Voclosporin

CEILING: 23.7 mg twice daily is the SPC's recommended dose and its explicit ceiling — where a dose has been reduced for an eGFR fall, the SPC permits re-escalation by 7.9 mg twice a day for each eGFR measurement that is ≥ 80 % of baseline but states 'the starting dose should not be exceeded'. Treatment should be initiated and supervised by a qualified physician experienced in the diagnosis and treatment of lupus nephritis. Lupkynis should be used in combination with mycophenolate mofetil. MISSED DOSE: take as soon as possible within 4 hours of missing the dose; beyond 4 hours take the next regular dose at the usual scheduled time — the next dose should not be doubled. REVIEW: '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 BY eGFR (SPC table 1; establish a baseline eGFR before starting, then assess every two weeks for the first month and every four weeks thereafter; adjustments apply where a reduction is confirmed on two consecutive assessments within 48 hours and eGFR is below 60 mL/min/1.73 m²): ≥ 30 % reduction from baseline — stop administration, restart upon eGFR recovery at 7.9 mg (1 capsule) twice daily and increase as tolerated based on renal function; > 20 % and < 30 % reduction — reduce dose by 7.9 mg (1 capsule) twice daily, retest within two weeks and if the eGFR decrease has not recovered reduce by a further 7.9 mg (one capsule) twice daily; ≤ 20 % reduction — maintain current dose and monitor. If eGFR remains ≥ 60 mL/min/1.73 m² no dose modification is required. MODERATE CYP3A4 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. HEPATIC IMPAIRMENT: mild and moderate (Child-Pugh A and B) — recommended starting dose 15.8 mg twice daily; severe (Child-Pugh C) — not assessed and not recommended. RENAL IMPAIRMENT: limited data at baseline eGFR 30 to < 45 mL/min/1.73 m² — use only if the benefit outweighs the risk, at a starting dose of 23.7 mg twice daily; not studied at eGFR < 30 mL/min/1.73 m² and not recommended unless the benefit outweighs the risk, and if used the recommended starting dose is 15.8 mg twice daily. ELDERLY: data are limited above 65 years and there are no data above 75 years — not recommended in patients > 75 years of age. BLOOD PRESSURE (§4.4 table 2): systolic > 130 and ≤ 165 mmHg with diastolic > 80 and ≤ 105 mmHg — antihypertensive therapy may be initiated/adjusted; blood pressure > 165/105 mmHg with symptoms of hypertension — stop administration of voclosporin and initiate/adjust antihypertensive therapy. The UK SPC §4.3 lists only hypersensitivity and co-administration with strong CYP3A4 inhibitors. The eGFR, hepatic and pregnancy items are 'not recommended' cautions in §4.2/§4.4/§4.6, not absolute contraindications, and are recorded as such above and under monitoring.

NO PAEDIATRIC DOSE IS AVAILABLE FROM THIS SOURCE — dosePerKg is deliberately null and must not be derived by scaling the adult dose. UK SPC §4.2, verbatim: '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.'