DefinitionThis section has been translated automatically.
Pharmacodynamics (Effect)This section has been translated automatically.
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Field of application/useThis section has been translated automatically.
IndicationThis section has been translated automatically.
Approved for the therapy of:
- Ovarian cancer: Paclitaxel is indicated for the first-line chemotherapy of ovarian cancer in patients with advanced ovarian cancer or a residual tumour (>1 cm) after previous laparotomy in combination with cisplatin.
- For second-line chemotherapy of ovarian cancer after failure of standard therapy with platinum-containing drugs.
- Breast cancer: Paclitaxel is indicated for the adjuvant therapy of patients with nodal-positive breast cancer following anthracycline/cyclophosphamide therapy.
- Paclitaxel is indicated for the initial treatment of patients with locally advanced or metastatic breast cancer either in combination with an anthracycline in patients for whom anthracycline therapy is indicated or in combination with trastuzumab if HER2 is classified as 3+ according to immunohistochemical determination and if anthracycline-containing therapy is not indicated.
- As a monotherapy, paclitaxel is indicated for the treatment of metastatic breast cancer in patients for whom standard therapy with anthracyclines has been unsuccessful or for whom therapy with an anthracycline is not indicated.
- Advanced non-small cell lung cancer: Paclitaxel in combination with cisplatin is indicated for the treatment of non-small cell lung cancer (NSCLC) in patients for whom potentially curative surgery and/or radiotherapy is not indicated.
- AIDS-associated Kaposi's sarcoma: Paclitaxel is indicated for the treatment of patients with AIDS-associated advanced Kaposi's sarcoma (KS) in whom previous liposomal anthracycline therapy has failed.
Pregnancy/nursing periodThis section has been translated automatically.
The data situation is not very meaningful. It can be assumed that paclitaxel causes serious damage to the unborn child if it is used during pregnancy. Paclitaxel showed both embryotoxic and fetotoxic properties in rabbits and reduced fertility in rats. Like other cytotoxic drugs, paclitaxel can cause fetal damage when used in pregnant women. Therefore, paclitaxel should not be used during pregnancy unless clearly necessary. Paclitaxel should also not be used in women of childbearing age who do not use effective contraception, unless it is absolutely necessary to treat the mother with paclitaxel.
Women of childbearing age should use a reliable contraceptive method during and up to 6 months after treatment with paclitaxel.
Note: Male patients treated with paclitaxel are advised not to conceive a child during and up to 6 months after treatment.
Dosage and method of useThis section has been translated automatically.
Undesirable effectsThis section has been translated automatically.
The frequency of side effects (see alsoMedDRA) was assessed according to the criteria "very frequent (≥1/10); frequent (≥1/100,<1/10);occasional (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000)".
- Anaphylactic reactions: Rare are severe hypersensitivity reactions with potentially lethal outcome (defined as hypotension, angioedema, respiratory distress requiring bronchodilator treatment or generalized urticaria); abdominal pain, pain in the extremities, diaphoresis and hypertension
- Frequently (in about 1/3 of the patients) slight hypersensitivity reactions. These reactions consist of volatile exanthema, which usually do not require treatment.
- Bone marrow suppression: most frequent serious side effect. Severe neutropenia (<500 cells/mm3) without febrile episodes occurred in 28 % of patients. Only 1% of patients had severe neutropenia for ≥7 days.
Thrombocytopenia was reported in 11% of the patients. Three percent of the patients had a thrombocyte nadir <50,000/mm3 at least once during the study. Anemia was observed in 64% of patients but was severe in only 6% (Hb <5 mmol/l). The incidence and severity of anaemia depends on the initial haemoglobin level.
Neurotoxicity (frequent): mainly peripheral neuropathy, mainly in combination with cisplatin. Rare is motor neuropathy (resulting in minor distal weakness)Very rare are grand mal seizures, autonomic neuropathy (resulting in paralytic ileus and orthostatic hypotension), encephalopathy, convulsions, dizziness, ataxia, headache
Arthralgia or myalgia were observed in 60% of patients; they were classified as severe in 13% of patients.
DIK: Disseminated intravascular coagulation (DIK), often associated with sepsis or multiorgan failure, has been reported.
Infections and Infestations:
- Very common are infections (mainly of the urinary tract and upper respiratory tract), with reports of lethal cases (septic shock). Rare are sepsis, peritonitis, pneumonia. Febrile neutropenia
- Very rare: Pseudomembranous colitis
Acute myeloid leukaemia, myelodysplastic syndrome occurs very rarely
- Very rare are disorders of the optic nerve and/or visual disorders (ciliated scotoma), especially in patients who received higher doses than recommended.
- Not known: macular edema, photopsy, vitreous opacities.
Diseases of the ear and the labyrinth:
- Very rare are hearing loss, ototoxicity, tinnitus, vertigo
Cardiac side effects
- Common: Bradycardia; occasionally, myocardial infarction, AV block and syncope, cardiomyopathy, asymptomatic ventricular tachycardia, tachycardia with bigeminy
- Rare: Heart failure
- Very rare are atrial fibrillation or supraventricular tachycardia
- Occasionally: thrombosis, hypertension, thrombophlebitis
Respiratory tract, chest and abdomen:
- Rare are respiratory insufficiency, pulmonary embolism, pulmonary fibrosis, interstitial pneumonia, dyspnoea, pleural effusion
Diseases of the gastrointestinal tract:
- Very common: diarrhoea, vomiting, nausea,
- Rare: obstruction of the colon, perforation of the colon, ischemic colitis, pancreatitis
- Very rare are mesenteric thrombosis, neutropenic colitis, ascites, esophagitis, constipation
Diseases of the skin and subcutaneous tissue:
- Hair loss is very common: Alopecia was observed in 87% of patients and occurred abruptly. In most patients with alopecia, a pronounced hair loss of ≥ 50 % can be expected.
- Often, temporary onycholysis occurs.
Common: reactions at the injection site (including localized edema, pain, erythema, induration; occasionally extravasation may lead to local inflammation, skin fibrosis and necrosis). Reactions at the injection site: during intravenous use may cause localized edema, pain, erythema and induration. It may also cause depigmentation of the skin. Arecurrence of skin reactions at the site of a previous extravasation when paclitaxel is injected at a different site(a so-called "recall") has only been reported sporadically. In some cases, reactions were delayed up to 10 days.
- Very rarely a Stevens-Johnson syndrome has been reported, erythema multiforme, urticaria. During treatment, patients should protect their hands and feet from sunlight.
- Frequently AST, SGOT, increase in alkaline phosphatase ↑↑ ↑↑↑
- occasionally: Bilirubins ↑↑
- rarely increase in blood creatinine levels.
- (paclitaxel + trastuzumab): the following events were more frequently observed: heart failure (8% vs. 1%), infection (46% vs. 27%), chills (42% vs. 4%), fever (47% vs. 23%), cough (42% vs. 22%), rash (39% vs. 18%), arthralgia (37% vs. 21%), tachycardia (12% vs. 4 %), diarrhoea (45 % vs. 30 %), hypertension (11 % vs. 3 %), nosebleed (18 % vs. 4 %), acne (11 % vs. 3 %), herpes simplex (12 % vs. 3 %), unintentional injuries (13 % vs. 3 %), insomnia (25 % vs. 13 %), rhinitis (22 % vs. 5 %), sinusitis (21 % vs. 7 %) and reactions at the injection site (7 % vs. 1 %).
- (paclitaxel + doxorubicin ) Anomaly of heart contraction (≥20 % reduction in left ventricular ejection fraction) was observed in 15% of patients compared to 10% with the standard FAC dosing regimen. When trastuzumab was used in combination with paclitaxel in patients previously treated with anthracyclines, the frequency and severity of cardiac dysfunction increased compared with paclitaxel monotherapy(NYHA Class I/II 10% vs. 0%; NYHA Class III/IV 2% vs. 1%) and was rarely associated with death (see Trastuzumab Fact Sheet). Except in these rare cases, all patients responded to appropriate medical treatment.
- Radiation pneumonitis was reported in patients who had received radiotherapy at the same time.
- AIDS-associated Kaposi's sarcoma: In addition to the ADRs already listed, neutropenia was the most important hematological toxicity. During the first treatment cycle, 20% of patients developed severe neutropenia (<500 cells/mm3). Over the entire treatment period, severe neutropenia was observed in 39% of patients. In 41% of the patients the neutropenia lasted 47 days and in 8% of the patients between 30 - 35 days. In all follow-up patients the neutropenia subsided within 35 days. The incidence of grade 4 neutropenia lasting at least 7 days was 22 %.
- Neutropenic fever associated with paclitaxel occurred in 14% of patients and 1.3% of treatment cycles. During paclitaxel use, 3 septic adverse events (2.8%) with fatal outcome occurred in connection with the drug.
PreparationsThis section has been translated automatically.
Note(s)This section has been translated automatically.
The metabolism of paclitaxel is partly catalysed by the cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Caution is therefore required when paclitaxel is used in combination with other drugs that inhibit either CYP2C8 or CYP3A4 (e.g. ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, clopidogrel, cimetidine, ritonavir, saquinavir, indinavir and nelfinavir) as the toxicity of paclitaxel may be increased due to the higher exposure to paclitaxel. The use of paclitaxel together with other drugs that induce either CYP2C8 or CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine) is not recommended as efficacy may be impaired due to lower paclitaxel exposure.
Studies in patients with Kaposi's sarcoma who received extensive concomitant medication suggest that the systemic clearance of paclitaxel was significantly reduced in the presence of nelfinavir and ritonavir, but not in the presence of indinavir. There is insufficient information on interactions with other protease inhibitors. Consequently, paclitaxel should be used with caution in patients receiving protease inhibitors as concomitant medication.
LiteratureThis section has been translated automatically.
- Marks DH et al (2018) Evaluation of Prevention Interventions for Taxane-Induced Dermatologic Adverse Events: A Systematic Review. JAMA Dermatol 154:1465-1472.
- Picard M (2017) Management of Hypersensitivity Reactions to Taxanes. Immunol Allergy Clin North Am 37:679-693.
- Sibaud V et al (2016) Dermatological adverse events with taxane chemotherapy. Eur J Dermatol 26:427-443.