Dosage & Administration
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Simponi ARIA Prescribing Information
SERIOUS INFECTIONS
Patients treated with SIMPONI ARIA are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions (5.1)] . Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Discontinue SIMPONI ARIA if a patient develops a serious infection.
Reported infections with TNF blockers, of which SIMPONI ARIA is a member, include:
- Active tuberculosis, including reactivation of latent tuberculosis. Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease. Test patients for latent tuberculosis before SIMPONI ARIA use and during therapy. Initiate treatment for latent tuberculosis prior to SIMPONI ARIA use.
- Invasive fungal infections including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
- Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.
Consider the risks and benefits of treatment with SIMPONI ARIA prior to initiating therapy in patients with chronic or recurrent infection.
Monitor patients closely for the development of signs and symptoms of infection during and after treatment with SIMPONI ARIA, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy [see Warnings and Precautions (5.1)] .
MALIGNANCY
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF-blockers, of which SIMPONI ARIA is a member [see Warnings and Precautions (5.2)] .
Rheumatoid Arthritis (RA)
SIMPONI ARIA, in combination with methotrexate (MTX), is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis.
Psoriatic Arthritis (PsA)
SIMPONI ARIA is indicated for the treatment of active psoriatic arthritis in patients 2 years of age and older.
Ankylosing Spondylitis (AS)
SIMPONI ARIA is indicated for the treatment of adult patients with active ankylosing spondylitis.
Polyarticular Juvenile Idiopathic Arthritis (pJIA)
SIMPONI ARIA is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (pJIA) in patients 2 years of age and older.
Dosage in Adults with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis
The SIMPONI ARIA dosage regimen is 2 mg per kg given as an intravenous infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter. Follow the dilution and administration instructions for SIMPONI ARIA [see Dosage and Administration (2.4)] .
For patients with rheumatoid arthritis (RA), SIMPONI ARIA should be given in combination with methotrexate.
The efficacy and safety of switching between intravenous and subcutaneous formulations and routes of administration have not been established.
Dosage in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis
The SIMPONI ARIA dosage regimen, based on body surface area (BSA), is 80 mg/m 2given as an intravenous infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter. Follow the dilution and administration instructions for SIMPONI ARIA [see Dosage and Administration (2.4)] .
Evaluation for Tuberculosis and Hepatitis B Prior to Dosage
Prior to initiating SIMPONI ARIA and periodically during therapy, evaluate patients for active tuberculosis and test for latent infection [see Warnings and Precautions (5.1)] . Prior to initiating SIMPONI ARIA, test patients for hepatitis B viral infection [see Warnings and Precautions (5.1)] .
Important Administration Instructions
SIMPONI ARIA solution for intravenous infusion should be diluted by a healthcare professional using aseptic technique as follows:
- Calculate the dosage and the number of SIMPONI ARIA vials needed based on the recommended adult dosage of 2 mg/kg and the patient's weight for RA, PsA and AS. Calculate the dosage and number of SIMPONI ARIA vials needed based on the recommended pediatric dosage of 80 mg/m 2and the patient's body surface area (BSA), for pJIA and pediatric patients with PsA. Each 4 mL vial of SIMPONI ARIA contains 50 mg of golimumab.
- Check that the solution in each vial is colorless to light yellow. The solution may develop a few fine translucent particles, as golimumab is a protein. Do not use if opaque particles, discoloration, or other foreign particles are present.
- Dilute the total volume of the SIMPONI ARIA solution with 0.9% Sodium Chloride Injection, USP to a final volume of 100 mL. For example, this can be accomplished by withdrawing a volume of the 0.9% Sodium Chloride Injection, USP from the 100-mL infusion bag or bottle equal to the total volume of SIMPONI ARIA. Slowly add the total volume of SIMPONI ARIA solution to the 100-mL infusion bag or bottle. Gently mix. Discard any unused solution remaining in the vials. Alternatively, SIMPONI ARIA can be diluted using the same method described above with 0.45% Sodium Chloride Injection, USP.
- Prior to infusion, visually inspect the diluted SIMPONI ARIA solution for particulate matter or discoloration. Do not use if these are present.
- Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter (pore size 0.22 micrometer or less).
- Do not infuse SIMPONI ARIA concomitantly in the same intravenous line with other agents. No physical biochemical compatibility studies have been conducted to evaluate the use of SIMPONI ARIA with other intravenous agents in the same intravenous line.
- Infuse the diluted solution over 30 minutes.
- Once diluted, the infusion solution can be stored for up to 4 hours at room temperature.
Injection: 50 mg/4 mL (12.5 mg/mL) colorless to light yellow solution in a single-dose vial.
Pregnancy
Risk Summary
Available data from postmarketing case reports with golimumab use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. An observational study of northern European births observed similar unadjusted rates of major birth defects in infants exposed in utero to golimumab compared to no treatment or non-biologic systemic therapy. However, this study had important limitations ( see Data).
Monoclonal antibodies, such as golimumab, are transported across the placenta during the third trimester of pregnancy and may affect immune response in the in uteroexposed infant. There are clinical considerations for the use of SIMPONI ARIA in pregnant women (see Clinical Considerations) . In an animal reproductive study, golimumab administered by the subcutaneous route to pregnant monkeys, during the period of organogenesis, at doses that produced exposures approximately 200 times the maximum recommended human dose (MRHD) had no adverse fetal effects.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and of miscarriage is 15–20%, respectively.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
Golimumab crosses the placenta during pregnancy. Another TNF-blocking monoclonal antibody administered during pregnancy was detected for up to 6 months in the serum of infants. Consequently, these infants may be at increased risk of infection. Administration of live vaccines to infants exposed to SIMPONI ARIA in uterois not recommended for 6 months following the mother's last SIMPONI ARIA infusion during pregnancy [see Warnings and Precautions (5.10)and Drug Interactions (7.3)] .
Data
Human Data
An observational, exposure-based, cohort study based on data from the Swedish, Danish, and Finnish Medical Birth Registers conducted between 2006–2020 (Sweden and Denmark) and 2006–2019 (Finland) compared the risk of major birth defects in 134 live-born infants exposed to golimumab (116 from women treated for rheumatic conditions, 18 from women treated for ulcerative colitis) to no treatment or nonbiologic systemic therapy. The unadjusted rate of major birth defects in infants exposed in uterowas similar across all groups. However, this study had important limitations such as a small number of pregnant women exposed to golimumab, a wide exposure ascertainment window, and incomplete risk adjustment for potential confounders.
Animal Data
In an embryofetal developmental toxicology study in which pregnant cynomolgus monkeys were treated with golimumab during the period of organogenesis from gestation days (GD) 20 to 51, exposures up to 200 times greater than the exposure at the MRHD (on an area under the curve (AUC) basis with maternal subcutaneous doses up to 50 mg/kg twice weekly) produced no evidence of fetal malformations or embryotoxicity. There was no evidence of maternal toxicity. Umbilical cord blood samples collected at the end of the second trimester showed that fetuses were exposed to golimumab during gestation.
In a pre- and postnatal developmental study in which pregnant cynomolgus monkeys were treated with golimumab from gestation day 50 to postpartum day 33, maximal drug concentrations up to 33 times greater than that found with the MRHD (on a maximum blood concentration (C max) basis at steady-state with maternal subcutaneous doses up to 50 mg/kg twice weekly) were not associated with any evidence of developmental defects in infants. There was no evidence of maternal toxicity. Golimumab was present in fetal serum at the end of the second trimester and in neonatal serum from the time of birth and for up to 6 months postpartum.
Lactation
Risk Summary
There is no information regarding the presence of SIMPONI ARIA in human milk, the effects on breastfed infants, or the effects on milk production. Maternal IgG is known to be present in human milk. Golimumab is present in the milk of lactating cynomolgus monkeys (see Data) . If golimumab is transferred into human milk, the effects of local exposure in the gastrointestinal tract and potential limited systemic exposure in the infant to golimumab are unknown. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for SIMPONI ARIA and any potential adverse effects on the breast-fed infants from SIMPONI ARIA, or from the underlying maternal condition.
Data
In the pre- and postnatal development study in cynomolgus monkeys in which golimumab was administered subcutaneously during pregnancy and lactation, golimumab was detected in the breast milk at concentrations that were approximately 400 fold lower than the maternal serum concentrations.
Pediatric Use
Safety and effectiveness of SIMPONI ARIA for active polyarticular juvenile idiopathic arthritis and PsA have been established in pediatric patients 2 years and older.
Use of SIMPONI ARIA in these age groups is supported by evidence from adequate and well-controlled studies of SIMPONI ARIA in adults with RA and PsA, pharmacokinetic data from adult patients with RA and PsA and pediatric patients with JIA with active polyarthritis, and safety data from a clinical study in 127 pediatric patients 2 to < 18 years of age with JIA with active polyarthritis. The observed pre-dose (trough) concentrations are generally comparable between adults with RA and PsA and pediatric patients with JIA with active polyarthritis, and the PK exposure is expected to be comparable between adult PsA and pediatric patients with PsA [see Adverse Reactions (6.1), Clinical Pharmacology (12.3)and Clinical Studies (14.2, 14.4)] .
Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with golimumab and other TNF-blocking agents [see Warnings and Precautions (5.2)].
The safety and effectiveness in pediatric patients below the age of 2 years have not been established in pJIA or in PsA. The safety and effectiveness of SIMPONI ARIA in pediatric patients with conditions other than pJIA and PsA have not been established.
Geriatric Use
In Trial RA, the number of patients ages 65 or older was too small to make comparisons with younger SIMPONI ARIA-treated patients. Because there is a higher incidence of infections in the geriatric population in general, caution should be used in treating geriatric patients with SIMPONI ARIA.
None.