Included as part of the PRECAUTIONS section.

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. Initiate 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.

There have been post marketing reports of the rapid appearance of multiple cutaneous squamous cell carcinomas in patients receiving STELARA® who had pre-existing risk factors for developing non-melanoma skin cancer. All patients receiving STELARA® should be monitored for the appearance of non-melanoma skin cancer. Patients greater than 60 years of age, those with a medical history of prolonged immunosuppressant therapy and those with a history of PUVA treatment should be followed closely [see ADVERSE REACTIONS].

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported post-marketing. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, discontinue STELARA® and institute appropriate therapy [see ADVERSE REACTIONS].

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].

Patient Counseling Information

“See FDA-approved patient labeling (Medication Guide)”

Instruct patients to read the Medication Guide before starting STELARA® therapy and to reread the Medication Guide each time the prescription is renewed.

Infections

Inform patients that STELARA® may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the doctor, and contacting their doctor if they develop any symptoms of infection.

Malignancies

Patients should be counseled about the risk of malignancies while receiving STELARA®.

Allergic Reactions

Advise patients to seek immediate medical attention if they experience any symptoms of serious allergic reactions.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of STELARA®. Published literature showed that administration of murine IL-12 caused an anti-tumor effect in mice that contained transplanted tumors and IL-12/IL-23p40 knockout mice or mice treated with anti-IL-12/IL-23p40 antibody had decreased host defense to tumors. Mice genetically manipulated to be deficient in both IL-12 and IL-23 or IL-12 alone developed UV-induced skin cancers earlier and more frequently compared to wild-type mice. The relevance of these experimental findings in mouse models for malignancy risk in humans is unknown.

A male fertility study was conducted with only 6 male monkeys per group administered subcutaneous doses of 0, 22.5, or 45 mg/kg ustekinumab twice weekly prior to mating and during the mating period for 13 weeks, followed by a 13-week treatment-free period. Although fertility and pregnancy outcomes were not evaluated in mated females, there were no treatment-related effects on parental toxicity or male fertility parameters.

A female fertility study was conducted in mice using an analogous IL-12/IL-23p40 antibody by subcutaneous administration at doses up to 50 mg/kg, twice weekly, beginning 15 days before cohabitation and continuing through GD 7. There were no treatment-related effects on maternal toxicity or female fertility parameters.

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 ustekinumabrelated 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 3117 psoriasis subjects exposed to STELARA®, a total of 183 were 65 years or older, and 21 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.

Last reviewed on RxList: 5/17/2013
This monograph has been modified to include the generic and brand name in many instances.