Paxene


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paclitaxel

Apo-Paclitaxel (CA), Paxene (UK)

Pharmacologic class: Antimicrotubule agent

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Box Warning

• Give injection under supervision of physician experienced in use of cancer chemotherapy, in facility with adequate diagnostic and treatment resources.

• Anaphylaxis and severe hypersensitivity reactions may occur despite premedication. All patients should be pretreated with corticosteroids, diphenhydramine, and histamine2 antagonists. Don't give drug to patients who've had previous severe reactions.

• Don't administer drug to patients with solid tumors whose baseline neutrophil counts are below 1,500 cells/mm3 or to patients with AIDS-related Kaposi's sarcoma whose baseline neutrophil counts are below 1,000 cells/mm3. To monitor for bone marrow suppression, obtain frequent peripheral blood cell counts on all patients.

• Albumin form of drug may substantially affect drug's functional properties. Don't substitute for or use with other paclitaxel forms.

Action

Stabilizes cellular microtubules to prevent depolymerization. This action inhibits microtubule network (essential for vital interphase and mitotic cellular functions) and induces abnormal microtubule arrays or bundles throughout cell cycle and during mitosis.

Availability

Concentrate for injection: 30 mg/5-ml vial, 100 mg/16.7-ml vial, 300 mg/50-ml vial

Indications and dosages

Advanced ovarian cancer

Adults: As first-line therapy, 175 mg/m2 I.V. over 3 hours q 3 weeks, or 135 mg/m2 I.V. over 24 hours q 3 weeks, followed by cisplatin. After failure of first-line therapy, 135 mg/m2 I.V. or 175 mg/m2 I.V. over 3 hours q 3 weeks.

Breast cancer after failure of combination chemotherapy

Adults: As adjuvant treatment for node-positive breast cancer, 175 mg/m2 I.V. over 3 hours q 3 weeks for four courses given sequentially with doxorubicin combination chemotherapy. After chemotherapy failure for metastatic disease or relapse within 6 months of adjuvant therapy, 175 mg/m2 I.V. over 3 hours q 3 weeks.

Non-small-cell lung cancer

Adults: 135 mg/m2 I.V. over 24 hours q 3 weeks, followed by cisplatin

AIDS-related Kaposi's sarcoma

Adults: 135 mg/m2 I.V. over 3 hours q 3 weeks, or 100 mg/m2 I.V. over 3 hours q 2 weeks

Dosage adjustment

• Advanced human immunodeficiency virus infection (when used for Kaposi's sarcoma)

Off-label uses

• Advanced head and neck cancer
• Small-cell lung cancer
• Upper GI tract adenocarcinoma
• Non-Hodgkin's lymphoma
• Pancreatic cancer
• Polycystic kidney disease

Contraindications

• Hypersensitivity to drug or castor oil
• Solid tumors when baseline neutrophil count is below 1,500 cells/mm3
• AIDS-related Kaposi's sarcoma when baseline neutrophil count is below 1,000 cells/mm3

Precautions

Use cautiously in:
• severe hepatic impairment, active infection, decreased bone marrow reserve, chronic debilitating illness
• patients with childbearing potential
• breastfeeding patients (not recommended)
• children (safety not established).

Administration

Follow facility protocol for handling chemotherapeutic drugs and preparing solutions.
• Dilute in dextrose 5% in water, normal saline solution, or dextrose 5% in lactated Ringer's solution per manufacturer's guidelines.
• Inspect solution for particles. Administer through polyethylene-lined administration set attached to 0.22-micron in-line filter.
• To prevent severe hypersensitivity reaction, premedicate with dexamethasone 20 mg 12 and 6 hours before infusion, as prescribed. Also give diphenhydramine 50 mg I.V., plus either cimetidine 300 mg or ranitidine 50 mg I.V. 30 to 60 minutes before paclitaxel.

Keep epinephrine available. If severe hypersensitivity reaction occurs, stop infusion immediately and give epinephrine, I.V. fluids, and additional antihistamine and corticosteroid doses, as indicated and prescribed.

Adverse reactions

CNS: peripheral neuropathy

CV: hypotension, hypertension, syncope, abnormal ECG, bradycardia, venous thrombosis

GI: nausea, vomiting, diarrhea, stomatitis, mucositis

Hematologic: anemia, leukopenia, neutropenia, bleeding, thrombocytopenia

Musculoskeletal: joint pain, myalgia

Skin: alopecia, radiation reactions

Other: infection, injection site reaction, hypersensitivity reactions including anaphylaxis

Interactions

Drug-drug. Carbamazepine, phenobarbital: decreased paclitaxel blood level and efficacy

Cisplatin: increased bone marrow depression (when paclitaxel dose follows cisplatin dose)

Cyclosporine, diazepam, doxorubicin, felodipine, ketoconazole, midazolam: inhibited paclitaxel metabolism and greater risk of toxicity

Doxorubicin: increased doxorubicin blood level and toxicity

Live-virus vaccines: decreased antibody response to vaccine, increased risk of adverse reactions

Other antineoplastics: increased risk of bone marrow depression

Drug-diagnostic tests.Liver function tests: abnormal results

Triglycerides: increased levels

Patient monitoring

Watch closely for hypersensitivity reaction.
• Monitor heart rate and blood pressure.
• Assess infusion site for local effects and extravasation, especially during prolonged infusion.

Monitor CBC, including platelet count. If neutropenia develops, monitor patient for infection; if thrombocytopenia develops, watch for signs and symptoms of bleeding.
• If patient has preexisting cardiac conduction abnormality, maintain continuous cardiac monitoring.

Patient teaching

• Instruct neutropenic patient to minimize infection risk by avoiding crowds, plants, and fresh fruits and vegetables.
• Tell thrombocytopenic patient to avoid activities that can cause injury. Advise him to use soft toothbrush and electric razor.

Advise patient to promptly report signs and symptoms of infection, bleeding, or peripheral neuropathy (such as numbness and tingling of feet and hands).
• Tell patient to promptly report pain or burning at injection site.
• Explain that temporary hair loss may occur.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

Paxene®

See Paclitaxel.
References in periodicals archive ?
Frank Condella, President, European Region for IVAX Pharmaceuticals said, "IVAX is already benefiting from marketing and sales of Paxene in Belgium, Finland, France, Germany, Ireland, Italy, Luxembourg, the Netherlands, Norway, Portugal, Sweden and United Kingdom, in partnership with Mayne Group Ltd.
Investors are cautioned that forward-looking statements involve risks and uncertainties which may affect the company's business and prospects, including the risks that the collaboration with Combino Pharm SL may not achieve the results expected and may not accelerate IVAX' oncology growth in Spain; that Combino Pharm SL may not be able to ensure Paxene is included in oncology center protocols throughout Spain; that IVAX has in the past and may in the future experience difficulties in obtaining raw materials and other components necessary for the production of paclitaxel on commercially reasonable terms; and the impact of competitive products and pricing and successful compliance with extensive, costly, complex and evolving governmental regulations and restrictions.
Nasdaq: NPRO) submitted a New Drug Application to the United States Food and Drug Administration seeking approval to manufacture and market Paxene in the United States for the treatment of Kaposi's sarcoma, an important cancer related to the immunocompromised state that accompanies AIDS.
As IVAX's exclusive supplier of raw material for Paxene, NaPro will receive revenue-related royalties based on IVAX's Paxene sales.
Paxene is IVAX' brand name for its formulation of the compound paclitaxel (which is referred to in some scientific and medical literature as taxol*).
Paxene marks IVAX' second new drug submission to FDA.