LUPKYNIS Dosage & Rx Info | Uses, Side Effects

Lupkynis Generic Name & Formulations

Legal Class

General Description

Voclosporin 7.9mg; soft gel caps; contains alcohol.

Pharmacological Class

Immunosuppressant (calcineurin-inhibitor).

How Supplied

Caps—60, 180

Storage

Store at controlled room temperature 20ºC to 25ºC (68ºF to 77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF).

Do not put Lupkynis in another container. Keep capsules in their original packaging until ready to be taken.

Manufacturer

Aurinia Pharmaceuticals Inc.

Generic Availability

Mechanism of Action

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.

Lupkynis Indications

Indications

Treatment of active lupus nephritis in combination with a background immunosuppressive therapy regimen.

Limitations of Use

Not recommended in combination with cyclophosphamide, as safety and efficacy have not been established.

Lupkynis Dosage and Administration

Adult

See full labeling. Swallow whole. Take on an empty stomach. Initially 23.7mg twice daily (approx. 12hrs apart) in combination with mycophenolate mofetil and corticosteroids. Adjust dose based on eGFR. If eGFR <60mL/min/1.73m² and reduced by >20% and <30% from baseline, reduce dose by 7.9mg twice daily. Reassess within 2 weeks; if eGFR is still reduced by >20% from baseline, reduce the dose again by 7.9mg twice daily. Discontinue if eGFR <60mL/min/1.73m² and reduced by ≥30% from baseline. Reassess within 2 weeks; consider re-initiating at a lower dose (7.9mg twice daily) only if eGFR has returned to ≥80% of baseline. For patients that had a decrease in dose due to eGFR, consider increasing the dose by 7.9mg twice daily for each eGFR measurement that is ≥80% of baseline; do not exceed the starting dose. All: if no therapeutic benefit by 24 weeks, consider treatment discontinuation. Severe renal impairment or mild/moderate hepatic impairment: 15.8mg twice daily. Concomitant moderate CYP3A4 inhibitors: reduce to 15.8mg in the AM and 7.9mg in the PM.

Children

Not established.

Lupkynis Contraindications

Contraindications

Concomitant strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin).

Lupkynis Boxed Warnings

Boxed Warning

Malignancies. Serious infections.

Lupkynis Warnings/Precautions

Warnings/Precautions

Increased risk of lymphomas, other malignancies (eg, skin). Avoid or limit sun exposure, UV light; examine for skin changes. Increased risk of infections (eg, bacterial, viral, fungal, protozoal), opportunistic infections, including cytomegalovirus, herpes zoster; monitor. Obtain eGFR at baseline; monitor every 2 weeks for the 1^st month, every 4 weeks through the 1^st year, and then quarterly thereafter. Consider dose reduction or discontinuation with decreases in eGFR from baseline; if persistent, evaluate for chronic nephrotoxicity. Check BP at baseline; do not initiate if BP >165/105mmHg or with hypertensive emergency. Monitor BP every 2 weeks for the 1^st month after initiation, then as clinically indicated. Treat new-onset or exacerbations of pre-existing hypertension. Consider discontinuation if increases in BP is not manageable with dose reduction or other appropriate intervention. Monitor for neurologic symptoms (eg, tremors, paresthesias, headache, mental status changes, others); consider dose reduction or discontinuation if neurotoxicity occurs. Monitor serum potassium periodically during treatment. Consider discontinuing if pure red cell aplasia is diagnosed. Severe hepatic impairment (Child-Pugh C): avoid. Renal impairment (eGFR ≤45mL/min/1.73m): not recommended. Elderly. Pregnancy: avoid. Nursing mothers.

Lupkynis Pharmacokinetics

Absorption

Median time to maximum concentration: 1.5 hours (range: 1–4 hours).

Distribution

Volume of distribution: 2154 L. Plasma protein bound: 97%.

Metabolism

Hepatic (CYP3A4).

Elimination

Fecal (92.7%), renal (2.1%). Half-life: ~30 hours. Clearance: 63.6 L/h.

Lupkynis Interactions

Interactions

See Contraindications. Potentiated by strong or moderate CYP3A4 inhibitors. Concomitant moderate CYP3A4 inhibitors (eg, verapamil, fluconazole, diltiazem); reduce dose (see Adults). Antagonized by strong or moderate CYP3A4 inducers (eg, rifampin, efavirenz); avoid concomitant use. Avoid live attenuated vaccines (eg, intranasal flu, measles, mumps, rubella, others), grapefruit or grapefruit juice. Concomitant with inactivated vaccines may not be sufficiently immunogenic. Increased risk of nephrotoxicity with nephrotoxic drugs. Increased risk of torsade de pointes with drugs that prolong the QTc interval. Concomitant drugs associated with hyperkalemia (eg, potassium-sparing diuretics, ACE inhibitors, ARBs); monitor. Potentiates P-gp substrates (eg, digoxin); reduce dose of substrate if needed. May potentiate OATP1B1/OATP1B3 substrates (eg, statins); monitor and reduce substrate dose.

Lupkynis Adverse Reactions

Adverse Reactions

GFR decreased, hypertension, diarrhea, headache, anemia, cough, UTI, upper abdominal pain, dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue, tremor, acute kidney injury, decreased appetite; hyperkalemia, QTc prolongation, pure red cell aplasia.

Lupkynis Clinical Trials

See Literature

Lupkynis Note

Not Applicable

Lupkynis Patient Counseling