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4.4 Special warnings and precautions for use
Infections
Serious infections, including sepsis and pneumonia, have been reported with abatacept (see section 4.8). Some of these infections have been fatal. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy which in addition to their underlying disease, could further predispose them to infections. Treatment with ORENCIA should not be initiated in patients with active infections until infections are controlled. Physicians should exercise caution when considering the use of ORENCIA in patients with a history of recurrent infections or underlying conditions which may predispose them to infections. Patients who develop a new infection while undergoing treatment with ORENCIA should be monitored closely. Administration of ORENCIA should be discontinued if a patient develops a serious infection.
4.8 Undesirable effects
Listed in Table 2 are adverse drug reactions based on experience in controlled clinical trials in adults that occurred with greater frequency (difference > 0.2%) in abatacept‑treated patients than in placebo‑treated patients. The list is presented by system organ class and frequency, using the following categories: 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). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
4.8 Undesirable effects
Malignancies
In placebo‑controlled clinical trials, malignancies were reported in 27 of 1,955 abatacept‑treated patients observed during 1,687 patient‑years, and in 11 of 989 placebo‑treated patients observed during 794 patient‑years.
In double‑ blind and open‑-label clinical trials, malignancies were reported in 66 of 2,688 abatacept‑treated 4,149 patients treated with abatacept during 4,76410,365 patient‑-years. This included 33 patients with non‑melanoma skin cancers, 28 with solid organ cancers, and 6 with hematologic malignancies (4 with lymphomas and 2 with myelodysplastic syndromes)., the incidence rate of malignancy was 1.41 per 100 patient-years. The incidence rates per 100 patients-years were 0.74 for non-melanomatous skin cancer, 0.59 for solid malignancies and 0.12 for hematologic malignancies. The most commonlyfrequently reported solid organ cancer was lung cancer (11 cases).0.16 per 100 patient-years), and the most common hematologic malignancy was lymphoma (0.07 per 100 patient-years). The incidence rate did not increase for malignancies overall, by major type (non-melanomatous skin cancer, solid tumors, and hematologic malignancies), or for individual tumor types in the double blind and open label period compared to the double-blind experience. The type and pattern of malignancies reported during the open‑label period of the trials were similar to those reported for the double‑blind experience.
The numberincidence rate of observed malignancies was consistent with that expected in an age‑ and gender‑matched rheumatoid arthritis population (see section 4.4).
Infusion‑related reactions
Acute infusion‑related events (adverse reactions occurring within 1 hour of the start of the infusion) in Studies II, III, and IV (see section 5.1) were more common in the abatacept‑treated patients than the placebo‑treated patients (9.8% for abatacept, 6.7% for placebo). The most frequently reported events with abatacept (1‑2%) were dizziness, headache, and hypertension.
Acute infusion‑related events that were reported in > 0.1% and ≤ 1% of patients treated with abatacept included cardiopulmonary symptoms such as hypotension, increased blood pressure, decreased blood pressure, and dyspnea; other symptoms included nausea, flushing, urticaria, cough, hypersensitivity, pruritus, rash, and wheezing. Most of these reactions were mild to moderate.
Hypersensitivity, anaphylaxis, and drug hypersensitivity reactions were uncommon. In 2,688 rarely reported in patients treated with abatacept‑treated patients during 4,764 patient‑years, there was 1 case of anaphylaxis. during controlled and open-label clinical trials. Other eventsreactions potentially associated with hypersensitivity to the medicinal product, such as hypotension, urticaria, and dyspnea, eachthat occurred in less than 0.6% of abatacept‑treated patients.within 24 hours of ORENCIA infusion, were uncommon.
6.3 Shelf life
Unopened vial: 23 years
After reconstitution: chemical and physical in‑use stability has been demonstrated for 24 hours at 2°C ‑ 8°C. From a microbiological point of view, the reconstituted solution should be diluted immediately.
After dilution: when the reconstituted solution is diluted immediately, the chemical and physical in‑use stability of the diluted infusion solution has been demonstrated for 24 hours at 2°C ‑ 8°C. From a microbiological point of view, the product should be used immediately.
8. MARKETING AUTHORISATION NUMBER(S)
EU/1/07/389/001 (1 vial)
10. DATE OF REVISION OF THE TEXT
21 May 200705/2009
Detailed information on this product is available on the website of the European Medicines Agency (EMEA) http://www.emea.europa.eu/
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