te drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc. The effect of tocilizumab on CYP450 enzyme activity may persist for several weeks after stopping therapy [see Clinical Pharmacology (12.3)].
7.3 Live Vaccines
Live vaccines should not be given concurrently with ACTEMRA [see Warnings and Precautions (5.8)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Teratogenic Effects. Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. ACTEMRA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
An embryo-fetal developmental toxicity study was performed in which pregnant cynomolgus monkeys were treated intravenously with tocilizumab (daily doses of 2, 10, or 50 mg/kg from gestation day 20-50) during organogenesis. Although there was no evidence for a teratogenic/dysmorphogenic effect at any dose, tocilizumab produced an increase in the incidence of abortion/embryo-fetal death at 10 mg/kg and 50 mg/kg doses (1.25 and 6.25 times the human dose of 8 mg/kg every 4 weeks based on a mg/kg comparison).
Nonteratogenic Effects. Testing of a murine analogue of tocilizumab in mice did not yield any evidence of harm to offspring during the pre- and postnatal development phase when dosed at 50 mg/kg intravenously with treatment every three days from implantation until day 21 after delivery (weaning). There was no evidence for any functional impairment of the development and behavior, learning ability, immune competence and fertility of the offspring.
Pregnancy Registry: To monitor the outcomes of pregnant women exposed to ACTEMRA, a pregnancy registry has been established. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-877-311-8972.
8.3 Nursing Mothers
It is not known whether tocilizumab is excreted in human milk or absorbed systemically after ingestion. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from ACTEMRA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
8.4 Pediatric Use
Safety and effectiveness of ACTEMRA in pediatric patients have not been established.
8.5 Geriatric Use
Of the 2644 patients who received ACTEMRA in Studies I to V [see Clinical Studies (14)], a total of 435 rheumatoid arthritis patients were 65 years of age and older, including 50 patients 75 years and older. The frequency of serious infection among ACTEMRA treated subjects 65 years of age and older was higher than those under the age of 65. As there is a higher incidence in infections in the elderly population in general, caution should be used when treating the elderly.
8.6 Hepatic Impairment
The safety and efficacy of ACTEMRA have not been studied in patients with hepatic impairment, including patients with positive HBV and HCV serology [see Warnings and Precautions (5.7)].
8.7 Renal Impairment
No dose adjustment is required in patients with mild renal impairment. ACTEMRA has not been studied in patients with moderate to severe renal impairment [see Clinical Pharmacology (12.3)].
9 DRUG ABUSE AND DEPENDENCE
No studies on the potential for ACTEMRA to cause dependence have been performed. However, there is no evidence from the available data that ACTEMRA treatment r |
