Cimzia 200 mg solution for injection

Each pre-filled syringe contains 200 mg certolizumab pegol in one ml.

Certolizumab pegol is a recombinant, humanised antibody Fab' fragment against tumour necrosis factor alpha (TNFα) expressed in Escherichia coli and conjugated to polyethylene glycol (PEG).

For a full list of excipients, see section 6.1.

Solution for injection in pre-filled syringe.

Clear to opalescent, colourless to yellow solution. The pH of the solution is approximately 4.7.

Cimzia, in combination with methotrexate (MTX), is indicated for the treatment of moderate to severe, active rheumatoid arthritis (RA) in adult patients when the response to disease-modifying antirheumatic drugs (DMARDs) including methotrexate, has been inadequate.

Cimzia can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.

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

Treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of rheumatoid arthritis. Patients should be given the special alert card.

Posology

The recommended starting dose of Cimzia for adult patients with rheumatoid arthritis is 400 mg (as 2 injections of 200 mg each on one day) at weeks 0, 2 and 4, followed by a maintenance dose of 200 mg every 2 weeks. MTX should be continued during treatment with Cimzia where appropriate.

Available data suggest that clinical response is usually achieved within 12 weeks of treatment. Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit within the first 12 weeks of treatment.

Missed dose

Patients who miss a dose should be advised to inject the next dose of Cimzia as soon as they remember and then continue injecting subsequent doses every 2 weeks as originally instructed.

Paediatric population (< 18 years old)

The safety and efficacy of Cimzia in children and adolescents below age 18 years have not yet been established. No data are available.

Elderly (65 years old)

No dose adjustment is required. Population pharmacokinetic analyses showed no effect of age (see section 5.2).

Renal and hepatic impairment

Cimzia has not been studied in these patient populations. No dose recommendations can be made (see section 5.2).

Method of administration

The total content (1 ml) of the pre-filled syringe should be administered as a subcutaneous injection only. Suitable sites for injection would include the thigh or abdomen.

After proper training in injection technique, patients may self-inject if their physician determines that it is appropriate and with medical follow-up as necessary.

Hypersensitivity to the active substance or to any of the excipients.

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

Moderate to severe heart failure (NHYA classes III/IV) (see section 4.4).

Infections

Patients must be monitored closely for signs and symptoms of infections including tuberculosis before, during and after treatment with Cimzia. Because the elimination of Cimzia may take up to 5 months, monitoring should be continued throughout this period (see section 4.3).

Treatment with Cimzia must not be initiated in patients with a clinically important active infection, including chronic or localised infections, until the infection is controlled (see section 4.3).

Patients who develop a new infection while undergoing treatment with Cimzia should be monitored closely. Administration of Cimzia should be discontinued if a patient develops a new serious infection until the infection is controlled. Physicians should exercise caution when considering the use of Cimzia in patients with a history of recurring infection or with underlying conditions which may predispose patients to infections, including the use of concomitant immunosuppressive medications.

Patients with rheumatoid arthritis may not manifest typical symptoms of infection, including fever, due to their disease and concomitant medicinal products. Therefore, early detection of any infection, particularly atypical clinical presentations of a serious infection, is critical to minimise delays in diagnosis and initiation of treatment.

Serious infections, including sepsis and tuberculosis (including miliary, disseminated and extrapulmonary disease), and opportunistic infections (e.g. histoplasmosis, nocardia, candidiasis) have been reported in patients receiving Cimzia. Some of these events have been fatal.

Tuberculosis

Before initiation of therapy with Cimzia, all patients must be eva luated for both active or inactive (latent) tuberculosis infection. This eva luation should include a detailed medical history for patients with a personal history of tuberculosis, with possible previous exposure to others with active tuberculosis, and with previous and/or current use of immunosuppressive therapy. Appropriate screening tests, e.g. tuberculin skin 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 prior to or during treatment, Cimzia therapy must not be initiated and must be discontinued (see section 4.3).

If inactive ('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 Cimzia therapy should be very carefully considered.

If latent tuberculosis is diagnosed, appropriate anti-tuberculosis therapy must be started before initiating treatment with Cimzia and in accordance with local recommendations.

Use of anti-tuberculosis therapy should also be considered before the initiation of Cimzia in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and in patients who have significant risk factors for tuberculosis despite a negative test for latent tuberculosis. Biological tests for tuberculosis screening should be considered before starting Cimzia treatment if there is any potential latent tuberculosis infection, regardless of BCG vaccination.

Patients should be instructed to seek medical advice if signs/symptoms (e.g. persistent cough, wasting/weight loss, low grade fever, listlessness) suggestive of a tuberculosis infection occur during or after therapy with Cimzia.

Hepatitis B Virus (HBV) reactivation

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

Patients should be tested for HBV infection before initiating treatment with Cimzia. For patients who test positive for HBV infection,