dence of harm to offspring during the pre- and postnatal development phase when dosed at 50 mg per 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.
8.3Nursing 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.
8.4Pediatric Use
Safety and effectiveness of ACTEMRA in pediatric patients with conditions other than SJIA have not been established. Children under the age of two have not been studied. Testing of a murine analogue of tocilizumab did not exert toxicity in juvenile mice. In particular, there was no impairment of skeletal growth, immune function and sexual maturation.
8.5Geriatric 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 of infections in the elderly population in general, caution should be used when treating the elderly.
8.6Hepatic 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)].
8.7Renal 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)].
9DRUG 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 results in dependence.
10OVERDOSAGE
There are limited data available on overdoses with ACTEMRA. One case of accidental overdose was reported in which a patient with multiple myeloma received a dose of 40 mg per kg. No adverse drug reactions were observed. No serious adverse drug reactions were observed in healthy volunteers who received single doses of up to 28 mg per kg, although all 5 patients at the highest dose of 28 mg per kg developed dose-limiting neutropenia.
In case of an overdose, it is recommended that the patient be monitored for signs and symptoms of adverse reactions. Patients who develop adverse reactions should receive appropriate symptomatic treatment.
11DESCRIPTION
ACTEMRA (tocilizumab) is a recombinant humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody of the immunoglobulin IgG1κ (gamma 1, kappa) subclass with a typical H2L2 polypeptide structure. Each light chain and heavy chain consists of 214 and 448 amino acid
