Ustekinumab and Pregnancy — Prescribing Information
The following information regarding pregnancy is taken directly from the STELARA™ package insert.
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.11997
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.11997
NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment of Fertility
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.11997
This concludes the discussion of the topic Pregnancy – Risk With Ustekinumab Therapy. We encourage you to read other topics on the MEDVERSATION™ website.
Content on this page was last changed on November 19, 2009.
References:| 11997. | Stelara [prescribing information]. Horsham, PA: Centocor Ortho Biotech Inc.; December 2009. |
Prescribing Information and Medication Guide
STELARA™ (ustekinumab) Indications and Important Safety Information
INDICATIONS AND USAGE
STELARA™ is indicated for the treatment of adult patients (18 years or older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
IMPORTANT SAFETY INFORMATION
Infections
STELARA™ (ustekinumab) may increase the risk of infections and reactivation of latent infections. Serious bacterial, fungal, and viral infections were reported. Infections requiring hospitalization included cellulitis, diverticulitis, osteomyelitis, gastroenteritis, pneumonia, and urinary tract infections. STELARA™ should not be given to patients with a clinically important active infection and 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 use of STELARA™ in patients with a chronic infection or a history of recurrent infection.
Theoretical Risk for Vulnerability to Particular Infections
Individuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections from mycobacterium, Salmonella, 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. Consider appropriate diagnostic testing as dictated by clinical circumstances.
Pre-Treatment Evaluation of Tuberculosis (TB)
Evaluate patients for TB prior to initiating treatment with STELARA™. STELARA™ should not be given to patients with active TB. Initiate treatment of latent TB before administering STELARA™. Patients should be monitored closely for signs and symptoms of active TB during and after treatment with STELARA™.
Malignancies
STELARA™ is an immunosuppressant and may increase the risk of malignancy. Malignancies were reported among patients who received STELARA™ in clinical studies. 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 (RPLS)
One case of RPLS has been reported in a STELARA™-treated patient. If RPLS is suspected,
discontinue STELARA™ and administer appropriate treatment.
RPLS is a neurological disorder, which is not caused by an infection or demyelination. RPLS
can present with headache, seizures, confusion, and visual disturbances. RPLS has been
associated with fatal outcomes.
Immunizations
Prior to initiating therapy with STELARA™, patients should receive all immunizations recommended by current guidelines. Patients being treated with STELARA™ should not receive live vaccines. BCG vaccines should not be given during treatment or within one year of initiating or discontinuing STELARA™. Exercise caution when administering live vaccines to household contacts of STELARA™ patients, as shedding and subsequent transmission to STELARA™ patients may occur. 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. The relevance of these findings in mouse models for malignancy risk in humans is unknown.
Most Common Adverse Reactions
The most common adverse reactions (≥3% and higher than that with placebo) in clinical trials for STELARA™ 45 mg, STELARA™ 90 mg, or placebo were: nasopharyngitis (8%, 7%, 8%), upper respiratory tract infection (5%, 4%, 5%), headache (5%, 5%, 3%), and fatigue (3%, 3%, 2%), respectively.
Please see Full Prescribing Information, and Medication Guide for STELARA™.