Voclosporin

Calcineurin Inhibitor (cyclic Peptide / Cyclosporin Analogue)Rx: PrescriptionCompound: Approved

Also known as: Cyclosporin analogue C, ISA-247, ISA247, Lupkynis

Educational Only — Not medical advice. Consult a qualified clinician before using any peptide.

Summary

Voclosporin (Lupkynis) is a next-generation calcineurin inhibitor derived from cyclosporin A with a single amino acid modification that enhances potency and provides a more predictable pharmacokinetic profile. It is approved in combination with mycophenolate mofetil and low-dose steroids for the treatment of active lupus nephritis (LN) in adults.

Mechanism of Action

Binds cyclophilin A to form a complex that inhibits calcineurin phosphatase activity, thereby blocking T-cell activation and IL-2 production; also stabilizes the podocyte cytoskeleton by inhibiting synaptopodin degradation

Routes of Administration

Oral

Goals & Uses

  • T-cell immunosuppressionImmunologyHigh
  • IgA nephropathy (investigational)RenalLow
  • Proteinuria reductionRenalHigh
  • Podocyte stabilizationRenalModerate
  • Lupus nephritis treatmentAutoimmune / RenalHigh

Contraindications

  • Live vaccinesVaccinationModerate
  • Active serious infectionsInfectiousHigh
  • Hypersensitivity to voclosporin or cyclosporin analoguesAllergyHigh
  • Severe renal impairment or eGFR <45 mL/min/1.73m² at initiationRenalHigh
  • Concurrent use of strong CYP3A4 inhibitorsDrug InteractionHigh

Adverse Effects

  • HypertensionCardiovascularCommonHigh blood pressure
  • HeadacheNeurologicCommonPain in the head or upper neck
  • TremorNeurologicUncommonInvoluntary shaking
  • Urinary tract infectionGenitourinaryCommon
  • HyperkalemiaElectrolyte ImbalanceCommon
  • Nephrotoxicity / decreased eGFRRenalCommon

Drug Interactions

  • Strong CYP3A4 inducers (e.g., rifampin, carbamazepine)High
  • Potassium-sparing diuretics / ACE inhibitors / ARBsModerate
  • Moderate CYP3A4 inhibitors (e.g., fluconazole, diltiazem)Moderate
  • Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin)High
  • Nephrotoxic agents (e.g., NSAIDs, aminoglycosides)Moderate

Population Constraints

  • PregnancyReproductive SafetyRelative
  • Pediatric patients (<18 years)AgeRelative
  • Patients with active or chronic serious infectionsInfectionRelative
  • Severe hepatic impairmentOrgan ImpairmentRelative
  • BreastfeedingReproductiveRelative

Regulatory Status

  • European UnionApprovedApproved: Active lupus nephritis in adults (in combination with mycophenolate mofetil and corticosteroids)EMA approved September 2022 under the brand name Lupkynis
  • United StatesApprovedApproved: Active lupus nephritis in adults (in combination with mycophenolate mofetil and low-dose corticosteroids)FDA approved January 22, 2021; first oral calcineurin inhibitor approved specifically for lupus nephritis
  • United KingdomApprovedApproved: Active lupus nephritis in adultsMHRA approved following EMA decision; marketed as Lupkynis in the UK

FDA approved January 2021 for lupus nephritis; EMA approved September 2022. Not indicated for transplant rejection prophylaxis. REMS not required but close monitoring of renal function and blood pressure recommended.

Evidence & Sources

No sources recorded yet.

Browse All PeptidesBuild My Stack