Xolremdi

Treatment should only be initiated by specialist physicians with experience in the diagnosis or management of immune deficiencies. Posology The recommended dose is: - Weight more than 50 kg: 400 mg (four 100 mg capsules) orally once daily on an empty stomach after an overnight fast, and at least 30 minutes before food.

- Weight less than or equal to 50 kg: 300 mg (three 100 mg capsules) orally once daily on an empty stomach after an overnight fast, and at least 30 minutes before food. Missed dose If a dose is missed, the next dose should be taken as scheduled.

The patient should not take a double dose to make up for a missed dose. Dose modifications Concomitant use of Xolremdi with strong or moderate CYP3A4 inhibitors When used concomitantly with a strong CYP3A4 inhibitor, daily dose should be reduced to 200 mg.

5), and the Xolremdi daily dose should be reduced by steps of 100 mg, as clinically necessary, but not to a dose less than 200 mg. 5), and the Xolremdi daily dose should be reduced by steps of 100 mg, as clinically necessary, but not to a dose less than 200 mg.

4). If dose reduction is required, the daily dose should be reduced by steps of 100 mg, but not to a dose less than 200 mg. 4). Elderly There are limited data on patients aged 65 years and older. Renal impairment The safety and efficacy of Xolremdi have not been established in patients with severe renal impairment (creatinine clearance 15 to less than 30 mL/min) or end-stage renal disease (creatinine clearance less than 15 mL/min).

It is not recommended to administer Xolremdi to patients with severe renal impairment or end-stage renal disease. No dose adjustment is recommended in patients with creatinine clearance ≥ 30 mL/min, including in patients with mild to moderate renal impairment.

Hepatic impairment The safety and efficacy of Xolremdi have not been established in patients with moderate to severe hepatic impairment (ChildPugh score ≥ 7). Xolremdi is not recommended for use in patients with moderate to severe hepatic impairment.

No dose adjustment is recommended in patients with mild hepatic impairment. Paediatric population The safety and efficacy of Xolremdi in children from 2 to 11 years of age have not yet been established. No data are available. 3). Method of administration Xolremdi is for oral use.

Summary of the safety profile The safety data described below reflect exposure in 38 patients with WHIM syndrome treated with mavorixafor, with a treatment duration range from less than 6 months (7 patients) to 4 years (7 patients), with median duration of exposure of 2 years.

5%). Gastrointestinal effects may occur after starting Xolremdi; these reactions usually resolve within the first 3 months even if Xolremdi is continued. Tabulated list of adverse reactions Adverse reactions reported in clinical trials with mavorixafor are listed below in Table 4.

These included two clinical trials in which 38 patients with WHIM syndrome were treated with mavorixafor. The adverse reactions are listed in Table 4 according to MedDRA system organ class and frequency. The frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), and not known (cannot be estimated from the available data).

Table 4:

Adverse reactions System organ class Adverse reaction Frequency Nervous system disorders Headache Very common Dizziness Common Syncope Common Respiratory, thoracic and mediastinal disorders Epistaxis Common 9 System organ class Adverse reaction Frequency Gastrointestinal disorders Nausea Very common Diarrhoea Very common Dyspepsia Very common Abdominal pain Very common Vomiting Very common Skin and subcutaneous tissue disorders Rash* Very common Dry skin Common Psoriasiform dermatitis Common *the following grouping contain the following MedDRA preferred terms: Rash: rash macular, rash pruritic, rash papular Paediatric population In the pivotal Phase 3 study X4P-001-103, 7 of 14 patients treated with mavorixafor were aged between 12 to < 18 years.

No patients in the Phase 2 study X4P-001-MKKA were younger than 18 years. The safety profile in patients 12 to < 18 years of age was similar to that observed in the overall population, including adults and adolescent patients. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

3). The pregnancy status of female patients of childbearing potential who are engaging in activities of reproductive potential should be verified prior to starting Xolremdi. g. 3). Male patients with female partners of childbearing potential should use condoms during sexual intercourse while taking Xolremdi and for at least three weeks after stopping treatment.

If exposure to mavorixafor during pregnancy has occurred, the female patient should contact their doctor promptly and treatment with mavorixafor discontinued. In order to assist healthcare professionals (HCPs) and patients to minimise the potential risk of embryo-foetal toxicity, a HCP guide will be distributed to the HCPs who are experienced in the treatment of WHIM syndrome and a patient card will be provided in the product package.

1). Concomitant use of Xolremdi with other products that prolong the QTc interval may result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation, including Torsade de Pointes, other serious arrythmias, and sudden death.

g. congestive heart failure, Long QT Syndrome, hypokalaemia) or receiving concomitant medicinal products that increase mavorixafor exposure and/or active substances with a known potential to prolong the QTc interval. 2) or discontinuation of Xolremdi may be required.

Patients without confirmed CXCR4 gene variants The efficacy and safety of Xolremdi have not been established in patients with WHIM-syndrome who do not carry pathogenic CXCR4 variants. Sodium content This medicinal product contains less than 1 mmol sodium (23 mg) per hard capsule, that is to say essentially ‘sodium- free’.

1. g. 5). 3).