Taxol

Paclitaxel.

Active Ingredient: Paclitaxel.
Galenic Form: Concentrate for infusion.
Quantity of Active Ingredient per Unit: Multidose vials at 30 mg/5 ml, 100 mg/16.7 ml.
Excipients/Inactive Ingredients: chromatographically purified Polyoxyethylated Castor Oil (Cremophor EL), Dehydrated Alcohol.

ATC Code: L01C D01.
Pharmacology: Pharmacodynamics: Mechanism of Action: Paclitaxel is an antimitotic agent of the taxane class. Paclitaxel promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for the interphase and parts of mitotic function.
During mitosis, paclitaxel furthermore induces abnormal bundles of microtubules and multiple asters of microtubules are formed.
Clinical Efficacy: Primary treatment of ovarian carcinoma: The safety and efficacy of Taxol for the primary treatment of ovarian carcinoma (with Taxol infusion over 3 and 24 hours, respectively) has been investigated in two randomized controlled studies (vs. cyclophosphamide 750 mg/m² / cisplatin 75 mg/m²).
In the Intergroup study (B-MS CA 139-209), more than 650 patients with FIGO stage IIb-c, III or IV primary ovarian carcinoma were included. The patients received a maximum of 9 treatment courses of Taxol (175 mg/m² over 3 hours), followed by cisplatin (75 mg/m²) or the control treatment cyclophosphamide/cisplatin.
The median time to progression was 15.3 months vs. 11.5 months, and median survival was 35.6 months vs. 25.9 months.
The second study (GOG-111/B-MS CA 139-022) evaluated more than 400 patients with FIGO stage III/IV primary ovarian carcinoma, with a >1 cm residual carcinoma following laparotomy, or with metastatic ovarian carcinoma. The patients received a maximum of 6 courses of Taxol (135 mg/m² over 24 hours), followed by cisplatin (75 mg/m²) or the control treatment cyclophosphamide/cisplatin.
The median time to progression was 16.6 months vs. 13.0 months, and median survival was 35.5 vs. 24.2 months.
In patients with advanced ovarian carcinoma treated with Taxol/cisplatin (3-hour infusion), increased neurotoxicity and arthralgia/myalgia but reduced myelosuppression, was observed as compared to cyclophosphamide/cisplatin treatment.
Treatment of non-small cell lung carcinoma: The safety and efficacy of Taxol in the treatment of non-small cell lung carcinoma has been evaluated in patients without previous chemotherapy in four phase II trials (n=224) and in two randomized phase III trials (n=931).
In the phase III trials, Taxol (in combination with 75 or 80 mg/m² cisplatin) was statistically significantly better as compared to treatment with etoposide or teniposide associated with cisplatin. The time to progression of the disease was between 4.3 and 5.1 months in the Taxol group, with a median survival of 9.3-10.0 months, and a one year survival rate of 36-41%. A significant improvement of quality in life of the persons treated with Taxol was observed in both trials.
Primary treatment of metastatic breast carcinoma, in combination with trastuzumab: Refer to information for healthcare professionals on Herceptin (trastuzumab).
Secondary treatment of metastatic breast carcinoma resistant to standard therapy: In a randomized multicenter phase III study, patients with relapse following adjuvant treatment or following premedication with combined chemotherapy received Taxol at a dosage of 175 mg/m² or 135 mg/m², administered as a 3-hour infusion. The overall response rate for the 454 evaluable patients was 26% (complete response in 17 cases, partial response in 99 cases).
The median duration of response, measured from the first day of treatment, was 8.1 months. The median time to progression was 3.0 months for patients with a dosage of 135 mg/m² and 4.2 months for patients with a dosage of 175 mg/m², respectively. Overall, the median survival (n=471) was 11.7 months.
Adjuvant treatment of breast carcinoma: In an open, randomized American intergroup study for adjuvant treatment of breast carcinoma in node positive patients, 3121 subjects with stage I-III were either treated with 4 courses of Taxol 175 mg/m² (T) following AC treatment (doxorubicin + cyclophosphamide) or with AC alone. Hormone receptor positive patients received tamoxifen additionally. The interim analysis of this study with a median duration of treatment of 52.2 months showed significantly better results on AC plus Taxol treatment. The advantage of additional Taxol treatment was 13% in DFS (hazard ratio 0.87) and 14% in OS (hazard ratio 0.86) while the recurrence rates were low in both treatment arms: 469/1551 (32.0%) for AC and 432/1570 (27.5%) for AC plus Taxol. It was only in patients with estrogen receptor negative tumors (without tamoxifen treatment) that additional Taxol treatment was highly significant with a hazard ratio of 0.71 in DFS (95% CI 0.58-0.88; p<0.001). In those patients with estrogen receptor positive tumors, who also received tamoxifen (i.e. in two thirds of the study population), there was no difference between AC and AC plus Taxol (hazard ratio in DFS 1.0). Furthermore, no significant differences with Taxol were observed in patients with small tumor (<2 cm, T1) or in high risk patients with 10 or more positive lymph nodes (LN) or tumors >5 cm (T3).
Pharmacokinetics: The pharmacokinetic parameters were determined following 3-hour and 24-hour intravenous infusion, respectively, at paclitaxel doses of 135 and 175 mg/m². Intrapatient variability in paclitaxel exposure was minimal. Pharmacokinetics, when short infusion was used, were determined primarily by Cremophor EL.
With the 3-hour infusion, increasing doses resulted in non-linear pharmacokinetics.
With the 24-hour infusion, kinetics are almost linear with dosage.
With the 3-hour infusion at 175 mg/m², C_max is 10-fold and AUC 3-fold higher than with the 24-hour infusion at 135 mg/m².
Distribution: The distribution of paclitaxel has not been fully elucidated in humans. Mean steady-state volume of distribution ranged from 198 to 688 L/m², indicating extensive tissue distribution and/or tissue binding.
In vitro binding studies indicate that 89-98% of drugs are bound to plasma proteins. The presence of cimetidine, ranitidine, dexamethasone or diphenhydramine does not affect protein binding.
There was no evidence for accumulation of paclitaxel with multiple treatment courses.
Metabolism: Paclitaxel is metabolized primarily by cytochrome P450 enzymes. 6α-hydroxypaclitaxel, 3'-p-hydroxypaclitaxel and 6α-3'-p-dihydroxypaclitaxel have been identified as primary metabolites. The formation of these metabolites is catalyzed by CYP2C8 and CYP3A4. The major metabolic pathway is metabolization to 6α-hydroxypaclitaxel via CYP2C8. Also refer to Interactions.
Elimination: Following intravenous administration, paclitaxel plasma levels exhibit a biphasic decline. Hepatic metabolism and biliary clearance are the two important mechanisms of elimination. The mean terminal half-life ranged from 3.0 to 52.7 hours, and the mean values for total body clearance ranged from 11.6 to 24.0 L/hr/m². Total body clearance appeared to decrease with increasing plasma concentrations of paclitaxel. Mean values for cumulative urinary recovery of unchanged drug have ranged from 1.3 to 12.6%, indicating extensive non-renal clearance.
Kinetics in Special Clinical Situations: Impaired renal function: The effect of reduced renal function on the disposition of paclitaxel following a 3-hour infusion has not been investigated yet. Paclitaxel is not dialyzable.
Impaired hepatic function: The pharmacokinetics of paclitaxel has been investigated in 35 patients with increased bilirubin levels. At bilirubin levels between 1 and 2x ULN, the AUC was increased however without toxicity increase; at bilirubin levels >2x ULN, an increased myelotoxicity has been observed.
Toxicology: Preclinical Data: There are no carcinogenicity studies. Based on its mechanism of action, paclitaxel is a potential carcinogenic and genotoxic agent. Paclitaxel has been shown to be mutagenic in animal studies (in vitro and in vivo).

Ovarian Carcinoma: Primary treatment of advanced ovarian carcinoma (FIGO-stage III, IV) or residual carcinoma (>1 cm) after laparotomy, in combination with cisplatin.
Treatment of metastatic ovarian carcinoma after failure of standard, platinum-containing chemotherapy.
Non-Small Cell Lung Carcinoma: Treatment of non-small cell lung carcinoma (NSCLC) in combination with cisplatin in patients who are not candidates for surgery and/or radiation therapy.
Breast Carcinoma: In combination with trastuzumab for the treatment of metastatic breast carcinoma when tumors overexpress HER2 and patients have not yet received chemotherapy against their metastatic disease.
Treatment of metastatic breast carcinoma in patients who have failed, or are not candidates, for standard anthracycline therapy.
Adjuvant treatment in patients with breast carcinoma and affected local regional lymph nodes (node positive) following anthracycline treatment with doxorubicin and cyclophosphamide.

Taxol shall only be handled by medical personnel experienced in the use of cytostatic chemotherapy. Furthermore, appropriate equipment must be available to treat possibly occurring complications.
Usual Dosage: Premedication: Prior to Taxol treatment, premedication with a corticosteroid, a H₁ and a H₂ antagonist is required (e.g. according to the following dosage regimen): See Table 1.

Click on icon to see table/diagram/image

Primary treatment of advanced ovarian carcinomas: The recommended dose of Taxol is 175 mg/m² body surface, administered as intravenous infusion over 3 hours, followed by cisplatin 75 mg/m². If a 24-hour infusion is selected, the dose of Taxol is 135 mg/m², followed by 75 mg/m² of cisplatin. A 3-week interval should be respected between treatment courses.
Taxol should always be administered prior to cisplatin. Also refer to Interactions. For cisplatin, refer to its product information.
Secondary treatment of metastatic ovarian carcinoma resistant to standard therapy: The recommended dose of Taxol is 175 mg/m² body surface, administered as intravenous infusion over 3 hours, with a 3-week interval between treatment courses.
Treatment of non-small cell lung carcinoma: The recommended dose of Taxol is 175 mg/m² body surface area, administered as intravenous infusion over 3 hours. The Taxol infusion is followed by a treatment with cisplatin (in the EORTC study 08925, 80 mg/m² cisplatin in combination with Taxol). A 3-week interval should be respected between treatment courses. Therapy should be limited to 6 courses.
Taxol should always be administered prior to cisplatin. Also refer to Interactions. For cisplatin, refer to its product information.
First-line therapy of metastatic breast carcinoma in combination with trastuzumab: The recommended dose of Taxol is 175 mg/m² body surface, administered as intravenous infusion over 3 hours. A 3-week interval should be respected between treatment courses. Taxol infusion is initiated the day following the first trastuzumab dose or immediately following the 2^nd trastuzumab dose if the initial trastuzumab dose was well tolerated. For trastuzumab, refer to its product information.
Secondary treatment of metastatic breast carcinoma resistant to standard therapy: The recommended dose of Taxol is 175 mg/m² body surface, administered as intravenous infusion over 3 hours, with a 3-week interval between treatment courses.
Adjuvant treatment in patients with breast carcinoma: Following administration of 4 courses of doxorubicin 60 mg/m² in combination with cyclophosphamide 600 mg/m², additional 4 courses of Taxol 175 mg/m² by 3-hr infusion are administered. An interval of 3 weeks should be respected between treatment courses.
The 4 Taxol courses must always be applied after the 4 doxorubicin/cyclophosphamide courses. Also refer to Interactions. For doxorubicin and cyclophosphamide, refer to their product information.
Dosage for the Treatment of Undesirable Effects: A treatment course with Taxol should not be considered before the neutrophil count is at least 1,500/mm³ and the platelet count at least 100,000/mm³.
In patients who, on Taxol treatment, develop severe neutropenia (neutrophil granulocytes <500/mm³) or severe peripheral neuropathy, dose reduction by 20% should be effected for the treatment courses.
Special Populations: Impaired liver function: Risk of toxicity is increased in case of mildly impaired liver function (in particular myelosuppression grade III-IV). Dose adjustment as shown in the following table is recommended in case of impaired liver function and patients should be carefully monitored for the development of profound myelosuppression. (See Table 2.)

Click on icon to see table/diagram/image

Pediatric use: The safety and effectiveness of Taxol in pediatric patients has not been established.

There is no antidote for Taxol overdose. In case of overdose, the primary anticipated complications are myelosuppression, peripheral neurotoxicity and mucositis.

History of severe hypersensitivity reactions to paclitaxel or other constituents of Taxol (especially Cremophor EL).
Neutropenia <1,500/mm³.
Pregnancy and lactation.

Monitoring of Vital Functions: Frequent monitoring of vital functions, especially during the first hours of Taxol infusion, is recommended in all patients. See also Cardiovascular Toxicity as follows.
Observation of the Infusion Site: As extravasation cannot be ruled out, keeping the infusion site under surveillance is recommended. See also Adverse Reactions.
Ethanol: As Taxol contains 0.4 g/ml ethanol, physicians should look out for any CNS and other effects.
Myelosuppression: Regular blood tests are required during Taxol treatment, as myelosuppression (primarily neutropenia) is the dose-limiting factor.
Myelosuppression is more pronounced with the 24-hour infusion compared to the 3-hour infusion. See also Adverse Reactions.
Nervous System: Although peripheral neuropathy is relatively common, severe symptoms occur rarely.
In patients with non-small cell lung cancer and in patients with ovarian cancer (who receive Taxol as first-line treatment), use of combination therapy of Taxol (infusion over 3 hours) and cisplatin resulted in a higher incidence rate of severe neurotoxicity than monotherapy with Taxol.
In patients who received Taxol as adjuvant therapy for breast cancer after anthracycline treatment, severe neurotoxicity was detected more often than in patients on AC therapy alone.
See also Adverse Reactions.
Hypersensitivity Reactions: Severe hypersensitivity reactions such as anaphylaxis have been observed during treatment with Taxol (histamine release). Therefore, premedication with corticosteroid, H₁ and H₂ antagonists must take place (see also Dosage & Administration). In rare cases, reactions were fatal despite appropriate premedication. If severe hypersensitivity reactions occur, the Taxol infusion must be discontinued immediately and symptomatic therapy initiated. Reuse of Taxol should not be be considered in this case.
Cardiovascular Toxicity: Severe cardiac conduction disorders occur rarely. In the case of a significant conduction disorder during Taxol infusion, appropriate therapy should be carried out. Further treatment with Taxol in this case should only be performed under close cardiac monitoring.
Hypotension, hypertension and bradycardia have been observed in patients with healthy hearts on Taxol treatment.
Patients were usually asymptomatic and no treatment was generally necessary.
Severe cardiac events occurred more frequently in individuals with non-small cell lung cancer than in patients with ovarian or breast cancer.
With combination treatment of Taxol with trastuzumab, cardiac function must be monitored by measurement of left ventricular ejection fraction (LVEF).
Non-Small Cell Lung Cancer: With regards to non-small cell lung cancer, there is no experience of treating individuals with brain metastases, individuals >75 years of age or individuals with non-compensated cardiovascular diseases with Taxol. Such patients should only be treated with particular caution.
Hepatic impairment: In the case of mild hepatic impairment, toxicity (especially grade III-IV myelosuppression) from Taxol may be increased. In mild to moderate hepatic impairment, the dose should be adjusted (see Dosage & Administration).
Use of Taxol is not recommended in the case of severe hepatic impairment.
Pseudomembranous colitis: In rare cases, pseudomembranous colitis has been reported during Taxol treatment, including in patients who have not received concurrent antibiotic treatment. This should be considered in the differential diagnosis of severe or persistent cases of diarrhoea occurring during or shortly after treatment with Taxol.
Vaccinations: Concomitant use of Taxol with a live vaccine can greatly accelerate replication of vaccine strains and/or potentiate the adverse reaction to the vaccine strain, as the normal defence mechanisms are potentially suppressed by Taxol. In a patient treated with Taxol, vaccination with a live vaccine can lead to a serious infection. The patient's antibody reaction to the vaccine may be reduced. Use of live vaccines should be avoided and the advice of a specialist should be sought.
Effect on the ability to drive and operate machines: Paclitaxel does not appear to reduce reactions. Impairment of the ability to drive or operate machines due to ethanol and administered premedication should be taken into account.

Pregnancy: In animal testing, paclitaxel was embryotoxic and foetotoxic and reduced fertility.
There is no experience in pregnant women. As with other cytotoxic substances, paclitaxel can cause harm to the foetus.
The drug is contraindicated during pregnancy (see Contraindications).
Patients should be instructed to avoid pregnancy during Taxol treatment and to consult the treating physician immediately if a pregnancy occurs.
Lactation: It is not known whether paclitaxel is excreted into breast milk. Therefore, Taxol is contraindicated during lactation (see Contraindications).
Fertility: Given the mutagenic potential of Taxol, effective contraception is required in both male and female patients during treatment and for up to six months after the end of treatment. As Taxol can impair male fertility, cryoconservation of sperm may be considered for the purposes of fathering children later (see Pharmacology: Toxicology: Preclinical Data under Actions).

Unless stated otherwise, the frequencies and severity of adverse reactions on Taxol treatment are generally comparable in individuals with ovarian cancer, breast cancer or non-small cell lung cancer.
The safety profile of Taxol was investigated in clinical studies in >3000 patients. Significant adverse reactions are myelotoxicity, neurotoxicity and hypersensitivity reactions.
Adverse effects are increased with combination therapy with doxorubicin (especially myocardial infarction) and trastuzumab (cardiomyopathy, infections [46% vs 27%]). The combination of Taxol with trastuzumab in individuals who underwent previous anthracycline treatment led to an increased and to more pronounced cardiac disorders compared to patients on Taxol monotherapy (NYHA class I/II 10% vs. 0%; NYHA class III/IV 2% vs. 1%) but was rarely associated with fatalities. With the exception of these rare cases, all individuals responded to an adequate treatment.
The frequency of the listed adverse reactions is defined as follows: "very common" (≥1/10); "common" (<1/10, ≥1/100); "uncommon" (<1/100, ≥1/1,000); "rare" (<1/1,000, ≥1/10,000); "very rare" (<1/10,000); "not known" (cannot be estimated based on the available data).
Infections and infestations: Very common: infection (24%; mainly urinary tract infections, upper respiratory tract infections).
Uncommon: septic shock, pneumonia, peritonitis.
Rare: pneumonia, sepsis.
Benign, malignant and non-specific neoplasias (including cysts and polyps): Very rare: acute myeloid leukaemia, myelodysplastic syndrome.
Blood and lymphatic system disorders: Very common: neutropenia (28-81%), anaemia (78%; Hb <8 g/dl 16%), thrombocytopenia (11%), haemorrhage (14%).
Rare: febrile neutropenia.
Immune system disorders: Very common: milder hypersensitivity reactions (approx. 34%, primarily reddening and skin rash).
Uncommon: severe hypersensitivity reactions requiring treatment (incl. hypotension, angioneurotic oedema, dyspnea, generalized urticaria, oedema, back pain, chills, pneumonitis).
Rare: anaphylactic reactions sometimes with fatal outcome.
For hypersensitivity reactions, see also Hypersensitivity Reactions under Precautions.
Metabolism and nutrition disorders: Very rare: anorexia.
Not known: tumor lysis syndrome.
Psychiatric disorders: Very rare: confusion.
Nervous system disorders: Very common: primarily peripheral neuropathy, especially paraesthesia (66%; on the 3-hour treatment regimen with Taxol/cisplatin 79%, grade III 11%, on the 24-hour regimen with Taxol/cisplatin 24%, grade III 3%).
Rare: motor neuropathy (with mild distal weakness).
Very rare: autonomic neuropathy with resulting paralytic ileus and orthostatic hypotension, grand mal seizures, other convulsions, encephalopathy, dizziness, headaches, ataxia.
Incidence and severity of neurologic manifestations are generally dose-dependent. In 1% of patients, peripheral neuropathy resulted in treatment discontinuation. Paraesthesia generally improved or disappeared within few months of discontinuing Taxol.
Eye disorders: Very rare: reversible optic nerve damage and/or visual disorders (scintillating scotomata), particularly in patients who have received higher doses than recommended.
Not known: macular oedema.
Ear and labyrinth disorders: Very rare: hearing loss and tinnitus, vertigo.
Cardiac disorders: Very common: ECG changes (approx. 17%).
Common: bradycardia (usually mild and did not require treatment).
Uncommon: cardiomyopathy, asymptomatic ventricular tachycardia, tachycardia with bigeminy, AV block, syncope, myocardial infarction.
Vascular disorders: Very common: hypotension (approx. 22%).
Uncommon: hypertension, thrombosis, thrombophlebitis.
Respiratory, thoracic and mediastinal disorders: Rare: dyspnoea, pleural effusion, respiratory insufficiency, interstitial pneumonia, pulmonary fibrosis, pulmonary embolism.
Very rare: cough, radiation pneumonia with concomitant radiotherapy.
Gastrointestinal disorders: Very common: nausea/vomiting (43%), diarrhoea (28%), mucositis (18%, observed more frequently on the 24-hour infusion than on the 3-hour infusion); these gastrointestinal adverse reactions are mild to moderate in nature.
Rare: bowel obstruction, bowel perforation, ischaemic colitis, pancreatitis.
Very rare: mesenteric thrombosis, pseudomembranous colitis, oesophagitis, constipation, ascites, neutropenic enterocolitis.
Hepatobiliary disorders: Common: severely elevated (>5x ULN) AST (SGOT) and alkaline phosphatase.
Uncommon: severely elevated bilirubin.
Very rare: liver necrosis (with fatal outcome), hepatic encephalopathy (with fatal outcome).
Skin and subcutaneous tissue disorders: Very common: alopecia (in virtually all cases).
Common: transient and mild changes to nails and skin.
Rare: pruritus, skin rash, phlebitis, erythema, cellulitis, skin flaking, necrosis and fibrosis, recurrence of radiation-induced skin reactions ("radiation recall").
Very rare: Stevens-Johnson syndrome, epidermal necrolysis, erythema multiforme, exfoliative dermatitis, urticaria, onycholysis.
Not known: scleroderma, cutaneous lupus erythematosus.
Musculoskeletal, connective tissue and bone disorders: Very common: arthralgia, myalgia (60%; severe in 13%).
More severe arthralgia/myalgia was observed in patients who received Taxol as adjuvant therapy for breast cancer than in patients on AC therapy alone.
Not known: systemic lupus erythematosus.
Renal and urinary disorders: Rare: elevated creatinine.
General disorders and administration site conditions: Common: local reactions at the application site in form of localised oedema, pain, erythema, and induration.
Uncommon: cellulitis, skin induration and/or flaking associated with extravasation, skin discoloration.
Rare: asthenia, malaise, fever, dehydration, oedema, recurrence of skin reactions at a site of previous extravasation when Taxol is injected at a different site ("recall").
Local reactions occurred more frequently on the 24-hour infusion than on the 3-hour infusion. They either occurred during the infusion or with a delay of 7-10 days.

Combination Therapy with Cisplatin: In combination therapy with cisplatin, Taxol should always be administered before cisplatin. In this case, the safety event profile of Taxol is similar to that reported in Taxol monotherapy.
Administration of Taxol after cisplatin treatment leads to about 20% decrease in paclitaxel clearance and greater myelosuppression.
Combination Therapy with Doxorubicin/Cyclophosphamide: In the sequential administration of four cycles of doxorubicin/cyclophosphamide followed by four cycles of Taxol for the adjuvant treatment of breast cancer, Taxol should always be administered after doxorubicin/cyclophosphamide. More pronounced neutropenia and stomatitis (due to doxorubicin) have been observed when Taxol was administered before doxorubicin/cyclophosphamide and beyond the recommended treatment duration.
Co-Medication with Substances that Influence CYP2C8 and 3A4: The metabolism of paclitaxel is catalyzed to a certain extent by the cytochrome P450 isoenzymes CYP2C8 and 3A4 (see also Pharmacology: Pharmacokinetics under Actions).
Therefore, caution is required when paclitaxel is used together with other drugs that inhibit either CYP2C8 or CYP3A4 (e.g. ketoconazole and other imidazole antimycotics, erythromycin, fluoxetine, gemfibrozil, clopidogrel, cimetidine, ritonavir, saquinavir, indinavir and nelfinavir) or induce them (e.g. rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine).

Preparation and Administration Precautions: Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. To minimize the risk of dermal exposure, always wear impervious gloves when handling vials containing Taxol Injection. If Taxol solution contacts the skin, wash the skin immediately and thoroughly with soap and water. Following topical exposure, events have included tingling, burning, and redness. If Taxol contacts mucous membranes, the membranes should be flushed thoroughly with water. Upon inhalation, dyspnea, chest pain, burning eyes, sore throat, and nausea have been reported.
Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration.
Preparation for Intravenous Administration: Taxol (paclitaxel) Injection must be diluted prior to infusion. Taxol should be diluted in 0.9% Sodium Chloride Injection, USP; 5% Dextrose Injection, USP; 5% Dextrose and 0.9% Sodium Chloride Injection, USP; or 5% Dextrose in Ringer's Injection 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, solutions may show haziness, which is attributed to the formulation vehicle. No significant losses in potency have been noted following simulated delivery of the solution through IV tubing containing an in-line (0.22 micron) filter.
Data collected 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. Consequently, the use of plasticized PVC containers and administration sets is not recommended. Taxol solutions should be prepared and stored in glass, polypropylene, or polyolefin containers. Non-PVC-containing administration sets, such as those which are polyethylene-lined, should be used.
Taxol should be administered through an in-line filter with a microporous membrane not greater than 0.22 microns. Use of filter devices which incorporate short inlet and outlet PVC-coated tubing has not resulted in significant leaching of DEHP.
The Chemo Dispensing Pin device or similar devices with spikes should not be used with vials of Taxol since they can cause the stopper to collapse resulting in loss of sterile integrity of the Taxol solution.

Store the vials in original cartons under controlled room temperature 15°C - 30°C. Retain in the original package to protect from light.
Stability: Unopened vials of Taxol (paclitaxel) Injection are stable until the date indicated on the package when stored under controlled room temperature 15°C - 30°C, in the original package. Neither freezing nor refrigeration adversely affects the stability of the product. Upon refrigeration, components in the Taxol vial may precipitate, but will redissolve upon reaching room temperature with little or no agitation. There is no impact on product quality under these circumstances. If the solution remains cloudy or if an insoluble precipitate is noted, the vial should be discarded. Solutions for infusion prepared as recommended are stable at ambient temperature (approximately 25°C) and lighting conditions for up to 27 hours.

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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