Posology : מינונים

4.2    Posology and method of administration

Humira treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of conditions for which Humira is indicated. Ophthalmologists are advised to consult with an appropriate specialist before initiation of treatment with Humira (see section 4.4).
Patients treated with Humira should be given the special alert card.

After proper training in injection technique, patients may self-inject with Humira if their physician determines that it is appropriate and with medical follow-up as necessary.

During treatment with Humira, other concomitant therapies (e.g., corticosteroids and/or immunomodulatory agents) should be optimised.

Posology

Rheumatoid arthritis
The recommended dose of Humira for adult patients with rheumatoid arthritis is 40 mg adalimumab administered every other week as a single dose via subcutaneous injection. Methotrexate should be continued during treatment with Humira.

Glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs, or analgesics can be continued during treatment with Humira. Regarding combination with disease modifying anti-rheumatic drugs other than methotrexate see sections 4.4 and 5.1.

In monotherapy, some patients who experience a decrease in their response may benefit from an increase in dose intensity to 40 mg adalimumab every week.

Available data suggest that the clinical response is usually achieved within 12 weeks of treatment.
Continued therapy should be reconsidered in a patient not responding within this time period.

Dose Interruption
There may be a need for dose interruption, for instance before surgery or if a serious infection occurs.

Available data suggest that re-introduction of Humira after discontinuation for 70 days or longer resulted in the same magnitudes of clinical response and similar safety profile as before dose interruption.

Ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS and psoriatic arthritis

The recommended dose of Humira for patients with ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS and for patients with psoriatic arthritis is 40 mg adalimumab administered every other week as a single dose via subcutaneous injection.

Available data suggest that the clinical response is usually achieved within 12 weeks of treatment.
Continued therapy should be reconsidered in a patient not responding within this time period.

Psoriasis
The recommended dose of Humira for adult patients is an initial dose of 80 mg administered subcutaneously, followed by 40 mg subcutaneously given every other week starting one week after the initial dose.

Continued therapy beyond 16 weeks should be carefully reconsidered in a patient not responding within this time period.

Beyond 16 weeks, patients with inadequate response may benefit from an increase in dosing frequency to 40 mg every week. The benefits and risks of continued weekly Humira therapy should be carefully reconsidered in a patient with an inadequate response after the increase in dosing frequency (see section 5.1). If adequate response is achieved with an increased dosing frequency, the dose may subsequently be reduced to 40 mg every other week.

Hidradenitis suppurativa

The recommended Humira dose regimen for adult patients with hidradenitis suppurativa (HS) is 160 mg initially at Day 1 (given as four 40 mg injections in one day or as two 40 mg injections per day for two consecutive days), followed by 80 mg two weeks later at Day 15 (given as two 40 mg injections in one day). Two weeks later (Day 29) continue with a dose of 40 mg every week. Antibiotics may be continued during treatment with Humira if necessary. It is recommended that the patient should use a topical antiseptic wash on their HS lesions on a daily basis during treatment with Humira.

Continued therapy beyond 12 weeks should be carefully reconsidered in a patient with no improvement within this time period.
Should treatment be interrupted, Humira 40 mg every week may be re-introduced (see section 5.1).

The benefit and risk of continued long-term treatment should be periodically evaluated (see section 5.1).


Crohn’s disease
The recommended Humira induction dose regimen for adult patients with Crohn’s disease is 160 mg at Week 0 (dose can be administered as four 40 mg injections in one day or as two 40 mg injections per day for two consecutive days), 80 mg at Week 2, followed by a maintenance dose of 40 mg every other week via subcutaneous injection beginning at Week 4.

Aminosalicylates, corticosteriods and/or immunomodulatory agents (e.g. 6-mercaptopurine and azathioprine) may be continued during treatment with Humira.

Some patients who experience decrease in their response may benefit from an increase in dosing frequency to 40 mg Humira every week.

Some patients who have not responded by Week 4 may benefit from continued maintenance therapy through Week 12. Continued therapy should be carefully reconsidered in a patient not responding within this time period.

Ulcerative colitis

The recommended Humira induction dose regimen for adult patients with moderate to severe ulcerative colitis is 160 mg at Week 0 (dose can be administered as four injections in one day or as two injections per day for two consecutive days) and 80 mg at Week 2. After induction treatment, the recommended dose is 40 mg every other week via subcutaneous injection.

During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice guidelines.

Some patients who experience decrease in their response may benefit from an increase in dosing frequency to 40 mg Humira every week.

Available data suggest that clinical response is usually achieved within 2-8 weeks of treatment.
Humira therapy should not be continued in patients failing to respond within this time period.

Uveitis
The recommended dose of Humira for adult patients with uveitis is an initial dose of 80 mg, followed by 40 mg given every other week starting one week after the initial dose. There is limited experience in the initiation of treatment with Humira alone. Treatment with Humira can be initiated in combination with corticosteroids and/or with other non-biologic immunomodulatory agents.
Concomitant corticosteroids may be tapered in accordance with clinical practice starting two weeks after initiating treatment with Humira.

It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a yearly basis (see section 5.1).

Intestinal Behcet's disease

The initial dose of Humira for adult intestinal Behcet's disease patients is 160mg as subcutaneous injection. The initial dose is followed by 80mg two weeks later. Four weeks after the initial dose begin 40mg every other week.


Humira should be used when the signs and symptoms caused by intestinal Behcet's disease remain clearly evident after appropriate treatment with existing drug (steroids or immunosuppressant, etc.).

Elderly

No dose adjustment is required.
Renal and/or hepatic impairment

Humira has not been studied in these patient populations. No dose recommendations can be made.

Paediatric population:
Juvenile Idiopathic Arthritis

Polyarticular juvenile idiopathic arthritis from 2 to 12 years of age 
The recommended dose of Humira for patients with polyarticular juvenile idiopathic arthritis, aged 2- 12 years, is 24 mg/m² body surface area up to a maximum single dose of 20 mg adalimumab (for patients aged 2-<4) and up to a maximum single dose of 40 mg adalimumab (for patients aged 4-12) administered every other week via subcutaneous injection. The volume for injection is selected based on the patients' height and weight (Table 1). A 40 mg/0.8ml paediatric vial is available for patients who need to administer less than the full 40 mg dose.

Table 1. Humira Dose in Milliliters (ml) by Height and Weight of patients for Polyarticular Juvenile Idiopathic Arthritis and Enthesitis-Related Arthritis 
Height                                  Total Body Weight (kg)
(cm)   10     15     20     25     30    35     40    45     50              55      60     65       70 80  0.2    0.3     0.3   0.3
90  0.2    0.3     0.3   0.4     0.4   0.4
100  0.3    0.3     0.3   0.4     0.4   0.4   0.5   0.5
110  0.3    0.3     0.4   0.4     0.4   0.5   0.5   0.5    0.5             0.6     0.6 120  0.3    0.4     0.4   0.4     0.5   0.5   0.5   0.6    0.6             0.6     0.6     0.7     0.7 130         0.4     0.4   0.5     0.5   0.5   0.6   0.6    0.6             0.6     0.7     0.7     0.7 140         0.4     0.4   0.5     0.5   0.6   0.6   0.6    0.7             0.7     0.7     0.7     0.8* 150                 0.5   0.5     0.6   0.6   0.6   0.7    0.7             0.7     0.7     0.8*    0.8* 160                 0.5   0.5     0.6   0.6   0.7   0.7    0.7             0.8*    0.8*    0.8*    0.8* 170                       0.6     0.6   0.6   0.7   0.7    0.8*            0.8*    0.8*    0.8*    0.8* 180                               0.6   0.7   0.7 0.8* 0.8*                0.8*    0.8*    0.8*    0.8* *Maximum single dose is 40 mg (0.8 ml)

Polyarticular Juvenile Idiopathic Arthritis from 13 years of age

For patients from 13 years of age, a dose of 40 mg is administered every other week regardless of body surface area.

Available data suggest that clinical response is usually achieved within 12 weeks of treatment.
Continued therapy should be carefully reconsidered in a patient not responding within this time period.

There is no relevant use of Humira in patients aged less than 2 years for this indication.
Enthesitis-related arthritis

The recommended dose of Humira for patients with enthesitis-related arthritis 6 years of age and older is 24 mg/m² body surface area up to a maximum single dose of 40 mg adalimumab administered every other week via subcutaneous injection. The volume for injection is selected based on the patients' height and weight (Table 1).
Humira has not been studied in patients with enthesitis-related arthritis aged less than 6 years.

Paediatric plaque psoriasis

The recommended Humira dose is 0.8 mg per kg body weight (up to a maximum of 40 mg per dose) administered subcutaneously weekly for the first two doses and every other week thereafter.
Continued therapy beyond 16 weeks should be carefully considered in a patient not responding within this time period.

If retreatment with Humira is indicated, the above guidance on dose and treatment duration should be followed.

The safety of Humira in paediatric patients with plaque psoriasis has been assessed for a mean of 13 months.

There is no relevant use of Humira in children aged less than 4 years for this indication.

The volume for injection is selected based on the patients' weight (Table 2).
Table 2: Humira Dose in Milliliters (ml) by Weight for Patients with Paediatric Psoriasis 
Body Weight (kg)                Paediatric Psoriasis Dose
13 – 16                          0.2 ml (10 mg)
17 – 22                          0.3 ml (15 mg)
23 – 28                          0.4 ml (20 mg)
29 – 34                          0.5 ml (25 mg)
35 – 40                          0.6 ml (30 mg)
41 – 46                          0.7 ml (35 mg)
47+                            0.8 ml (40 mg)

Adolescent hidradenitis suppurativa (from 12 years of age, weighing at least 30 kg) 
There are no clinical trials with Humira in adolescent patients with HS. The posology of Humira in these patients has been determined from pharmacokinetic modelling and simulation (see section 5.2).

The recommended Humira dose is 80 mg at Week 0 followed by 40 mg every other week starting at Week 1 via subcutaneous injection.

In adolescent patients with inadequate response to Humira 40 mg every other week, an increase in dosing frequency to 40 mg every week may be considered.

Antibiotics may be continued during treatment with Humira if necessary. It is recommended that the patient should use a topical antiseptic wash on their HS lesions on a daily basis during treatment with Humira.

Continued therapy beyond 12 weeks should be carefully reconsidered in a patient with no improvement within this time period.

Should treatment be interrupted, Humira may be re-introduced as appropriate.

The benefit and risk of continued long-term treatment should be periodically evaluated (see adult data in section 5.1)

There is no relevant use of Humira in children aged less than 12 years in this indication.

Paediatric Crohn's disease
Paediatric Crohn's disease patients < 40 kg:
The recommended Humira induction dose regimen for paediatric subjects with moderately to severely active Crohn's disease is 40 mg at Week 0 followed by 20 mg at Week 2. In case there is a need for a more rapid response to therapy, the regimen 80 mg at Week 0 (dose can be administered as two injections in one day); 40 mg at Week 2 can be used, with the awareness that the risk for adverse events may be higher with use of the higher induction dose.

After induction treatment, the recommended dose is 20 mg every other week via subcutaneous injection. Some subjects who experience insufficient response may benefit from an increase in dosing frequency to 20 mg Humira every week.

Paediatric Crohn's disease patients ≥ 40 kg:

The recommended Humira induction dose regimen for paediatric subjects with moderately to severely active Crohn's disease is 80 mg at Week 0 followed by 40 mg at Week 2. In case there is a need for a more rapid response to therapy, the regimen 160 mg at Week 0 (dose can be administered as four injections in one day or as two injections per day for two consecutive days), 80 mg at Week 2 can be used, with the awareness that the risk for adverse events may be higher with use of the higher induction dose.

After induction treatment, the recommended dose is 40 mg every other week via subcutaneous injection. Some subjects who experience insufficient response may benefit from an increase in dosing frequency to 40 mg Humira every week.

Continued therapy should be carefully considered in a subject not responding by Week 12.

There is no relevant use of Humira in children aged less than 6 years for this indication.
Paediatric uveitis


In paediatric uveitis, there is no experience in the treatment with Humira without concomitant treatment with methotrexate.

Paediatric uveitis patients < 30 kg:

The recommended dose of Humira is 20 mg every other week in combination with methotrexate.
When Humira therapy is initiated, a loading dose of 40 mg may be administered one week prior to the start of maintenance therapy. No clinical data are available on the use of a Humira loading dose in children < 6 years of age (see section 5.2).

Paediatric uveitis patients ≥ 30 kg:

The recommended dose of Humira is 40 mg every other week in combination with methotrexate.
When Humira therapy is initiated, a loading dose of 80 mg may be administered one week prior to the start of maintenance therapy.

There is no relevant use of Humira in children aged less than 2 years in this indication.

It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a yearly basis (see section 5.1).


Paediatric ulcerative colitis
The safety and efficacy of Humira in children aged 4-17 years have not yet been established. No data are available. There is no relevant use of Humira in children aged <4 years for this indication.

Psoriatic arthritis and axial spondyloarthritis including ankylosing spondylitis 
There is no relevant use of Humira in the paediatric population in the indications of ankylosing spondylitis and psoriatic arthritis.

Method of administration

Humira is administered by subcutaneous injection. Full instructions for use are provided in the package leaflet.

A 40 mg pen and a 40 mg prefilled syringe are available for patients to administer a full 40 mg dose.

A 40 mg paediatric vial is available for patients who need to administer less than the full 40 mg dose.