Section 2
First sentence changed from:
Caelyx contains 2 mg/ml doxorubicin hydrochloride in a pegylated liposomal formulation.
To:
One ml of Caelyx contains 2 mg doxorubicin hydrochloride in a pegylated liposomal formulation.
Last sentence changed from:
For excipients, see section 6.1.
To:
For a full list of excipients, see section 6.1.
Section 4.2
Section entitled Paediatric patients: changed from:
Paediatric patients: Safety and effectiveness in patients less than 18 years of age have not been established.
To:
Paediatric patients: The experience in children is limited. Caelyx is not recommended in patients below 18 years of age.
Section 4.3
Changed from:
· hypersensitivity to the active substance or to any of the excipients
· breast-feeding
Caelyx must not be used to treat AIDS-KS that may be treated effectively with local therapy or systemic alfa-interferon.
To:
· Hypersensitivity to the active substance or to any of the excipients.
Caelyx must not be used to treat AIDS-KS that may be treated effectively with local therapy or systemic alfa-interferon.
Section 4.5
First sentence has been changed from:
No formal drug interaction studies have been conducted with Caelyx, although phase II combination trials with conventional chemotherapy agents have been conducted in patients with gynaecological malignancies
To:
No formal medicinal product interaction studies have been performed with Caelyx, although phase II combination trials with conventional chemotherapy agents have been conducted in patients with gynaecological malignancies.
Section 4.6
Pregnancy: Second sentence has been changed from:
Therefore, Caelyx should not be used unless clearly necessary.
To:
Therefore, Caelyx should not be used during pregnancy unless clearly necessary.
Lactation: First sentence changed from:
It is not known whether Caelyx is excreted in human milk and because of the potential for serious adverse reactions in nursing infants, therefore mothers must discontinue nursing prior to beginning Caelyx treatment.
To:
It is not known whether Caelyx is excreted in human milk. Because many medicinal products, including anthracyclines, are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants, therefore mothers must discontinue nursing prior to beginning Caelyx treatment.
Section 4.8
Section entitled Breast Cancer Program: (heading amended to Breast cancer program).
Last sentence of second paragraph changed from:
See Table 4 for complete listing of undesirable effects reported in ³ 5 % of Caelyx-treated patients.
To:
See Table 4 for complete listing of undesirable effects reported in Caelyx-treated patients.
Paragraph 3 changed from:
Anaemia, leukopaenia and thrombocytopaenia were infrequently reported among Caelyx patients at incidences of 5 %, 2 %, and 1 %, respectively. The incidence of life threatening (Grade IV) haematologic effects was < 1.0 % and sepsis was reported in 1 % of patients. Growth factor support or transfusion support was necessary in 5.1 % and 5.5 % of patients, respectively (see section 4.2).
To:
The incidence of life threatening (Grade IV) haematologic effects was < 1.0 % and sepsis was reported in 1 % of patients. Growth factor support or transfusion support was necessary in 5.1 % and 5.5 % of patients, respectively (see section 4.2).
Table 4 completely updated in respect of Adverse Events.
First paragraph after Table 4 (Undesirable effects reported between ….) has been deleted.
Next paragraph changed from:
Ovarian cancer program: 512 patients with ovarian cancer (a subset of 876 solid tumour patients) were treated with Caelyx at a dose of 50 mg/m2 in clinical trials. See Table 4 for undesirable effects reported in ³ 5 % of Caelyx-treated patients.
To:
Ovarian cancer program: 512 patients with ovarian cancer (a subset of 876 solid tumour patients) were treated with Caelyx at a dose of 50 mg/m2 in clinical trials. See Table 5 for undesirable effects reported in Caelyx-treated patients.
New Table 5 added
Following paragraph changed from:
Myelosuppression was mostly mild or moderate and manageable. Leukopaenia was the most frequently reported haematological adverse effect, followed by anaemia, neutropaenia and thrombocytopaenia. Life threatening (Grade IV) haematological effects were reported at incidences of 1.6 %, 0.4 %, 2.9 %, 0.2 % respectively. Sepsis related to leukopaenia was observed infrequently (< 1 %). Growth factor support was required infrequently (< 5 %) and transfusion support was required in approximately 15 % of patients (see section 4.2).
To:
Myelosuppression was mostly mild or moderate and manageable. Sepsis related to leukopaenia was observed infrequently (< 1 %). Growth factor support was required infrequently (< 5 %) and transfusion support was required in approximately 15 % of patients (see section 4.2).
The following paragraph has been deleted:
Undesirable effects reported between 1 % and 5 % in Caelyx-treated patients were headache, allergic reaction, chills, infection, chest pain, back pain, malaise, vasodilatation, cardiovascular disorder, oral moniliasis, mouth ulceration, esophagitis, nausea and vomiting, gastritis, dysphagia, dry mouth, flatulence, gingivitis, hypochromic anaemia, peripheral oedema, weight loss, dehydration, cachexia, myalgia, dizziness, insomnia, anxiety, neuropathy, depression, hypertonia, dyspnoea, increased cough, vesiculobullous rash, pruritus, exfoliative dermatitis, skin disorder, maculopapular rash, sweating, acne, herpes zoster, skin ulcer, conjunctivitis, taste perversion, urinary tract infection, dysuria and vaginitis.
Under section entitled AIDS-KS program, paragraph changed from:
Clinical studies on AIDS-KS patients treated at 20 mg/m2 with Caelyx show that myelosuppression was the most frequent undesirable effect considered related to Caelyx occurring in approximately one-half of the patients.
To:
Clinical studies on AIDS-KS patients treated at 20 mg/m2 with Caelyx show that myelosuppression was the most frequent undesirable effect considered related to Caelyx occurring very commonly (in approximately one-half of the patients).
The following paragraph has been deleted:
Other frequently (³ 5 %) observed undesirable effects were nausea, asthenia, alopecia, fever, diarrhoea, infusion-associated acute reactions, and stomatitis.
The first sentence of next paragraph has been amended slightly from:
Respiratory undesirable effects frequently (³ 5 %) occurred in clinical studies of Caelyx and may be related to opportunistic infections in the AIDS population.
To:
Respiratory undesirable effects commonly occurred in clinical studies of Caelyx and may be related to opportunistic infections in the AIDS population.
After this paragraph, the following has been added:
Undesirable effects observed in patients with AIDS-KS according to CIOMS III frequency categories (Very common (> 1/10); Common (> 1/100, < 1/10); Uncommon (> 1/1,000, < 1/100)) were as follows:
Infections and infestations:
Common: oral moniliasis
Blood and lymphatic system disorders:
Very common: neutropaenia, anaemia, leukopaenia
Common: thrombocytopaenia
Metabolism and nutrition disorders:
Common: anorexia
Psychiatric disorders:
Uncommon: confusion
Nervous system disorders:
Common: dizziness
Uncommon: paresthesia
Eye disorders:
Common: retinitis
Vascular disorders:
Common: vasodilatation
Respiratory, thoracic and mediastinal disorders:
Common: dyspnoea
Gastrointestinal disorders:
Very common: nausea
Common: diarrhoea, stomatitis, vomiting, mouth ulceration, abdominal pain, glossitis, constipation, nausea and vomiting
Skin and subcutaneous tissue disorders:
Common: alopecia, rash
Uncommon: palmar-plantar erythrodysesthesia (PPE)
General disorders and administration site conditions:
Common: asthenia, fever, infusion-associated acute reactions
Investigations:
Common: weight loss.
The next paragraph has been changed from:
Other less frequently (< 5 %) observed undesirable effects included palmar-plantar erythrodysesthesia, oral moniliasis, nausea and vomiting, vomiting, weight loss, rash, mouth ulceration, dyspnoea, abdominal pain, hypersensitivity reactions including anaphylactic reactions, vasodilatation, dizziness, anorexia, glossitis, constipation, paresthesia, retinitis and confusion. Following marketing, bullous eruption has been reported rarely in this population.
To:
Other less frequently (< 5 %) observed undesirable effects included hypersensitivity reactions including anaphylactic reactions, Following marketing, bullous eruption has been reported rarely in this population.
In the paragraph starting All patients: the word “drug” has been changed to “medicinal product”.
The following paragraph has been added to this section:
Myelosuppression associated with anaemia, thrombocytopaenia, leukopaenia, and rarely febrile neutropaenia, has been reported in Caelyx -treated patients.
The following paragraphs have been added at the end of Section 4.8:
Following the marketing of Caelyx, serious skin conditions including erythema multiforme, Stevens Johnson syndrome and toxic epidermal necrolysis have been reported very rarely.
In patients treated with Caelyx, cases of venous thromboembolism, including thrombophlebitis, venous thrombosis and pulmonary embolism have been seen uncommonly. However, because patients with cancer are at increased risk for thromboembolic disease, a causal relationship cannot be determined.
Section 5.2
Table 5 and all references to Table 5 have been changed to Table 6
Section 6.4
The following sentence has been added:
For storage conditions of the diluted medicinal product, see section 6.3.
Section 10
Date of revision of text updated
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