Paclib

Paclib

paclitaxel

Manufacturer:

UNILAB, Inc

Distributor:

UNILAB, Inc
Full Prescribing Info
Contents
Paclitaxel.
Indications/Uses
Ovarian Cancer: First-line treatment of advanced ovarian cancer in combination with cisplatin.
Subsequent treatment of advanced ovarian cancer.
Breast Cancer: Adjuvant treatment of node positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy.
Treatment of breast cancer after the failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior chemotherapy should have included an anthracycline unless clinically contraindicated.
For the initial treatment of locally advanced or metastatic breast cancer: In combination with an anthracycline in patients for whom anthracycline therapy is suitable, OR; In combination with trastuzumab, in patients who over-express human epidermal growth factor receptor 2 (HER-2) at a 3+ level as determined by immunohistochemistry and for whom anthracycline is not suitable.
Advanced Non-small Cell Lung Cancer (NSCLC): First-line treatment, in combination with cisplatin, of patients with NSCLC who are not candidates for surgery and/or radiation therapy.
AIDS-related Kaposi's Sarcoma: Palliative treatment of advanced or refractory AIDS-related Kaposi's sarcoma in patients who have failed prior liposomal anthracycline therapy.
Dosage/Direction for Use
Premedication Regimen: Premedicate all patients with oral dexamethasone (20 mg) approximately 12 and 6 hours before paclitaxel administration, IV diphenhydramine or its equivalent (50 mg) 30 to 60 minutes before paclitaxel, and either IV cimetidine (300 mg) or IV ranitidine (50 mg) 30 to 60 minutes before paclitaxel in order to reduce the incidence of hypersensitivity reactions.
Patients with HIV infection may follow the same premedication regimen with the exception of a reduced dose of oral dexamethasone (10 mg).
Paclitaxel Injection must be diluted prior to intravenous infusion. (See Table 1.)

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General Dosing Information: Monitor vital signs regularly, particularly during the first hour of administration. Cardiac monitoring is not required except in patients with preexisting cardiac abnormalities.
Closely monitor the infusion site for possible infiltration during drug administration particularly during longer periods of infusion (e.g., 24 hours). Local reactions may appear 7 to 10 days after completion of paclitaxel infusion.
Dose Adjustments: For patients with solid tumors (ovary, breast, NSCLC): Paclitaxel courses should not be repeated until the patient's neutrophil count is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
Reduce dose by 20% for subsequent courses of paclitaxel in patients who experience severe neutropenia (neutrophil <500 cells/mm3 for a week or longer) or severe peripheral neuropathy during paclitaxel therapy.
For AIDS-related Kaposi's Sarcoma: Initiate or repeat treatment only if the neutrophil count is at least 1000 cells/mm3.
Reduce dose by 20% for subsequent courses of paclitaxel in patients who experience severe neutropenia (neutrophil <500 cells/mm3 for a week or longer).
Initiate concomitant hematopoietic growth factor (G-CSF) as clinically needed.
Dosing in Patients with Hepatic Impairment: See Table 2.

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Contraindications
Hypersensitivity to paclitaxel, Cremophor EL (polyoxyethylated castor oil), or any component of the product.
Since the product contains ethyl alcohol as an excipient, it should not be administered to pregnant women, children, and patients with hepatic dysfunction, alcoholism and epilepsy.
Patients with solid tumors who have baseline neutrophil count of less than 1500 cells/mm3.
Patients with AIDS-related Kaposi's Sarcoma who have baseline neutrophil counts of less than 1000 cells/mm3 and those with concurrent, serious, uncontrolled infections.
Warnings
Paclitaxel 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.
Anaphylaxis and severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria have occurred in 2 to 4% of patients receiving paclitaxel in clinical trials. Fatal reactions have occurred in patients despite premedication. All patients should be pretreated with corticosteroids, diphenhydramine and H2-antagonists. Patients who experience severe hypersensitivity reactions to paclitaxel should not be rechallenged with the drug.
Paclitaxel therapy should not be administered to patients with solid tumors who have baseline neutrophil counts below 1500 cells/mm3 and should not be administered to patients with AIDS-related Kaposi's sarcoma if baseline neutrophil count is below 1000 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving paclitaxel (See Contraindications).
Special Precautions
General: Paclitaxel has a low therapeutic index. Therapeutic response is not likely to occur without evidence of toxicity. It should also be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents.
Cardiovascular: Hypotension, hypertension and bradycardia have been reported but patients are usually asymptomatic and generally do not require treatment. Severe cases of conduction abnormalities have been reported in <1% of patients receiving paclitaxel. In severe cases, paclitaxel infusions may need to be interrupted or discontinued at the discretion of the physician. Cardiac function monitoring is recommended in patients with preexisting cardiac abnormalities and when paclitaxel is co-administered with doxorubicin in patients with metastatic breast cancer.
If patients develop significant cardiac function abnormalities during administration, appropriate therapy should be administered and continuous electrocardiographic monitoring should be performed during subsequent therapy with paclitaxel.
Hepatic: Patients with hepatic impairment may be at an increased risk of toxicity mainly grade III to IV myelosuppression. Increased myelosuppression may be observed in patients with moderate to severe hepatic impairment. Paclitaxel is not recommended in patients with severely impaired hepatic function (transaminase levels ≥10 x ULN or bilirubin levels >7.5 mg/dL or > 5 x ULN; see Dosage & Administration).
Neurologic: Peripheral neuropathy (dose-dependent) may occur frequently. Carefully monitor patient with pre-existing peripheral neuropathy and in severe cases, reduce all subsequent doses by 20% (see Dosage & Administration).
Hypersensitivity: Patients with a history of severe hypersensitivity reaction to products containing Cremophor EL should not be treated with paclitaxel (see Contraindications). Minor symptoms such as flushing, skin reactions, dyspnea, hypotension or tachycardia do not require interruption of therapy. However, immediate discontinuation of paclitaxel and aggressive symptomatic therapy should be done in cases of severe reactions such as hypotension requiring treatment, dyspnea requiring bronchodilators, angioedema, or generalized urticaria.
Injection Site Reaction: Erythema, tenderness, skin discoloration, or swelling at the injection site may occur. Recurrence of skin reactions at a previous site of extravasation (i.e., "recall" reactions) after paclitaxel administration at a different injection site has been reported rarely. More severe events such as phlebitis, cellulitis, induration, skin exfoliation, necrosis, and fibrosis have also been reported rarely (see Dosage & Administration).
Gastrointestinal: Exclude bowel perforation in patients receiving paclitaxel who complain of abdominal pain with other signs and symptoms.
Infectious Complications: Patients should be informed to take extra precautions to reduce the risk of infection or bleeding (e.g., avoiding people with infection, getting cut or bruised).
The risk-benefit should be considered when administering paclitaxel to patients with the following conditions: Varicella or recent exposure to such disease.
Herpes Zoster.
Infection.
Precaution must be taken in patients who have undergone therapies with cytotoxic drugs, including radiotherapy.
Effects on the Ability to Drive or Use Machines: The alcohol content in the product may impair the ability to perform hazardous activities requiring mental alertness following paclitaxel infusion, particularly when high doses of the drug are administered over short periods (e.g., 3 hours). Concomitant use with CNS depressants should be done with caution.
Hepatic and Renal Impairment: The use of paclitaxel in patients with impaired renal and hepatic function has not been fully established. Since paclitaxel is metabolized in the liver, dose reduction is recommended in patients with moderate to severe liver failure. Dose reduction may not be necessary in patients with renal failure. (See Dosage & Administration).
Carcinogenicity, Mutagenicity, Fertility: There is no study on the carcinogenic potential of paclitaxel. Paclitaxel has been shown to be clastogenic in vitro (chromosome aberrations in human lymphocytes) and in vivo (micronucleus test in mice) mammalian test system but was not mutagenic in the Ames test or the CHO/HGPRT gene mutation assay.
Reproduction studies in rats and rabbits showed evidence of maternal toxicity, embryotoxicity and fetotoxicity during organogenesis at IV doses of 1 mg/kg (6 mg/m2 or systemic exposures approximately equivalent to 0.04 times the maximum recommended human dose on a mg/m2 basis) and 3 mg/kg (33 mg/m2 or systemic exposures approximately equivalent to 0.2 times the maximum recommended human dose on a mg/m2 basis), respectively. These resulted in intrauterine mortality, increased resorptions, increased fetal deaths and reduced fertility. Paclitaxel produced low fertility in rats at an IV dose of 1 mg/kg (6 mg/m2).
Use in Children: The safety and efficacy of paclitaxel in children have not been established. In a clinical trial in children, high dose paclitaxel (350 to 420 mg/m2 or more than two times the recommended dose) infused over 3 hours caused CNS toxicity (rarely associated with death). The toxicity is attributed to the high dose alcohol content (vehicle) given over a short infusion time. Concomitant use of antihistamines may intensify this effect.
Use in Elderly: The safety and efficacy of paclitaxel in elderly patients have not been clearly established. However, most of the patients treated for refractory metastatic ovarian carcinoma are older than 60 years. There is no evidence of age-related differences in the safety or dose tolerance between young and old patients. However, clinical studies show that severe myelosuppression, severe neuropathy and cardiovascular events were more frequent in elderly patients. Estimates of efficacy appeared similar between elderly and younger patients but comparative efficacy could not be determined due to a small number of elderly patients studied.
Use In Pregnancy & Lactation
Use in Pregnancy: Category D: Paclitaxel can cause fetal harm when administered to pregnant women. Women who are pregnant or those wanting to become pregnant should be advised to avoid becoming pregnant during paclitaxel therapy. Paclitaxel should be used only when clearly needed and when potential benefits outweigh the unknown hazards to the baby.
Use in Lactation: It is not known whether paclitaxel is excreted in human milk. Breastfeeding is not recommended during chemotherapy because of the potential serious adverse reactions to paclitaxel by the breastfeeding infant.
Adverse Reactions
Bone marrow suppression is the most frequent significant undesirable effect of paclitaxel use. Other severe reactions associated with the use of paclitaxel are peripheral neuropathy, arthralgia, myalgia, hypersensitivity reaction (with possible fatal outcome), and injection site reactions.
The frequency and severity of hematologic toxicity increase with dose, especially at paclitaxel doses exceeding 190 mg/m2. Dose- and schedule-dependent paclitaxel-induced neutropenia is generally rapidly reversible. The onset of neutropenia usually occurs 8 to 10 days and neutrophil nadirs generally occur at a median of 10 to 12 days after paclitaxel administration. Neutrophil counts commonly recover 15 to 21 days after administration.
The following adverse reactions have also been reported with paclitaxel use: Infections and Infestations: Infection (mainly urinary tract and upper respiratory tract infections), with reported cases of fatal outcome, septic shock, pneumonia, peritonitis, sepsis, pseudomembranous colitis.
Neoplasms benign, malignant and unspecified (including cysts and polyps): Acute myeloid leukemia, myelodysplastic syndrome, tumour lysis syndrome.
Blood and lymphatic system disorders: Myelosuppression, neutropenia, anemia, thrombocytopenia, leukopenia, eosinophilia, bleeding, febrile neutropenia, neutropenic enterocolitis.
Immune system disorders: Minor hypersensitivity reactions (mainly flushing and rash), significant hypersensitivity reactions requiring therapy (e.g., hypotension, angioneurotic edema, respiratory distress, generalised urticaria, chills, back pain, chest pain, tachycardia, abdominal pain, pain in extremity, diaphoresis, and hypertension), anaphylactic reactions, anaphylactic shock, Stevens-Johnson Syndrome, erythema multiforme, exfoliative dermatitis, scleroderma.
Metabolism and nutrition disorders: Anorexia, respiratory failure, dehydration, edema.
Psychiatric disorders: Confusional state.
Nervous system disorders: Neurotoxicity (mainly peripheral neuropathy), motor neuropathy (with resultant minor distal weakness), autonomic neuropathy (resulting in paralytic ileus and orthostatic hypotension), grand mal seizures, convulsions, encephalopathy, dizziness, headache, paresthesia, hypoesthesia, perioral numbness, hyperesthesia, acute and temporary worsening of Parkinsonian Syndrome, stroke, hepatic coma, photopsia, hepatic encephalopathy (both with reported cases of fatal outcome).
Eye disorders: Optic nerve and/or visual disturbances (scintillating scotomata) particularly in patients who have received higher doses than recommended, macular edema, vitreous floaters, keratitis, conjunctivitis, increased lacrimation.
Ear and labyrinth disorders: hearing loss, tinnitus, vertigo.
Cardiac disorders: Bradycardia, cardiomyopathy, asymptomatic ventricular tachycardia, tachycardia with bigeminy, atrio-ventricular block and syncope, myocardial infarction, cardiac failure, atrial fibrillation, supraventricular tachycardia, arrhythmia, acute pulmonary edema, cardiac arrest, congestive heart failure.
Vascular disorders: Hypotension, hypertension, thrombosis, thrombophlebitis, shock, hemorrhage, embolism, transient ischemic attack, ischemic colitis.
Respiratory, thoracic and mediastinal disorders: Pleural effusion, interstitial pneumonia, lung fibrosis, pulmonary embolism, cough, dyspnea, radiation pneumonitis, transient pulmonary infiltration.
Gastrointestinal disorders: Nausea, vomiting, diarrhea, bowel perforation, pancreatitis, mesenteric thrombosis, esophagitis, constipation, oral candidiasis, intestinal obstruction, dysphagia.
Hepatobiliary disorders: Hepatic necrosis, ascites.
Skin and subcutaneous tissue disorders: Alopecia, transient and mild nail and skin changes, pruritus, rash, erythema, onycholysis (patients on therapy should wear sun protection on hands and feet), skin exfoliation, acral erythema, generalized pustular dermatosis, dermatitis bullous.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, systemic lupus erythematosus.
Renal and urinary disorders: Acute renal failure, renal toxicity.
General disorders and administration site conditions: Asthenia, pyrexia, malaise, mucositis, induration, fatigue, lethargy, ataxia, mucosal inflammation.
Investigations: Severe elevation in aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)), severe elevation in alkaline phosphatase, severe elevation in bilirubin, increase in blood creatinine, abnormal electrocardiogram.
Injury, poisoning and procedural complications: Phlebitis, radiation recall reaction, ototoxicity, epidermal necrolysis, injection site reactions (including localized edema, pain, erythema, induration, on occasion extravasation can result in cellulitis, skin fibrosis and skin necrosis).
Drug Interactions
Antineoplastic Agents: Administration of paclitaxel with other antineoplastic agents showed sequence-dependent interactions and may affect their toxicities.
It is recommended that paclitaxel be administered before cisplatin to decrease the risk of increased severity of myelosuppression.
When cyclophosphamide is administered after paclitaxel (by 24-hour IV infusion), the severity of neutropenia and thrombocytopenia has been reported to increase.
Plasma levels of doxorubicin and its active metabolite doxorubicinol may be increased when paclitaxel and doxorubicin are used concomitantly. Paclitaxel should be administered 24 hours after doxorubicin.
Fluorouracil pretreatment was reported to inhibit the action of paclitaxel.
Myelosuppressive Agents: The combination of paclitaxel with other myelosuppressive agents may increase the severity of myelosuppression depending on the dose.
Similar rates of neutropenia but less severe thrombocytopenia was reported when carboplatin is administered after paclitaxel compared with carboplatin administered alone.
Blood Dyscrasia: The combination of paclitaxel with these drugs can cause blood dyscrasia, usually in a minority of patients, and not dose-related: aminopyrine, angiotensin-converting enzyme (ACE) inhibitors, anticonvulsants, tricyclic antidepressants, oral antidiabetic agents, non-steroidal anti-inflammatory drugs (NSAIDs), carbamazepine, chloramphenicol, clozapine, dapsone, foscarnet, levamisole, penicillamine, phenothiazine, primaquine, primidone, procainamide, propafenone, rifampicin, sulfonamides, thioxanthenes, trimethoprim, valproate, and valproic acid.
Drugs Affecting Hepatic Enzymes: Concomitant use of drugs which induce or inhibit the action of cytochrome P450 isoenzymes may reduce or increase the plasma concentrations of paclitaxel, respectively.
Potential interactions between paclitaxel, a substrate of CYP3A4 and protease inhibitors (e.g., ritonavir, saquinavir, indinavir, and nelfinavir), which are substrates and/or inhibitors of CYP3A4, have not been evaluated.
Ketoconazole may inhibit the metabolism of paclitaxel when given together.
CNS Depressants: CNS depression due to the alcohol content of the formulation may be potentiated when paclitaxel and CNS depressants such as antihistamines or opiates are used together.
Vaccines: Paclitaxel may cause immunosuppression. The interval between the discontinuation of paclitaxel and the patient's capacity to respond to the vaccine depends on the type and intensity of immunosuppression. The estimated time is between 3 months and 1 year.
Immunization with oral poliovirus vaccine must be postponed in people who are in close contact with patients undergoing paclitaxel therapy, especially family members.
ATC Classification
L01CD01 - paclitaxel ; Belongs to the class of plant alkaloids and other natural products, taxanes. Used in the treatment of cancer.
Presentation/Packing
Concentrate for soln for infusion (vial) 5 mL x 1's, 16.6 mL x 1's.
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