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4.2 Posology and method of administration Text updated to
Paediatric population
The safety and efficacy of STELARA in children less than 18 years have not yet been established. No data are available. 4.6 Fertility, pregnancy and lactation New sub heading
Women of childbearing potential Addition of
Fertility
The effect of ustekinumab on human fertility has not been evaluated (see section 5.3).
4.8 Undesirable effects Table 1 addition of Infections and infestations - Uncommon: Herpes zoster Addition of Among 3,117 patients treated in 4 psoriasis clinical trials of ustekinumab representing 6,791 patient‑years of exposure (1,129 patients treated for at least 3 years, and 619 patients for at least 4 years), the rates of infection or serious infection were similar to those described above. Among 3,117 patients treated in 4 psoriasis clinical trials of ustekinumab (1,129 patients treated for at least 3 years, and 619 patients for at least 4 years), malignancies excluding non‑melanoma skin cancers were reported in 42 patients in 6,779 patient‑years of follow‑up (incidence of 0.62 per 100 patient-years of follow-up for ustekinumab‑treated patients). This rate of malignancies reported in ustekinumab‑treated patients was comparable to the rate expected in the general population (standardized incidence ratio = 1.1 [95% confidence interval: 0.76, 1.43]). The most frequently observed malignancies, other than non‑melanoma skin cancer, were prostate, colorectal and breast cancers, and melanoma in situ. The incidence of non‑melanoma skin cancer was 0.61 per 100 patient‑years of follow‑up for ustekinumab‑treated patients (41 patients in 6,770 patient‑years of follow‑up) (see section 4.4).
5.1 Pharmacodynamic properties Text updated In Psoriasis Study 1 maintenance of PASI 75 was significantly superior with continuous treatment compared with treatment withdrawal (p < 0.001). Similar results were seen with each dose of ustekinumab. At 1 year (Week 52), 89% of patients re‑randomised to maintenance treatment were PASI 75 responders compared with 63% of patients re‑randomised to placebo (treatment withdrawal) (p < 0.001). At 18 months (Week) 76, 84% of patients re‑randomised to maintenance treatment were PASI 75 responders compared with 19% of patients re‑randomised to placebo (treatment withdrawal). At 3 years (Week 148), 82% of patients re‑randomized to maintenance treatment were PASI 75 responders.
Addition of
The European Medicines Agency has waived the obligation to conduct studies with ustekinumab in plaque psoriasis in paediatric patients aged from birth to less than 6 years.
The European Medicines Agency has deferred the obligation to submit the results of studies with ustekinumab in moderate to severe plaque psoriasis in paediatric patients aged from 6 years to less than 18 years. 10. DATE OF REVISION OF THE TEXT Changed to - 13/01/2012
No interaction studies have been performed in humans. In the population pharmacokinetic analysis of the phase III studies, the effect of the most frequently used concomitant medicinal products in patients with psoriasis (including paracetamol, ibuprofen, acetylsalicylic acid, metformin, atorvastatin, levothyroxine) on pharmacokinetics of ustekinumab was explored. There were no indications of an interaction with these concomitantly administered medicinal products. The basis for this analysis was that at least 100 patients (> 5% of the studied population) were treated concomitantly with these medicinal products for at least 90% of the study period.
Live vaccines should not be given concurrently with STELARA (see section 4.4).
The results of an in vitro study do not suggest the need for dose adjustments in patients who are receiving concomitant CYP450 substrates (see section 5.2).
The safety and efficacy of STELARA in combination with other immunosuppressants, including biologics, or phototherapy have not been evaluated (see section 4.4).
Special populations
No pharmacokinetic data are available in patients with impaired renal or hepatic function.
No specific studies have been conducted in elderly patients.
The pharmacokinetics of ustekinumab were generally comparable between Asian and non‑Asian patients with psoriasis.
In the population pharmacokinetic analysis, there were no indications of an effect of tobacco or alcohol on the pharmacokinetics of ustekinumab.
Regulation of CYP450 enzymes
The effects of IL‑12 or IL‑23 on the regulation of CYP450 enzymes were evaluated in an in vitro study using human hepatocytes, which showed that IL‑12 and/or IL‑23 at levels of 10 ng/mL did not alter human CYP450 enzyme activities (CYP1A2, 2B6, 2C9, 2C19, 2D6, or 3A4; see section 4.5).