LUPKYNIS Soft capsule Ref.[50195] Active ingredients: Voclosporin

Lupkynis treatment should be initiated and supervised by a qualified physician experienced in the diagnosis and treatment of lupus nephritis.

Posology

The recommended dose is 23.7 mg (three 7.9 mg soft capsules), twice daily.

It is recommended that Lupkynis is administered consistently as close to a 12-hour schedule as possible and with a minimum of 8 hours between each dose. If a dose is missed, it should be taken as soon as possible within 4 hours after missing the dose; beyond the 4-hour time frame, the next regular dose should be taken at the usual scheduled time. The next dose should not be doubled.

Lupkynis should be used in combination with mycophenolate mofetil.

Physicians should evaluate the efficacy of treatment at a time point of at least 24 weeks and make an appropriate risk-benefit analysis for continuation of therapy.

Dose adjustment based on eGFR

It is recommended to establish a baseline estimated glomerular filtration rate (eGFR) before starting treatment with voclosporin, and assess every two weeks for the first month, and every four weeks thereafter.

Dose adjustments are required for those individuals whose eGFR is confirmed to be reduced (i.e., two consecutive assessments within 48 hours) and below 60 mL/min/1.73 m². If eGFR remains ≥60 mL/min/1.73 m² no dose modification is required (see table 1).

Table 1. Recommended dose adjustments based on eGFR:

¹ If eGFR remains ≥60 mL/min/1.73 m² no action is required

It is recommended that patients requiring a reduction in dose are reassessed for eGFR recovery within two weeks. For patients that had a decrease in dose due to eGFR reduction, increasing the dose by 7.9 mg twice a day for each eGFR measurement that is ≥80% of baseline should be considered; the starting dose should not be exceeded.

Co-administration with moderate CYP3A4 inhibitors

When co-administering Lupkynis with moderate cytochrome P450 (CYP)3A4 inhibitors (e.g., verapamil, fluconazole, diltiazem), daily dose must be reduced to 15.8 mg in the morning and 7.9 mg in the evening (see section 4.5).

Hepatic impairment

In patients with mild and moderate hepatic impairment (Child-Pugh Class A and B, respectively), the recommended starting dose is 15.8 mg twice daily. The effect of voclosporin in patients with severe hepatic impairment (Child-Pugh Class C) has not been assessed and voclosporin is not recommended in this patient population (see sections 4.4 and 5.2).

Renal impairment

Careful monitoring of renal function is recommended (see table 1 and section 4.4). Limited data are available on the use of Lupkynis in patients with baseline eGFR 30 to <45 mL/min/1.73 m². It is recommended to use Lupkynis in these patients, only if the benefit outweighs the risk, and at a starting dose of 23.7 mg twice daily.

Lupkynis has not been studied in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) and is not recommended in these patients unless the benefit outweighs the risk. If used, the recommended starting dose is 15.8 mg twice daily (see section 5.2).

Elderly

Data are limited in LN patients >65 years, and there are no data in patients aged >75 years. Lupkynis is not recommended in patients >75 years of age (see section 5.2).

Paediatric population

The safety and efficacy of Lupkynis in children and adolescents aged 5 to 18 years have not yet been established. No data are available.

There is no relevant use of Lupkynis in children below the age of 5 years in lupus nephritis.

Method of administration

Oral use.

The soft capsules must be swallowed whole and can be taken with or without food.

It is recommended not to take Lupkynis with grapefruit or grapefruit juice (see section 4.5).

Cases of accidental overdose have been reported with voclosporin; symptoms included tremor and tachycardia. In an interaction study in healthy volunteers, co-administration of ketoconazole and voclosporin resulted in an 18.6-fold increase in voclosporin exposure and increases in serum creatinine, decreases in serum magnesium and increases in blood pressure were observed. Symptoms of overdose with other calcineurin inhibitors (but not observed with voclosporin) include headache, nausea and vomiting, infections, urticaria, lethargy, changes in electrolyte levels and increases in blood urea nitrogen, and alanine aminotransferase.

No specific antidote to voclosporin therapy is available. If overdose occurs, general supportive measures and symptomatic treatment should be conducted, including temporarily stopping treatment with voclosporin and assessing blood urea nitrogen, serum creatinine, eGFR and alanine aminotransferase levels.

3 years.

Store in the original blister in order to protect from moisture.

Soft capsules are available in cold-formed aluminium blisters, laminated backing and lidding materials that are thermo-sealed together. Each blister contains 18 soft capsules. One carton contains 180 or 576 soft capsules.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.