Voclosporin

Brand Names: Lupkynis

Drug Class: Calcineurin Inhibitor Immunosuppressant

Overview

11 DESCRIPTION LUPKYNIS (voclosporin) capsules, a calcineurin-inhibitor immunosuppressant, is available for administration as soft gelatin capsules containing 7.9 mg voclosporin per capsule. Inactive ingredients include alcohol, Vitamin E polyethylene glycol succinate (NF), polysorbate 40 (NF), medium-chain triglycerides (NF), gelatin, sorbitol, glycerin, iron oxide yellow, iron oxide red,...

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 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.

Indications

  • 1 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. LUPKYNIS is a calcineurin-inhibitor immunosuppressant indicated in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis (LN).

Common Doses

  • 45 mL
  • 23.7 mg
  • 60 mL
  • 7.9 mg

Dosage

2 DOSAGE AND ADMINISTRATION Administration : LUPKYNIS must be swallowed whole on an empty stomach. ( 2.1 ) Administer consistently as close to a 12-hour schedule as possible, and with at least 8 hours between doses. ( 2.1 ) If a dose is missed, instruct the patient to take it as soon as possible within 4 hours after missing the dose. Beyond the 4-hour time frame, instruct the patient to wait until the usual scheduled time to take the next regular dose. Instruct the patient not to double the next dose. ( 2.

Black Box Warning

WARNING: MALIGNANCIES AND SERIOUS INFECTIONS 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 )]. WARNING: MALIGNANCIES AND SERIOUS INFECTIONS See full prescribing information for complete boxed warning. Increased risk for developing serious infections and malignancies with LUPKYNIS or other immunosuppressants that may lead to hospitalization or death. ( 5.1 , 5.2 )

Contraindications

  • 4 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 )] .

Side Effects

  • 6 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.

Interactions

  • 7 DRUG INTERACTIONS Moderate CYP3A4 inhibitors: Reduce LUPKYNIS daily dosage to 15.8 mg in the morning and 7.9 mg in the evening. ( 2.5 , 7.1 , 12.3 ) Strong and moderate CYP3A4 inducers: Avoid co-administration. ( 7.1 , 12.3 ) Certain P-gp substrates: Reduce dosage of certain P-gp substrates with a narrow therapeutic window when co-administered with LUPKYNIS. ( 7.2 , 12.3 ) 7.1 Effect of Other Drugs on LUPKYNIS Strong and Moderate CYP3A4 Inhibitors Voclosporin is a sensitive CYP3A4 substrate.