Posology : מינונים

4.2 Posology and method of administration

Xolair treatment should be initiated by physicians experienced in the diagnosis and treatment of moderate to severe persistent asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) or chronic spontaneous urticaria.

Posology

Allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP)

Dosing for allergic asthma and CRSwNP follows the same dosing principles. The appropriate dose and frequency of Xolair for these conditions is determined by baseline IgE (IU/mL), measured before the start of treatment, and body weight (kg). Prior to administration of the initial dose, patients should have their IgE level determined by any commercial serum total IgE assay for their dose assignment. See Table 1 for a conversion chart and the dose determination tables below (Table 2, Table 3, Table 4, Table 5, Table 6, Table 7 and Table 8) for appropriate dose assignment.

Allergic asthma patients with baseline IgE lower than 76 IU/ml were less likely to experience benefit (see section 5.1). Prescribing physicians should ensure that adult and adolescent patients with IgE below 76 IU/ml and children (6 to < 12 years of age) with IgE below 200 IU/ml have unequivocal in vitro reactivity (RAST) to a perennial allergen before starting therapy.

Patients whose baseline IgE levels or body weight in kilograms are outside the limits of the dose table should not be given Xolair.

The maximum recommended dose is 600 mg omalizumab every two weeks.

Table 1: Conversion from dose to number of vials, number of injections and total injection volume for each administration

Dose (mg)      Number of vials         Number of injections       Total injection volume (ml) 150 mgb
75                    1a                        1                              0.6 150                    1                        1                              1.2 225                   2a                        2                              1.8 300                    2                        2                              2.4 375                   3a                        3                              3.0 450                    3                        3                              3.6 525                   4a                        4                              4.2 600                    4                        4                              4.8 a
To make up the correct injection volume use 0.6 ml from one Xolair 150 mg vial. b
1.2 ml = maximum delivered volume per vial (Xolair 150 mg).




XOL_POW_API_30MAR2022 V3                                          Baesd on EU SmPC DEC21 2
Severe Asthma -Adults and Adolescents (12 years of age and older)

Table 2: ADMINISTRATION EVERY 4 WEEKS. Xolair doses (milligrams per dose) administered by subcutaneous injection every 4 weeks for adults and adolescents (12 Years of age and older) with Severe Asthma

Body weight (kg)
Baseline
IgE          ≥20-    >25-    >30- 4   >40- 5   >50- 6   >60- 7    >70- 8   >80- 9   >90-   >125- (IU/ml)       25      30        0       0        0        0         0        0      125     150 ≥30-100       75      75       75      150      150      150       150      150     300     300 
>100-200     150     150      150      300       300     300       300      300     450    600 
>200-300     150     150      225      300       300     450       450      450     600 
>300-400     225     225      300      450       450     450       600      600 
>400-500     225     300      450      450       600     600

>500-600     300     300      450      600       600

>600-700     300              450      600

>700-800

>800-900                                        ADMINISTRATION EVERY 2 WEEKS
SEE TABLE 3
>900-
1000
>1000-
1100

Table 3: ADMINSTRATION EVERY 2 WEEKS. Xolair doses (milligrams per dose) administered by subcutaneous injection every 2 weeks for adults and adolescents (12 Years of age and older) with Severe Asthma

Body weight (kg)
Baseline
IgE          ≥20-    >25-    >30- 4   >40-     >50- 6   >60- 7    >70- 8   >80- 9   >90-   >125- (IU/ml)       25      30       0       50        0        0         0        0      125     150 ≥30-100      ADMINISTRATION EVERY 4 WEEKS
SEE TABLE 2
>100-200

>200-300                                                                                   375 
>300-400                                                                            450    525 
>400-500                                                           375      375     525    600 
>500-600                                                 375       450      450     600 
>600-700             225                        375      450       450      525 
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  >700-800        225    225   300       375   450    450      525       600 
>800-900        225    225   300       375   450    525      600

>900-           225    300   375       450   525    600
1000
>1000-          225    300   375       450   600
1100
>1100-          300    300   450       525   600     Insufficient data to recommend a dose 1200
>1200-          300    375   450       525
1300
>1300-          300    375   525       600
1500


Moderate Asthma - Adults and Adolescents (12 years of age and older)

Table 4: ADMINISTRATION EVERY 4 WEEKS Xolair Doses (milligrams) Administered by Subcutaneous Injection Every 4 Weeks for Adults and Adolescents (12 Years of Age and Older) with Moderate Asthma

Pre-treatment                                       Body weight (kg)
Serum IgE
Baseline IgE (IU/ml)           30-60           > 60-70             > 70-90          > 90-150 ≥30-100                         150              150                 150               300 > 100-200                       300              300                 300
> 200-300                       300
> 300-400                                            SEE TABLE 5
> 400-500
> 500-600

Table 5: ADMINISTRATION EVERY 2 WEEKS Xolair Doses (milligrams) Administered
by Subcutaneous Injection Every 2 Weeks for Adults and Adolescents (12 Years of Age and Older) with Moderate Asthma

Pre-treatment                                 Body weight (kg)
Serum IgE
(IU/mL)                30-60            > 60-70             > 70-90          > 90-150 Baseline IgE (IU/ml)
≥30-100
> 100-200                  SEE TABLE 4                                         225 > 200-300                             225                   225                300 > 300-400               225           225                   300
> 400-500               300           300                   375
> 500-600               300           375             Insufficient Data to Recommend a Dose
> 600-700               375




XOL_POW_API_30MAR2022 V3                                      Baesd on EU SmPC DEC21 4
Severe Asthma - Pediatric patients (ages of 6 to <12 years)
Pediatric patients (ages of 6 to <12 years): Initiate dosing according to Table 6. 
Table 6: Subcutaneous Xolair Doses Every 2 or 4 Weeks* for Pediatric Patients (ages of 6 to <12 years) with Severe Asthma Who Begin Xolair Treatment.
Pre-treatment            Body Weight
Dosing
Serum IgE       Freq.
(IU/mL)                 20-25 >25-30 >30-40 >40-50 >50-60 >60-70 >70-80 >80-90 >90-125 >125-150 kg     kg     kg     kg     kg     kg      kg      kg     kg     kg
Dose (mg)
30-100                   75     75     75    150    150    150     150     150    300    300 >100-200                 150   150    150    300    300    300     300     300    225    300 >200-300                 150   150    225    300    300    225     225     225    300    375 >300-400                 225   225    300    225    225    225     300     300 Every 4
>400-500        weeks    225   300    225    225    300    300     375     375 >500-600                 300   300    225    300    300    375
>600-700                 300   225    225    300    375
>700-800                 225   225    300    375                  Insufficient Data >800-900                 225   225    300    375               to Recommend a Dose >900-1000       Every 2 225    300    375
weeks
>1000-1100               225   300    375
>1100-1200               300   300
>1200-1300               300   375




XOL_POW_API_30MAR2022 V3                                          Baesd on EU SmPC DEC21 5
Chronic rhinosinusitis with nasal polyps (CRSwNP)

Table 7:     ADMINISTRATION EVERY 4 WEEKS. Xolair doses (milligrams per dose) administered by subcutaneous injection every 4 weeks for adults (18 years and above) with severe CRSwNP 

Body weight (kg)
Baseline
IgE          ≥20-    >25-    >30-    >40-    >50-    >60-      >70-   >80-    >90-   >125- (IU/ml)      25*     30*      40      50      60      70        80     90     125     150 ≥30-100       75      75      75     150     150     150       150    150     300     300 
>100-200      150     150     150     300     300     300      300    300     450     600 
>200-300      150     150     225     300     300     450      450    450     600 
>300-400      225     225     300     450     450     450      600    600

>400-500      225     300     450     450     600     600

>500-600      300     300     450     600     600

>600-700      300             450     600

>700-800

>800-900                                     ADMINISTRATION EVERY 2 WEEKS
SEE TABLE 8
>900-
1000
>1000-
1100
*Body weights below 30 kg were not studied in the pivotal trials for CRSwNP.




XOL_POW_API_30MAR2022 V3                                     Baesd on EU SmPC DEC21 6
Table 8:     ADMINSTRATION EVERY 2 WEEKS. Xolair doses (milligrams per dose) administered by subcutaneous injection every 2 weeks for adults (18 years and above) with severe CRSwNP 
Body weight (kg)
Baseline
IgE          ≥20-  >25-   >30-  >40-  >50-             >60-     >70-    >80-    >90-    >125- (IU/ml)      25*   30*     40     50   60               70       80      90     125      150 ≥30-100      ADMINISTRATION EVERY 4 WEEKS
SEE TABLE 2
>100-200

>200-300                                                                                 375 
>300-400                                                                         450     525 
>400-500                                                        375     375      525     600 
>500-600                                               375      450     450      600 
>600-700              225                      375     450      450     525

>700-800      225     225     300     375      450     450      525     600

>800-900      225     225     300     375      450     525      600

>900-         225     300     375     450      525     600
1000
>1000-        225     300     375     450      600
1100
>1100-        300     300     450     525      600      Insufficient data to recommend a dose 1200
>1200-        300     375     450     525
1300
>1300-        300     375     525     600
1500
*Body weights below 30 kg were not studied in the pivotal trials for CRSwNP.

Treatment duration, monitoring and dose adjustments

Allergic asthma
Xolair is intended for long-term treatment. Clinical trials have demonstrated that it takes at least 12-16 weeks for Xolair treatment to show effectiveness. At 16 weeks after commencing Xolair therapy patients should be assessed by their physician for treatment effectiveness before further injections are administered. The decision to continue Xolair following the 16-week time point, or on subsequent occasions, should be based on whether a marked improvement in overall asthma control is seen (see section 5.1, Physician’s overall assessment of treatment effectiveness).

Chronic rhinosinusitis with nasal polyps (CRSwNP)
In clinical trials for CRSwNP, changes in nasal polyps score (NPS) and nasal congestion score (NCS) were observed at 4 weeks. The need for continued therapy should be periodically reassessed based upon the patient’s disease severity and level of symptom control.




XOL_POW_API_30MAR2022 V3                                       Baesd on EU SmPC DEC21 7
Allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP)
Discontinuation of Xolair treatment generally results in a return to elevated free IgE levels and associated symptoms.
Total IgE levels are elevated during treatment and remain elevated for up to one year after the discontinuation of treatment. Therefore, re-testing of IgE levels during Xolair treatment cannot be used as a guide for dose determination. Dose determination after treatment interruptions lasting less than one year should be based on serum IgE levels obtained at the initial dose determination. Total serum IgE levels may be re-tested for dose determination if treatment with Xolair has been interrupted for one year or more.

Doses should be adjusted for significant changes in body weight (see Tables 2,3,4,5 and 6). 
Chronic spontaneous urticaria (CSU)

The recommended dose is 300 mg by subcutaneous injection every four weeks.
Prescribers are advised to periodically reassess the need for continued therapy. Clinical trial experience of long-term treatment beyond 6 months in this indication is limited. 
Special populations
Elderly (65 years of age and older)
There are limited data available on the use of Xolair in patients older than 65 years but there is no evidence that elderly patients require a different dose from younger adult patients. 
Renal or hepatic impairment
There have been no studies on the effect of impaired renal or hepatic function on the pharmacokinetics of omalizumab. Because omalizumab clearance at clinical doses is dominated by the reticular endothelial system (RES) it is unlikely to be altered by renal or hepatic impairment. While no particular dose adjustment is recommended for these patients, Xolair should be administered with caution(see section 4.4).

Paediatric population
In allergic asthma, the safety and efficacy of Xolair in patients below the age of 6 years have not been established. No data are available.

In CRSwNP, the safety and efficacy of Xolair in patients below the age of 18 years have not been established.

In CSU, the safety and efficacy of Xolair in patients below the age of 12 years have not been established.

Method of administration

For subcutaneous administration only. Xolair must not be administered by the intravenous or intramuscular route.

Doses of more than 150 mg (Table 1) should be divided across two or more injection sites. 
There is limited experience with self-administration of Xolair powder and solvent for solution for injection. Therefore, treatment with this formulation is intended to be administered by a healthcare provider only.
XOL_POW_API_30MAR2022 V3                                          Baesd on EU SmPC DEC21 8
For instructions on reconstitution of the medicinal product before administration, see section 6.6 and also information for the healthcare professional section of the package leaflet.