Posology : מינונים

4.2   Posology and method of administration

Treatment should be initiated and supervised by a healthcare professional experienced in the diagnosis and treatment of atopic dermatitis.

Posology

The recommended starting dose is 100 mg or 200 mg once daily based on individual patient characteristics:
•     A starting dose of 100 mg once daily is recommended for patients at higher risk of venous thromboembolism (VTE), major adverse cardiovascular event (MACE) and malignancy (see section 4.4). If the patient does not respond adequately to 100 mg once daily, the dose can be increased to 200 mg once daily.
•      A dose of 200 mg once daily may be appropriate for patients who are not at higher risk of VTE, MACE and malignancy with high disease burden or for patients with an inadequate response to 100 mg once daily. Upon disease control, dose should be decreased to 100 mg once daily. If disease control is not maintained after dose reduction, re-treatment with 200 mg once daily can be considered.

The lowest effective dose for maintenance should be considered.

Discontinuation of treatment should be considered in patients who show no evidence of therapeutic benefit after 24 weeks.

Cibinqo can be used with or without medicated topical therapies for atopic dermatitis.



Laboratory monitoring
Table 1. Laboratory measures and monitoring guidance
Laboratory measures        Monitoring guidance                                      Action Platelets: Treatment should be discontinued if platelet counts are
< 50 × 103/mm3.
ALC: Treatment should be
Complete blood count                                                interrupted if ALC is including Platelet                                                  < 0.5 × 103/mm3 and may be restarted Count, Absolute            Before treatment initiation, 4 weeks     once ALC returns above this value.
Lymphocyte Count           after initiation and thereafter          Treatment should be discontinued if (ALC), Absolute            according to routine patient             confirmed.
Neutrophil Count           management.                              ANC: Treatment should be (ANC) and                                                           interrupted if ANC is < 1 × 103/mm3 Haemoglobin (Hb)                                                    and may be restarted once ANC returns above this value.
Hb: Treatment should be interrupted if Hb is < 8 g/dL and may be restarted once Hb returns above this value.
Before treatment initiation, 4 weeks after initiation and thereafter          Patients should be monitored Lipid parameters           according to the patient’s risk for      according to clinical guidelines for cardiovascular disease and clinical      hyperlipidaemia.
guidelines for hyperlipidaemia.

Treatment initiation
Treatment should not be initiated in patients with a platelet count < 150 × 103/mm3, an absolute lymphocyte count (ALC) < 0.5 × 103/mm3, an absolute neutrophil count (ANC) < 1.2 × 103/mm3 or who have a haemoglobin value < 10 g/dL (see section 4.4).

Dose interruption
If a patient develops a serious infection, sepsis or opportunistic infection, dose interruption should be considered until the infection is controlled (see section 4.4).

Interruption of dosing may be needed for management of laboratory abnormalities as described in Table 1.

Missed doses
If a dose is missed, patients should be advised to take the dose as soon as possible unless it is less than 12 hours before the next dose, in which case the patient should not take the missed dose. Thereafter, dosing should be resumed at the regular scheduled time.

Interactions
In patients receiving dual strong inhibitors of CYP2C19 and moderate inhibitors of CYP2C9, or strong inhibitors of CYP2C19 alone (e.g. fluvoxamine, fluconazole, fluoxetine and ticlopidine), the recommended dose should be reduced by half to 100 mg or 50 mg once daily (see section 4.5).

Treatment is not recommended concomitantly with moderate or strong inducers of CYP2C19/CYP2C9 enzymes (e.g.
rifampicin, apalutamide, efavirenz, enzalutamide, phenytoin) (see section 4.5).

In patients receiving acid reducing agents (e.g. antacids, proton pump inhibitors and H2 receptor antagonists), 200 mg once daily dose of abrocitinib should be considered (see section 4.5).



Special populations

Renal impairment
No dose adjustment is required in patients with mild renal impairment, i.e. estimated glomerular filtration rate (eGFR) of 60 to < 90 mL/min.

Abrocitinib has not been studied in patients with eGFR < 40 mL/min. The recommended dose is based on extrapolation.

In patients with moderate (eGFR 30 to < 60 mL/min) renal impairment, the recommended dose of abrocitinib should be reduced by half to 100 mg or 50 mg once daily (see section 5.2).

In patients with severe (eGFR < 30 mL/min) renal impairment, 50 mg once daily is the recommended starting dose.
The maximum daily dose is 100 mg (see section 5.2).

Abrocitinib has not been studied in patients with end-stage renal disease (ESRD) on renal replacement therapy.
Hepatic impairment
No dose adjustment is required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment.
Abrocitinib is contraindicated to patients with severe (Child Pugh C) hepatic impairment (see section 4.3).

Elderly
For patients 65 years of age and older, the recommended dose is 100 mg once daily (see section 4.4).

Paediatric population
The safety and efficacy of Cibinqo in children under 12 years of age have not yet been established. No data are available.

Cibinqo has been studied in adolescents 12 to < 18 years of age. However, because of bone findings in juvenile rats (comparable to a 3-month-old human) (see section 5.3), additional long-term data in growing adolescents is needed to conclude that the benefits outweigh the risks. Currently available data are described in sections 4.8, 5.1 and 5.2.

Method of administration

This medicinal product is to be taken orally once daily with or without food at approximately the same time each day.
In patients who experience nausea, taking tablets with food may improve nausea.

Tablets should be swallowed whole with water and should not be split, crushed or chewed because these methods have not been studied in clinical trials.