Dosage & Administration
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Simponi Prescribing Information
SERIOUS INFECTIONS
Patients treated with SIMPONI 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 if a patient develops a serious infection.
Reported infections with TNF blockers, of which SIMPONI 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 use and during therapy. Initiate treatment for latent TB prior to SIMPONI 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 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, 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 is a member[see Warnings and Precautions (5.2)] .
Rheumatoid Arthritis
SIMPONI, in combination with methotrexate, is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis.
Psoriatic Arthritis
SIMPONI, alone or in combination with methotrexate, is indicated for the treatment of adult patients with active psoriatic arthritis.
Ankylosing Spondylitis
SIMPONI is indicated for the treatment of adult patients with active ankylosing spondylitis.
Ulcerative Colitis
SIMPONI is indicated in adult patients with moderately to severely active ulcerative colitis who have demonstrated corticosteroid dependence or who have had an inadequate response to or failed to tolerate oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurine for:
- inducing and maintaining clinical response
- improving endoscopic appearance of the mucosa during induction
- inducing clinical remission
- achieving and sustaining clinical remission in induction responders [see Clinical Studies (14.4)].
Dosage in Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis
The SIMPONI dose regimen is 50 mg administered by subcutaneous injection once a month.
For patients with rheumatoid arthritis (RA), SIMPONI should be given in combination with methotrexate and for patients with psoriatic arthritis (PsA) or ankylosing spondylitis (AS), SIMPONI may be given with or without methotrexate or other nonbiologic Disease-Modifying Antirheumatic Drugs (DMARDs). For patients with RA, PsA, or AS, corticosteroids, non-biologic DMARDs, and/or NSAIDs may be continued during treatment with SIMPONI.
Dosage in Moderately to Severely Active Ulcerative Colitis
The recommended SIMPONI induction dosage regimen is a 200-mg subcutaneous injection at Week 0, followed by 100 mg at Week 2, and then maintenance therapy with 100 mg every 4 weeks.
Monitoring to Assess Safety
Prior to initiating SIMPONI and periodically during therapy, evaluate patients for active tuberculosis and tested for latent infection [see Warnings and Precautions (5.1)] . Prior to initiating SIMPONI, patients should be tested for hepatitis B viral infection [see Warnings and Precautions (5.1)] .
Important Administration Instructions
SIMPONI is intended for use under the guidance and supervision of a healthcare provider. After proper training in subcutaneous injection technique, a patient may self-inject with SIMPONI if a physician determines that it is appropriate. Instruct patients to follow the directions provided below [see Instructions for Use] :
- To ensure proper use, allow the prefilled syringe or autoinjector to sit at room temperature outside the carton for at least 30 minutes prior to subcutaneous injection. Do not warm SIMPONI in any other way.
- Prior to administration, visually inspect the solution for particles and discoloration through the viewing window. SIMPONI is clear to slightly opalescent and colorless to light yellow. Do not use SIMPONI, if the solution is discolored, or cloudy, or if foreign particles are present.
- Do not use any leftover product remaining in the prefilled syringe or prefilled autoinjector.
- Instruct patients sensitive to latex not to handle the needle cover on the prefilled syringe or the needle cover of the prefilled syringe within the autoinjector cap because it contains dry natural rubber (a derivative of latex).
- At the time of dosing, if multiple injections are required, administer the injections at different sites on the body.
- Rotate injection sites and never give injections into areas where the skin is tender, bruised, red, or hard.
Injection: 50 mg/0.5 mL and 100 mg/mL clear to slightly opalescent, colorless to light yellow solution in a single-dose prefilled syringe or single-dose SmartJect ®autoinjector.
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 (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 360 times the maximum recommended human dose (MRHD) had no adverse fetal effects (see Data) . In a pre- and post-natal development study with pregnant monkeys, subcutaneous administration of golimumab, during the later gestational and lactation periods, at doses producing maximal maternal blood concentrations approximately 460 times those found with the MRHD had no adverse developmental effects on infants (see Data)
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 in utero is not recommended for 6 months following the mother's last SIMPONI injection 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 organogenesis from gestation days (GD) 20 to 51, exposures up to 360 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 approximately 460 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 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 and any potential adverse effects on the breast-fed infants from SIMPONI, 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
Effectiveness of SIMPONI in pediatric patients less than 18 years of age has not been established.
The safety and efficacy of SIMPONI were evaluated in a multicenter, placebo-controlled, double-blind, randomized-withdrawal, parallel group study in 173 children (2 to 17 years of age) with active polyarticular juvenile idiopathic arthritis (pJIA) despite treatment with MTX for at least 3 months. Subjects were maintained on their stable dose of MTX at the same dose (mg/week) at study entry. Concurrent use of stable doses of oral corticosteroids (≤10 mg/day or 0.2 mg/kg/day prednisone or equivalent, whichever was less) and/or NSAIDs was permitted. In the 16 week open-label phase, all patients received MTX and SIMPONI 30 mg/m 2(maximum 50 mg) subcutaneously every 4 weeks. Patients who achieved an ACR Ped 30 response at Week 16 entered the randomized-withdrawal phase of the study and received MTX and either SIMPONI 30 mg/m 2(maximum 50 mg) or placebo every 4 weeks through Week 48.
The primary endpoint of the study was the proportion of patients who did not experience a flare between Week 16 and Week 48, among all subjects who entered the randomized withdrawal phase. The efficacy of SIMPONI in the treatment of pJIA was not demonstrated in this study because there was no statistical evidence of differences in flare rate between SIMPONI-treated patients and placebo patients between Weeks 16 and 48.
In this study, the frequency and type of the adverse reactions seen in children were generally similar to those observed in adults.
Geriatric Use
In the Phase 3 trials in RA, PsA, and AS, there were no overall differences in SAEs, serious infections, and AEs in SIMPONI-treated patients ages 65 or older (N=155) compared with younger SIMPONI-treated patients. In UC, there were insufficient numbers of patients aged 65 and over to determine whether they respond differently from patients aged 18 to 65. Because there is a higher incidence of infections in the geriatric population in general, caution should be used in treating geriatric patients with SIMPONI.
None.