Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

SIMPONI (BLA-125289)

(GOLIMUMAB)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

Expand all

10/07/2025 (SUPPL-157)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Malignancies

Additions and/or revisions underlined:

…

In the controlled portions of clinical trials of TNF blockers, including SIMPONI, more cases of lymphoma have been observed among patients receiving anti-TNF treatment compared with patients in the control groups. During the controlled portions of the Phase 2 trials in RA, and the Phase 3 trials in RA, PsA and AS, the incidence of lymphoma per 100 patient-years of follow-up was 0.21 (95% CI: 0.03, 0.77) in the combined SIMPONI group compared with an incidence of 0 (95% CI: 0, 0.96) in the placebo group. In the controlled and uncontrolled portions of these clinical trials in 2347 SIMPONI-treated patients with a median follow-up of 1.4 years, the incidence of lymphoma was 3.8-fold higher than expected in the general U.S. population according to the 1964-2004 data from SEER database (adjusted for age, gender, and race).

…

During the controlled portions of the Phase 2 trial in RA, and the Phase 3 trials in RA, PsA and AS, the incidence of malignancies other than lymphoma per 100 patient-years of follow-up was not elevated in the combined SIMPONI group compared with the placebo group. In the controlled and uncontrolled portions of these trials, the incidence of malignancies, other than lymphoma, in SIMPONI-treated patients was similar to that expected in the general U.S. population according to the 1969-2004 SEER database (adjusted for age, gender, and race). In the 6-week placebo-controlled portions of the SIMPONI Phase 2/3 clinical trials in UC, the incidence of non-lymphoma malignancies (excluding nonmelanoma skin cancer) was similar between the SIMPONI and the placebo group. Through Week 60, the incidence of non-lymphoma malignancies (excluding nonmelanoma skin cancer) was similar to the general U.S. population according to the 1969-2004 SEER database (adjusted for age, gender, and race). Short follow-up periods, such as those of one year or less in the studies above, may not adequately reflect the true incidence of malignancies.

…

5.11 Vaccinations/Therapeutic Infectious Agents

Additions and/or revisions underlined:

If possible, it is recommended that prior to initiating therapy with SIMPONI, pediatric patients be brought up to date with all immunizations in agreement with current immunization guidelines.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Serious Infections [see Warnings and Precautions (5.1)]
• Malignancies [see Warnings and Precautions (5.2)]
• Congestive Heart Failure [see Warnings and Precautions (5.3)]
• Demyelinating Disorders [see Warnings and Precautions (5.4)]
• Hepatitis B Reactivation [see Warnings and Precautions (5.5)]
• Autoimmunity [see Warnings and Precautions (5.6)]
• Hematologic Cytopenias [see Warnings and Precautions (5.10)]
• Hypersensitivity Reactions [see Warnings and Precautions (5.12)]

6.1 Clinical Trials Experience

Extensive changes; please refer to label for complete information

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Risk Summary

…

Data suggest that there are risks to the mother and the fetus associated with rheumatoid arthritis and ulcerative colitis in pregnancy (see Clinical Considerations). All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The 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

Disease-associated Maternal and/or Embryo/Fetal Risk

Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with rheumatoid arthritis or ulcerative colitis. Adverse pregnancy outcomes include preterm delivery (before 37 weeks gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.

…

8.4 Pediatric Use

Newly added information:

Ulcerative Colitis

The safety and effectiveness of SIMPONI for the treatment of moderately to severely active ulcerative colitis have been established in pediatric patients weighing at least 15 kg. Use of SIMPONI for this indication is supported by evidence from adequate and well-controlled studies in adults with additional safety and efficacy data from an open-label, study in 69 pediatric patients (4 to 17 years of age). The adverse reaction profile in these pediatric patients was similar to adults [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.5)]. Additionally, headache (17%) and pyrexia (10%) were reported in at least 10% of pediatric patients in the trial.

The safety and effectiveness of SIMPONI for the treatment of moderately to severely active ulcerative colitis have not been established in pediatric patients weighing less than 15 kg.

Polyarticular Juvenile Idiopathic Arthritis (pJIA)

…

8.5 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. Clinical studies of SIMPONI in patients with moderately to severely active ulcerative colitis did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger adult 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 [see Warnings and Precautions (5.1, 5.5)].

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Infections

Inform patients that SIMPONI may lower the ability of their immune system to fight infections. Advise patients not to start taking SIMPONI if they have an active infection. Instruct patients to contact their healthcare provider if they develop any symptoms of infection, including tuberculosis, invasive fungal infections, and hepatitis B reactivation [see Warnings and Precautions (5.1, 5.5)].

Malignancies

Inform patients that SIMPONI may increase their risk of lymphoma and other malignancies while receiving SIMPONI [see Warnings and Precautions (5.2)].

Hypersensitivity Reactions

Advise patients to stop taking SIMPONI and contact their healthcare provider immediately if they experience any symptoms of hypersensitivity reactions while taking SIMPONI [see Warnings and Precautions (5.12)].

…

Other Medical Conditions

Advise patients to report any signs of new or worsening medical conditions such as congestive heart failure, demyelinating disorders, autoimmune diseases, liver disease, or cytopenias [see Warnings and Precautions (5.3, 5.4, 5.5, 5.6, 5.10)].

Instructions for Safe Administration

The first injection should be performed under the supervision of a qualified healthcare professional. Only the prefilled syringe is recommended for pediatric self-injection.

SIMPONI Prefilled Syringe

• Adult and pediatric patients 12 years of age and older may self-inject with SIMPONI prefilled syringe.

SIMPONI SmartJect® Autoinjector

• Adult patients may self-inject with SIMPONI SmartJect® autoinjector.

• Use of the SmartJect® autoinjector for pediatric self-administration has not been evaluated.

MEDICATION GUIDE

Additions and/or revisions underlined:

What is SIMPONI?

SIMPONI is a prescription medicine called a Tumor Necrosis Factor (TNF) blocker. SIMPONI is used to treat:

• adults with the medicine methotrexate to treat moderately to severely active rheumatoid arthritis (RA)

• adults with active psoriatic arthritis (PsA) alone or with methotrexate

• adults with active ankylosing spondylitis (AS)

• adults and children weighing at least 33 pounds (15 kg) with moderately to severely active ulcerative colitis (UC)

You may continue to use other medicines that help treat your condition while taking SIMPONI, such as non-steroidal anti-inflammatory drugs (NSAIDs) and prescription steroids, as recommended by your doctor.

It is not known if SIMPONI is safe and effective in children under 18 years of age in RA, PsA, AS and or weighing less than 33 pounds (15 kg) in pediatric ulcerative colitis.

…

How should I use SIMPONI?

…

• If your doctor decides that you, your child, or a caregiver may be able to give your injections of SIMPONI at home, you should receive training on the right way to prepare and inject SIMPONI. Do not try to inject SIMPONI yourself until you have been shown the right way to give the injections by your doctor or nurse.

o Adults and children 12 years of age and older may self-inject with SIMPONI prefilled syringe.

o Only adults may self-inject with SIMPONI SmartJect autoinjector.

…

What are the possible side effects of SIMPONI?

See “What is the most important information I should know about SIMPONI?”

Serious Infections.

• Some patients have an increased chance of getting serious infections while receiving SIMPONI. These serious infections include TB and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some patients die from these infections. Do not start using SIMPONI if you have an active infection. If you get an infection while receiving treatment with SIMPONI your doctor will treat your infection and may need to stop your SIMPONI treatment.

…

Allergic Reactions. Allergic reactions can happen in people who use TNF-blocker medicines, including SIMPONI.

Some reactions may be serious and can be life-threatening. Some of these reactions can happen after receiving your first dose of SIMPONI. Stop using SIMPONI and call your doctor right away if you have any of these symptoms of an allergic reaction:

…

How should I store SIMPONI?

…

• Do not use SIMPONI after the expiration date on the carton or on the prefilled syringe, prefilled pen or SmartJect® autoinjector.

…

04/18/2025 (SUPPL-155)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

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).

…

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 utero was 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.

…

8.2 Lactation

Additions and/or revisions underlined:

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.

…

09/24/2019 (SUPPL-146)

Approved Drug Label (PDF)

6 Adverse Reactions

6.3 Postmarketing Experience

(additions and/or revisions are underlined)

The following adverse reactions have been identified during post-approval use of golimumab. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to SIMPONI exposure.

Immune system disorders: Serious systemic hypersensitivity reactions (including anaphylactic reaction), sarcoidosis

Neoplasms benign, malignant and unspecified: Melanoma, Merkel cell carcinoma

Respiratory, thoracic and mediastinal disorders: Interstitial lung disease

Skin and subcutaneous tissue disorders: Skin exfoliation, lichenoid reactions, rash, bullous skin reactions

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

(extensive revisions; please refer to labeling for complete information)

PATIENT COUNSELING INFORMATION

(additions and/or revisions are underlined)

…

Instructions for Safe Administration

The first self-injection should be performed under the supervision of a qualified healthcare professional. If a patient or caregiver is to administer SIMPONI, he/she should be instructed in injection techniques and their ability to inject subcutaneously should be assessed to ensure the proper administration of SIMPONI.

Advise the patient to read the FDA-approved Instructions for Use and provide the following instructions to patients:

• Prior to use, remove the prefilled syringe or the prefilled SmartJect autoinjector from the refrigerator and allow SIMPONI to sit at room temperature outside of the carton for at least 30 minutes and out of the reach of children.

• Do not warm SIMPONI in any other way. For example, do not warm SIMPONI in a microwave or in hot water.

• Do not remove the prefilled syringe needle cover or SmartJect autoinjector cap while allowing SIMPONI to reach room temperature. Remove these immediately before injection.

• Do not pull the autoinjector away from the skin until you hear a first “click” sound and then a second “click” sound (the injection is finished and the needle is pulled back). It usually takes about 3 to 6 seconds but may take up to 15 seconds for you to hear the second “click” after the first “click”. If the autoinjector is pulled away from the skin before the injection is completed, a full dose of SIMPONI may not be administered.

• A puncture-resistant container for disposal of needles and syringes should be used. Patients or caregivers should be instructed in the technique of proper syringe and needle disposal, and be advised not to reuse these items.

03/06/2018 (SUPPL-139)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Immunogenicity

(subsection added, information revised)

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to golimumab in the trials described below with the incidence of antibodies in other trials or to other products may be misleading.

Results from the EIA Method

(please refer to label)

Results from the Drug-Tolerant EIA Method

(please refer to label)

02/09/2018 (SUPPL-141)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.9 Hematologic Cytopenias

Additions and/or revisions underlined:

There have been reports of pancytopenia, leukopenia, neutropenia, agranulocytosis, aplastic anemia, and thrombocytopenia in patients receiving golimumab. Caution should be exercised …

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Addition of the following:

What are the possible side effects of SIMPONI? SIMPONI can cause serious side effects, including:

See “What is the most important information I should know about SIMPONI?”

Serious Infections.

·         Some patients have an increased chance of getting serious infections while receiving SIMPONI. These serious infections include TB and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some patients die from these infections. If you get an infection while receiving treatment with SIMPONI your doctor will treat your infection and may need to stop your SIMPONI treatment. Tell your doctor right away if you have any of the following signs of an infection while taking or after taking SIMPONI:

·         a fever

·         feel very tired

·         have a cough
have flu-like symptoms

·         warm, red, or painful skin

·         Your doctor will examine you for TB and perform a test to see if you have TB. If your doctor feels that you are at risk for TB, you may be treated with medicine for TB before you begin treatment with SIMPONI and during treatment with SIMPONI. Even if your TB test is negative your doctor should carefully monitor you for TB infections while you are taking SIMPONI. People who had a negative TB skin test before receiving SIMPONI have developed active TB.

Tell your doctor if you have any of the following symptoms while taking or after taking SIMPONI:

• cough that does not go away

• low grade fever
  weight loss

• loss of body fat and muscle (wasting)

06/22/2017 (SUPPL-133)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Immunogenicity

Additions and/or revisions underlined:

… For these reasons, comparison of the incidence of antibodies to SIMPONI with the incidence of antibodies to other products or results from different assays may be misleading.

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion; as below:

Risk Summary

There are no adequate and well-controlled trials of SIMPONI in pregnant women. Monoclonal antibodies, such as golimumab, are transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant. 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.. SIMPONI should be used during pregnancy only if clearly needed.

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.

Data

Human Data

Limited data on use of SIMPONI in pregnant women from observational studies, published case reports, and postmarketing surveillance are insufficient to inform a drug associated risk.

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 (Cmax) 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.

8.2 Lactation

PLLR conversion; as below:

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. 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

Animal 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.

8.4 Pediatric Use

Addition of the following:

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 (greater than or equal to 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/m2 (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/m2 (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.

01/30/2017 (SUPPL-135)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Malignancies

Additions underlined:

… Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocking agents, including SIMPONI. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer …

6 Adverse Reactions

6.2 Postmarketing Experience

Additions underlined:

The following adverse reactions have been identified during post-approval use of golimumab. Because these reactions are reported voluntarily from a population of uncertain size …

Neoplasms benign, malignant and unspecified: Melanoma, Merkel cell carcinoma …

01/08/2016 (SUPPL-127)

Approved Drug Label (PDF)

5 Warnings and Precautions

Malignancies

Malignancies in Adult Patients

• section updated

Congestive Heart Failure

• … Some cases had a fatal outcome.

Autoimmunity

• Treatment with TNF blockers, including SIMPONI ARIA, may result in the formation of antinuclear antibodies (ANA). Rarely, treatment with TNF blockers, may result in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with SIMPONI ARIA, treatment should be discontinued.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

• updated with information regarding leukemia, congestive heart failure, and autoimmune processes