Voclosporin (1 brand name, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- LUPKYNIS
Boxed Warning
Increased risk for developing malignancies and serious infections with LUPKYNIS or other immunosuppressants that may lead to hospitalization or death [see Warnings and Precautions ( 5.1, 5.2)].
Indications and Usage
LUPKYNIS is indicated in combination with a background immunosuppressive therapy regimen [see Clinical Studies ( 14)] for the treatment of adult patients with active lupus nephritis (LN). Limitations of Use: Safety and efficacy of LUPKYNIS have not been established in combination with cyclophosphamide. Use of LUPKYNIS is not recommended in this situation.
Contraindications
LUPKYNIS is contraindicated in: Patients concomitantly using strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) because these medications can significantly increase exposure to LUPKYNIS which may increase the risk of acute and/or chronic nephrotoxicity [see Warnings and Precautions ( 5.3), Drug Interactions ( 7.1), and Pharmacokinetics ( 12.3)] . Patients with a history of serious or severe hypersensitivity reaction, including anaphylaxis, to LUPKYNIS or any of its excipients [see Warnings and Precautions ( 5.8)] .
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Lymphoma and Other Malignancies [see Warnings and Precautions ( 5.1)] Serious Infections [see Warnings and Precautions ( 5.2)] Nephrotoxicity due to LUPKYNIS and Drug Interactions [see Warnings and Precautions ( 5.3)] Hypertension [see Warnings and Precautions ( 5.4)] Neurotoxicity [see Warnings and Precautions ( 5.5)] Hyperkalemia [see Warnings and Precautions ( 5.6)] QTc Prolongation [see Warnings and Precautions ( 5.7)] Hypersensitivity Reactions [see Warnings and Precautions ( 5.8)] Immunizations [see Warnings and Precautions ( 5.9 )] Pure Red Cell Aplasia [see Warnings and Precautions ( 5.10 )]
Mechanism of Action
LUPKYNIS is a calcineurin-inhibitor immunosuppressant. The mechanism of voclosporin suppression of calcineurin has not been fully established. Activation of lymphocytes involves an increase in intracellular calcium concentrations that bind to the calcineurin regulatory site and activate calmodulin binding catalytic subunit and through dephosphorylation activates the transcription factor, Nuclear Factor of Activated T-Cell Cytoplasmic (NFATc). The immunosuppressant activity results in inhibition of lymphocyte proliferation, T-cell cytokine production, and expression of T-cell activation surface antigens. Studies in animal models also support a non-immunological role for calcineurin inhibition in kidney function to stabilize actin cytoskeleton and stress fibers in podocytes leading to increased podocyte integrity in glomeruli.
Overdosage
Cases of accidental overdose have been reported with LUPKYNIS; symptoms may include tremor, headache, nausea and vomiting, infections, tachycardia, urticaria, lethargy, and increases in blood urea nitrogen, serum creatinine, and alanine aminotransferase levels. No specific antidote to LUPKYNIS therapy is available. If overdose occurs, general supportive measures and symptomatic treatment should be conducted, including stopping treatment with LUPKYNIS and assessing blood urea nitrogen, serum creatinine, eGFR and alanine aminotransferase levels. Consider contacting a poison center (1-800-222-1222) or medical toxicologist for advice and review of overdosage management recommendations.