Important Administration Instructions

• LUPKYNIS capsules must be swallowed whole and must not be opened, crushed, or divided.
• LUPKYNIS should be taken on an empty stomach consistently as close to a 12-hour schedule as possible, and with a minimum of 8 hours between doses.
• 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.
• Instruct patients to avoid eating grapefruit or drinking grapefruit juice while taking LUPKYNIS [see Drug Interactions ( 7.1)] .

Prior to Initiating LUPKYNIS Therapy

Establish an accurate baseline estimated glomerular filtration rate (eGFR). Use of LUPKYNIS is not recommended in patients with a baseline eGFR ≤45 mL/min/1.73 m 2 unless the benefit exceeds the risk; these patients may be at increased risk for acute and/or chronic nephrotoxicity [see Warnings and Precautions ( 5.3)] .

Check blood pressure (BP) at baseline. Do not initiate LUPKYNIS in patients with BP >165/105 mmHg or with hypertensive emergency [see Warnings and Precautions ( 5.4)] .

Dosage Recommendations

The recommended starting dose of LUPKYNIS is 23.7 mg twice a day.

Use LUPKYNIS in combination with mycophenolate mofetil (MMF) and corticosteroids [see Clinical Studies ( 14)] .

Safety and efficacy of LUPKYNIS have not been established in combination with cyclophosphamide. Use of LUPKYNIS is not recommended in this situation.

Dosage of LUPKYNIS is based on the patient’s eGFR. Modify LUPKYNIS dosage based on eGFR [see Warnings and Precautions ( 5.3)] :

• Assess eGFR every two weeks for the first month, and every four weeks thereafter.
• If eGFR <60 mL/min/1.73 m 2 and reduced from baseline by >20% and <30%, reduce the dose by 7.9 mg twice a day. Re-assess eGFR within two weeks; if eGFR is still reduced from baseline by >20%, reduce the dose again by 7.9 mg twice a day.
• If eGFR <60 mL/min/1.73 m 2 and reduced from baseline by ≥30%, discontinue LUPKYNIS. Re-assess eGFR within two weeks; consider re-initiating LUPKYNIS at a lower dose (7.9 mg twice a day) 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 7.9 mg twice a day for each eGFR measurement that is ≥80% of baseline; do not exceed the starting dose.

Monitor blood pressure every two weeks for the first month after initiating LUPKYNIS, and as clinically indicated thereafter [see Warnings and Precautions ( 5.4)] . For patients with BP >165/105 mmHg or with hypertensive emergency, discontinue LUPKYNIS and initiate antihypertensive therapy.

If the patient does not experience therapeutic benefit by 24 weeks, consider discontinuation of LUPKYNIS.

Safety and efficacy have not been established beyond one year [see Clinical Trials Experience ( 6.1) and Clinical Studies ( 14)] . Consider the risks and benefits of longer durations of treatment in light of the patient’s treatment response and risk of worsening nephrotoxicity [see Warnings and Precautions ( 5.3)] .

Dosage Recommendations in Patients with Renal and Hepatic Impairment

Use of LUPKYNIS is not recommended in patients with a baseline eGFR ≤45 mL/min/1.73 m 2 unless the benefit exceeds the risk; LUPKYNIS has not been studied in patients with a baseline eGFR ≤45 mL/min/1.73 m 2. If used in patients with severe renal impairment at baseline, the recommended starting dose is 15.8 mg twice a day [see Use in Specific Populations ( 8.6) and Clinical Pharmacology ( 12.3)] .

In patients with mild and moderate hepatic impairment (Child-Pugh A and Child-Pugh B), the recommended dose is 15.8 mg twice daily. LUPKYNIS is not recommended to be used in patients with severe hepatic impairment (Child-Pugh C) [see Use in Specific Populations ( 8.7) and Clinical Pharmacology ( 12.3)] .

Dosage Adjustments due to Drug Interactions

When co-administering LUPKYNIS with moderate CYP3A4 inhibitors (e.g., verapamil, fluconazole, diltiazem), reduce LUPKYNIS daily dosage to 15.8 mg in the morning and 7.9 mg in the evening. No dose adjustment of LUPKYNIS is recommended when LUPKYNIS is co-administered with mild CYP3A4 inhibitors [see Drug Interactions ( 7.1) and Clinical Pharmacology ( 12.3)] .