Xelpac6 mg/ml

Ovarian Carcinoma: Xelpac 6 mg/ml is indicated as first line and subsequent therapy for the treatment of advanced carcinoma of the ovary. As first line therapy, Xelpac 6 mg/ml is indicated in combination with cisplatin.Breast Carcinoma: Xelpac 6 mg/ml is indicated for ... Read moreOvarian Carcinoma: Xelpac 6 mg/ml is indicated as first line and subsequent therapy for the treatment of advanced carcinoma of the ovary. As first line therapy, Xelpac 6 mg/ml is indicated in combination with cisplatin.Breast Carcinoma: Xelpac 6 mg/ml is indicated for the adjuvant treatment of node-positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy. Xelpac 6 mg/ml is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracline unless clinically contraindicated. Xelpac 6 mg/ml is indicated for the first-line therapy of advanced or metastatic breast cancer either in combination with an anthracycline in patients for whom anthracline therapy is suitable or in combination with trastuzumab in patients who overexpress HER2 at a 2+ or 3+ level as determined by immuno-histochemistry.Gemcitabine, in combination of Xelpac 6 mg/ml, is indicated in the treatment of patients with unresectable, locally recurrent or metastatic breast cancer who have relapsed following adjuvant/neoadjuvant chemotherapy. Prior chemotherapy should have included an anthracycline unless clinically contraindicated.Xelpac 6 mg/ml is indicated for the treatment of metastatic cancer of the breast, in combination with trastuzumab, in patients who have tumors that over-express HER2 and who have not received previous chemotherapy for their metastatic disease.Non-Small Cell Lung Carcinoma: Xelpac 6 mg/ml, in combination with cisplatin, is indicated for the first line treatment of non-small cell lung cancerin patients who are not candidates for potential curative surgery and/or radiation therapy.Kaposi's Sarcoma: Xelpac 6 mg/ml is indicated for the second line treatment of AIDS related Kaposi's Sarcoma.Gastric Carcinoma: Xelpac 6 mg/ml is indicated for the treatment of Gastric Carcinoma.

Cytotoxic Chemotherapy

Xelpac 6 mg/ml promotes microtubule formation by enhancing the action of tubulin dimers, stabilising existing microtubules and preventing their disassembly, thereby disrupting normal cell division in the late G2 mitotic phase of the cell cycle. This results in the inhibition of cell replication.

Advanced non-small cell lung cancer: 135 mg/m2 over 24 hr or 175 mg/m2 over 3 hr, followed by cisplatin and repeated at 3 wk intervals.Ovarian carcinoma: Primary treatment (in combination with cisplatin or carboplatin): 135 mg/m2 infused over 24 hr followed by cisplatin and repeated at 3 wk intervals. Secondary treatment (as a single agent): 135 or 175 mg/m2 infused over 3 hr once every 3 weeks.Breast cancer: Adjuvant therapy; 2nd line monotherapy or 1st line treatment with trastuzumab: 175 mg/m2 infused over 3 hr once every 3 wk for 4 courses; when used with trastuzumab, the dose should be given the day after the 1st dose of trastuzumab or immediately after subsequent doses if well-tolerated. 1st line with doxorubicin: 220 mg/m2 over 3 hr every 3 wk, the dose to be administered 24 hr after doxorubicin.AIDS-related Kaposi's sarcoma: 135 mg/m2 over 3 hr every 3 weeks. Alternatively, 100 mg/m2 over 3 hr every 2 wk especially in patients with poor performance status.

All patients should be premedicated prior to Xelpac 6 mg/ml administration in order to prevent severe hypersensitivity reactions. Such premedication may consist of dexamethasone 20 mg PO administered approximately 12 and 6 hours before Xelpac 6 mg/ml, diphenhydramine (or its equivalent) 50 mg IV 30 to 60 minutes prior to Xelpac 6 mg/ml, and cimetidine (300 mg) or ranitidine (50 mg) IV 30 to 60 minutes before Xelpac 6 mg/ml.First-line treatment of ovarian cancer: Although alternative medication regimens for Xelpac 6 mg/ml are under investigation at present, a combination therapy of Xelpac 6 mg/ml and cisplatin is recommended. Depending on the duration of infusion, two different dosages are recommended for Xelpac 6 mg/ml treatment: 175 mg/m2 of Xelpac 6 mg/ml is administered as an intravenous infusion over a period of three hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals, or 135 mg/m2 of Xelpac 6 mg/ml is administered as an intravenous infusion over a period of 24 hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals.Second-line treatment of ovarian cancer: The recommended dose of Xelpac 6 mg/ml is 175 mg/m2 administered over 3 hours, with a 3-week interval between courses.Adjuvant chemotherapy in breast carcinoma: The recommended dose of Xelpac 6 mg/ml is 175 mg/m2 administered over a period of 3 hours every 3 weeks for four courses, following AC therapy.First-line chemotherapy of breast carcinoma: When used in combination with doxorubicin (50 mg/m2), Xelpac 6 mg/ml should be administered 24 hours after doxorubicin. The recommended dose of Xelpac 6 mg/ml is 220 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. When used in combination with trastuzumab, the recommended dose of Xelpac 6 mg/ml is 175 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. Xelpac 6 mg/ml infusion may be started the day following the first dose of trastuzumab or immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.Second-line chemotherapy of breast carcinoma: The recommended dose of Xelpac 6 mg/ml is 175 mg/m2 administered over a period of 3 hours, with a 3-week interval between courses.Advanced non-small-cell lung cancer: The recommended dose of Xelpac 6 mg/ml is 175 mg/m2 administered over 3 hours followed by 80 mg/m2 of cisplatin, with a 3-week interval between courses.Treatment of AIDS-related KS: The recommended dose of Xelpac 6 mg/ml is 100 mg/m2 administered as a 3-hour intravenous infusion every two weeks.Dose adjustment: Subsequent doses of Xelpac 6 mg/ml should be administered according to individual patient tolerance. Xelpac 6 mg/ml should not be re-administered until the neutrophil count is >1.5 x 109/1 (>1 x 109/1 for KS patients) and the platelet count is >100 x 109/1 (>75 x 109/1 for KS patients).

Xelpac 6 mg/ml clearance is not affected by cimetidine premedication.Cisplatin: Administration of Xelpac 6 mg/ml after cisplatin treatment leads to greater myelosuppression and about a 20% decrease in Xelpac 6 mg/ml clearance. Patients treated with Xelpac 6 mg/ml and cisplatin may have an increased risk of renal failure as compared to cisplatin alone in gynecological cancers.Doxorubicin: Since the elimination of doxorubicin and its active metabolites can be reduced when Xelpac 6 mg/ml and doxorubicin are given closer in time, Xelpac 6 mg/ml for initial treatment of metastatic breast cancer should be administered 24 hours after doxorubicin. Sequence effects characterized by more profound neutropenic and stomatitis episodes have been observed with combination use of Xelpac 6 mg/ml and doxorubicin when Xelpac 6 mg/ml was administered before doxorubicin and using longer than recommended infusion times (Xelpac 6 mg/ml administered over 24 hours; doxorubicin over 48 hours).Active substances metabolized in the liver: The metabolism of Xelpac 6 mg/ml is catalysed, in part, by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Therefore, in the absence of a PK drug-drug interaction study, caution should be exercised when administering Xelpac 6 mg/ml concomitantly with medicines known to inhibit either CYP2C8 or CYP3A4 (e.g. ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, clopidogrel, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) because toxicity of Xelpac 6 mg/ml may be increased due to higher Xelpac 6 mg/ml exposure. Administering Xelpac 6 mg/ml concomitantly with medicines known to induce either CYP2C8 or CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine) is not recommended because efficacy may be compromised because of lower Xelpac 6 mg/ml exposures.

Xelpac 6 mg/ml is contraindicated in patients with severe hypersensitivity reactions to Xelpac 6 mg/ml, macrogolglycerol ricinoleate (polyoxyl castor oil.) Xelpac 6 mg/ml is contraindicated during lactation. Xelpac 6 mg/ml should not be used in patients with baseline neutrophils <1.5x109/I (<1x109/I for KS patients) or platelets <100x109/I (<75x109/I for KS patients). In KS, Xelpac 6 mg/ml is also contraindicated in patients with concurrent, serious, uncontrolled infections. Patients with severe hepatic impairment must not be treated with Xelpac 6 mg/ml.

Common: Low blood counts leading to increased risk for infection, anemia and/or bleeding, hair loss, arthralgias and myalgias, pain in the joints and muscles, peripheral neuropathy, nausea, vomiting (usually mild), diarrhea, Mouth sores, hypersensitivity reaction, fever, facial flushing, chills, shortness of breath, or hives after Xelpac 6 mg/ml is given.Rare: swelling of the feet or ankles (edema), liver problems, low blood pressure, darkening of the skin where previous radiation treatment has been given.

Category D: There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Xelpac 6 mg/ml should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Since significant hypersensitivity reactions may occur, appropriate supportive equipment should be available. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Xelpac 6 mg/ml should be given before cisplatin when used in combination.Significant hypersensitivity reactions, as characterised by dyspnoea and hypotension requiring treatment, angioedema, and generalised urticaria have occurred in <1% of patients receiving Xelpac 6 mg/ml after adequate premedication. Fatal hypersensitivity reactions have occurred in patients despite premedication. These reactions are probably histamine-mediated. In the case of severe hypersensitivity reactions, Xelpac 6 mg/ml infusion should be discontinued immediately. Bone marrow suppression, primarily neutropenia, is the dose-limiting toxicity. Neutrophil nadirs occurred at a median of 11 days. Frequent monitoring of blood counts should be instituted. Patients should not be retreated until the neutrophil count is ≥1.5 x 109/1 (≥1 x 109/1 for KS patients) and the platelets recover to ≥100 x 109/1 (≥75 x 109/1 for KS patients).Severe cardiac conduction abnormalities have been reported rarely with single agent Xelpac 6 mg/ml. If patients develop significant conduction abnormalities during Xelpac 6 mg/ml administration, appropriate therapy should be administered and continuous cardiac monitoring should be performed during subsequent therapy with Xelpac 6 mg/ml.

There is no known antidote for Xelpac 6 mg/ml overdose. In case of overdose, the patient should be closely monitored. Treatment should be directed at the primary anticipated toxicities, which consist of bone marrow suppression, peripheral neurotoxicity and mucositis. Overdoses in paediatric patients may be associated with acute ethanol toxicity.

Keep in a dry place and store below 30°C. Protect from light and keep out of the reach of children. Use only freshly prepared solution.

Hepatic Impairment:Advanced non-small cell lung cancer: Do not use in severe impairment, increased risk of hepatotoxicity. For detailed dosing recommendation, consult local protocol.Ovarian carcinoma: Do not use in severe impairment, increased risk of hepatotoxicity. For detailed dosing recommendations, consult local protocol.Breast cancer: Do not use in severe impairment, increased risk of hepatotoxicity. For detailed dosing recommendation, consult local protocol.AIDS-related Kaposi's sarcoma: Do not use in severe impairment, increased risk of hepatotoxicity. For detailed dosing recommendation, consult local protocol.

Xelpac 6 mg/ml must be diluted before infusion. It can be diluted in 0.9% sodium chloride inj, 5% dextrose inj, 5% dextrose and 0.9% sodium chloride inj or 5% dextrose in lactated Ringer's inj to a concentration of 0.3-1.2 mg/ml.

Xelpac 6 mg/ml is a novel anti-microtubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, Xelpac 6 mg/ml induces abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. Following intravenous administration of Xelpac 6 mg/ml, Xelpac 6 mg/ml plasma concentrations declined in a biphasic manner. The initial rapid decline represents distribution to the peripheral compartment and elimination of the drug. The later phase is due, in part, to a relatively slow efflux of Xelpac 6 mg/ml from the peripheral compartment.

Pregnancy Category D. There is no adequate data from the use of Xelpac 6 mg/ml in pregnant women, however as with other cytotoxic medicinal products, Xelpac 6 mg/ml may cause foetal harm when administered to pregnant women. Xelpac 6 mg/ml is contraindicated during lactation.

Patients who experience severe neutropenia: (neutrophil count <0.5 x 109/1 for a minimum of 7 days) or severe peripheral neuropathy, should receive a dose reduction of 20% for subsequent courses (25% for KS patients).Patients with hepatic impairment: Inadequate data are available to recommend dosage alterations in patients with mild to moderate hepatic impairments. Patients with severe hepatic impairment must not be treated with Xelpac 6 mg/ml.Pediatric use: Xelpac 6 mg/ml is not recommended for use in children below 18 years due to lack of data on safety and efficacy