Wormadole 400mg Tablet

INNOTERE is indicated for the following:

• Breast Cancer: INNOTERE, in combination with doxorubicin and cyclophosphamide, is indicated for the adjuvant treatment of patients with operable node-positive breast cancer. INNOTERE, in combination with doxorubicin, is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for this condition. INNOTERE monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer, after failure of cytotoxic therapy. INNOTERE, in combination with capecitabine, is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline.
• Non-small Cell Lung Cancer (NSCLC): INNOTERE, in combination with cisplatin, is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer, who have not previously received chemotherapy for this condition. INNOTERE is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer, even after failure of platinum-based chemotherapy.
• Ovarian Cancer: INNOTERE is indicated, after failure of first-line or subsequent chemotherapy, for treatment of metastatic carcinoma of the ovary.
• Prostate Cancer: INNOTERE, in combination with prednisone or prednisolone, is indicated for the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer.
• Head and Neck Cancer: INNOTERE, in combination with cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with inoperable locally advanced squamous cell carcinoma of the head and neck.

The use of docetaxel should be confined to units specialised in the administration of cytotoxic chemotherapy and it should only be administered under the supervision of a medical practitioner qualified in the use of anticancer chemotherapy.

RECOMMENDED DOSE: INNOTERE should be administered by intravenous infusion only. Dosage: A premedication consisting of a corticosteroid (see below for prostate cancer), such as oral dexamethasone 16 mg per day (e.g. 8 mg twice daily) for 3 days, starting on day prior to INNOTERE administration, unless contraindicated, can be used. For prostate cancer, given the concurrent use of prednisone or prednisolone, the recommended premedication regimen is oral dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the INNOTERE infusion. Prophylactic G-CSE may be used to mitigate the risk of haematological toxicities. INNOTERE is administered as a one-hour infusion every three weeks.

1. Breast Cancer: In the adjuvant treatment of operable node-positive breast cancer, the recommended INNOTERE dose is 75 mg/mu00b2 administered one hour after doxorubicin 50 mg/mu00b2 and cyclophosphamide 500 mg/mu00b2 every 3 weeks for 6 cycles (see also u201cDosage adjustments during therapyu201d). In the first-line treatment, INNOTERE 75 mg/mu00b2 is administered in combination therapy with doxorubicin (50 mg/mu00b2). For the second-line treatment of breast cancer the recommended dosage of INNOTERE therapy is 100 mg/mu00b2 in monotherapy. In combination with capecitabine, the recommended dose of INNOTERE is 75 mg/mu00b2 every three weeks, combined with capecitabine at 1 250 mg/mu00b2 orally twice daily (within 30 minutes after a meal) for 2 weeks followed by 1-week rest period. For capecitabine dose calculation according to body surface area, see the professional information for capecitabine.
2. Non-small Cell Lung Cancer (NSCLC): In combination therapy (chemotherapy nau00efve patients): The recommended dosage regimen is INNOTERE 75 mg/mu00b2 immediately followed by cisplatin 75 mg/mu00b2 over 30-60 minutes. In monotherapy (for previously treated patients): The recommended dosage of INNOTERE therapy is 100 mg/mu00b2 as a single medicine.
3. Ovarian Cancer: The recommended dosage of INNOTERE therapy is 100 mg/mu00b2.
4. Prostate Cancer: The recommended dose of INNOTERE is 75 mg/mu00b2. Prednisone or prednisolone 5 mg orally twice daily is administered continuously. Patients should be observed closely, especially during the first and second infusion of INNOTERE, because of the risk of hypersensitivity reactions.
5. Head and Neck Cancer: For the induction treatment of locally advanced inoperable squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of INNOTERE is 75 mg/mu00b2 as a 1-hour infusion followed by cisplatin 75 mg/mu00b2 over 1 hour, on day one, followed by 5-fluorouracil as a continuous infusion at 750 mg/mu00b2 per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy. Patients must receive premedication with anti-emetic and appropriate hydration (prior to and after cisplatin administration). Prophylaxis for neutropenic infections should be administered. For cisplatin and 5-fluorourcil dose modifications, see the professional information for these medicines.

Dosage adjustments during treatment: General: Only the doctor can modify the schedule of administration. INNOTERE should be administered when the neutrophil count is u2265 1 500 cells/mmu00b3. Patients who experienced either febrile neutropenia, neutrophil count u02c2 500 cells/mmu00b3 for more than one week, severe or cumulate cutaneous or severe neurosensory signs and/or symptoms, during INNOTERE therapy, should have the dosage of INNOTERE reduced, during the subsequent cycle, from 100 mg/mu00b2 to 75 mg/mu00b2 and/or from 75 mg/mu00b2 to 60 mg/mu00b2. If the patient continues to experience these reactions at 60 mg/mu00b2, the treatment should be discontinued.

INNOTERE is contraindicated in patients who have a history of hypersensitivity reactions to the INNOTERE or polysorbate 80 or any of the ingredients listed in section 6.1. INNOTERE should not be used in patients with baseline neutrophil count of u02c2 1500 cells/mmu00b3. INNOTERE is contraindicated in pregnancy and lactation as it was found to be teratogenic in animals (see section 4.6). The safe use of INNOTERE in children has not been established. INNOTERE should not be used in patients with severe liver impairment since there is no data available (see section 4.4 and section 4.2). Contraindications for other medicines also apply when combined with INNOTERE.

INNOTERE (docetaxel) concentrate for solution should be administered under the supervision of a qualified doctor experienced in the use of antineoplastic medicines. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available. The incidence of treatment-related mortality associated with INNOTERE therapy is increased in patients with abnormal liver function and in patients receiving higher doses. INNOTERE should generally not be given to patients with serum bilirubin levels u02c3 upper limits of normal (ULN), or to patients with AST and/or ALT u02c3 1.5 x ULN concomitant with alkaline phosphatase levels u02c3 2.5 x ULN. Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of grade 4 neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity and toxic death. Patients with isolated elevations of transaminase u02c3 1.5 x ULN also have a higher rate of febrile neutropaenia grade 4, but do not have an increased incidence of toxic death. Bilirubin, AST or ALT and alkaline phosphatase values should be obtained prior to each cycle of INNOTERE therapy and reviewed by the treating doctor. INNOTERE therapy should not be given to patients with neutrophil counts of u02c2 1 500 cells/mmu00b3. In order to monitor the occurrence of neutropenia, which may be severe and results in infections, frequent blood cell counts should be performed on all patients receiving INNOTERE. Severe hypersensitivity reactions characterised by hypotension and/or bronchospasm, or generalised rash/erythema occurs in patients who receive the recommended 3-day dexamethasone premedication. Hypersensitivity reactions requiring discontinuation of the INNOTERE infusion were reported. These reactions resolved after discontinuation of the infusion and the administration of appropriate therapy. INNOTERE must not be given to patients who have a history of severe hypersensitivity reactions to docetaxel, as contained in INNOTERE or to other medicines formulated with polysorbate 80. Severe fluid retention may occur in patients despite the use of a recommended dexamethasone premedication regimen. It is characterised by one or more of the following events: severe peripheral oedema, generalised oedema, pleural effusion requiring urgent drainage, dyspnoea at rest, cardiac tamponade or pronounced abdominal distention (due to ascites). The use of INNOTERE should be confined to units specialised in the administration of cytotoxic chemotherapy and it should only be administered under the supervision of a qualified oncologist. Since significant hypersensitivity reactions may occur, appropriate supportive equipment should be available. During the infusion, it is recommended that vital functions should be closely monitored. Premedication consisting of an oral corticosteroid (see below for prostate) such as dexamethasone 16 mg per day (e.g. 8 mg twice daily) for 3 days, starting one day prior to INNOTERE administration, unless contraindicated, may reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions.

There have been no formal clinical studies to evaluate the interactions of docetaxel, as contained in INNOTERE. In vitro studies show that the metabolism of docetaxel may be modified by the concomitant administration of medicines which induce, inhibit or are metabolised by (and thus may inhibit the enzyme competitively) cytochrome P450-3A such as ciclosporin, ketoconazole, erythromycin and troleandomycin. As a result, caution should be exercised when treating patients with these medicines as concomitant therapy, since there is a potential for a significant interaction. In case of combination with CYP3A4 inhibitors, the occurrence of INNOTERE adverse reactions may increase, as a result of reduced metabolism. If the concomitant use of a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole) cannot be avoided, a close clinical surveillance is warranted and a dose-adjustment of INNOTERE may be suitable during the treatment with the strong CYP3A4 inhibitor. The co-administration of INNOTERE with the strong CYP3A4 inhibitor ketoconazole may lead to a significant decrease in docetaxel clearance (by 49%). Docetaxel is highly protein bound (u02c3 95 %). Although the possible in vivo interaction of INNOTERE with concomitantly administered medicine has not been investigated formally, in vitro interactions with tightly protein-bound medicines such as erythromycin, diphenhydramine, propranolol, propafenone, phenytoin, salicylate, sulfamethoxazole and sodium valproate did not affect protein binding of INNOTERE. When used in combination with doxorubicin, INNOTERE clearance is increased. In addition, dexamethasone did not affect protein binding of INNOTERE. INNOTERE does not influence the binding of digoxin.

Pregnancy: Pregnancy is contraindicated as INNOTERE is teratogenic in animals (see section 4.3).

Lactation: Lactation is contraindicated during treatment with INNOTERE (see section 4.3).

Women of childbearing potential/Contraception in males and females: Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to inform the treating doctor immediately should this occur. Contraceptive measures must be taken during treatment and for at least four months after cessation of INNOTERE therapy for men and at least seven months after cessation of INNOTERE therapy for women.

Fertility: In non-clinical studies, docetaxel, as contained in INNOTERE, had genotoxic effects and may alter male fertility. Therefore, men being treated with INNOTERE are advised not to father a child during and up to 4 to 6 months after treatment and to seek advice on conservation of sperm prior to treatment.

There are no results on studies performed on the effects on the ability to drive and use machines. The amount of alcohol in this medicine may impair the ability to drive or use machines (see section 4.4).

a. Summary of the safety profile: In clinical trials with docetaxel, as contained in INNOTERE, the most commonly reported adverse reactions of INNOTERE alone were: neutropenia (which was reversible and not cumulative; the median day to nadir was 7 days and the median duration of severe neutropenia (< 500 cells/mm 3 ) was 7 days), anaemia, alopecia, nausea, vomiting, stomatitis, diarrhoea and asthenia. The severity of adverse events of INNOTERE may be increased when it is given in combination with other chemotherapeutic medicines.

The following undesirable effects are frequently observed with INNOTERE:

• Immune system disorders: Hypersensitivity reactions have occurred within a few minutes following the start of the infusion of INNOTERE and were usually mild to moderate. The most frequently reported symptoms were flushing, rash with or without pruritus, chest tightness, back pain, dyspnoea and fever or chills. Severe reactions were characterised by hypotension and/or bronchospasm or generalised rash/erythema (see section 4.4).
• Nervous system disorders: The development of severe peripheral neurotoxicity requires a reduction of dose (see sections 4.2 and 4.4). Mild to moderate neuro-sensory signs are characterised by paraesthesia, dysesthesia or pain including burning. Neuro-motor events are mainly characterised by weakness.
• Skin and subcutaneous tissue disorders: Reversible cutaneous reactions have been observed and were generally considered as mild to moderate. Reactions were characterised by a rash including localised eruptions mainly on the feet and hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently associated with pruritus. Eruptions occurs within one week after the INNOTERE infusion. Less frequently, severe symptoms such as eruptions followed by desquamation which may lead to interruption or discontinuation of INNOTERE treatment are reported (see sections 4.2 and 4.4). Severe nail disorders are characterised by hypo- or hyperpigmentation and sometimes pain and onycholysis.
• General disorders and administration site conditions: Infusion site reactions are generally mild and consisted of hyper pigmentation, inflammation, redness or dryness of the skin, phlebitis or extravasation and swelling of the vein. Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower extremities and may become generalised with a weight gain of 3 kg or more. Fluid retention is cumulative in incidence and severity (see section 4.4).

b. Tabulated summary of adverse reactions:

MedDRA system organ classes:

• Frequent undesirable effects: Infections and infestations: oral candidiasis, Infection, fever in the absence of infection, neutropenic infection.
• Blood and lymphatic system disorders: Neutropenia, febrile neutropenia, thrombocytopenia, anaemia, infections, fever, severe anaphylactic reaction (characterised by hypotension and/or bronchospasm or in absence of infection, neutropenic infection, hyperbilirubinemia, generalised rash/erythema).
• Immune system disorders: Flushing, rash with or without pruritus, chest tightness, back pain, dyspnoea, drug fever, chills, hypersensitivity reaction.
• Metabolism and nutrition disorders: Anorexia, weight gain, decreased appetite, dehydration, decreased weight.
• Nervous system disorders: Paraesthesia, dysaesthesia, pain, weakness, neuropathy sensory, neuro-cortical, neuropathy motor, neuro-cerebellar, taste disturbance, dizziness, syncope, headache, peripheral neuropathy.
• Eye disorders: Lacrimation, conjunctivitis.
• Cardiac disorders: Hypotension, cardiac dysrhythmias, vasodilation, cardiac left ventricular function, ischaemic myocardial, venous, lower limb oedema, cardiac left ventricular function.
• Vascular disorders: Peripheral oedema, pleural effusion, pericardial effusion, ascites, increased capillary permeability, weight gain, fluid retention.
• Respiratory, thoracic and mediastinal disorders: Cough, sore throat, dyspnoea, epistaxis.
• Gastrointestinal disorders: Nausea, vomiting, diarrhoea, anorexia, constipation, stomatitis, dehydration, gastrointestinal perforation, ischemic taste perversion, upper abdominal pain, dry mouth, pharyngitis, odynophagia, gastrointestinal pain/cramping, heartburn, gastrointestinal bleeding, oesophagitis/dysphagia, colitis, colitis, and neutropenic enterocolitis.
• Hepatobiliary disorders: ALT increase, AST increase, bilirubin increase, alkaline phosphatase increase, hepatitis.
• Skin and subcutaneous disorders: Rash (including local eruptions), pruritis, nail disorders (including pain and onycholysis for the nails), alopecia, nail disorders, skin toxicity, hand-foot syndrome, nail discolouration, onycholysis, desquamation, dry skin.
• Musculoskeletal, connective tissue and bone disorders: Asthenia, myalgia, arthralgia, back pain.
• Renal and urinary disorders: Dysuria, haematuria, oliguria, urinary incontinence, enuresis, nocturia, renal failure and urethral pain.
• Reproductive system and Breast disorders: Amenorrhoea, Breast pain, pelvic pain, vaginal discharge, vaginal discomfort, vaginal dryness, vaginal haemorrhage and vulval disorders.
• General disorders and administrative site conditions: Alopecia, asthenia, myalgia, infusion site reactions, pain, pyrexia, fatigue, weakness, pain in limb, lethargy, taste, sense of smell altered, altered hearing, cancer pain, weight loss.
• Investigations: Injury and poisoning: Decreased haemoglobin, Oesophageal burn and neurotoxicity.

In case of overdose, the patient should be kept in a specialised unit and vital functions closely monitored. There is no known antidote for INNOTERE overdosage. The primary anticipated complications of overdosage would consist of neutropenia, mucositis, cutaneous reactions and paraesthesia. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. Other appropriate symptomatic measures should be taken, as needed.