ot recommended (see section 4.4).
Co-administration of Cimzia with methotrexate had no significant effect on the pharmacokinetics of methotrexate. In study-to-study comparison, the pharmacokinetics of certolizumab pegol appeared similar to those observed previously in healthy subjects.
4.6 Pregnancy and lactation
Women of childbearing potential
Women of childbearing potential should use adequate contraception to prevent pregnancy and continue its use for at least 5 months after the last Cimzia administration.
Pregnancy
There are no adequate data from the use of Cimzia in pregnant women.
Animal studies using a rodent anti-rat TNFα did not reveal evidence of impaired fertility or harm to the foetus. However, these are insufficient with respect to human reproductive toxicity (see section 5.3). Due to its inhibition of TNFα, Cimzia administered during pregnancy could affect normal immune response in the newborn. Therefore, Cimzia should not be used in pregnancy.
Breast-feeding
There is insufficient information on the excretion of certolizumab pegol in human or animal breast milk. Since immunoglobulins are excreted into human breast milk, a risk to the breast-feeding child cannot be excluded. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Cimzia should be made taking into account the benefit of breast-feeding to the child and the benefit of Cimzia therapy to the woman.
Fertility
Effects on sperm motility measures and a trend of reduced sperm count in male rodents have been observed with no apparent effect on fertility (see section 5.3). The clinical relevance of this finding is unknown.
4.7 Effects on ability to drive and use machines
Cimzia may have a minor influence on the ability to drive and use machines. Dizziness (including vertigo, vision disorder and fatigue) may occur following administration of Cimzia (see section 4.8)
4.8 Undesirable effects
Cimzia was studied in 2,367 patients with rheumatoid arthritis in controlled and open label trials for up to 57 months. The data in Table 1 are based primarily on the pivotal controlled Studies involving 1,774 patients receiving Cimzia and 647 patients receiving placebo during the controlled period.
In the placebo-controlled studies, patients receiving Cimzia had an approximately 4 times greater duration of exposure compared with the placebo group. This difference in exposure is primarily due to patients on placebo being more likely to withdraw early. In addition, Studies RA-I and RA-II had a mandatory withdrawal for non-responders at Week 16, the majority of whom were on placebo.
The proportion of patients who discontinued treatment due to adverse events during the controlled trials was 5% for patients treated with Cimzia and 2.5% for patients treated with placebo.
The most common adverse reactions belonged to the system organ classes Infections and infestations, reported in 15.5% of patients on Cimzia and 7.6% of patients on placebo, and General disorders and administration site conditions, reported in 10.0% of patients on Cimzia and 9.7% of patients on placebo.
Adverse reactions reported in rheumatoid arthritis clinical trials and postmarketing at least possibly related to Cimzia are listed in Table 1 below, according to frequency and system organ class. Frequency categories are defined as follows: Very common ( 1/10); Common ( 1/100 to < 1/10); Uncommon ( 1/1000 to <1/100); Rare ( 1/10, |
