Posology : מינונים

4.2    Posology and method of administration
Treatment with upadacitinib should be initiated and supervised by physicians experienced in the diagnosis and treatment of conditions for which upadacitinib is indicated.

Posology

Rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis
The recommended dose of upadacitinib is 15 mg once daily.


Consideration should be given to discontinuing treatment in patients with ankylosing spondylitis who have shown no clinical response after 16 weeks of treatment. Some patients with initial partial response may subsequently improve with continued treatment beyond 16 weeks.

Atopic dermatitis

Adults
The recommended dose of upadacitinib is 15 mg or 30 mg once daily based on individual patient presentation.

•   A dose of 15 mg is recommended for patients at higher risk of venous thromboembolism (VTE), major adverse cardiovascular events (MACE) and malignancy (see section 4.4) •   A dose of 30 mg once daily may be appropriate for patients with high disease burden who are not at higher risk of VTE, MACE and malignancy (see section 4.4) or patients with an inadequate response to 15 mg once daily.
•   The lowest effective dose to maintain response should be used.

For patients 65 years of age and older, the recommended dose is 15 mg once daily (see section 4.4).

Adolescents (from 12 to 17 years of age)
The recommended dose of upadacitinib is 15 mg once daily for adolescents weighing at least 30 kg.
Concomitant topical therapies
Upadacitinib can be used with or without topical corticosteroids. Topical calcineurin inhibitors may be used for sensitive areas such as the face, neck, and intertriginous and genital areas.

Consideration should be given to discontinuing upadacitinib treatment in any patient who shows no evidence of therapeutic benefit after 12 weeks of treatment.

Ulcerative colitis

Induction
The recommended induction dose of upadacitinib is 45 mg once daily (one tablet of 45mg or three tablets of 15 mg) for 8 weeks. For patients who do not achieve adequate therapeutic benefit by week 8, upadacitinib 45 mg once daily may be continued for an additional 8 week period (see section 5.1).
Upadacitinib should be discontinued in any patient who shows no evidence of therapeutic benefit by week 16.

Maintenance
The recommended maintenance dose of upadacitinib is 15 mg (one tablet of 15 mg) or 30 mg (one tablet of 30 mg or two tablets of 15 mg) once daily based on individual patient presentation: • A dose of 15 mg is recommended for patients at higher risk of VTE, MACE and malignancy (see section 4.4).
• A dose of 30 mg once daily may be appropriate for some patients, such as those with high disease burden or requiring 16 week induction treatment who are not at higher risk of VTE, MACE and malignancy (see section 4.4) or who do not show adequate therapeutic benefit to 15 mg once daily.
• The lowest effective dose to maintain response should be used.

For patients 65 years of age and older, the recommended dose is 15 mg once daily (see section 4.4).

In patients who have responded to treatment with upadacitinib, corticosteroids may be reduced and/or discontinued in accordance with standard of care.


Crohn’s disease

Induction
The recommended induction dose of upadacitinib is 45 mg once daily (one tablet of 45mg or three tablets of 15 mg) for 12 weeks. For patients who have not achieved adequate therapeutic benefit after the initial 12-week induction, prolonged induction for an additional 12 weeks with a dose of 30 mg (one tablet of 30 mg or two tablets of 15 mg) once daily may be considered. For these patients, upadacitinib should be discontinued if there is no evidence of therapeutic benefit after 24 weeks of treatment.

Maintenance
The recommended maintenance dose of upadacitinib is 15 mg (one tablet of 15 mg) or 30 mg (one tablet of 30 mg or two tablets of 15 mg) once daily based on individual patient presentation: • A dose of 15 mg is recommended for patients at higher risk of VTE, MACE and malignancy (see section 4.4).
• A dose of 30 mg once daily may be appropriate for patients with high disease burden who are not at higher risk of VTE, MACE and malignancy (see section 4.4) or who do not show adequate therapeutic benefit to 15 mg once daily.
• The lowest effective dose to maintain response should be used.

For patients 65 years of age and older, the recommended maintenance dose is 15 mg once daily (see section 4.4).

In patients who have responded to treatment with upadacitinib, corticosteroids may be reduced and/or discontinued in accordance with standard of care.


Interactions

For patients with ulcerative colitis and Crohn’s disease receiving strong inhibitors of cytochrome P450 (CYP) 3A4 (e.g., ketoconazole, clarithromycin), the recommended induction dose is 30 mg once daily and the recommended maintenance dose is 15 mg once daily (see section 4.5).

Dose initiation

Treatment should not be initiated in patients with an absolute lymphocyte count (ALC) that is < 0.5 x 109 cells/L, an absolute neutrophil count (ANC) that is < 1 x 109 cells/L or who have haemoglobin (Hb) levels that are < 8 g/dL (see sections 4.4 and 4.8).


Dose interruption
Treatment should be interrupted if a patient develops a serious infection until the infection is controlled.

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



Table 1. Laboratory measures and monitoring guidance

Laboratory measure                           Action                   Monitoring guidance Treatment should be interrupted      Evaluate at baseline and if ANC is < 1 x 109 cells/L and      then no later than 12
Absolute Neutrophil Count (ANC)                                              weeks after initiation of may be restarted once ANC returns above this value             treatment. Thereafter evaluate according to
Treatment should be interrupted      individual patient
Absolute Lymphocyte Count               if ALC is < 0.5 x 109 cells/L and    management.
(ALC)                                   may be restarted once ALC returns above this value

Treatment should be interrupted if Hb is < 8 g/dL and may be
Haemoglobin (Hb) restarted once Hb returns above this value
Evaluate at baseline and
Treatment should be temporarily      thereafter according to
Hepatic transaminases                   interrupted if drug-induced liver    routine patient injury is suspected                  management.

Evaluate 12 weeks after
Patients should be managed           initiation of treatment according to international           and thereafter according
Lipids clinical guidelines for              to international clinical hyperlipidaemia                      guidelines for hyperlipidaemia

Special populations
Elderly

Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis

There are limited data in patients 75 years of age and older (see section 4.4).
Atopic dermatitis
For atopic dermatitis, doses higher than 15 mg once daily are not recommended in patients 65 years of age and older (see sections 4.4 and 4.8).

Ulcerative colitis and Crohn’s disease
For ulcerative colitis and Crohn’s disease, doses higher than 15 mg once daily for maintenance therapy are not recommended in patients 65 years of age and older (see sections 4.4 and 4.8). The safety and efficacy of upadacitinib in patients 75 years of age and older have not yet been established.

Renal impairment



No dose adjustment is required in patients with mild or moderate renal impairment. There are limited data on the use of upadacitinib in subjects with severe renal impairment (see section 5.2). Upadacitinib was not evaluated in clinical trials in patients with eGFR<40 mL/min/1.73 m2. Upadacitinib should be used with caution in patients with severe renal impairment as described in Table 2. The use of upadacitinib has not been studied in subjects with end stage renal disease and is therefore not recommended for use in these patients.

Table 2 Recommended dose for severe renal impairmenta
Therapeutic indication                          Recommended once daily dose Rheumatoid arthritis, psoriatic arthritis,      15 mg ankylosing spondylitis, atopic dermatitis


Ulcerative colitis, Crohn’s disease             Induction: 30 mg
Maintenance: 15 mg a estimated glomerular filtration rate (eGFR) 15 to < 30 ml/min/1.73m2

Hepatic impairment

No dose adjustment is required in patients with mild (Child -Pugh A) or moderate (Child -Pugh B) hepatic impairment (see section 5.2). Upadacitinib should not be used in patients with severe (Child - Pugh C) hepatic impairment (see section 4.3).

Paediatric population

The safety and efficacy of RINVOQ in children with atopic dermatitis below the age of 12 years have not been established. No data are available.

The safety and efficacy of RINVOQ in children and adolescents with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and Crohn’s disease, aged 0 to less than 18 years have not yet been established. No data are available.

Method of administration

RINVOQ is to be taken orally once daily with or without food and may be taken at any time of the day. Tablets should be swallowed whole and should not be split, crushed, or chewed in order to ensure the entire dose is delivered correctly.