lupkynis

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. ( 2.1 ) Instruct patients to avoid eating grapefruit or drinking grapefruit juice while taking LUPKYNIS. ( 2.1 , 7.1 ) Dosage Recommendations : Before initiating LUPKYNIS, establish an accurate baseline estimated glomerular filtration rate (eGFR) and check blood pressure (BP). 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. ( 2.2 , 5.3 ) Do not initiate LUPKYNIS in patients with baseline BP >165/105 mmHg or with hypertensive emergency. ( 2.2 , 5.4 ) Recommended starting dose: 23.7 mg orally, twice a day. ( 2.3 ) Use LUPKYNIS in combination with mycophenolate mofetil (MMF) and corticosteroids. ( 2.3 ) Modify the LUPKYNIS dose based on eGFR ( 2.3 , 5.3 ): Assess eGFR every two weeks for the first month, every four weeks through the first year, and…

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 )] The most commonly reported adverse reactions (≥3%) were: glomerular filtration rate decreased, hypertension, diarrhea, headache, anemia, cough, urinary tract infection, abdominal pain upper, dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue, tremor, acute kidney injury, and decreased appetite. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurinia Pharmaceuticals at 1-833-672-0028 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the…

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 )] . Patients concomitantly using strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin). ( 4 ) History of serious or severe hypersensitivity reaction, including anaphylaxis, to LUPKYNIS or any of its excipients. ( 4 )

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.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

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. Co-administration with strong or moderate CYP3A4 inhibitors increases voclosporin exposure [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of LUPKYNIS adverse reactions. Co-administration of LUPKYNIS with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) is contraindicated [see Contraindications ( 4 )] . Reduce LUPKYNIS dosage when co-administered with moderate CYP3A4 inhibitors (e.g., verapamil, fluconazole, diltiazem) [see Dosage and Administration ( 2.5 ] . Avoid food or drink containing grapefruit when taking LUPKYNIS. Strong and Moderate CYP3A4 Inducers Voclosporin is a sensitive CYP3A4 substrate. Co-administration with strong or moderate CYP3A4 inducers decreases voclosporin exposure [see Clinical Pharmacology ( 12.3 )] , which may decrease the efficacy of LUPKYNIS. Avoid co-administration of LUPKYNIS with strong or moderate CYP3A4 inducers. 7.2 Effect of LUPKYNIS on Other Drugs Certain P-gp Substrates Voclosporin is a P-gp inhibitor. Co-administration of voclosporin increases exposure of P-gp substrates [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of adverse reactions of these substrates. For certain P-gp substrates with a narrow therapeutic window, reduce the dosage of the substrate as recommended in its prescribing information, if needed. OATP1B1 Substrates Voclosporin is an inhibitor of OATP1B1 and OATP1B3 transporters. In one clinical study the concomitant administration of a single 40 mg dose of simvastatin with 23.7 mg BID voclosporin increased C max and AUC of the active metabolite simvastatin acid (an OATP1B1 substrate) by 3.1-fold and 1.8-fold, respectively [see Clinical Pharmacology ( 12.3 )] . Monitor for adverse reactions such as myopathy and rhabdomyolysis when OATP1B1/OATP1B3 substrates (e.g., simvastatin, atorvastatin, pravastatin, rosuvastatin, pitavastatin, fluvastatin) are used concomitantly with LUPKYNIS and reduce the dosage of these substrates as recommended in their prescribing information. For example, when taking LUPKYNIS with simvastatin, limit the simvastatin dosage to 20 mg daily, or 40 mg daily for patients who have previously tolerated simvastatin 80 mg daily for at least one year without evidence of muscle toxicity.