Simponi 50 mg solution for injection in pre-filled pen.

Simponi 50 mg solution for injection in pre-filled syringe.

One 0.5 ml pre-filled pen or pre-filled syringe contains 50 mg of golimumab*.

* Human IgG1κ monoclonal antibody produced by a murine hybridoma cell line with recombinant DNA technology.

Excipient:

Each pre-filled pen or pre-filled syringe contains 20.5 mg sorbitol per 50 mg dose.

For a full list of excipients, see section 6.1.

Solution for injection in pre-filled pen (injection), SmartJect

Solution for injection in pre-filled syringe (injection)

The solution is clear to slightly opalescent, colourless to light yellow.

Rheumatoid arthritis (RA)

Simponi, in combination with methotrexate (MTX), is indicated for:

• the treatment of moderate to severe, active rheumatoid arthritis in adults when the response to disease-modifying anti-rheumatic drug (DMARD) therapy including MTX has been inadequate.

• the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with MTX.

Simponi, in combination with MTX, has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function.

Psoriatic arthritis (PsA)

Simponi, alone or in combination with MTX, is indicated for the treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying anti-rheumatic drug (DMARD) therapy has been inadequate. Simponi has been shown to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease (see section 5.1) and to improve physical function.

Ankylosing spondylitis (AS)

Simponi is indicated for the treatment of severe, active ankylosing spondylitis in adults who have responded inadequately to conventional therapy.

Simponi treatment is to be initiated and supervised by qualified physicians experienced in the diagnosis and treatment of rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis. Patients treated with Simponi should be given the Patient Alert Card.

Posology

Rheumatoid arthritis

Simponi 50 mg given once a month, on the same date each month.

Simponi should be given concomitantly with MTX.

Psoriatic arthritis

Simponi 50 mg given once a month, on the same date each month.

Ankylosing spondylitis

Simponi 50 mg given once a month, on the same date each month.

Available data suggest that clinical response is usually achieved within 12 to 14 weeks of treatment (after 3-4 doses). Continued therapy should be reconsidered in patients who show no evidence of therapeutic benefit within this time period.

In patients weighing more than 100 kg who do not achieve an adequate clinical response after 3 or 4 doses, increasing the dose of golimumab to 100 mg once a month may be considered, taking into account the increased risk of certain serious adverse reactions with the 100 mg dose compared with the 50 mg dose (see section 4.8). Continued therapy should be reconsidered in patients who show no evidence of therapeutic benefit after receiving 3 to 4 additional doses of 100 mg.

Missed dose

If a patient forgets to inject Simponi on the planned date, the forgotten dose should be injected as soon as the patient remembers. Patients should be instructed not to inject a double dose to make up for the forgotten dose.

The next dose should be administered based on the following guidance:

• if the dose is less than 2 weeks late, the patient should inject his/her forgotten dose and stay on his/her original monthly schedule.

• if the dose is more than 2 weeks late, the patient should inject his/her forgotten dose and a new once-monthly schedule should be established from the date of this injection.

Elderly patients ( 65 years)

No dose adjustment is required in the elderly.

Renal and hepatic impairment

Simponi has not been studied in these patient populations. No dose recommendations can be made.

Paediatric population

The safety and efficacy of Simponi in patients aged less than 18 have not yet been established. No data are available.

Method of administration

For subcutaneous use. After proper training in subcutaneous injection technique, patients may self-inject with Simponi if their physician determines that this is appropriate, with medical follow-up as necessary. Patients should be instructed to inject the full amount of Simponi according to the comprehensive instructions for administration provided in the package leaflet. For administration instructions, see section 6.6.

Hypersensitivity to the active substance or to any of the excipients (see section 6.1).

Active tuberculosis (TB) or other severe infections such as sepsis, and opportunistic infections (see section 4.4).

Moderate or severe heart failure (NYHA class III/IV) (see section 4.4).

Infections

Patients must be monitored closely for infections including tuberculosis before, during and after treatment with Simponi. Because the elimination of golimumab may take up to 5 months, monitoring should be continued throughout this period. Further treatment with Simponi must not be given if a patient develops a serious infection or sepsis (see section 4.3).

Simponi should not be given to patients with a clinically important, active infection. Caution should be exercised when considering the use of Simponi in patients with a chronic infection or a history of recurrent infection. Patients should be advised of, and avoid exposure to, potential risk factors for infection as appropriate.

Patients taking TNF-blockers are more susceptible to serious infections.

Bacterial (including sepsis and pneumonia), mycobacterial (including TB), invasive fungal and opportunistic infections, including fatalities, have been reported in patients receiving Simponi. Some of these serious infections have occurred in patients on concomitant immunosuppressive therapy that, in addition to their underlying disease, could predispose them to infections. Patients who develop a new infection while undergoing treatment with Simponi should be monitored closely and undergo a complete diagnostic eva luation. Administration of Simponi should be discontinued if a patient develops a new serious infection or sepsis, and appropriate antimicrobial or antifungal therapy should be initiated until the infection is controlled. For patients who have resided in or travelled to regions where invasive fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic, the benefits and risks of Simponi treatment should be carefully considered before initiation of Simponi therapy.

Tuberculosis

There have been reports of tuberculosis in patients receiving Simponi. It should be noted that in the majority of these reports, tuberculosis was extrapulmonary presenting as either local or disseminated disease.

Before starting treatment with Simponi, all patients must be eva luated for both active and inactive ('latent') tuberculosis. This eva luation should include a detailed medical history with personal history of tuberculosis or possible previous contact with tuberculosis and previous and/or current immunosuppressive therapy. Appropriate screening tests, i.e. tuberculin skin or blood test and chest X-ray, should be performed in all patients (local recommendations may apply). It is recommended that the conduct of these tests should be recorded in the patient's alert card. Prescribers are reminded of the risk of false negative tuberculin skin test results, especially in patients who are severely ill or immunocompromised.

If active tuberculosis is diagnosed, Simponi therapy must not be initiated (see section 4.3).

If latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be consulted. In all situations described below, the benefit/risk balance of Simponi therapy should be very carefully considered.

If inactive ('latent') tuberculosis is diagnosed, treatment for latent tuberculosis must be started with anti-tuberculosis therapy before the initiation of Simponi, and in accordance with local recommendations.

In patients who have several or significant risk factors for tuberculosis and have a negative test for latent tuberculosis, anti-tuberculosis therapy should be considered before the initiation of Simponi. Use of anti-tuberculosis therapy should also be considered before the initiation of Simponi in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed.

All patients should be informed to seek medical advice if signs/symptoms suggestive of tuberculosis (e.g. persistent cough, wasting/weight loss, low-grade fever) appear during or after Simponi treatment.

Hepatitis B virus reactivation

Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including Simponi, who are chronic carriers of this virus (i.e., surface antigen positive). Some cases have had fatal outcome.

Patients should be tested for HBV infection before initiating treatment with Simponi. For patients who test positive for HBV infection, consultation with a physician with expertise in the treatment of hepatitis B is recommended.

Carriers of HBV who require treatment with Simponi should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy. Adequate data of treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF-antagonist therapy to prevent HBV reactivation are not available. In patients who develop HBV reactivation, Simponi should be stopped and effective anti-viral therapy with appropriate supportive treatment should be initiated.

Malignancies and lymphoproliferative disorders

The potential role of TNF-blocking therapy in the development of malignancies is not known. Based on the current knowledge, a possible risk for the development of lymphomas, leukaemia or other malignancies in patients treated with a TNF-antagonist cannot be excluded. Caution should be exercised when considering TNF-blocking therapy for patients with a history of malignancy or when considering continuing treatment in patients who develop malignancy.

Paediatric malignancy

Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 22 years of age) treated with TNF-blocking agents (initiation of therapy 18 years of age) in the post marketing setting. Approximately half the cases were lymphomas. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression. A risk for the development of malignancies in children and adolescents treated with TNF-blockers cannot be excluded.

Lymphoma and leukaemia

In the controlled portions of clinical trials of all the TNF-blocking agents including Simponi, more cases of lymphoma have been observed among patients receiving anti-TNF treatment compared with control patients. During the Simponi Phase IIb and Phase III clinical trials, the incidence of lymphoma in Simponi-treated patients was higher than expected in the general population. In the post-marketing setting, cases of leukaemia have been reported in patients treated with a TNF-antagonist. There is an increased background risk for lymphoma and leukaemia in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, which complicates risk estimation.

Malignancies other than lymphoma

In the controlled portions of the Simponi Phase IIb and Phase III clinical trials in RA, PsA, and AS, the incidence of non-lymphoma malignancies (excluding non-melanoma skin cancer) was similar between the Simponi and the control groups.

In an exploratory clinical trial eva luating the use of Simponi in patients with severe persistent asthma, more malignancies were reported in patients treated with Simponi compared with control patients (see section 4.8). The significance of this finding is unknown.

In an exploratory clinical trial eva luating the use of another anti-TNF agent, infliximab, in patients with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in the lung or head and neck, were reported in infliximab-treated patients compared with control patients. All patients had a history of heavy smoking. Therefore, caution should be exercised when using any TNF-antagonist in COPD patients, as well as in patients with an increased risk of malignancy due to heavy smoking.

Congestive heart failure (CHF)

Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers, including Simponi. In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased mortality due to CHF have been observed. Simponi has not been studied in patients with CHF. Simponi should be used with caution in patients with mild heart failure (NYHA class I/II). Patients should be closely monitored and Simponi must be discontinued in patients who develop new or worsening symptoms of heart failure (see section 4.3).

Neurological events

Use of TNF-blocking agents, including Simponi, has been associated with cases of new-onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disorders, including multiple sclerosis and peripheral demyelinating disorders. In patients with pre-existing or recent onset of demyelinating disorders, the benefits and risks of anti-TNF treatment should be carefully considered before initiation of Simponi therapy. Discontinuation of Simponi should be considered if these disorders develop (see section 4.8).

Surgery

There is limited safety experience of Simponi treatment in patients who have undergone surgical procedures, including arthroplasty. The long half-life should be taken into consideration if a surgical procedure is planned. A patient who requires surgery while on Simponi should be closely monitored for infections, and appropriate actions should be taken.

Immunosuppression

The possibility exists for TNF-blocking agents, including Simponi, to affect host defences against infections and malignancies since TNF mediates inflammation and modulates cellular immune responses.

Autoimmune processes

The relative deficiency of TNF_α caused by anti-TNF therapy may result in the initiation of an autoimmune process. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with Simponi and is positive for antibodies against double-stranded DNA, treatment with Simponi should be discontinued (see section 4.8).

Haematologic reactions

There have been post-marketing reports of pancytopaenia, leucopaenia, neutropaenia, aplastic anaemia, and thrombocytopaenia in patients receiving TNF-blockers. Cytopaenias including pancytopaenia have been infrequently reported with Simponi in clinical trials. All patients should be advised to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias (e.g. persistent fever, bruising, bleeding, pallor). Discontinuation of Simponi therapy should be considered in patients with confirmed significant haematologic abnormalities.

Concurrent administration of TNF-antagonists and anakinra

Serious infections and neutropenia were seen in clinical studies with concurrent use of anakinra and another TNF-blocking agent, etanercept, with no added clinical benefit. Because of the nature of the adverse events seen with this combination therapy, similar toxicities may also result from the combination of anakinra and other TNF-blocking agents. The combination of Simponi and anakinra is not recommended.

Concurrent administration of TNF-antagonists and abatacept

In clinical studies concurrent administration of TNF-antagonists and abatacept has been associated with an increased risk of infections including serious infections compared to TNF-antagonists alone, without increased clinical benefit. The combination of Simponi and abatacept is not recommended.

Switching between biological DMARDs

When switching from one biologic to another, patients should be monitored for signs of infection.

Vaccinations

Patients treated with Simponi may receive concurrent vaccinations, except for live vaccines (see sections 4.5 and 4.6). No data are available on the response to vaccination, risk of infection or transmission of infection with the administration of live vaccines to patients receiving Simponi.

Allergic reactions

In post-marketing experience, serious systemic hypersensitivity reactions (including anaphylactic reaction) have been reported following Simponi administration. Some of these reactions occurred after the first administration of Simponi. If an anaphylactic reaction or other serious allergic reactions occurs administration of Simponi should be discontinued immediately and appropriate therapy initiated.

Latex sensitivity

The needle cover on the pre-filled pen or pre-filled syringe is manufactured from dry natural rubber containing latex, and may cause allergic reactions in individuals sensitive to latex.

Special populations

Elderly patients ( 65 years)

In the Phase III studies in RA, PsA, and AS, no overall differences in adverse events (AEs), serious adverse events (SAEs) , and serious infections in patients age 65 or older (n=155) who received Simponi were observed compared with younger patients. However, caution should be exercised when treating the elderly and particular attention paid with respect to occurrence of infections.

Renal and hepatic impairment

Specific studies of Simponi have not been conducted in patients with renal or hepatic impairment. Simponi should be used with caution in subjects with impaired hepatic function (see section 4.2).

Excipients

Simponi contains sorbitol (E420). Patients with rare hereditary problems of fructose intolerance should not take Simponi.

No interaction studies have been performed.

Concurrent use with anakinra and abatacept

The combination of Simponi and anakinra or abatacept is not recommended (see sections 4.4).

Live vaccines

Live vaccines should not be given concurrently with Simponi (see sections 4.4 and 4.6).

Methotrexate

Although concomitant use of MTX results in higher steady-state trough concentrations of Simponi in patients with RA, PsA or AS, the data do not suggest the need for dose adjustment of either Simponi or MTX (see section 5.2).

Women of childbearing potential

Women of childbearing potential must use adequate contraception to prevent pregnancy and continue its use for at least 6 months after the last golimumab treatment.

Pregnancy

There are no adequate data on the use of golimumab in pregnant women. Due to its inhibition of TNF, golimumab administered during pregnancy could affect normal immune responses in the newborn. Studies in animals do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). The use of golimumab in pregnant women is not recommended; golimumab should be given to a pregnant woman only if clearly needed.

Golimumab crosses the placenta. Following treatment with a TNF-blocking monoclonal antibody during pregnancy, the antibody has been detected for up to 6 months in the serum of the infant born by the treated woman. Consequently, these infants may be at increased risk of infection. Administration of live vaccines to infants exposed to golimumab in utero is not recommended for 6 months following the mother's last golimumab injection during pregnancy (see sections 4.4 and 4.5).

Breastfeeding

It is not known whether golimumab is excreted in human milk or absorbed systemically after ingestion. Golimumab was shown to pass over to breast milk in monkeys, and because human immunoglobulins are excreted in milk, women must not breast feed during and for at least 6 months after golimumab treatment.

Fertility

No animal fertility studies have been conducted with golimumab. A fertility study in mice, using an analogous antibody that selectively inhibits the functional activity of mouse TNFα, showed no relevant effects on fertility (see section 5.3).

Simponi may have a minor influence on the ability to drive and use machines. Dizziness may occur following administration of Simponi (see section 4.8).

Upper respiratory tract infection was the most common adverse drug reaction (ADR) reported in the controlled Phase III RA, PsA, and AS studies through week 16, occurring in 7.2% of golimumab-treated patients as compared with 5.8% of control patients. The most serious ADRs that have been reported for Simponi include serious infections (including sepsis, pneumonia, TB, invasive fungal and opportunistic infections), demyelinating disorders, lymphoma, HBV reactivation, CHF, autoimmune processes (lupus-like syndrome) and haematologic reactions (see section 4.4).

ADRs observed in clinical studies and reported from world-wide post-marketing use of golimumab are listed in Table 1. Within the designated system organ classes, the adverse drug reactions are listed under headings of frequency and using the following convention: Very common ( 1/10); Common ( 1/100 to < 1/10); Uncommon ( 1/1,000 to < 1/100); Rare ( 1/10,000 to < 1/1,000); Very rare (< 1/10,000); Not known (cannot be estimated from the available data).

Table 1

Tabulated list of ADRs

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