Calcineurin Inhibitor (CNI) — Cyclosporin Analogue Pregnancy: Avoid during treatment — no adequate human safety data; calcineurin inhibitors generally considered acceptable in pregnancy under specialist supervision but voclosporin specifically lacks data; teratogenicity not established.

Voclosporin (Calcineurin Inhibitor — Lupus Nephritis)

Brand names: Lupkynis

Adult dose

Dose: 23.7 mg oral three times daily (in combination with mycophenolate mofetil 2 g/day and low-dose glucocorticoids)

Route: Oral

Frequency: Three times daily (every 8 hours)

Max: 23.7 mg three times daily

Novel cyclosporin analogue with improved metabolic profile (does not increase blood pressure or LDL as much as standard cyclosporin). Used as triple therapy with MMF and low-dose steroids for active Class III/IV (±V) lupus nephritis. FDA and MHRA approved 2021. Dose reduced based on eGFR — suspend if eGFR falls >20% from baseline.

Paediatric dose

Route:

Not licensed in paediatrics.

Dose adjustments

Renal

Reduce dose to 15.8 mg TDS if eGFR 45–60 mL/min. Suspend if eGFR falls >20% from baseline. Avoid if eGFR <45 mL/min at baseline.

Hepatic

Avoid in severe hepatic impairment — primarily hepatically metabolised (CYP3A4).

Clinical pearls

AURORA-1 trial (Rovin et al. NEJM 2021): voclosporin + MMF + low-dose steroids vs MMF + high-dose steroids — complete renal response at 52 weeks: 41% vs 23% (significantly superior). This triple combination represents a paradigm shift: targeting both T-cell activation (voclosporin) and B-cell activation (MMF) simultaneously with steroid minimisation
Advantage over standard cyclosporin: voclosporin has a more predictable PK profile (consistent absorption, less food-effect), lower lipotoxicity profile (reduced LDL elevation), and less hypertension — important in SLE patients already at high CV risk
Triple therapy principle: the combination (voclosporin + MMF + steroids) works synergistically — CNI suppresses T-cells and has direct podocyte-stabilising effects (reduces proteinuria independently of immunosuppression); MMF targets B-cells and plasma cells; low-dose steroids suppress residual inflammation; three distinct mechanisms outperforming any two alone

Contraindications

Calcineurin inhibitor allergy
eGFR <45 mL/min at baseline
Concurrent strong CYP3A4 inhibitors (increases voclosporin levels — nephrotoxicity risk)
Concurrent live vaccines

Side effects

Nephrotoxicity (calcineurin inhibitor class effect — monitor eGFR; reduce dose if decline)
Hypertension (less than cyclosporin — key advantage)
Headache
Urinary tract infection
Hyperkalaemia
Anaemia
Lymphopenia

Interactions

Strong CYP3A4 inhibitors (azole antifungals, clarithromycin — significantly increase voclosporin levels; avoid or drastically reduce dose)
Strong CYP3A4 inducers (rifampicin, phenytoin — reduce voclosporin levels; avoid)
P-gp inhibitors (verapamil, amiodarone — increase voclosporin exposure)
Nephrotoxic agents (NSAIDs, aminoglycosides, contrast — additive nephrotoxicity)

Monitoring

eGFR and creatinine (before starting, then 2-weekly for first 3 months, monthly thereafter — dose reduction/suspension protocol)
Blood pressure
Serum potassium (hyperkalaemia)
Urinalysis (proteinuria — primary efficacy endpoint)
Anti-dsDNA and complement C3/C4 (disease activity)
Opportunistic infection surveillance

Reference: BNFc; BNF 90; Rovin et al. NEJM 2021 (AURORA-1 trial); FDA Lupkynis PI 2021; MHRA Approval 2022; BSR SLE Guidelines 2023. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways