LUPKYNIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LUPKYNIS (LUPKYNIS).
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.
| 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. |
| Molecular Weight | 525.6 |
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. |
| 1st trimester | Teratogenic in animal studies; human data limited; avoid unless benefit outweighs risk. |
| 2nd trimester | May cause fetal harm; use only if clearly needed. |
| 3rd trimester | May cause neonatal immunosuppression; avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for LUPKYNIS (LUPKYNIS).
| Placental transfer | Crosses placenta in animal studies; human data suggest transfer. |
| Breastfeeding | Excreted in human milk; potential for serious adverse reactions in nursing infants. Discontinue drug or discontinue nursing. |
| Lactation Rating | L5 (Contraindicated) |
■ FDA Black Box Warning
Increased risk of infection and lymphoma; increased risk of nephrotoxicity and hypertension; increased risk of neurotoxicity.
| Serious Effects |
Severe hepatic impairmentConcomitant use with strong CYP3A4 inducersHypersensitivity to voclosporin or any excipient
| 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. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they increase voclosporin exposure. No other specific food interactions are known. |
Loading safety data…
| 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. |
| Fetal Monitoring | Monitor maternal blood pressure and renal function (serum creatinine, eGFR) throughout pregnancy. Monitor fetal growth via serial ultrasounds due to potential for intrauterine growth restriction (IUGR). Check calcineurin inhibitor trough levels (if applicable) as pregnancy may alter pharmacokinetics. |
| Fertility Effects | No dedicated human studies. Animal studies showed no impairment of male or female fertility at clinically relevant exposures. However, calcineurin inhibitors may cause reversible amenorrhea or oligospermia based on class effects. |
| Clinical Pearls | Monitor for hematuria, proteinuria, and eGFR during treatment. Lupkynis (voclosporin) is a calcineurin inhibitor; do not co-administer with other CNIs or strong CYP3A4 inhibitors. Reduce dose in patients with eGFR <45 mL/min per 1.73 m². Concomitant use with mycophenolate mofetil and corticosteroids is standard. Check blood pressure and serum potassium regularly. Live vaccines contraindicated. |
| Patient Advice | Take exactly as prescribed; do not stop or change dose without consulting your doctor. · You will need regular blood and urine tests to monitor kidney function and drug levels. · Report any signs of infection (fever, sore throat), high blood pressure (severe headache, vision changes), or changes in urine output/color. · Avoid grapefruit and grapefruit juice during treatment. · Do not receive live vaccines while taking this medication. · Use effective contraception during treatment and for 12 weeks after last dose if of childbearing potential. · Tell your doctor about all medications, including over-the-counter drugs and supplements. |