9;s disease patients, there are indications that concomitant use of methotrexate and other immunomodulators reduces the formation of antibodies against infliximab and increases the plasma concentrations of infliximab. However, the results are uncertain due to limitations in the methods used for serum analyses of infliximab and antibodies against infliximab.
Corticosteroids do not appear to affect the pharmacokinetics of infliximab to a clinically relevant extent.
The combination of Remicade and anakinra or abatacept is not recommended (see section 4.4).
It is recommended that live vaccines not be given concurrently with Remicade (see section 4.4).
4.6 Pregnancy and lactation
Women of childbearing potential
Women of childbearing potential must use adequate contraception to prevent pregnancy and continue its use for at least 6 months after the last Remicade treatment.
Pregnancy
The moderate number (approximately 450) of prospectively collected pregnancies exposed to infliximab with known outcomes, including a limited number (approximately 230) exposed during the first trimester, does not indicate unexpected effects on pregnancy outcome. Due to its inhibition of TNFα, infliximab administered during pregnancy could affect normal immune responses in the newborn. In a developmental toxicity study conducted in mice using an analogous antibody that selectively inhibits the functional activity of mouse TNFα, there was no indication of maternal toxicity, embryotoxicity or teratogenicity (see section 5.3).
The available clinical experience is too limited to exclude a risk, and administration of infliximab is therefore not recommended during pregnancy.
Infliximab crosses the placenta and has been detected up to 6 months in the serum of infants born to women treated with infliximab during pregnancy. Consequently, these infants may be at increased risk for infection. Administration of live vaccines to infants exposed to infliximab in utero is not recommended for 6 months following the mother's last infliximab infusion during pregnancy (see sections 4.4 and 4.5).
Lactation
It is not known whether infliximab is excreted in human milk or absorbed systemically after ingestion. Because human immunoglobulins are excreted in milk, women must not breast feed for at least 6 months after Remicade treatment.
Fertility
There are insufficient preclinical data to draw conclusions on the effects of infliximab on fertility and general reproductive function (see section 5.3).
4.7 Effects on ability to drive and use machines
Remicade may have a minor influence on the ability to drive and use machines. Dizziness may occur following administration of Remicade (see section 4.8).
4.8 Undesirable effects
Upper respiratory tract infection was the most common adverse drug reaction (ADR) reported in clinical trials, occurring in 25.3% of infliximab-treated patients compared with 16.5% of control patients. The most serious ADRs associated with the use of TNF blockers that have been reported for Remicade include HBV reactivation, CHF, serious infections (including sepsis, opportunistic infections and TB), serum sickness (delayed hypersensitivity reactions), haematologic reactions, systemic lupus erthematosus/lupus-like syndrome, demyelinating disorders, hepatobiliary events, lymphoma, HSTCL, intestinal or perianal abscess (in Crohn's disease), and serious infusion reactions (see section 4.4).
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