Intaxel

Paclitaxel.

Paclitaxel Injection USP (INTAXEL) is a clear colorless to slightly yellow viscous solution. It is supplied as a non-aqueous solution intended for dilution with a suitable parenteral fluid prior to intravenous infusion. INTAXEL is available as 5 mL, 17 mL, 43.4 mL and 50 mL multi dose vials. Each mL of sterile solution contains 6 mg Paclitaxel USP, 527 mg of Polyoxyl 35 Castor Oil USNF and 49.7% (v/v) Dehydrated Alcohol USP.
Paclitaxel is a product with antitumour activity. The chemical name for Paclitaxel is 5β,20-epoxy- 1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one4,10-diacetate2-benzoate13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine.
Paclitaxel is a white to off white crystalline powder with the empirical formula C₄₇H₅₁NO₁₄ and a molecular weight of 853.9. It is highly lipophilic, insoluble in water, soluble in alcohol and melts at around 216-217 °C.

Pharmacology: Pharmacodynamics: Mechanism of Action: Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers. It stabilizes microtubules by preventing depolymerization resulting in the inhibition of the normal dynamic reorganization of the microtubule network essential for cellular functions. Paclitaxel also induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.
Clinical Studies: Ovarian Cancer: Four trials of Paclitaxel as single agent in patients who had received prior platinum based first line treatment, confirmed its efficacy as salvage therapy for ovarian carcinoma. These trials, which enrolled a total of 177 patients, were conducted at John Hopkins Oncology Centre, Albert Einstein Cancer Centre, GOG and NCI, used a dose ranging between 170-250 mg/m². Out of the 157 patients evaluable, there were 55 responders giving an overall response rate of 35% with 16 CRs (10%) and 39 PRs (25%). Out of the 52 patients categorized as clinically platinum resistant, 15 (29%) responded. These four trials led two significant conclusions. First, Paclitaxel is clearly active against ovarian carcinoma previously treated with platinum based chemotherapy. Second, the level of activity does not appear to be influenced by the results or prior platinum based therapy.
In yet another study at NCI a total of 1819 patients were enrolled to be treated with Paclitaxel 135 mg/m² over 24 hrs every 3 weeks. A report on the first 1000 patients noted 935 evaluable patients, 650 of whom had clinically measurable disease. Among these 23 CRs (4%) and 118 PRs (18%) were observed for an overall response rate of 22%.
Metastatic Breast Cancer: After the observation of significant antitumour activity of Paclitaxel in women with stage IV breast cancer (minimally pretreated), a phase II study was initiated in 33 women with anthracycline resistance breast cancer, at those of Paclitaxel 175 mg/m² in a 3 h infusion every 3 weeks. There were 2 CRs (6%) and 12 PRs (36%) giving an overall response rate of 42%, median time to progression was 24 weeks and median survival was 41 weeks. Another phase II study conducted at MSKCC yielded 28% response rate in 51 patients who had received a median of 3 prior chemotherapeutic regiments for metastatic disease.
Non-small cell lung cancer: In a Phase III open label randomized study conducted by the ECOG, 599 patients were randomized to either Paclitaxel (P) 135 mg/m² as a 24-hour infusion in combination with cisplatin (c) 75 mg/m², Paclitaxel (P) 250 mg/m² as a 24-hour infusion in combination with cisplatin (c) 75 mg/m² with G-CSF support, or cisplatin (c) 75 mg/m² on day 1, followed by etoposide (VP) 100 mg/m² on days 1, 2 and 3 (control).
Response rates, median time to progression, median survival, and one year survival rates are given in the following table. The reported p-values have not been adjusted for multiple comparisons. There were statistically significant differences favoring each of the Paclitaxel plus cisplatin arms for response rate and time to tumor progression. There was no statistically significant difference in survival between Paclitaxel plus cisplatin arm and the cisplatin plus etoposide arm. See table.

Click on icon to see table/diagram/image

In the ECOG study, the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire had seven subscales that measured subjective assessment of treatment. Of the seven, the Lung Cancer Specific Symptoms subscale favored the paclitaxel 135 mg/m²/24 hour plus cisplatin arm compared to the cisplatin/etoposide arm. For all other factors, there was no difference in the treatment groups.
Pharmacokinetics: Absorption: With a 24-hour infusion, a 30% increase in dose increased the C_max by 87% with a 3-hour infusion, a 30% dose increase resulted in a 68% increase in the C_max.
Distribution: The mean steady state volume of distribution has range from 227 to 688 L/m², indicating extensive extravascular distribution and/or tissue binding. 89% to 98% of drug is bound to plasma proteins.
Metabolism: In vitro studies with human liver microsomes and tissue slices showed that paclitaxel was metabolized primarily to 6α, 3'-p-hydroxypaclitaxel the cytochrome P450 isozyme CYP2C8; and to two minor metabolites, 3-p-hydroxypaclitaxel and 6α, 3'-p-hydroxypaclitaxel by CYP3A4. In vitro, the metabolism of paclitaxel to 6α-hydroxypaclitaxel was inhibited by a number of agents such as ketoconazole, verapamil, diazepam, quinidine, dexamethasone, cyclosporine, teniposide, etoposide and vincristine.
Excretion: Following intravenous administration, paclitaxel exhibits a biphasic decline in plasma concentrations. The initial rapid decline represents distributions to the peripheral compartment and elimination of the drug. The later phase is due, in part, to a relatively slow efflux of paclitaxel from the peripheral compartment. In patients treated with doses of 135 and 175 mg/m² given as 3 and 24 hour infusions, mean terminal half-life has ranged from 13.1 to 52.7 hours and total body clearance has ranged from 12.2 to 23.8 L/h/m².
Elimination: After intravenous administration of 15-275 mg/m² doses of Paclitaxel as 1, 6 or 24-hour infusions, mean values for cumulative urinary recovery unchanged drug ranged from 1.3% to 12.6% of the dose. This indicates extensive non-renal clearance of paclitaxel.
CLINICAL PHARMACOLOGY: The pharmacokinetics of Paclitaxel has been evaluated in adult cancer patients who received single doses of 15-135 mg/m² given by 1-hour infusion (n=15), 30-275 mg/m² given by 6-hour infusions (n=36), and 135-275 mg/m² given by 24 hour infusions (n=54). Following intravenous administration of Paclitaxel, the drug exhibited a biphasic decline in plasma concentrations. The initial rapid decline represents distribution to the peripheral compartment and significant elimination of the drug. The later phase was due, in part, to a relatively slow efflux of Paclitaxel from the peripheral compartment. Values for mean terminal phase half-life; total body clearance and apparent volume of distribution at steady state were determined following 1 hour and 6 hour infusions at dosing levels of 15-275 mg/m². Mean (standard deviation) terminal half-life was estimated to range from 5.3 (4.6) to 17.4 (4.7) hours. Mean (SD) values for total body clearance ranged from 5.8 (2.3) to 16.3 (2.3) l/h/m². The mean (SD) steady state volume of distribution ranged from 42 (15) to 162 (133) l/m², indicating extravascular distribution and/or tissue binding of Paclitaxel.
In vitro studies of binding to human serum proteins, using Paclitaxel concentrations ranging from 0.1 to 50 micrograms/ml, indicated that between 89-98% of the drug is bound; the presence of cimetidine, ranitidine or dexamethasone did not effect the protein binding of Paclitaxel. Mean (SD) C_max values ranged from 435 (111) to 802 (260) ng/ml following 24 hour infusions at doses of Paclitaxel of 200 to 275 mg/m², and were approximately 10-30% of those following 6 hour infusions of equivalent doses. After administration of doses of Paclitaxel of 170 mg/m² or higher by infusion lasting 6 or 24 hours, plasma concentrations above 85 ng/ml, the level shown to be pharmacologically active in vitro, were regularly observed for at least 6 to 12 hours. The disposition of Paclitaxel has not been fully elucidated in humans. After intravenous administration of 15-175 mg/m² doses of Paclitaxel as 1, 6, 24 hour infusions, mean (SD) values for cumulative urinary recovery of unchanged drug ranged from 1.3% (0.5%) to 12.6% (16.2%) of the dose, indicating extensive non-renal clearance. Paclitaxel has been shown to be metabolized in the liver in animals and there is evidence suggesting hepatic metabolism in human. High Paclitaxel concentrations have been reported in the bile of patients treated with the drug. The effect of renal of hepatic dysfunction on the disposition of Paclitaxel has not been investigated. Possible interactions of Paclitaxel with concomitantly administered medications have been formally investigated.
Toxicology: Preclinical Safety Data: Carcinogenesis, Mutagenesis, Impairment of Fertility: The carcinogenic potential of Paclitaxel has not been studied. Paclitaxel has been shown to be mutagenic in vitro (chromosome aberrations in human lymphocytes) and in vivo (micronucleus test in mice) mammalian test systems, however, it did not induce mutagenicity in the Ames test or the CHO/HGPRT gene mutation assay. Paclitaxel at an I.V. dose of 1 mg/kg (6 mg/m²) produced low fertility and fetal toxicity in rats. Paclitaxel has also been shown to be maternal and embryo-fetal toxic in rabbits receiving the drug at an I.V. dose of 3 mg/kg (33 mg/m²) during organogenesis. (See Warnings.)

INTAXEL is indicated for the treatment of the following: Ovarian Cancer: As first line therapy in combination with cisplatin for the treatment of advance carcinoma of the ovary.
Second line therapy for the treatment of advanced metastatic carcinoma of the ovary.
Breast Cancer: Adjuvant treatment of node positive breast cancer administered sequentially to standard combination therapy.
Second line therapy after failure of anthracycline combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy which have included an anthracycline.
Non-Small Cell Lung Cancer: Intaxel in combination with cisplatin is effective for NSCLC patients who are not candidates for potentially curative surgery and/or radiation therapy.
Kaposi's Sarcoma: Second-line treatment of AIDS-related Kaposi's Sarcoma.

Recommended dosage: Ovarian Cancer: Combination therapy: For previously untreated patients, the recommended dosing regimen, given every 3 weeks, is INTAXEL administered intravenously over 3 hours at a dose of 175 mg/m² followed by a platinum compound.
Alternatively, a more myelosuppressive regimen of INTAXEL may also be administered intravenously at a dose of 135 mg/m² over 24 hours followed by a platinum compound, every 3 weeks.
Single-agent therapy, second-line therapy for the treatment of advanced metastatic carcinoma of the ovary: In patients previously treated with chemotherapy the recommended regimen is 175 mg/m² administered intravenously over 3 hours every 3 weeks.
Breast Cancer: Adjuvant therapy: INTAXEL 175 mg/m² administered intravenously over 3 hours every 3 weeks for 4 courses sequentially to standard combination therapy.
Single-agent second-line therapy after failure of anthracycline combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy which have included an anthracycline INTAXEL 175 mg/m² administered intravenously over 3 hours every 3 weeks.
Non-small cell lung cancer: Combination therapy: For previously untreated patients, the recommended dosing regimen given with a 3 week interval between courses is, INTAXEL 175 mg/m² administered intravenously over 3 hours followed by a platinum compound.
Alternatively, a more myelosuppressive regimen of INTAXEL may be administered intravenously 135 mg/m² over 24 hours followed by a platinum compound, with a 3 week interval between courses.
Kaposi's Sarcoma: Second-line therapy: INTAXEL 135 mg/m² administered intravenously over 3 hours with a 3 week interval between courses or 100 mg/m² administered intravenously over 3 hours with a 2 week interval between courses (dose intensity 45-50 mg/m²/week).
Based upon the immunosuppression observed in patients with advanced HIV disease, the following modifications are recommended in these patients.
The dose of dexamethasone as one of the three premedication drugs should be reduced to 10 mg orally.
Treatment with INTAXEL should be initiated or repeated only if the neutrophil count is at least 1,000 cells/mm³.
The dose of subsequent courses of INTAXEL should be reduced by 20% for those patients who experience severe neutropenia (<500 cell/mm³ for a week or longer).
Concomitant hematopoietic growth factor (G-CSF), should be initiated as clinically indicated.
Precautions and Premedication Regimen with Paclitaxel: All the patients should be pretreated with steroids; antihistamines and it needed H₂-receptor antagonist.
Cardiac functions should be checked before INTAXEL administrations.
PREMEDICATION REGIMENS: Dexamethasone 20 mg orally 12 and 6 hours prior INTAXEL therapy and; cimetidine 300 mg IV or ranitidine 50 mg IV 30 minutes prior to therapy and; diphenhydramine 50 mg IV 30 minutes prior to therapy.
Preparations and Administration Precaution: Paclitaxel is a cytotoxic anticancer drug and as with other potentially toxic compounds, caution should be exercised in handling INTAXEL injection. The use of glove is recommended. If INTAXEL solution contacts the skin, wash the skin immediately and thoroughly with soap and water. If INTAXEL contacts the mucous membranes, the membranes should be flushed thoroughly with water.
Preparations for Intravenous Administration: Paclitaxel Injection USP must be diluted prior to infusion. INTAXEL injection should be diluted in 0.9% Sodium chloride injection USP, 5% Dextrose Injection USP, 5% Dextrose and 0.9% Sodium chloride Injection USP to a final concentration of 0.3 to 1.2 mg/mL. The solutions are physically and chemically stable for up to 27 hours at ambient temperature (approximately 25°C) and room lighting conditions.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Upon preparation, solution may show haziness, which is attributed to the formulation vehicle. No significant losses in potency have been noted following stimulated delivery of the solution through I.V. tubing containing an in line (0.22 micron) filter. Published data for the presence of the extractable plasticizer DEHP [di-(2-ethylhexyl)phthalate] show that levels increase with time and concentration when dilutions are prepared in PVC containers and administration sets is not recommended. INTAXEL solutions should be prepared and stored in glass, polypropylene, or polyolefin containers. Non-PVC containing administration sets such as those that are polyethylene lined should be used. Intaxel should be administered through an in line filter with a microporous membrane not greater than 0.22 microns.

There is no known antidote for Paclitaxel overdosage. The primary anticipated complications of overdosage would consist of bone marrow suppression, peripheral neurotoxicity and mucositis.

INTAXEL is contraindicated in patients who have a history of hypersensitivity reaction to Paclitaxel or other drugs formulated in Polyoxyl 35 Castor Oil USNF.
INTAXEL should not be used in patients with baseline neutrophil count of <1,500 cells/mm³.

Paclitaxel (INTAXEL) should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available. Patients should be pretreated with corticosteroids (such as dexamethasone), diphenhydramine or promethazine hydrochloride and H2 antagonists (such as cimetidine or ranitidine) before receiving Intaxel (see Dosage & Administration). Severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema and generalized urticaria have been reported in 2% of the patients receiving Paclitaxel. These reactions were probably histamine mediated. Patients who experience severe hypersensitivity reactions to Paclitaxel should not be rechallenged with the drug. Bone marrow suppression (primarily neutropenia) is dose-dependent and is the dose limiting toxicity. Neutrophil nadirs have been reported at a median of 11 days. INTAXEL should not be administered to patients with baseline neutrophil counts of less than 1500 cells/mm³. Frequent monitoring of blood counts should be instituted during INTAXEL treatment. Patients should not be retreated with subsequent cycle of INTAXEL until neutrophils recover to a level of >1,500 cells/mm³ and platelets recover to a level of >100,000 cells/mm³.
Severe conduction abnormalities have been documented in less than 1% patients during Paclitaxel therapy. In one case insertion of a pacemaker was required due to the recurrence of atrioventricular block.
Use in Pregnancy: In rats and rabbits, Paclitaxel was shown to result in abortions, decreased corpora lutea, a decrease in implantation and live fetuses, increased reabsorptions and embryo-fetal deaths. No gross external, soft issue or skeletal alterations occurred. There are no studies in pregnant women. If INTAXEL is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with INTAXEL.

Contact of the undiluted concentrate with plasticized polyvinyl chloride (PVC) equipment or devices used to prepare solutions for infusions is not recommend. In order to minimize patient exposure to the plasticizer DEHP [di -(2 ethylhexyl)phthalate], which may be leached from PVC infusion bags or sets, diluted INTAXEL solutions should preferably be stored in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administers through polyethylene lined administration sets.
INTAXEL should be administered through as in line with a microporous membrane not greater than 0.22 microns.
Use in Children: The safety and effectiveness of Paclitaxel in children has not been established.

Pregnancy: In rats and rabbits, Paclitaxel was shown to result in abortions, decreased corpora lutea, a decrease in implantation and live fetuses, increased reabsorptions and embryo-fetal deaths. No gross external, soft issue or skeletal alterations occurred.
There are no studies in pregnant women. If INTAXEL is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with INTAXEL.
Nursing mothers: It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk and because the potential for serious adverse reactions in nursing infants, it is recommend that nursing be discontinued when receiving Intaxel therapy.

Myelosuppression: Neutropenia is the principle dose limiting toxicity of Paclitaxel on all administration schedules evaluated to date. The onset of neutropenia has usually occurred by day 8 and the nadir neutrophil counts have generally occurred on day 8-11 with rapid recovery by days 15-21. McGuire et al have reported that 213 of 281 courses of Paclitaxel in heavily pretreated patients with ovarian cancer were associated with grades 3 or 4 neutropenia (neutrophil count <1000 cell/µl). However, only 14 patients (21 out of 281 courses) required hospitalization for fever associated with neutropenia, but neutropenia is not cumulative and neutrophil count nadirs have generally remained unchange during successive courses indicating that Paclitaxel may not be irreversibly toxic to hematopoietic cells. Published reports on Paclitaxel given as a 3 hr. infusion indicate that shorter drug infusions may induce less severe neutropenia. The extent of prior myelosuppressive therapy is another predisposing factor for severe neutropenia. Hematopoietic colony stimulating factors have been demonstrated to ameliorate Paclitaxel induced neutropenia. More specify, absolute neutrophil count (ANC) nadirs are generally higher and the duration of severe grade 4 neutropenia (ANC <500 µl) was usually short (<5 days). Day 8 or 9 was consistently the median day of nadir for platelets.
The nursing management of hematological reactions should include a complete blood count (CBC) before each course of treatment. The White Blood Count (WBC) and platelet count should be >1500 cells/mm³ and 1,000,000 cells/mm² respectively, before re-treatment.
Frequent monitoring of blood is uncommon and almost never severe. Bleeding episodes are reported but most of the hemorrhagic episodes are localized. Anemia is also observed in 78% of patients and is severe in 16% of cases. Red cell transfusion is required in 25% of patients.
Hypersensitivity Reactions: A review of early phase I experience has identified reports of hypersensitivity in 25 of 159 patients (16%), 12 of which were classified as major reactions. The majority (53%) of HSRs occurred within 2 to 3 min. of beginning the Paclitaxel infusion and 78% began within 10 minutes. Although it is unclear whether Paclitaxel itself or Polyoxyl 35 castor oil vehicle induces the hypersensitivity reactions (HSRs), Polyoxyl 35 castor oil more likely to be responsible since other drugs formulated in Polyoxyl 35 castor oil have also been associated with HSRs. However following adoption of longer infusion schedules (primarily 24 hrs.) and use of prophylactic antiallergic premedication, incidence of severe hypersensitivity reactions fell substantially.
Severe symptoms manifest most frequently as dyspnea, hypotension and chest pains. In some patients, interruptions of the infusion are the only treatment requires. Other patients require therapy with bronchodilators, epinephrine, antihistamines and corticosteroids as single agents or in combination. Minor signs and symptoms such as flushing (36%) and rash (11%) have not been associated with subsequent development of major HSRs. None if these minor reactions require interruption of Paclitaxel for injection concentrate infusion or prevented completion of treatment.
Infections: Infections episodes in 30% of patients and 9% of courses; these episodes were fatal in 1% of patients and include sepsis, pneumonia and peritonitis. Infections episodes were reported in 19% of the patients given either 135 or 175 mg/m² dose by a 3 hour infusion. Urinary tract infections and upper respiratory tract infections were the most frequently reported infections complications.
Cardiovascular Adverse Effects: The most common cardiac rhythm disturbance noted during Paclitaxel administration is a transient asymptomatic bradycardia with heart rates occasionally decreasing to less than 40 beats/minute. It has been noted in 13 out of 45 patients (29%) in phase II trials. However, bradycardia alone is not an indication for discounting treatment, since the vast majority of these cases are totally asymptomatic. Instead, Paclitaxel should be continued unless bradycardia is associated with progressive atrioventricular (AV) conduction disturbances, and/or clinically significant hemodynamic effects, e.g. symptomatic hypotension.
Additionally, one case of progressive AV block, a fatal myocardial infarction and episodes of cheat discomfort have occurred in several patients at the time of Paclitaxel treatment in early trials.
Cardiac disturbances in recent trials have principally occurred in patients with cardiac risk factors. Since severe cardiac disturbances have been rare and inconsequential, routine cardiac monitoring during Paclitaxel infusion is not required for patients without cardiac risk factors.
In addition, the relative contributions of Paclitaxel, its Polyoxyl 35 castor oil formulation vehicle and H₁ & H₂ histamine antagonist premedication used to prevent HSRs, in inducing these cardiac disturbances is not clear.
Neurotoxicity: The neurotoxic manifestations of Paclitaxel can be categorized into those resulting from: Sensory neuropathy; Motor neuropathy; Autonomic neuropathy; Myopathy.
Sensory Neuropathy: It is most common neurotoxic effect of Paclitaxel. It invariably occurs when the Paclitaxel dose approaches 250 mg/m² (24 hr. infusion). The most common initial symptoms include numbness, tingling and/or burning pain in a glove and stocking distribution. The distal lower extremely are usually affected first. Mild sensory symptoms have usually improved or resolved completely within several months after discontinuation of Paclitaxel. However, some symptoms and deficits may persist for long periods after therapy in patients who develop more severe neuropathic symptoms.
Motor Neuropathy: Unlike sensory neuropathy, motor neuropathy is not well recognized. This is due to the fact that mild distal weakness rarely affects function.
Autonomic Neuropathy: Paralytic ileus and symptomatic orthostatic manifestation have been observed in patients receiving high doses of Paclitaxel - (250-275 mg/m²) and in those patients with diabetic mellitus who may be more predisposed to developing toxic neuropathies.
Myopathy and Myopathic Effects: Transient myalgia and/or arthralgia is commonly observed after treatment with moderate to high doses of Paclitaxel administered over 6 to 24 hrs. Symptoms generally occur 2 to 3 days after treatment and resolve within 5-6 days. While these symptoms are usually mild and infrequent at Paclitaxel doses less than 170 mg/m², they become more frequent and severe at Paclitaxel doses greater than 200 mg/m². Dose appears to be the most important risk factor for the development of significant neurotoxicity. Other factors that may predispose patients to developing severe peripheral neurotoxicity during Paclitaxel treatment are prior exposure to know neurotoxic agent and antecedent medical disorder (e.g. diabetes mellitus)
Gastrointestinal Toxicities: Paclitaxel relates gastrointestinal toxic effects include anorexia, nausea, vomiting and diarrhea. Although anorexia may frequently occur especially at high dosage, it is generally brief and rarely severe. Nausea, vomiting and diarrhea are also rarely severe and do not usually require symptomatic treatment. In phase II studies of Paclitaxel (24 hr. infusions) have experienced severe NCI (National Cancer Institute) grade 3 and 4 elevation of SGPT, SGOT, alkaline phosphate and bilirubin.
Other Toxicities: Alopecia has been reported in almost all patients treated with 24 hr. infusions of Paclitaxel at dose equal or greater than 135 mg/m². Like alopecia caused by other antineoplastic agents, Paclitaxel induced alopecia is also reversible. Transient skin changes caused by paclitaxel related hypersensitivity reactions have been observed, but no other skin toxicities have significantly been associated with administration. Nail changes (changes in pigmentation or discoloration of nail bed) were uncommon (2%).
Arthralgia/Myalgia usually consisting of pain in the large joints of the arms and legs have been reported in about 50% of the patients and were usually mild. These symptoms were usually transient occurring two or three days after Paclitaxel administration and resolving within a few days.

In a Phase I trial using escalating doses of Paclitaxel (110-200 mg/m²) and cisplatin (50 or 75 mg/m²) given as sequential infusions myelosuppresstion was more profound when Paclitaxel was given after cisplatin than with the alternate sequence (i.e. Paclitaxel before cisplatin). Pharmacokinetic data from these patients demonstrated in Paclitaxel clearance of approximately 33% when Paclitaxel was administered following cisplatin. Based in in vitro data, there is the possibility of an inhibition of Paclitaxel metabolism in patients treated with ketoconazole. As a result, caution should be exercised when treating patients with Intaxel when they are receiving ketoconazole as concomitant therapy.

Stability: Unopened vials of Paclitaxel Injection USP (INTAXEL Injection) are stable until the date indicated on the package when stored under recommended storage condition in the original package. Freezing does not adversely affect the product. Solution should use within 28 days after opening.
Handling and Disposal: Unused portion and all materials that have been utilized for dilution and administration should be disposed of according to standard procedures for anticancer drugs.

Store the vials in the original cartons below 30°C. Protect from light.

Cytotoxic Chemotherapy

L01CD01 - paclitaxel ; Belongs to the class of taxanes from plant alkaloids and other natural products. Used in the treatment of cancer.

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