Paclitaxel Albumin Teva

/ Teva Israel LTD, Israel

The drug should only be administered under the supervision of a qualified oncologist in units specialised in the administration of cytotoxic agents. It should not be substituted for or with other paclitaxel formulations.
Breast cancer
The recommended dose of the drug is 260 mg/m² administered intravenously over 30 minutes every 3 weeks.
Dose adjustments during treatment of breast cancer
Patients who experience severe neutropenia (neutrophil count <500 cells/mm³ for a week or longer) or severe sensory neuropathy during the drug therapy should have the dose reduced to 220 mg/m² for subsequent courses. Following recurrence of severe neutropenia or severe sensory neuropathy, additional dose reduction should be made to 180 mg/m². The drug should not be administered until neutrophil counts recover to >1500 cells/mm3. For Grade 3 sensory neuropathy, withhold treatment until resolution to Grade 1 or 2, followed by a dose reduction for all subsequent courses.
Pancreatic adenocarcinoma
The recommended dose in combination with gemcitabine is 125 mg/m² administered intravenously over 30 minutes on Days 1, 8 and 15 of each 28-day cycle. The concurrent recommended dose of gemcitabine is 1000 mg/m² administered intravenously over 30 minutes immediately after the completion of the drug administration on Days 1, 8 and 15 of each 28-day cycle.
Method of administration
This medical product is for intravenous use. Administer reconstituted dispersion intravenously using an infusion set incorporating a 15 μm filter. Following administration, it is recommended that the intravenous line be flushed with sodium chloride 9 mg/ml (0.9%) solution for injection to ensure administration of the complete dose.
See prescribing information for full details.

Treatment as monotherapy is indicated for the treatment of metastatic breast cancer in adult patients who have failed first-line treatment for metastatic disease and for whom standard, anthracycline containing therapy is not indicated.
Treatment in combination with gemcitabine is indicated for the first-line treatment of adult patients with metastatic adenocarcinoma of the pancreas.

* Hypersensitivity to the active substance or to any of the excipients.
* Lactation.
* Baseline neutrophil counts <1500 cells/ml.

The drug is an albumin-bound nanoparticle formulation of paclitaxel, which may have substantially different pharmacological properties compared to other formulations of paclitaxel. It should not be substituted for or with other paclitaxel formulations.
Hypersensitivity
Rare occurrences of severe hypersensitivity reactions, including very rare events of anaphylactic reactions with fatal outcome, have been reported. If a hypersensitivity reaction occurs, the medicinal product should be discontinued immediately, symptomatic treatment should be initiated, and the patient should not be rechallenged with paclitaxel.
Haematology
Bone marrow suppression (primarily neutropenia) occurs frequently with human serum albumin-paclitaxel nanoparticles. Neutropenia is dose-dependent and a dose-limiting toxicity. Frequent monitoring of blood cell counts should be performed during human serum albumin-paclitaxel nanoparticles therapy. Patients should not be retreated with subsequent cycles of human serum albumin-paclitaxel nanoparticles until neutrophils recover to >1500 cells/mm3 and platelets recover to >100,000 cells/mm³.
Neuropathy
Sensory neuropathy occurs frequently with human serum albumin-paclitaxel nanoparticles, although development of severe symptoms is less common. The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose reduction. When this medical product is used as monotherapy, if Grade 3 sensory neuropathy develops, treatment should be withheld until resolution to Grade 1 or 2, followed by a dose reduction for all subsequent courses of the drug is recommended. For combination use of the drug and gemcitabine, if Grade 3 or higher peripheral neuropathy develops, withhold the drug; continue treatment with gemcitabine at the same dose. Resume at reduced dose when peripheral neuropathy improves to Grade 0 or 1. For combination use of the drug and carboplatin, if Grade 3 or higher peripheral neuropathy develops, treatment should be withheld until improvement to Grade 0 or 1, followed by a dose reduction for all subsequent courses of the drug and carboplatin.
Sepsis
Sepsis was reported at a rate of 5% in patients with or without neutropenia who received human serum albumin-paclitaxel nanoparticles in combination with gemcitabine. Complications due to the underlying pancreatic cancer, especially biliary obstruction or presence of biliary stent, were identified as significant contributing factors. If a patient becomes febrile (regardless of neutrophil count), initiate treatment with broad-spectrum antibiotics. For febrile neutropenia, withhold the drug and gemcitabine until fever resolves and ANC ≥1500 cells/mm³, then resume treatment at reduced dose levels.
Pneumonitis
Pneumonitis occurred in 1% of patients when human serum albumin-paclitaxel nanoparticles were used as monotherapy and in 4% of patients when human serum albumin-paclitaxel nanoparticles were used in combination with gemcitabine. Closely monitor all patients for signs and symptoms of pneumonitis. After ruling out infectious etiology and upon making a diagnosis of pneumonitis, permanently discontinue treatment with the drug and gemcitabine and promptly initiate appropriate treatment and supportive measures.
Hepatic impairment
Because the toxicity of paclitaxel can be increased with hepatic impairment, administration of the drug in patients with hepatic impairment should be performed with caution. Patients with hepatic impairment may be at increased risk of toxicity, particularly from myelosuppression; such patients should be closely monitored for development of profound myelosuppression.
The drug is not recommended in patients who have total bilirubin >5 x ULN or AST >10 x ULN. In addition, the drug is not recommended in patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment (total bilirubin >1.5 x ULN and AST ≤10 x ULN).
Cardiotoxicity
Rare reports of congestive heart failure and left ventricular dysfunction have been observed among individuals receiving human serum albumin-paclitaxel nanoparticles. Most of the individuals were previously exposed to cardiotoxic medicinal products such as anthracyclines or had underlying cardiac history. Thus, patients receiving the drug should be vigilantly monitored by physicians for the occurrence of cardiac events.
Eye disorders
Cystoid macular oedema (CMO) has been reported in patients treated with human serum albumin-paclitaxel nanoparticles. Patients with impaired vision should undergo a prompt and complete ophthalmologic examination. In case CMO is diagnosed, the drug treatment should be discontinued and appropriate treatment initiated.
Patients 75 years and older
For patients of 75 years and older, no benefit for the combination treatment of human serum albumin-paclitaxel nanoparticles and gemcitabine in comparison to gemcitabine monotherapy has been demonstrated. In the very elderly (≥75 years) who received human serum albumin-paclitaxel nanoparticles and gemcitabine, there was a higher incidence of serious adverse reactions and adverse reactions that led to treatment discontinuation including haematologic toxicities, peripheral neuropathy, decreased appetite and dehydration. Patients with pancreatic adenocarcinoma aged 75 years and older should be carefully assessed for their ability to tolerate the drug in combination with gemcitabine with special consideration to performance status, co-morbidities and increased risk of infections.
Other
Erlotinib should not be co-administered with paclitaxel plus gemcitabine.
See prescribing information for full details.

The most common clinically significant adverse reactions associated with the use of human serum albumin-paclitaxel nanoparticles have been neutropenia, peripheral neuropathy, arthralgia/myalgia and gastrointestinal disorders.
See prescribing information for full details

The metabolism of paclitaxel 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 paclitaxel 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 paclitaxel may be increased due to higher paclitaxel exposure. Administering paclitaxel 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 paclitaxel exposures.
The drug should not be used in combination with other anticancer agents.
See prescribing information for full details

Contraception in males and females
Women of childbearing potential should use effective contraception during treatment and for at least six months after the last dose.
Male patients with female partners of reproductive potential are advised to use effective contraception and to avoid fathering a child during and for at least three months after the last dose.
Pregnancy: There are very limited data on the use of paclitaxel in human pregnancy. Paclitaxel is suspected to cause serious birth defects when administered during pregnancy. Women of childbearing potential should have a pregnancy test prior to starting treatment with the drug. The drug should not be used in pregnancy, and in women of childbearing potential not using effective contraception, unless the clinical condition of the mother requires treatment with paclitaxel.
Lactation: It is not known if paclitaxel is excreted in human milk. Because of potential serious adverse reactions in breast-feeding infants, the drug is contraindicated during lactation. Breast-feeding must be discontinued for the duration of therapy.
Fertility: Male patients should seek advice on conservation of sperm prior to treatment because of the possibility of irreversible infertility due to therapy.

There is no known antidote for paclitaxel overdose. In the event of an overdose, the patient should be closely monitored. Treatment should be directed at the major anticipated toxicities, which are bone marrow suppression, mucositis and peripheral neuropathy.

Unopened vials: Store below 25°C.
Stability of reconstituted dispersion in the vial: Chemical and physical in-use stability has been demonstrated for 24 hours at 2-8 °C when the vial is protected from bright light.
Stability of the reconstituted dispersion in the infusion bag: Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C-8°C, protected from light followed by 4 hours at 15°C-25°C.