Source: European Medicines Agency (EU) Revision Year: 2026 Publisher: X4 Pharmaceuticals (Austria) GmbH, Hohenstaufengasse 9/DG, 1010 Vienna, Austria
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Use with medicinal products highly dependent on CYP2D6 for clearance (e.g. dextromethorphan, codeine, tramadol) (see section 4.5).
During pregnancy (see sections 4.4, 4.6 and 5.3).
Based on its mechanism of action, mavorixafor may cause foetal harm when administered to a pregnant woman (see sections 4.3, 4.6 and 5.3).
The pregnancy status of female patients of childbearing potential who are engaging in activities of reproductive potential should be verified prior to starting Xolremdi. Female patients of childbearing potential must avoid becoming pregnant by using an effective method of contraception (e.g. double- barrier contraception) during treatment with Xolremdi and for three weeks after the final dose (see sections 4.6 and 5.3).
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.
Mavorixafor causes concentration-dependent QTc prolongation (see section 5.1). 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.
Any modifiable risk factors for QTc prolongation should be corrected, and QTc should be assessed at baseline and monitored during treatment as clinically indicated in patients with risk factors for QTc prolongation (e.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. Dose reduction (see section 4.2) or discontinuation of Xolremdi may be required.
The efficacy and safety of Xolremdi have not been established in patients with WHIM-syndrome who do not carry pathogenic CXCR4 variants.
This medicinal product contains less than 1 mmol sodium (23 mg) per hard capsule, that is to say essentially 'sodium-free'.
Drug interaction information for Xolremdi with potential concomitant medicinal products is summarized in Table 1, Table 2 and Table 3.
Interaction studies have only been performed in adults.
Table 1. Effect of Xolremdi on other medicinal products (examples include, but are not limited to):
| Medicinal product by therapeutic areas | Effects on drug levels. Mean ratio (90% confidence interval) for AUC, Cmax, Cmina | Recommendation concerning co-administration with Xolremdi |
| CYP2D6 substrates | ||
| e.g. dextromethorphan, codeine, tramadol | Dextromethorphanb ↑ Cmax by 6.5-fold (5.1 to 8.3) ↑ AUC by 9-fold (6.5 to 12.3). | Mavorixafor is a CYP2D6 inhibitor. Concomitant use of Xolremdi with medicinal products highly dependent on CYP2D6 for clearance is contraindicated (see section 4.3). Following discontinuation of mavorixafor, the inhibitory effect on CYP2D6 may persist; a washout period of approximately 30 days (corresponding to 9 half-lives) should be considered prior to initiating treatment with medicinal products highly dependent on CYP2D6 for clearance. |
| CYP3A4 substrates | ||
| e.g. midazolam, alprazolam, everolimus, telithromycin, telaprevir, ceritinib, ribociclib, atazanavir. | Midazolamb ↑ Cmax by 1.1-fold (1.0 to 1.3) ↑ AUC by 1.7-fold (1.4 to 2.1). | Mavorixafor is a CYP3A4 inhibitor. When used concomitantly with CYP3A4 substrates, where minimal substrate concentration changes may lead to serious adverse reactions, CYP3A4 substrate related adverse reactions should be monitored more frequently. |
| P-gp substrates | ||
| digoxin | Digoxinc ↑ Cmax by 1.5-fold (1.3 to 1.8) ↑ AUC by 1.6-fold (1.4 to 1.9) | When Xolremdi is used concomitantly with digoxin, the serum concentrations of digoxin should be measured before initiating concomitant use of Xolremdi, and monitoring of serum digoxin concentrations should be continued as recommended in the digoxin SmPC. |
| Other P-gp substrates e.g. dabigatran etexilate, edoxaban, fexofenadine | Interaction not studied. | When Xolremdi is used concomitantly with other P-gp substrates where minimal substrate concentration changes may lead to serious adverse reactions, P-gp substrate related adverse reactions should be monitored more frequently. |
| OCT2/MATE1 substrates | ||
| metformin | Metformind ↓ Cmax by 35% (17 to 49%) ↓ AUC by 35% (20 to 47%) | Monitor for glycemic control and adjust the dose of metformin as necessary. Mavorixafor may decrease the mean Cmax and AUC of metformin, which may reduce metformin's effectiveness. The mechanism of this interaction is unknown. |
a All interactions studies conducted in healthy subjects.
b Concomitant use with Xolremdi 400 mg
c Concomitant use of a single oral dose of a transporter cocktail containing 0.25 mg of digoxin with Xolremdi dosed to steady state (400 mg/day).
d Concomitant use of a single oral dose of a transporter cocktail containing 10 mg of metformin with Xolremdi dosed to steady state (400 mg/day)
Table 2. Effect of other medicinal products on Xolremdi (examples include, but are not limited to):
| Medicinal product by therapeutic areas | Effects on drug levels. Mean ratio (90% confidence interval) for AUC, Cmax, Cmina | Recommendation concerning co- administration with Xolremdi |
|---|---|---|
| CYP3A4 inducers | ||
| e.g. apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampicin, phenobarbital, St. John's wort | Interaction not studied. Expected: ↓ Mavorixafor Cmax ↓ Mavorixafor AUC | Mavorixafor is a CYP3A4 substrate. Concomitant use with a strong CYP3A4 inducer is expected to decrease the concentration of mavorixafor, which may reduce the therapeutic effect of Xolremdi. Concomitant use is not recommended. |
| Strong or moderate CYP3A4 inhibitors | ||
| e.g. itraconazole, amiodarone, diltiazem, fluconazole, ketoconazole, clarithromycin, erythromycin, nefazodone. | Itraconazoleb ↑Mavorixafor exposure by approximately 2-fold Expected: ↑ Mavorixafor Cmax ↑ Mavorixafor AUC | Mavorixafor is a CYP3A4 substrate. Concomitant use with a strong or moderate CYP3A4 inhibitors is expected to increase the exposure of mavorixafor and may increase the risk of adverse reactions. When used with a strong CYP3A4 inhibitor, the daily dose should be reduced to 200 mg (see section 4.2). When used with a moderate CYP3A4 inhibitor, adverse reactions should be monitored more frequently and the daily dose should be reduced by steps of 100 mg, as clinically necessary, but not to a dose less than 200 mg (see section 4.2). |
| P-gp inhibitors | ||
| itraconazole (200 mg), verapamil | Itraconazoleb ↑Mavorixafor exposure by approximately 2-fold Expected: ↑ Mavorixafor Cmax ↑ Mavorixafor AUC | Mavorixafor is a substrate of P-gp. When Xolremdi is used concomitantly with P-gp inhibitors, Xolremdi adverse reactions that may be associated with an increase in mavorixafor exposure should be monitored more frequently, 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 (see section 4.2). |
a All interactions studies conducted in healthy subjects.
b Concomitant use of Xolremdi 200 mg with 200 mg itraconazole.
Table 3. Interaction of anti-arrhythmic medicinal products and other medicinal products that may prolong the QT interval:
| Medicinal product by therapeutic areas | Effects on drug levels. Mean ratio (90% confidence interval) for AUC, Cmax, Cmin | Recommendation concerning co- administration with Xolremdi |
| Anti-arrhythmic medicinal products (including, but not limited to, amiodarone, disopyramide, procainamide, quinidine and sotalol) Other medicinal products that are known to prolong the QT interval (including, but not limited to, chloroquine, halofantrine, clarithromycin, ciprofloxacin, levofloxacin, azithromycin, haloperidol, methadone, moxifloxacin, bepridil, pimozide and intravenous ondansetron) | Interaction not studied. Expected to prolong QTc interval | Xolremdi causes concentration-dependent QTc prolongation. Concomitant use of Xolremdi with other products that are associated with QTc prolongation may lead to an increase in the QTc interval (see sections 4.4 and 5.1). When used concomitantly with medicinal product with a known potential to prolong the QTc interval, QTc assessment and monitoring is required (see sections 4.2 and 4.4). 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. Discontinuation of Xolremdi may be required (see sections 4.2 and 4.4). |
Patients should be advised to avoid eating or drinking products with grapefruit, as grapefruit is a strong CYP3A4 inhibitor and may increase the risk of adverse reactions from Xolremdi.
The pregnancy status of female patients of childbearing potential who are engaging in activities of reproductive potential should be verified prior to starting Xolremdi. Female patients of childbearing potential must avoid becoming pregnant by using an effective method of contraception (e.g., double-barrier contraception) during treatment with Xolremdi and for three weeks after the final dose (see section 4.4).
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.
There are no or a limited amount of data from the use of mavorixafor in pregnant women.
Based on its mechanism of action, mavorixafor may cause foetal harm when administered to a pregnant woman (see section 5.3).
Xolremdi is contraindicated during pregnancy (see section 4.3).
If exposure to mavorixafor during pregnancy has occurred, the female patient should contact their doctor promptly and treatment with mavorixafor discontinued.
Mavorixafor has not been studied in breast-feeding women. It is unknown whether mavorixafor/metabolites are excreted in human and animal milk.
A risk to the suckling child cannot be excluded.
A decision must be made whether to discontinue breast-feeding during treatment and for three weeks after the final dose or to discontinue Xolremdi therapy, considering the benefit of breast-feeding for the child and the benefit of Xolremdi therapy for the woman.
The effect of mavorixafor on human fertility is unknown. The effect of mavorixafor on male or female fertility was not studied in designated reproductive toxicology studies. In chronic duration repeat-dose toxicity studies, testicular changes were observed in one study in which treatment was initiated in young prepubertal dogs. The relevance of these findings for male patients is not known (see section 5.3).
Xolremdi may have influence on the ability to drive and use machines. Patients should be advised not to drive or use machines if they are experiencing nervous system adverse reactions.
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. The most common adverse reactions observed, of any grade reported, were gastrointestinal effects [nausea (21.1%), diarrhoea (18.4%), vomiting (13.2%), dyspepsia (10.5%), abdominal pain (10.5%)], rash (13.2%), and headache (10.5%).
Gastrointestinal effects may occur after starting Xolremdi; these reactions usually resolve within the first 3 months even if Xolremdi is continued.
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 |
| 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
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 suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Not applicable.
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