Lupkynis (Voclosporin): Benefits, Dosage, Side Effects & Safety Tips

What is Lupkynis?

Lupkynis is an oral drug developed to treat lupus nephritis (LN), a serious kidney complication of lupus. It offers better drug absorption and stability compared to older treatments. It’s taken orally alongside other immunosuppressive medications. Adding voclosporin to background therapy helps patients reach their target urine protein levels more effectively at 3, 6, and 12 months. The U.S. FDA approved it in 2021 for adults with biopsy-proven LN (class III, IV, or V).^1,2

Composition Analysis: Voclosporin as the Active Agent 

Chemical class: Cyclosporine A analogue^1,2

Voclosporin is a novel calcineurin inhibitor (CNI) and serves as the active pharmaceutical ingredient in lupkynis. It is a structural analog of cyclosporine A, with a modification at the amino acid 1 residue, which enhances its potency and improves its pharmacokinetic profile. Compared to older CNIs like cyclosporine, tacrolimus, and sirolimus, voclosporin offers more consistent drug levels and better predictability. Its optimized structure plays a key role in helping manage lupus nephritis more effectively when used alongside background immunosuppressive therapy.^1,2

Mechanism of Action and Pharmacological Impact 

Voclosporin works by binding to a protein called cyclophilin A in T-cells. This binding blocks another protein, calcineurin, from activating NFAT (nuclear factor of activated T-cells), which normally triggers the production of cytokines like interleukin-2 (IL-2). IL-2 helps T-cells grow and multiply, so by stopping its production, voclosporin reduces the immune system's overactivity. ²

Voclosporin also helps protect the kidneys by stabilizing the structure of podocytes, specialized kidney cells. Normally, activated calcineurin leads to the breakdown of a protein called synaptopodin, which weakens the podocyte structure and causes protein loss in urine (proteinuria). Voclosporin prevents this breakdown, helping reduce proteinuria. ²

Its unique chemical structure allows it to be more potent, better absorbed, and cleared more efficiently, which means blood level monitoring isn’t needed.²

Recommended Dosage and Use Instructions¹ 

LUPKYNIS should be taken whole on an empty stomach, around the same time every 12 hours, with at least 8 hours between doses. If a dose is missed, it can be taken within 4 hours; otherwise, skip it and take the next dose as scheduled, never double up. Grapefruit or grapefruit juice should be avoided while on LUPKYNIS.

Before starting treatment, estimated glomerular filtration rate (eGFR) and blood pressure (BP) is assessed. Do not start LUPKYNIS if eGFR is ≤45 mL/min/1.73 m² unless benefits outweigh risks, or if BP is >165/105 mmHg or there's a hypertensive emergency.

The starting dose is 23.7 mg orally twice a day, alongside MMF and corticosteroids. Check eGFR every 2 weeks in the first month, then monthly.

   - If eGFR drops by >20% and <30% from baseline, reduce dose by 7.9 mg twice daily.

   - If the drop is ≥30%, stop treatment. Re-start only if eGFR recovers to ≥80% of baseline, at a lower dose (7.9 mg twice daily).

   - If eGFR recovers, increase dose by 7.9 mg twice daily per improvement (≥80%), without exceeding the original dose.

BP is monitored every 2 weeks during the first month and as needed later. If BP exceeds 165/105 mmHg or in hypertensive emergency, stop treatment and manage BP.

If no clear benefit is seen by 24 weeks, consider stopping treatment. Long-term use beyond one year should weigh risks vs. benefits, particularly around kidney toxicity.

Dose adjustments:

   - Severe renal impairment: 15.8 mg twice daily

   - Mild to moderate liver impairment: 15.8 mg twice daily

Risk Warnings and Medical History Review¹

LUPKYNIS is contraindicated in patients who are taking strong CYP3A4 inhibitors (such as ketoconazole, itraconazole, or clarithromycin) and in those with known serious or severe hypersensitivity to the drug or its excipients.

Caution is advised due to the risk of nephrotoxicity. Renal function should be closely monitored, and dose adjustments may be required. Hypertension may occur and might require treatment with antihypertensives.

Neurotoxicity has been reported. Patients should be observed for neurological symptoms, and the dose should be reduced or discontinued if needed. Hyperkalemia has been observed and may be worsened when used with other potassium-elevating agents. Serum potassium levels should be regularly checked.

QT prolongation has been noted, especially in high-risk individuals. Electrocardiograms and electrolyte levels should be monitored accordingly. Live vaccines should be avoided during treatment.

Cases of pure red cell aplasia have been reported and may require discontinuation of therapy.

Potential Side Effects and What to Watch For

The most commonly reported adverse reactions (occurring in ≥3% of patients) included decreased glomerular filtration rate, hypertension, diarrhea, headache, anemia, cough, urinary tract infection, upper abdominal pain, dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue, acute kidney injury, and decreased appetite.¹

Electrolyte imbalances such as high potassium or low magnesium levels may occur, which in some cases can affect heart rhythm. Mild liver enzyme elevations have been observed, though serious liver injury is rare. Therefore, it’s important to monitor kidney function, blood pressure, and electrolyte levels regularly during treatment.²

Handling, Storage, and Safe Administration 

LUPKYNIS capsules are to be swallowed whole and must not be opened, crushed, or divided. The medication should be taken on an empty stomach consistently, with doses spaced as close to 12 hours apart as possible, and with a minimum interval of 8 hours between doses.¹

Capsules are provided in child-resistant packaging to prevent accidental ingestion.
 The medication must be stored at controlled room temperature (20ºC to 25ºC / 68ºF to 77ºF), with permissible excursions between 15ºC and 30ºC (59ºF to 86ºF). Capsules must be kept in their original packaging and not transferred to another container.¹

Lupkynis vs. Other Immunomodulators

Voclosporin stands out among immunosuppressive treatments for lupus nephritis because of its more predictable pharmacokinetics compared to older calcineurin inhibitors like cyclosporine and tacrolimus. This means doctors don't need to monitor blood levels of the drug as closely, making it easier to manage in clinical practice. When added to a standard lupus nephritis regimen of mycophenolate mofetil and corticosteroids, voclosporin has shown encouraging results, helping patients achieve better kidney response rates. It’s also associated with a potentially more favorable side effect profile.^1-3

How to Access Lupkynis in India via the Named Patient Program 

Lupkynis is not yet commercially available in India but can be procured through a Named Patient Program (NPP) under government regulations.

Rx4U offers end-to-end support for procuring Lupkynis via NPP:

   - Assistance with form submissions

   - Coordination with global suppliers for authentic Aurinia-manufactured Lupkynis

   - Logistics, customs clearance, and delivery

   - Ongoing patient support and prescription verification

   - Contact Rx4U today to start your Named Patient import process and ensure timely access to Lupkynis.

Summary: What Makes Lupkynis Effective

Lupkynis combines potent calcineurin inhibition with podocyte stabilization, achieving rapid and sustained renal responses in active lupus nephritis. Its predictable pharmacokinetics, lower metabolite nephrotoxicity, and steroid-sparing potential distinguish it from traditional CNIs and other immunomodulators.^1,2

FAQs About Lupkynis

1. Can I take Lupkynis with other immunosuppressants?
Yes, it is approved only in combination with mycophenolate mofetil and low-dose corticosteroids.^1,2

2. What monitoring is required?
eGFR every 2 weeks initially, then monthly; blood pressure at each visit; periodic CBC and liver enzymes.^1,2

3. How do I import Lupkynis into India?
Through a Named Patient Program with Rx4U assistance for documentation, regulatory approval, and supply chain management.

Note:

The information provided is for education purpose only and is subjected to prescribing information of the drug and the guidance of your treating physician. Always consult your health care provider before making any medical decision for starting your treatment.

Disclaimer:

Rx4U procures prescribed medicines directly from manufacturers or authorized distributors. It does not claim ownership of any trademarks and complies with the provisions of the Trademark Act, 1999, particularly Sections 30 and 30(1) concerning ‘Fair Use’. It solely facilitates access to new launches through named patient import.

Reference:

1. S. Food and Drug Administration. LUPKYNIS (voclosporin) capsules [prescribing information]. FDA; January 22, 2021. Accessed July 24, 2025.
2. Shah VR, Bankole A. Voclosporin. [Updated 2023 Jun 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK592419/
3. McArn AC, Nixon AR, Jarrell KL. Voclosporin: A Novel Calcineurin Inhibitor for the Treatment of Lupus Nephritis. Ann Pharmacother. Published online February 15, 2022. doi:10.1177/10600280221075331