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Taltz ® (ixekizumab) injektion
Denna information är endast avsedd för sjukvårdspersonal verksam i Sverige och som svar på din fråga. Informationen nedan är på engelska
This summary contains information on dosages and dosing regimens that are not consistent with the information contained in the paragraph 4.2 (Posology and method of administration) of the Summary of Product Characteristics (SmPC). Please refer to the SmPC for full prescribing information.
Following a single subcutaneous dose of ixekizumab in patients with psoriasis, mean peak concentrations were achieved within 4 to 7 days, across a dose range of 5 to 160 mg. The mean (SD) maximum plasma concentration (Cmax) of ixekizumab, after the 160 mg starting dose, was 19.9 (8.15) µg/ml.
After the 160 mg starting dose, steady state was achieved by Week 8 with the 80 mg Q2W dosing regimen. Mean (SD) Cmax,ss, and C trough,ss estimates are 21.5 (9.16) µg/ml, and 5.23 (3.19) µg/ml.
After switching from the 80 mg Q2W dosing regimen to the 80 mg Q4W dosing regimen at Week 12, steady state would be achieved after approximately 10 weeks. Mean (SD) Cmax,ss, and Ctrough,ss estimates are 14.6 (6.04) µg/ml, and 1.87 (1.30) µg/ml.
The average bioavailability of ixekizumab after subcutaneous administration was 54 % to 90 % across analyses.1
From population pharmacokinetic analyses, the mean total volume of distribution at steady state was 7.11 L.1
Ixekizumab is a monoclonal antibody and is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.1
In the population PK analysis, mean serum clearance was 0.0161 L/hr. Clearance is independent of dose. The mean elimination half-life, as estimated from population pharmacokinetic analysis, is 13 days in patients with plaque psoriasis.1
Exposure (AUC) increased proportionally over a dose range of 5 to 160 mg given as a subcutaneous injection.1
Pharmacokinetic Properties Across Indications
The pharmacokinetic properties of ixekizumab were similar across the plaque psoriasis, psoriatic arthritis, radiographic axial spondyloarthritis and non-radiographic axial spondyloarthritis indications.1
Pharmacokinetics in Elderly
Of the 4,204 plaque psoriasis patients exposed to ixekizumab in clinical studies, a total of 301 were 65 years of age or older and 36 patients were 75 years of age or older. Of the 1,118 psoriatic arthritis patients exposed to ixekizumab in clinical studies, a total of 122 patients were 65 years of age or older and 6 patients were 75 years of age or older.
Based on population pharmacokinetic analysis with a limited number of elderly patients (n = 94 for age ≥ 65 years and n = 12 for age ≥ 75 years), clearance in elderly patients and patients less than 65 years of age was similar.1
Pharmacokinetics in Patients with Renal or Hepatic Impairment
Specific clinical pharmacology studies to evaluate the effects of renal impairment and hepatic impairment on the PK of ixekizumab have not been conducted. Renal elimination of intact ixekizumab, an IgG MAb, is expected to be low and of minor importance; similarly, IgG MAbs are mainly eliminated via intracellular catabolism and hepatic impairment is not expected to influence clearance of ixekizumab.1
Ixekizumab is a humanized IgG4 monoclonal antibody that selectively binds with the interleukin 17A cytokine and inhibits its interaction with the IL-17 receptor. Theoretical considerations and case reports for other IgG mAb suggest that renal impairment does not affect the PK and likely not the PD of mAb-based therapeutics. However, there is only limited published experience with regard to the use of other IgG mAb in patients with renal impairment.2
Table 1 summarizes information regarding the PK profile for ixekizumab.
Following a single SC dose of ixekizumab in patients with psoriasis:
steady state was achieved by week 8 with the 80 mg Q2W dosing regimen following a 160 mg starting dose.
SC bioavailability was estimated to be in the range of 54% to 90%
From population PK analyses the mean total volume of distribution at steady-state was 7.11 L.
Ixekizumab is a monoclonal antibody and is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgGs.
In the population PK analysis, mean serum clearance was 0.0161L/hr. Clearance is independent of dose.
The mean elimination half-life, as estimated from population pharmacokinetic analysis, is 13 days in plaque psoriasis patients.
Abbreviations: ADME = absorption, distribution, metabolism, elimination; Cmax = maximum concentration; IgG = immunoglobulin G; L/h = liters per hour; µg/mL = microgram per milliliter; PK = pharmacokinetic; SC = subcutaneous.
Note: The table contains information on dosing that is not consistent with the approved dosing from the label. Please refer to the Taltz Summary of Product Characteristics for approved dosing.1
2. Meibohm B, Zhou H. Characterizing the impact of renal impairment on the clinical pharmacology of biologics. J Clin Pharmacol. 2012;52(s1):54S-62S. http://dx.doi.org/10.1177/0091270011413894
AS/r-axSpA = ankylosing spondylitis/radiographic axial spondyloarthritis
AUC(0-tlast) = area under the concentration versus time curve, where tlast is time of the last sample (14 days ± 24 hours)
Cmax = maximum concentration
CrCl = creatinine clearance
hsCRP = high sensitivity C-reactive protein
IgG = immunoglobulin G
IgG4 = immunoglobulin G subclass 4
IL-17 = interleukin-17
IL-17A = interleukin-17A
nr-axSpA = nonradiographic axial spondyloarthritis
PASI = Psoriasis Area and Severity Index
PBO = placebo
PD = pharmacodynamic(s)
PK = pharmacokinetic(s)
PsA = psoriatic arthritis
Q2W = every 2 weeks
▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
Datum fӧr senaste ӧversyn 2018 M10 17