day of birth. The last dose of Humira was given between 1 and 56 days prior to delivery. Adalimumab concentrations were 0.16-19.7 µg/mL in cord blood, 4.28-17.7 µg/mL in infant blood, and 0-16.1 µg/mL in maternal blood. In all but one case, the cord blood level of adalimumab was higher than the maternal level, suggesting adalimumab actively crosses the placenta. In addition, one infant had levels at each of the following: 6 weeks (1.94 µg/mL), 7 weeks (1.31 µg/mL), 8 weeks (0.93 µg/mL), and 11 weeks (0.53 µg/mL), suggesting adalimumab can be detected in the serum of infants exposed in utero for at least 3 months from birth.
Animal Data
An embryo-fetal perinatal developmental toxicity study has been performed in cynomolgus monkeys at dosages up to 100 mg/kg (266 times human AUC when given 40 mg subcutaneously with methotrexate every week or 373 times human AUC when given 40 mg subcutaneously without methotrexate) and has revealed no evidence of harm to the fetuses due to adalimumab.
Nursing Mothers
Limited data from published literature indicate that adalimumab is present in low levels in human milk and is not likely to be absorbed by a breastfed infant. However, no data is available on the absorption of adalimumab from breastmilk in newborn or preterm infants. Caution should be exercised when Humira is administered to a nursing woman.
Pediatric Use
Safety and efficacy of Humira in pediatric patients for uses other than juvenile idiopathic arthritis (JIA) have not been established. Due to its inhibition of TNFα, Humira administered during pregnancy could affect immune response in the in utero-exposed newborn and infant. Data from eight infants exposed to Humira in utero, suggest adalimumab crosses the placenta [see Use in Specific Populations (8.1)]. The clinical significance of elevated adalimumab levels in infants is unknown. The safety of administering live or live-attenuated vaccines in exposed infants is unknown. Risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants.
Juvenile Idiopathic Arthritis
In the JIA trial, Humira was shown to reduce signs and symptoms of active polyarticular JIA in patients 4 to 17 years of age [see Clinical Studies (14.2)]. Humira has not been studied in children less than 4 years of age, and there are limited data on Humira treatment in children with weight <15 kg.
The safety of Humira in pediatric patients in the JIA trial was generally similar to that observed in adults with certain exceptions [see Adverse Reactions (6.1)].
Post-marketing cases of malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blockers including Humira [see Warnings and Precautions (5.2)].
Geriatric Use
A total of 519 RA patients 65 years of age and older, including 107 patients 75 years of age and older, received Humira in clinical studies RA-I through IV. No overall difference in effectiveness was observed between these subjects and younger subjects. The frequency of serious infection and malignancy among Humira treated subjects over 65 years of age was higher than for those under 65 years of age. Because there is a higher incidence of infections and malignancies in the elderly population, use caution when treating the elderly.
Overdosage
Doses up to 10 mg/kg have been administered to patients in clinical trials without evidence of dose-limiting toxicities. In case of |
