Simponi Aria

Pregnancy

There are no adequate and well-controlled trials in pregnant women; monoclonal antibodies are transported across the placenta during the third trimester and may affect immune response in the in utero exposed infant

Use during pregnancy only if clearly needed

Golimumab crosses the placenta during pregnancy; another TNF-blocking monoclonal antibody administered during pregnancy detected for up to 6 months in serum of infants; consequently, infants may be at increased risk of infection; administration of live vaccines to infants exposed to drug in utero is not recommended for 6 months following the mother’s last injection during pregnancy

Live vaccines administration to infants exposed to golimumab in utero is not recommended for 6 months following the mother’s last dose during pregnancy

Lactation

There is no information regarding the presence in human milk, the effects on breastfed infants, or the effects on milk production

Maternal IgG is known to be present in human milk; the effects of local exposure in gastrointestinal tract and potential limited systemic exposure in the infant to golimumab are unknown; developmental and health benefits of breast-feeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breast-fed infants or from the underlying maternal condition

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Mechanism of Action

Human anti-TNF-alpha monoclonal antibody, blocks inflammatory activity of TNF-alpha

Absorption

Bioavailability: 53% (SC)

Peak Plasma Time (50 mg dose): 2-6 days

Peak Plasma Concentration: 2.5 mcg/mL

Distribution

Vd: 58-126 mL/kg

Elimination

Half Life: 2 wk

Clearance: 4.0-6.7 mL/kg/day

Simponi Aria is a prescription medication used, along with another medication called methotrexate, to treat moderate to severe rheumatoid arthritis in adults. Simponi Aria belongs to class of medications called tumor necrosis factor (TNF) inhibitors. These work by blocking the action of TNF, a substance in the body that promote inflammation.

This medication is available in an injectable form to be given directly into a vein by a healthcare professional, typically every 8 weeks. 

Common side effects of Simponi Aria include upper respiratory tract infections, viral infections, and skin rashes.

Simponi Aria can also cause dizziness. Do not drive or operate heavy machinery until you know how Simponi Aria affects you.

Simponi Aria is a prescription medication used, along with another medication called methotrexate, to treat moderately to severely active rheumatoid arthritis in adults.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with Simponi Aria. See the “Simponi Aria Precautions” section.

Common side effects of Symponi Aria include:

• upper respiratory infections such as runny nose, sore throat, and hoarseness or laryngitis
• redness and/or pain at the injection site
• skin rashes
• bronchitis
• high blood pressure
• viral infections such as flu and/or cold sores in the mouth

This is not a complete list of Symponi Aria side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Use Simponi Aria as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Signs of lupus like a rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs.
• Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• Chest pain or pressure.
• Feeling very tired or weak.
• Swollen gland.
• Night sweats.
• A big weight loss.
• Any unexplained bruising or bleeding.
• Pale skin.
• Red scaly patches or bumps that are pus filled.
• A skin lump or growth.
• Heart failure has happened with this medicine, as well as heart failure that has gotten worse in people who already have it. Sometimes, this has been deadly. Tell your doctor if you have heart disease. Call your doctor right away if you have shortness of breath, a big weight gain, a heartbeat that is not normal, or swelling in the arms or legs that is new or worse.
• Rarely, people using drugs like this one have had nervous system problems. Sometimes, these problems have not gone away. Call your doctor right away if you have a burning, numbness, or tingling feeling that is not normal; change in eyesight; dizziness; seizures; or weakness in your arms or legs.

Rheumatoid Arthritis

Simponi Aria, in combination with methotrexate (MTX), is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis.

Rheumatoid Arthritis

The Simponi Aria dosage regimen is 2 mg per kg given as an intravenous infusion over 30 minutes at weeks 0 and 4, then every 8 weeks thereafter.

Simponi Aria should be given in combination with methotrexate. Other non-biologic DMARDs, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or analgesics may be continued during treatment with Simponi Aria.

The efficacy and safety of switching between intravenous and subcutaneous formulations and routes of administration have not been established.

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:

1. Calculate the dosage and the number of Simponi Aria vials needed based on the recommended dosage of 2 mg/kg and the patient's weight. Each 4 mL vial of Simponi Aria contains 50 mg of golimumab.
2. 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.
3. 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.
4. Prior to infusion, visually inspect the diluted Simponi Aria solution for particulate matter or discoloration. Do not use if these exist.
5. Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter (pore size 0.22 micrometer or less).
6. 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.
7. Infuse the diluted solution over 30 minutes.
8. Once diluted, the infusion solution can be stored for 4 hours at room temperature.

Serious Infections

Patients treated with Simponi Aria are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death.

Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, or parasitic organisms including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, and tuberculosis have been reported with TNF-blockers. Patients have frequently presented with disseminated rather than localized disease. The concomitant use of a TNF-blocker and abatacept or anakinra was associated with a higher risk of serious infections; therefore, the concomitant use of Simponi Aria and these biologic products is not recommended [see Warnings and Precautions (5.6, 5.7) and Drug Interactions (7.2)].

Treatment with Simponi Aria should not be initiated in patients with an active infection, including clinically important localized infections. Patients greater than 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants such as corticosteroids or methotrexate may be at greater risk of infection. Consider the risks and benefits of treatment prior to initiating Simponi Aria in patients:

• with chronic or recurrent infection;
• who have been exposed to tuberculosis;
• with a history of an opportunistic infection;
• who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or
• with underlying conditions that may predispose them to infection.

Monitoring

Closely monitor patients for the development of signs and symptoms of infection during and after treatment with Simponi Aria. Discontinue Simponi Aria if a patient develops a serious infection, an opportunistic infection, or sepsis. For patients who develop a new infection during treatment with Simponi Aria, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient and initiate appropriate antimicrobial therapy and closely monitor them.

Tuberculosis

Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving TNF-blockers, including patients who have previously received treatment for latent or active tuberculosis. Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating Simponi Aria and periodically during therapy.

Treatment of latent tuberculosis infection prior to therapy with TNF-blockers has been shown to reduce the risk of tuberculosis reactivation during therapy. Prior to initiating Simponi Aria, assess if treatment for latent tuberculosis is needed; An induration of 5 mm or greater is a positive tuberculin skin test, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG).

Consider anti-tuberculosis therapy prior to initiation of Simponi Aria in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate for an individual patient.

Cases of active tuberculosis have occurred in patients treated with the subcutaneous formulation of golimumab during and after treatment for latent tuberculosis. Monitor patients for the development of signs and symptoms of tuberculosis including patients who tested negative for latent tuberculosis infection prior to initiating therapy, patients who are on treatment for latent tuberculosis, or patients who were previously treated for tuberculosis infection.

Consider tuberculosis in the differential diagnosis in patients who develop a new infection during Simponi Aria treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis.

Invasive Fungal Infections

If patients develop a serious systemic illness and they reside or travel in regions where mycoses are endemic, consider invasive fungal infection in the differential diagnosis. Consider appropriate empiric antifungal therapy and take into account both the risk for severe fungal infection and the risks of antifungal therapy while a diagnostic workup is being performed. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. To aid in the management of such patients, consider consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections.

Hepatitis B Virus Reactivation

The use of TNF-blockers, of which Simponi Aria is a member, has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic hepatitis B carriers (i.e., surface antigen positive). In some instances, HBV reactivation occurring in conjunction with TNF-blocker therapy has been fatal. The majority of these reports have occurred in patients who received concomitant immunosuppressants.

All patients should be tested for HBV infection before initiating TNF-blocker therapy. For patients who test positive for hepatitis B surface antigen, consultation with a physician with expertise in the treatment of hepatitis B is recommended before initiating TNF-blocker therapy. The risks and benefits of treatment should be considered prior to prescribing TNF-blockers, including Simponi Aria, to patients who are carriers of HBV. Adequate data are not available on whether antiviral therapy can reduce the risk of HBV reactivation in HBV carriers who are treated with TNF-blockers. Patients who are carriers of HBV and require treatment with TNF-blockers should be closely monitored for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy.

In patients who develop HBV reactivation, TNF-blockers should be stopped and antiviral therapy with appropriate supportive treatment should be initiated. The safety of resuming TNF-blockers after HBV reactivation has been controlled is not known. Therefore, prescribers should exercise caution when considering resumption of TNF-blockers in this situation and monitor patients closely.

Malignancies

Malignancies in Pediatric Patients

Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blocking agents (initiation of therapy ≤ 18 years of age), of which Simponi Aria is a member. Approximately half the cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression, and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months (range 1 to 84 months) after the first dose of TNF-blocker therapy. Most of the patients were receiving concomitant immunosuppressants. These cases were reported postmarketing and are derived from a variety of sources, including registries and spontaneous postmarketing reports. Use of Simponi Aria in patients under 18 years of age has not been established.

Malignancies in Adult Patients

The risks and benefits of TNF-blocker treatment including Simponi Aria should be considered prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing a TNF-blocker in patients who develop a malignancy.

In the controlled portions of clinical trials of TNF-blockers including the subcutaneous formulation of golimumab more cases of lymphoma have been observed among patients receiving anti-TNF treatment compared with patients in the control groups. Patients with RA and other chronic inflammatory diseases, particularly patients with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF-blocking therapy. Cases of acute and chronic leukemia have been reported with TNF-blocker use, including Simponi Aria, in rheumatoid arthritis and other indications. Even in the absence of TNF-blocker therapy, patients with rheumatoid arthritis may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia.

Rare postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF-blocking agents. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. Nearly all of the reported TNF-blocker associated cases have occurred in patients with Crohn's disease or ulcerative colitis. The majority were in adolescent and young adult males. Almost all these patients had received treatment with azathioprine (AZA) or 6-mercaptopurine (6–MP) concomitantly with a TNF-blocker at or prior to diagnosis. A risk for the development for hepatosplenic T-cell lymphoma in patients treated with TNF-blockers cannot be excluded.

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

In controlled trials of other TNF-blockers in patients at higher risk for malignancies (e.g., patients with chronic obstructive pulmonary disease [COPD], patients with Wegener's granulomatosis treated with concomitant cyclophosphamide) a greater portion of malignancies occurred in the TNF-blocker group compared to the controlled group. In an exploratory clinical trial evaluating the use of the subcutaneous formulation of golimumab in patients with severe persistent asthma, more patients treated with golimumab reported malignancies compared with control patients. The significance of this finding is unknown.

During the controlled portion of the Phase 3 trial in RA for Simponi Aria, the incidence of malignancies other than lymphoma and NMSC per 100-patient-years of follow-up was 0.56 (95% CI: 0.01, 3.11) in the Simponi Aria group compared with an incidence of 0 (95% CI: 0.00, 3.79) in the placebo group.

Congestive Heart Failure

Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF-blockers, including Simponi Aria. Some cases had a fatal outcome. In several exploratory trials of other TNF-blockers in the treatment of CHF, there were greater proportions of TNF-blocker treated patients who had CHF exacerbations requiring hospitalization or increased mortality. Simponi Aria has not been studied in patients with a history of CHF and Simponi Aria should be used with caution in patients with CHF. If a decision is made to administer Simponi Aria to RA patients with CHF, these patients should be closely monitored during therapy, and Simponi Aria should be discontinued if new or worsening symptoms of CHF appear.

Demyelinating Disorders

Use of TNF-blockers, of which Simponi Aria is a member, has been associated with rare cases of new onset or exacerbation of central nervous system (CNS) demyelinating disorders, including multiple sclerosis (MS) and peripheral demyelinating disorders, including Guillain-Barré syndrome. Cases of central demyelination, MS, optic neuritis, and peripheral demyelinating polyneuropathy have rarely been reported in patients treated with the subcutaneous formulation of golimumab. Prescribers should exercise caution in considering the use of TNF-blockers, including Simponi Aria, in patients with central or peripheral nervous system demyelinating disorders. Discontinuation of Simponi Aria should be considered if these disorders develop.

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 [see Adverse Reactions (6.1)]. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with Simponi Aria, treatment should be discontinued.

Use with Abatacept

In controlled trials, the concurrent administration of another TNF-blocker and abatacept was associated with a greater proportion of serious infections than the use of a TNF-blocker alone; and the combination therapy, compared to the use of a TNF-blocker alone, has not demonstrated improved clinical benefit in the treatment of RA. Therefore, the combination of TNF-blockers, including Simponi Aria, and abatacept is not recommended [see Drug Interactions (7.2)].

Use with Anakinra

Concurrent administration of anakinra (an interleukin-1 antagonist) and another TNF-blocker was associated with a greater portion of serious infections and neutropenia and no additional benefits compared with the TNF-blocker alone. Therefore, the combination of anakinra with TNF-blockers, including Simponi Aria, is not recommended [see Drug Interactions (7.2)].

Switching Between Biological Disease Modifying Antirheumatic Drugs (DMARDs)

Care should be taken when switching from one biologic product to another biologic product since overlapping biological activity may further increase the risk of infection.

Hematologic Cytopenias

There have been postmarketing reports of pancytopenia, leukopenia, neutropenia, aplastic anemia, and thrombocytopenia in patients receiving TNF-blockers. In clinical studies, cases of pancytopenia, leukopenia, neutropenia, and thrombocytopenia have also occurred in Simponi Aria-treated patients. Caution should be exercised when using TNF-blockers, including Simponi Aria, in patients who have or have had significant cytopenias.

Vaccinations/Therapeutic Infectious Agents

Live Vaccines

Patients treated with Simponi Aria may receive vaccinations, except for live vaccines. In patients receiving anti-TNF therapy, limited data are available on the response to live vaccination, or on the secondary transmission of infection by live vaccines. Use of live vaccines could result in clinical infections, including disseminated infections.

Therapeutic Infectious Agents

Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g., BCG bladder instillation for the treatment of cancer) could result in clinical infections, including disseminated infections. It is recommended that therapeutic infectious agents not be given concurrently with Simponi Aria.

Hypersensitivity Reactions

In postmarketing experience, serious systemic hypersensitivity reactions (including anaphylaxis) have been reported following administration of the subcutaneous and intravenous formulations of golimumab including Simponi Aria. Hypersensitivity reactions including hives, pruritus, dyspnea, and nausea, were reported during infusion and generally within an hour after infusion. Some of these reactions occurred after the first administration of golimumab. If an anaphylactic or other serious allergic reaction occurs, administration of Simponi Aria should be discontinued immediately and appropriate therapy instituted.