WARNINGS AND PRECAUTIONS
Infections
STELARA™ may increase the risk of infections and reactivation of latent infections. Serious bacterial, fungal, and viral infections were observed in subjects receiving STELARA™ [see Adverse Reactions].
STELARA™ should not be given to patients with any clinically important active infection. STELARA™ should not be administered until the infection resolves or is adequately treated. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. Exercise caution when considering the use of STELARA™ in patients with a chronic infection or a history of recurrent infection.
Serious infections requiring hospitalization occurred in the psoriasis development program. These serious infections included cellulitis, diverticulitis, osteomyelitis, viral infections, gastroenteritis, pneumonia, and urinary tract infections.
Theoretical Risk for Vulnerability to Particular Infections
Individuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections from mycobacteria (including nontuberculous, environmental mycobacteria), salmonella (including nontyphi strains), and Bacillus Calmette-Guerin (BCG) vaccinations. Serious infections and fatal outcomes have been reported in such patients.
It is not known whether patients with pharmacologic blockade of IL-12/IL-23 from treatment with STELARA™ will be susceptible to these types of infections. Appropriate diagnostic testing should be considered, e.g., tissue culture, stool culture, as dictated by clinical circumstances.
Pre-treatment Evaluation for Tuberculosis
Evaluate patients for tuberculosis infection prior to initiating treatment with STELARA™.
Do not administer STELARA™ to patients with active tuberculosis. Initate treatment of latent tuberculosis prior to administering STELARA™. Consider anti-tuberculosis therapy prior to initiation of STELARA™ in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed. Patients receiving STELARA™ should be monitored closely for signs and symptoms of active tuberculosis during and after treatment.
Malignancies
STELARA™ is an immunosuppressant and may increase the risk of malignancy. Malignancies were reported among subjects who received STELARA™ in clinical studies [see Adverse Reactions]. In rodent models, inhibition of IL-12/IL-23p40 increased the risk of malignancy [see Nonclinical Toxicology].
The safety of STELARA™ has not been evaluated in patients who have a history of malignancy or who have a known malignancy.
Reversible Posterior Leukoencephalopathy Syndrome
One case of reversible posterior leukoencephalopathy syndrome (RPLS) was observed during the clinical development program which included 3523 STELARA™-treated subjects. The subject, who had received 12 doses of STELARA™ over approximately two years, presented with headache, seizures and confusion. No additional STELARA™ injections were administered and the subject fully recovered with appropriate treatment.
RPLS is a neurological disorder, which is not caused by demyelination or a known infectious agent. RPLS can present with headache, seizures, confusion and visual disturbances. Conditions with which it has been associated include preeclampsia, eclampsia, acute hypertension, cytotoxic agents and immunosuppressive therapy. Fatal outcomes have been reported.
If RPLS is suspected, STELARA™ should be discontinued and appropriate treatment administered.
Immunizations
Prior to initiating therapy with STELARA™, patients should receive all immunizations appropriate for age as recommended by current immunization guidelines. Patients being treated with STELARA™ should not receive live vaccines. BCG vaccines should not be given during treatment with STELARA™ or for one year prior to initiating treatment or one year following discontinuation of treatment. Caution is advised when administering live vaccines to household contacts of patients receiving STELARA™ because of the potential risk for shedding from the household contact and transmission to patient.
Non-live vaccinations received during a course of STELARA™ may not elicit an immune response sufficient to prevent disease.
Concomitant Therapies
The safety of STELARA™ in combination with other immunosuppressive agents or phototherapy has not been evaluated. Ultraviolet-induced skin cancers developed earlier and more frequently in mice genetically manipulated to be deficient in both IL-12 and IL-23 or IL-12 alone [see Nonclinical Toxicology].
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category B
There are no studies of STELARA™ in pregnant women. STELARA™ should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. No teratogenic effects were observed in the developmental and reproductive toxicology studies performed in cynomolgus monkeys at doses up to 45 mg/kg ustekinumab, which is 45 times (based on mg/kg) the highest intended clinical dose in psoriasis patients (approximately 1 mg/kg based on administration of a 90 mg dose to a 90 kg psoriasis patient).
Ustekinumab was tested in two embryo-fetal development toxicity studies. Pregnant cynomolgus monkeys were administered ustekinumab at doses up to 45 mg/kg during the period of organogenesis either twice weekly via subcutaneous injections or weekly by intravenous injections. No significant adverse developmental effects were noted in either study.
In an embryo-fetal development and pre- and post-natal development toxicity study, three groups of 20 pregnant cynomolgus monkeys were administered subcutaneous doses of 0, 22.5, or 45 mg/kg ustekinumab twice weekly from the beginning of organogenesis in cynomolgus monkeys to Day 33 after delivery. There were no treatment-related effects on mortality, clinical signs, body weight, food consumption, hematology, or serum biochemistry in dams. Fetal losses occurred in six control monkeys, six 22.5 mg/kg-treated monkeys, and five 45 mg/kg-treated monkeys. Neonatal deaths occurred in one 22.5 mg/kg-treated monkey and in one 45 mg/kg-treated monkey. No ustekinumab-related abnormalities were observed in the neonates from birth through six months of age in clinical signs, body weight, hematology, or serum biochemistry. There were no treatment-related effects on functional development until weaning, functional development after weaning, morphological development, immunological development, and gross and histopathological examinations of offsprings by the age of 6 months.
Nursing Mothers
Caution should be exercised when STELARA™ is administered to a nursing woman. The unknown risks to the infant from gastrointestinal or systemic exposure to ustekinumab should be weighed against the known benefits of breast-feeding. Ustekinumab is excreted in the milk of lactating monkeys administered ustekinumab. IgG is excreted in human milk, so it is expected that STELARA™ will be present in human milk. It is not known if ustekinumab is absorbed systemically after ingestion; however, published data suggest that antibodies in breast milk do not enter the neonatal and infant circulation in substantial amounts.
Pediatric Use
Safety and effectiveness of STELARA™ in pediatric patients have not been evaluated.
Geriatric Use
Of the 2266 psoriasis subjects exposed to STELARA™, a total of 131 were 65 years or older, and 14 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects.
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