Paclitaxel

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Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Paclitaxel.jpg

[edit] MECHANISM OF ACTION

Paclitaxel, belongs to the group of anticancer medicines known as the taxanes.

Paclitaxel promotes the assembly of microtubules from tubulin dimers and stabilises microtubules by preventing depolymerisation. This stability results in the inhibition of the normal dynamic reorganisation of the microtubule network that is essential for vital interphase and mitotic cellular functions.

[edit] INDICATIONS

  • Breast Cancer:
    • Treatment of metastatic breast cancer in adults whose first treatment has stopped working and for whom standard treatment including an anthracycline is not suitable.
    • Adjuvant treatment of node-positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy
  • Non-small Cell Lung Cancer
    • Locally advanced or metastatic non-small cell lung cancer (NSCLC), as first-line treatment in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy
  • Pancreas cancer:
    • Metastatic adenocarcinoma of the pancreas as first-line treatment, in combination with gemcitabine.
  • Ovarian Cancer
    • First-line and subsequent therapy for the treatment of advanced carcinoma of the ovary. As first-line therapy, Paclitaxel is indicated in combination with cisplatin
  • AIDS-related Kaposi's Sarcoma (2nd-line Treatment)

[edit] DOSAGE

ABRAXANE

  • Metastatic Breast Cancer: Recommended dosage is 260 mg/m2 intravenously over 30 minutes every 3 weeks.
  • Non-Small Cell Lung Cancer: Recommended dosage is 100 mg/m2 intravenously over 30 minutes on Days 1, 8, and 15 of each 21-day cycle; administer carboplatin on Day 1 of each 21-day cycle immediately after Paclitaxel.
  • Adenocarcinoma of the Pancreas: Recommended dosage is 125 mg/m2 intravenously over 30-40 minutes on Days 1, 8 and 15 of each 28-day cycle; administer gemcitabine on Days 1, 8 and 15 of each 28-day cycle immediately after Paclitaxel.

[edit] CONTRAINDICATIONS

  • Severe hypersensitivity reaction to Paclitaxel
  • Patients who have baseline neutrophil counts <1500 cells/mm3
  • Patients with AIDS-related Kaposi’s sarcoma with baseline neutrophil counts of <1000 cells/mm3.

[edit] WARNINGS AND PRECAUTIONS

  • It is recommended that frequent peripheral blood cell counts be performed to monitor the occurrence of bone marrow suppression.
  • Sensory neuropathy occurs frequently and may require dose reduction or treatment interruption.
  • Severe hypersensitivity reactions with fatal outcome have been reported. Do not re-challenge with this drug.
  • Exposure and toxicity of paclitaxel can be increased in patients with hepatic impairment.
  • Fetal harm may occur when administered to a pregnant woman.
  • Advise men not to father a child while on Paclitaxel

[edit] INTERACTIONS

  • The metabolism of paclitaxel is catalyzed by CYP2C8 and CYP3A4.

Caution should be exercised when administering Paclitaxel concomitantly with medicines known to inhibit (e.g., ketoconazole and other imidazole antifungals, erythromycin, Clarithromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) or induce (e.g., rifampicin, carbamazepine, phenytoin, efavirenz, and nevirapine) either CYP2C8 or CYP3A4.

[edit] PREGNANCY AND LACTATION

[edit] SIDE EFFECTS

The most common side effects are neutropenia (low levels of neutrophils, a type of white blood cell), anemia (low red blood cell counts), leucopenia (low white blood cell counts), thrombocytopenia (low blood platelet counts), lymphopenia (low levels of lymphocytes, a type of white blood cell), bone marrow suppression (reduced production of blood cells),neuropathy (nerve damage including damage to the nerves in the hand and feet), hypoaesthesia (reduced sense of touch), paraesthesia (unusual sensations like pins and needles), nausea, diarrhea, vomiting, constipation, stomatitis, alopecia, rash, arthralgia, myalgia, loss of appetite, fatigue, asthenia and pyrexia (fever).

[edit] RELATED LINKS

[edit] BIBLIOGRAPHY

[edit] REFERENCES