced fetal weight at maternally toxic doses. There are no adequate human studies. Avoid use during pregnancy unless potential benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Increased risk of infection and lymphoma; increased risk of nephrotoxicity and hypertension; increased risk of neurotoxicity.

Side Effect Profile

Serious Effects

Absolute Contraindications

Concurrent use with chronic immunosuppressive therapies other than mycophenolate mofetil (MMF) or mycophenolic acid (MPA). Known hypersensitivity to voclosporin or any component of the formulation.

Clinical Precautions

Precautions

["Nephrotoxicity and hypertension require regular monitoring. Neurotoxicity including posterior reversible encephalopathy syndrome (PRES). Increased susceptibility to infections including opportunistic infections. Malignancies including lymphoma. Monitor for Epstein-Barr virus serology. Use with caution with CYP3A4 inhibitors and inducers. Avoid live vaccines."]

Clinical Tips & Counseling

Drug interactions

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LUPKYNIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LUPKYNIS (LUPKYNIS).

How it works

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; minor contribution from CYP3A5.
Excretion	Primarily hepatic metabolism; <1% excreted unchanged in urine; approximately 66% of total radioactivity recovered in feces (mainly metabolites) and 22% in urine (mainly metabolites).
Half-life	Terminal elimination half-life approximately 30 hours; supports once-daily dosing; steady-state reached by day 4.
Protein binding	Greater than 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Apparent Vd/F ~24 L (approximately 0.34 L/kg assuming 70 kg); indicates distribution into tissues.
Bioavailability	Oral bioavailability approximately 35% (range 20–50%) under fasting conditions; high-fat meal reduces Cmax and AUC by about 50%.
Onset of Action	Oral: maximal urinary protein reduction observed within 4 weeks; initial decline in proteinuria as early as 2 weeks.
Duration of Action	Once-daily dosing maintains therapeutic effect; sustained reduction in proteinuria with continuous treatment; effect wanes after discontinuation.

Classification & Brands

Dosing & administration

23.7 mg orally twice daily with food.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for GFR ≥30 mL/min. Avoid use in severe renal impairment (GFR <30 mL/min) due to lack of data.
Liver impairment	Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose to 15.8 mg orally twice daily. Child-Pugh Class C: Not recommended.
Pediatric use	Safety and efficacy not established in pediatric patients; no approved dose.
Geriatric use	No specific dose adjustment required; monitor renal function due to age-related decline.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LUPKYNIS (LUPKYNIS).

Breastfeeding	It is unknown if voclosporin is excreted in human milk. In animal studies, voclosporin and its metabolites were detected in milk of lactating rats. No M/P ratio available for humans. Due to potential for serious adverse reactions in nursing infants, advise women not to breastfeed during treatment and for 4 weeks after last dose.
Teratogenic Risk	LUPKYNIS (voclosporin) is a calcineurin inhibitor. Based on animal studies, there is a risk of fetal harm in all trimesters. In rats and rabbits, voclosporin administration during organogenesis resulted in increased embryofetal mortality and reduced fetal weight at maternally toxic doses. There are no adequate human studies. Avoid use during pregnancy unless potential benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Increased risk of infection and lymphoma; increased risk of nephrotoxicity and hypertension; increased risk of neurotoxicity.

Side Effect Profile

Serious Effects

Absolute Contraindications

Concurrent use with chronic immunosuppressive therapies other than mycophenolate mofetil (MMF) or mycophenolic acid (MPA). Known hypersensitivity to voclosporin or any component of the formulation.