Vinorelbine Tartrate

Name: Vinorelbine Tartrate

How supplied

Dosage Forms And Strengths

NAVELBINE Injection

Clear colorless to pale yellow solution in single use vials:

1 mL (10 mg/ 1 mL)
5 mL (50 mg/ 5 mL)

Storage And Handling

NAVELBINE Injection is a clear, colorless to pale yellow aqueous solution available in single-dose vials with royal blue caps, individually packaged in a carton as:

10 mg/1 mL (NDC 64370-532-01).
50 mg/5 mL (NDC 64370-532-02).

Store the vials at 2° to 8°C (36° to 46°F) in the carton. Protect from light. DO NOT FREEZE. Unopened vials of NAVELBINE are stable at 25°C (77°F) for up to 72 hours.

NAVELBINE is a cytotoxic drug. Follow applicable special handling and disposal procedures.1

REFERENCES

1. OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

Manufactured by: Pierre Fabre Médicament 45 place Abel Gance -92100 Boulogne –FRANCE. Distributed by: Pierre Fabre Pharmaceuticals, Inc. Parsippany, NJ 07054. Revised: 03/2014

Side effects

The following serious adverse reactions, which may include fatalities, are discussed in greater detail in other sections of the label:

  • Myelosuppression [see WARNINGS AND PRECAUTIONS]
  • Pulmonary Toxicity and Respiratory Failure [see WARNINGS AND PRECAUTIONS]
  • Constipation and Bowel Obstruction [see WARNINGS AND PRECAUTIONS]
  • Extravasation Tissue Injury [see WARNINGS AND PRECAUTIONS]
  • Neurologic Toxicity [see WARNINGS AND PRECAUTIONS]
  • Hepatic Toxicity [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under varying designs and in different patient populations, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.

Single Agent

The data below reflect exposure to NAVELBINE as a single agent administered at a dose of 30 mg/m² on a weekly basis to 365 patients enrolled in 3 controlled studies for metastatic NSCLC and advanced breast cancer. The population included 143 previously untreated metastatic NSCLC patients (Study 3) who received a median of 8 doses of NAVELBINE. The patients were aged 32 to 79 (median 61 years), 71% were male, 91% Caucasian, 48% had adenocarcinoma histology. The data also reflect exposure to NAVELBINE in 222 patients with previously treated advanced breast cancer who received a median of 10 doses of NAVELBINE. NAVELBINE is not indicated for the treatment of breast cancer.

Selected adverse reactions reported in these studies are provided in Tables 1 and 2. The most common adverse reactions ( ≥ 20%) of single agent NAVELBINE were leukopenia, neutropenia, anemia, Aspartate aminotransferase (AST) elevation, nausea, vomiting, constipation, asthenia, injection site reaction, and peripheral neuropathy. The most common ( ≥ 5%) Grade 3 or 4 adverse reactions were neutropenia, leukopenia, anemia, increased total bilirubin, AST elevation, injection site reaction and asthenia. Approximately 49% of NSCLC patients treated with Navelbine experienced at least one dose reduction due to an adverse reaction. Thirteen percent of patients discontinued NAVELBINE due to adverse reactions. The most frequent adverse reactions leading to NAVELBINE discontinuation were asthenia, dyspnea, nausea, constipation, anorexia, myasthenia and fever.

Table 1: Hematologic Adverse Reactions Experienced in > 5% of Patients Receiving NAVELBINE*†

    All patients
(n=365)		 NSCLC
(n= 143)
Laboratory Hematologic
Neutropenia < 2,000 cells/mm³ 90% 80%
< 500 cells/mm³ 36% 29%
Leukopenia < 4,000 cells/mm³ 92% 81%
< 1,000 cells/mm³ 15% 12%
Thrombocytopenia < 100,000 cells/mm³ 5% 4%
Anaemia < 11 g/dl 83% 77%
< 8 g/dl 9% 1%
Hospitalizations due to neutropenic complications 9% 8%
*Grade based on modified criteria from the National Cancer Institute version 1.
†Patients with NSCLC had not received prior chemotherapy. The majority of the remaining patients had received prior chemotherapy.

Table 2: Non-hematologic Adverse Reactions Experienced in ≥ 5% of Patients Receiving NAVELBINE*†

  All grades Grades 3+4
All Patients NSCLC All Patients NSCLC
Laboratory
Hepatic
  AST increased (n=346) 67% 54% 6% 3%
  bilirubin increased (n=351) 13% 9% 7% 5%
Clinical
  Nausea 44% 34% 2% 1%
  Asthenia 36% 27% 7% 5%
  Constipation 35% 29% 3% 2%
  Injection site reaction 28% 38% 2% 5%
  Injection site pain 16% 13% 2% 1%
  Neuropathy peripheral} 25% 20% < 2% 1%
  Vomiting 20% 15% 2% 1%
  Diarrhea 17% 13% 1% 1%
  Alopecia 12% 12%

Overdose

There is no known antidote for overdoses of NAVELBINE. Overdoses involving quantities up to 10 times the recommended dose (30 mg/m²) have been reported. The toxicities described were consistent with those listed in the ADVERSE REACTIONS section including paralytic ileus, stomatitis, and esophagitis. Bone marrow aplasia, sepsis, and paresis have also been reported. Fatalities have occurred following overdose of NAVELBINE. If overdosage occurs, general supportive measures together with appropriate blood transfusions, growth factors, and antibiotics should be instituted as deemed necessary by the physician.

Patient information

Inform patients of the following:

  • Myelosuppression
    Advise patients to contact a healthcare provider for new onset fever, or symptoms of infection [see WARNINGS AND PRECAUTIONS]
  • Constipation and bowel obstruction
    Advise patients to follow a diet rich in fibers, drink fluids to stay well hydrated and use stool softeners to avoid constipation. Contact a health care provider for severe constipation, new onset abdominal pain, nausea and vomiting [see WARNINGS AND PRECAUTIONS]
  • Neurologic toxicity
    Advise patients to contact a health care provider for new onset or worsening of numbness, tingling, decrease sensation or muscle weakness [see WARNINGS AND PRECAUTIONS]
  • Pulmonary Toxicity
    Advise patients to contact a healthcare provider for new onset or worsening of shortness of breath, cough, wheezing or other new pulmonary symptoms [see WARNINGS AND PRECAUTIONS]
  • Females and Males of Reproductive Potential
    • NAVELBINE can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use highly effective contraception during treatment with NAVELBINE, and to contact their healthcare provider if they become pregnant, or if pregnancy is suspected [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].
    • NAVELBINE may damage sperm. Advise males to use highly effective contraception during and for 3 months after therapy [see Use in Specific Population and Nonclinical Toxicology].
    • NAVELBINE, may cause decreased fertility in males [see Nonclinical Toxicology].

What is vinorelbine (navelbine)?

Vinorelbine is cancer medication that interferes with the growth of cancer cells and slows their spread in the body.

Vinorelbine is used to treat non-small cell lung cancer.

Vinorelbine is sometimes used in combination with other cancer medications.

Vinorelbine may also be used for other purposes not listed in this medication guide.

Uses for Vinorelbine Tartrate

Non-Small Cell Lung Cancer

Used alone or in combination with cisplatin as first-line therapy in ambulatory patients for the palliative treatment of unresectable, advanced non-small cell lung cancer (NSCLC).1 19 91 b c

Used alone or in combination with cisplatin in patients with Stage IV NSCLC.1 19 91 b c

Use in combination with cisplatin is preferred treatment of advanced NSCLC in patients with good performance status because of improved response and survival.1 12 19 99 112

Used in combination with cisplatin in patients with Stage III NSCLC.1 19 91 b c

Use in combination with cisplatin is being investigated for adjuvant treatment of completely resected NSCLC†.110 111

Breast Cancer

Use in combination with trastuzumab is being investigated for the treatment of HER2-overexpressing metastatic breast cancer†.19 104 105 106

Has been used as first-line or salvage therapy for metastatic breast cancer in combination with various other agents†, including anthracyclines (e.g., doxorubicin), fluoropyrimidines (e.g., fluorouracil, capecitabine), mitoxantrone, cisplatin, taxanes (e.g., docetaxel, paclitaxel), ifosfamide, or gemcitabine.122

Has been used as monotherapy in first-line or salvage (e.g., second-line or subsequent) treatment of metastatic breast cancer†.19 106

Cervical Cancer

Use in the treatment of metastatic or recurrent cervical cancer† is being investigated.19 97 98

Use in combination with other antineoplastic agents (e.g., cisplatin) is being evaluated in patients with metastatic or recurrent cervical cancer†.98

Adult Soft Tissue Sarcomas

Has been used in the treatment of adult soft tissue sarcomas†.19

Esophageal Cancer

Has been used in the treatment of esophageal cancer†.19

Interactions for Vinorelbine Tartrate

Drugs Affecting Hepatic Microsomal Enzymes

Metabolized by CYP isoenzymes, principally CYP3A.1 b c

Inhibitors of CYP3A: Potential pharmacokinetic interaction (inhibition of vinorelbine metabolism). 1 b Use concomitantly with caution.1 b c

Ototoxic Drugs

Since varying degrees of permanent or temporary hearing impairment associated with eighth cranial nerve damage have been reported in patients receiving vinca alkaloids, use concomitantly with other potentially ototoxic drugs with extreme caution.1 93 (See Specific Drugs under Interactions.)

Specific Drugs and Procedures

Drug

Interaction

Comments

Aprepitant

May inhibit or induce CYP3A4103

Use concomitantly with caution and careful monitoring103

Consider dosage reduction of vinorelbine 103

Cisplatin

Incidence of of granulocytopenia increased with combined use1 b c

Closely monitor CBC with differentials before, during and after therapy1 b c

Itraconazole

Possible increased plasma concentrations of vinorelbine102

Possible neurotoxicity; consider vinorelbine dosage reduction102

Use with caution, earlier onset and/or increased severity of adverse effects may occur1 b c

Ketoconazole

Possible increased plasma concentrations of vinorelbine102

Possible neurotoxicity; consider vinorelbine dosage reduction102

Use with caution, earlier onset and/or increased severity of adverse effects may occur1 b c

Mitomycin

Possible acute pulmonary reactions 1 b (See Respiratory Effects under Cautions)

Ototoxic drugs (e.g., platinum-containing antineoplastic agents)

Potential additive ototoxic effect1 93

Varying degrees of permanent or temporary hearing impairment associated with eighth cranial nerve damage use with extreme caution1 93

Paclitaxel

Possible increased risk of neuropathy1

Monitor for signs and symptoms of neuropathy1 b c

Radiation Therapy

Prior or concomitant radiation may result in radiosensitizing effectsb c

Voriconazole

Possible increased plasma concentrations of vinorelbine102

Possible neurotoxicity; consider vinorelbine dosage reduction102

Use with caution, earlier onset and/or increased severity of adverse effects may occur1 b c

Stability

Storage

Parenteral

Injection

2–8°C; do not freeze.1 b c ; protect from light.1 b c

Unopened vials stable at 25°C for up to 72 hours.1 b c

May store diluted solutions at normal room light (in polypropylene syringes or polyvinyl chloride bags) at 5–30°C up to 24 hours.b c

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibilityb c HID

Compatible

Dextrose 5% in water

Sodium chloride 0.9%
Drug Compatibility Y-Site CompatibilityHID

Compatible

Amikacin sulfate

Aztreonam

Bleomycin sulfate

Bumetanide

Buprenorphine HCl

Butorphanol tartrate

Calcium gluconate

Carboplatin

Carmustine

Cefotaxime sodium

Ceftazidime

Ceftizoxime sodium

Chlorpromazine HCl

Cimetidine HCl

Cisplatin

Clindamycin phosphate

Cyclophosphamide

Cytarabine

Dacarbazine

Dactinomycin

Daunorubicin HCl

Dexamethasone sodium phosphate

Diphenhydramine HCl

Doxorubicin HCl

Doxorubicin HCl liposome injection

Doxycycline hyclate

Droperidol

Enalaprilat

Etoposide

Famotidine

Filgrastim

Floxuridine

Fluconazole

Fludarabine phosphate

Gallium nitrate

Gatifloxacin

Gemcitabine HCl

Gentamicin sulfate

Granisetron HCl

Haloperidol lactate

Hydrocortisone sodium phosphate

Hydrocortisone sodium succinate

Hydromorphone HCl

Hydroxyzine HCl

Idarubicin HCl

Ifosfamide

Imipenem–cilastatin sodium

Lorazepam

Mannitol

Melphalan HCl

Meperidine HCl

Mesna

Methotrexate sodium

Metoclopramide HCl

Metronidazole

Mitoxantrone HCl

Morphine sulfate

Nalbuphine HCl

Ondansetron HCl

Oxaliplatin

Potassium chloride

Prochlorperazine edisylate

Promethazine HCl

Rantidine HCl

Streptozocin

Teniposide

Ticarcillin disodium–clavulanate potassium

Tobramycin sulfate

Vancomycin HCl

Vinblastine sulfate

Vincristine sulfate

Zidovudine

Incompatible

Acyclovir sodium

Allopurinol sodium

Aminophylline

Amphotericin B

Amphotericin B cholesteryl sulfate complex

Ampicillin sodium

Cefazolin sodium

Cefotetan disodium

Ceftriaxone sodium

Cefuroxime sodium

Co-trimoxazole

Fluorouracil

Furosemide

Ganciclovir sodium

Lansoprazole

Methylprednisolone sodium succinate

Mitomycin

Sodium bicarbonate

Thiotepa

Variable

Heparin sodium
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