Navelbine
Navelbine Medication Information:
Navelbine medication comes in several different strengths; click on the strength you need to view prices from pharmacies competing to earn your business.
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Navelbine 20 mg
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Navelbine 30 mg
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Pharmacology
Pharmacokinetics
Following i.v. administration, vinorelbine concentration in plasma decays in a triphasic manner. The initial rapid decline represents distribution of drug to peripheral compartments and metabolism of the drug. The prolonged terminal phase is due to relatively slow efflux of vinorelbine from peripheral compartments. The terminal phase half-life averaged 27.7 to 43.6 hours; the mean plasma clearances ranged from 0.97 to 1.26 L/hr/kg; and steady state volume of distribution (Vss) values ranged from 25.4 to 40.1 L/kg.
The disposition of radiolabeled vinorelbine has been studied in a limited number of patients. Approximately 18% of the administered dose was recovered in the urine and 46% in the feces. Incomplete recovery in humans is consistent with results in animals. A separate study of the urinary excretion of vinorelbine showed that 10.9%±0.7% of a 30 mg/m2 i.v. dose was excreted unchanged in the urine.
One metabolite of vinorelbine, deacetylvinorelbine, has been shown to possess antitumor activity. This metabolite has been detected but not quantified in human plasma. The effects of renal or hepatic dysfunction on the disposition of vinorelbine have not been assessed.
The pharmacokinetics of vinorelbine are not influenced by the concurrent administration of cisplatin with vinorelbine (see Precautions, Drug Interactions).
Indications
In the treatment of advanced non-small cell lung cancer (NSCLC), as a single agent or in combination.
Also indicated for the treatment of patients with metastatic breast cancer who have failed standard first-line chemotherapy for metastatic disease. In addition, vinorelbine is indicated for the treatment of patients with metastatic breast cancer who have relapsed within 6 months of anthracycline-based adjuvant therapy.
Precautions
Drug Interactions
Acute pulmonary reactions have been reported with vinorelbine and other vinca alkaloids used in conjunction with mitomycin (see General). Vinorelbine should be administered with caution in combination with mitomycin. Although the pharmacokinetics of vinorelbine are not influenced by the concurrent administration of cisplatin, the incidence of toxicities, specifically granulocytopenia, high-frequency hearing loss and tinnitus, with the combination of vinorelbine and cisplatin is higher than with single-agent vinorelbine.
Patients who receive vinorelbine and paclitaxel, either concomitantly or sequentially, should be monitored for signs and symptoms of neuropathy. Administration of vinorelbine to patients with prior or concomitant radiation therapy may result in radiosensitizing effects.
Geriatrics
Of the total number of patients in North American clinical studies of i.v. vinorelbine, approximately one-third were 65 years of age or greater. No overall differences in effectiveness or safety were observed between these patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Hematologic
Since dose-limiting clinical toxicity is the result of depression of the white blood cell count, it is imperative that complete blood counts with differentials be obtained prior to each dose of vinorelbine (see Adverse Effects, Hematologic).
General
In all instances where the use of vinorelbine is considered for chemotherapy, the physician must evaluate the need and usefulness of the drug against the risk of adverse events. Most drug-related adverse reactions are reversible. If severe adverse events occur, the drug should be reduced in dosage or discontinued and appropriate corrective measures should be taken based on the clinical judgment of the physician. Reinstitution of therapy with vinorelbine should be carried out with caution and alertness as to possible recurrence of toxicity.
Vinorelbine should be used with extreme caution in patients whose bone marrow reserve may have been compromised by prior irradiation or chemotherapy, or whose marrow function is recovering from previous chemotherapy.
Administration of vinorelbine to patients with prior radiation therapy may result in radiation recall reactions (see Adverse Effects and Drug Interactions).
Patients with a prior history of pre-existing neuropathy, regardless of etiology, should be monitored for new or worsening signs and symptoms of neuropathy while receiving vinorelbine.
Acute shortness of breath and severe bronchospasm have been reported infrequently following the administration of vinorelbine and of other vinca alkaloids. These events have been encountered most commonly when the vinca alkaloid was used in combination with mitomycin and may require aggressive treatment, particularly when there is pre-existing pulmonary dysfunction. Bronchodilators, steroids and/or oxygen have produced symptomatic relief.
Care must be exercised to avoid contamination of the eye with vinorelbine. Accidental exposure should be treated immediately with a large volume of irrigation solution (water or sodium chloride).
Pregnancy
See Warnings.
Information to Be Provided to the Patient
Patients should be informed that vinorelbine is a vesicant and can produce phlebitis or extravasation injury, and that the major acute toxicities of vinorelbine are related to bone marrow toxicity, specifically granulocytopenia with increased susceptibility to infection, and neuropathy. They should also be advised to report fever or chills immediately. Vinorelbine should not be used in pregnancy unless the physician feels the potential benefit justifies the risk of potential harm to the fetus.
Hepatic
There is no evidence that the toxicity of vinorelbine is enhanced in patients with elevated liver enzymes; no data are available for patients with severe baseline cholestasis. However, pharmacologic evidence suggests that the liver plays an important role in the metabolism of vinorelbine. Although there are no data available from patients with severe liver disease, caution should be exercised when administering vinorelbine to patients with severe hepatic injury or impairment.
Supplied
Each mL of clear, colorless to pale yellow aqueous solution contains: vinorelbine tartrate equivalent to vinorelbine base 10 mg. Additive- and preservative-free. Single-dose clear flint glass vials of 1 and 5 mL. Store vials under refrigeration (2 to 8°C) in the original package to protect from light. This product should not be frozen.
Contraindications
In patients with known hypersensitivity to vinorelbine.
As with other vinca alkaloids, vinorelbine is contraindicated in patients who have drug-induced severe granulocytopenia or severe thrombocytopenia.
Warnings
Lactation
It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk and because of its potential for serious adverse reactions in nursing infants, it is recommended that nursing be discontinued in women who are receiving therapy with vinorelbine.
Children
Safety and effectiveness in children have not been established.
Pregnancy
There are no studies in pregnant women. Vinorelbine has been shown to be embryotoxic and/or fetotoxic in animals. Vinorelbine should not be used in pregnancy.
Adverse Effects
Gastrointestinal
Dysphagia and mucositis have been reported.
Hematologic
Thromboembolic events including pulmonary embolus and deep venous thrombosis have been reported, primarily in seriously ill and debilitated patients with known predisposing risk factors for these events.
Musculoskeletal
Headache has been reported with and without other musculoskeletal aches and pains.
Neurologic
Peripheral neurotoxicities such as, but not limited to, muscle weakness and disturbance of gait have been observed in patients with and without prior symptoms. Vestibular and auditory deficits have been observed with vinorelbine, usually when used in combination with cisplatin. There may be increased potential for neurotoxicity in patients with pre-existing neuropathy, regardless of etiology, who receive vinorelbine. Patients who receive vinorelbine and paclitaxel, either concomitantly or sequentially, should be monitored for signs and symptoms of neuropathy (see Precautions).
Skin
Injection site reactions, including localized rash and urticaria, blister formation and skin sloughing have been observed in clinical practice. Some of these reactions may be delayed in appearance.
Observed During Clinical Practice
In a randomized study in NSCLC patients, 206 patients received treatment with vinorelbine plus cisplatin and 206 patients received single-agent vinorelbine. The incidence of severe nausea and vomiting was 30% for vinorelbine/cisplatin compared to <2% for single-agent vinorelbine. Cisplatin did not appear to increase the incidence of neurotoxicity observed with single-agent vinorelbine. However, myelosuppression, specifically Grade 3 and 4 granulocytopenia, was greater with the combination of vinorelbine/cisplatin (79%) than with single-agent vinorelbine (53%). The incidence of fever and infection may be increased with the combination.
In addition to adverse events reported from clinical trials, the following events have been identified during postmarketing use of vinorelbine. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to combination of their seriousness, frequency of reporting, or potential causal connection to vinorelbine or a combination of these factors.
Other
Pain in tumor-containing tissue, back pain and abdominal pain have been reported. Electrolyte abnormalities, including hyponatremia consistent with the syndrome of inappropriate ADH secretion, have been reported in seriously ill and debilitated patients.
Pulmonary
Pneumonia has been reported.
Vinorelbine can produce acute and subacute pulmonary reactions. The acute reaction usually resembles an allergic event and may respond to bronchodilators. Subacute pulmonary reactions occur shortly after drug administration and may be characterized by cough, dyspnea, hypoxemia, and interstitial infiltration. Subacute pulmonary reactions may respond to corticosteroid therapy.
Body as a Whole
Systemic allergic reactions reported as anaphylaxis, pruritus, urticaria and angioedema, flushing and radiation recall events such as dermatitis and esophagitis (see Precautions) have been reported.
Dermatologic
Alopecia was reported in only 12% of patients and was usually mild.
Vinorelbine is a moderate vesicant. Injection site reactions, including erythema, pain at injection site, and vein discoloration occurred in approximately one-third of all patients; 2% were severe. Chemical phlebitis along the vein proximal to the site of injection was reported.
Combination Use
Patients with prior exposure to paclitaxel and who have demonstrated neuropathy should be monitored closely for new or worsening neuropathy. Patients who have experienced neuropathy with previous drug regimens should be monitored for symptoms of neuropathy while receiving vinorelbine. Vinorelbine may result in radiosensitizing effects with prior or concomitant radiation therapy (see Precautions).
Navelbine
Summary of Adverse Events Occurring in ≥5% of 365 Patients Receiving Single-agent Navelbine that are Possibly Attributable to the Study Medicationa , b
| Adverse Event | % Incidence All Grades | % Incidence Grade 3 | % Incidence Grade 4 | |||
|---|---|---|---|---|---|---|
| ABC n=222 | NSCLC n=143 | ABC n=222 | NSCLC n=143 | ABC n=222 | NSCLC n=143 | |
| General | ||||||
| Injection Site Reaction | 21 | 38 | 1 | 5 | 0 | 0 |
| Asthenia | 41 | 25 | 8 | 5 | 0 | 0 |
| Pain | 16 | 15 | 3 | 2 | 0 | 0 |
| Pain Injection Site | 18 | 13 | 3 | 1 | 0 | 0 |
| Fever | 19 | 10 | 1 | 0 | 0 | 1 |
| Pain Abdomen | 12 | 6 | 1 | 1 | 0 | 0 |
| Pain Chest | 8 | 5 | 1 | 2 | 0 | 0 |
| Phlebitis | 5 | 10 | 0 | 1 | 0 | 0 |
| Digestive | ||||||
| Nausea | 50 | 33 | 3 | 1 | 0 | 0 |
| Constipation | 38 | 28 | 3 | 2 | 0 | 0 |
| Anorexia | 19 | 16 | <1 | 2 | 0 | 0 |
| Stomatitis | 16 | 15 | 0 | 0 | 0 | 0 |
| Vomiting | 23 | 14 | 2 | 1 | 0 | 0 |
| Diarrhea | 20 | 13 | <1 | 1 | 0 | 0 |
| Musculoskeletal | ||||||
| Myasthenia | 9 | 5 | 2 | 1 | <1 | 0 |
| Nervous System | ||||||
| Paresthesia | 20 | 11 | 0 | 1 | 0 | 0 |
| Hypesthesia | 11 | 10 | <1 | 0 | <1 | 0 |
| Respiratory | ||||||
| Dyspnea | 9 | 3 | 1 | 2 | 1 | 0 |
| Skin and Appendages | ||||||
| Alopecia | 12 | 12 | 0 | 1 | 0 | 0 |
| Rash | 5 | 5 | 0 | 0 | 0 | 0 |
b. Patients with NSCLC had not received prior chemotherapy. The majority of patients with advanced breast cancer had received prior chemotherapy.
Legend
ABC=Advanced Breast Cancer.
NSCLC=Non-Small Cell Lung Cancer.
Hepatic
Transient elevations of liver enzymes were reported without clinical symptoms.
Cardiovascular
Hypertension, hypotension, vasodilation, tachycardia and pulmonary edema have been reported.
Overdose
Symptoms
The primary anticipated complications of overdosage would consist of bone marrow suppression and peripheral neurotoxicity.
Treatment
There is no known antidote for vinorelbine overdosage. 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 Effects section including paralytic ileus, stomatitis, and esophagitis. Bone marrow aplasia, sepsis, and paresis have also been reported. Fatalities have occurred following overdose of vinorelbine. If overdosage occurs, general supportive measures together with appropriate blood transfusions, growth factors and antibiotics should be instituted as deemed necessary by the physician.
Dosage
This preparation is for i.v. administration only. It should be administered by individuals experienced in the administration of cancer chemotherapeutic drugs.
The usual initial dose is 30 mg/m2 administered weekly. The recommended method of administration is an i.v. injection over 6 to 10 minutes. In controlled trials, single-agent vinorelbine was given weekly until progression or dose-limiting toxicity.
No dose adjustments are required for renal insufficiency. If moderate or severe neurotoxicity develops, vinorelbine should be discontinued. The dosage should be adjusted according to hematologic toxicity or hepatic insufficiency.
Dose Modifications for Hematologic Toxicity: Granulocyte counts should be ≥1000 cells/mm3 prior to the administration of vinorelbine. In the referenced North American trial, in which hematologic adverse events were observed, the dose adjustment scheme in Table 3 was employed and should be followed in patients receiving vinorelbine.
Table 3: Navelbine
Dose Adjustments Based on Granulocyte Counts
| Granulocytes (cells/mm3) on days of Treatment | Dose of Navelbine (mg/m2) |
|---|---|
| ≥1500 | 30 |
| 1000 to 1499 | 15 |
| <1000 | Do not administer. Repeat granulocyte count in 1 week. If granulocyte count is <1000 cells/mm3 for >3 weeks, discontinue Navelbine. |
| Note: For patients who, during treatment with vinorelbine, have experienced fever and/or sepsis while granulocytopenic or required a delay in dosing of up to 3 weeks due to granulocytopenia, the dose of vinorelbine should be: 22.5 mg/m2 for granulocytes ≥1500 cells/m3 and 11.25 mg/m2 for granulocytes 1000 to 1499 cells/m3. | |
Vinorelbine should be administered with caution to patients with hepatic insufficiency. In patients who develop hyperbilirubinemia during treatment with vinorelbine, the dose should be adjusted for total bilirubin.
Administration Precautions: Vinorelbine must be administered i.v. It is extremely important that the i.v. needle or catheter be properly positioned before any vinorelbine is injected. Leakage into surrounding tissue during i.v. administration of vinorelbine may cause considerable irritation, local tissue necrosis and/or thrombophlebitis. If extravasation occurs, the injection should be discontinued immediately, and any remaining portion of the dose should then be introduced into another vein. The application of moderate heat to the area of leakage in the form of warm compress applied for 15 to 20 minutes at least 4 times per day for the first 24 to 48 hours in addition to rest and elevation of the affected site for 48-72 hours has been reported to help disperse drug and minimize discomfort associated with the extravasation of other vinca alkaloids.
As with other toxic compounds, caution should be exercised in handling and preparing the solution of vinorelbine. Skin reactions may occur with accidental exposure. The use of gloves is recommended. If the solution of vinorelbine contacts the skin or mucosa, immediately wash the skin or mucosa thoroughly with soap and water. Severe irritation of the eye has been reported with accidental contamination of the eye with another vinca alkaloid. If this happens with vinorelbine, the eye should be washed with water immediately and thoroughly.
Preparation for Administration: Vinorelbine injection must be diluted in either a syringe or i.v. bag using one of the recommended solutions. The diluted vinorelbine should be administered over 6 to 10 minutes into the side port of a free-flowing i.v. followed by flushing with at least 75 to 125 mL of one of the solutions. For diluents that may be used, see Dosage, Reconstituted Solutions.
Syringe: The calculated dose of vinorelbine should be diluted to a concentration between 1.5 and 3 mg/mL.
I.V. Bag: The calculated dose of vinorelbine should be diluted to a concentration between 0.5 and 2 mg/mL.
Reconstituted Solutions: Syringe: Vinorelbine diluted to a concentration between 1.5 and 3 mg/mL may be used for up to 24 hours when stored in polypropylene syringes at 5 to 30°C. The following solutions may be used for dilution: 5% Dextrose Injection, USP; 0.9% Sodium Chloride Injection, USP.
I.V. Bag: Vinorelbine diluted to a concentration between 0.5 and 2 mg/mL may be used for up to 24 hours when stored in polyvinylchloride bags at 5 to 30°C. The following solutions may be used for dilution: 5% Dextrose Injection, USP; 0.9% Sodium Chloride Injection, USP; 0.45% Sodium Chloride Injection, USP; 5% Dextrose and 0.45% Sodium Chloride Injection, USP; Ringer's Injection, USP; Lactated Ringer's Injection, USP.
Potassium chloride injection solutions are found to be compatible with vinorelbine.
As with all the parenteral drug products, i.v. admixtures should be inspected visually for clarity, particulate matter, discoloration and leakage prior to administration, whenever solution and container permit. Any unused portion should be discarded.
Special Instructions: Since vinorelbine is a cytostatic agent, established procedures specific to the handling and use of such agents must be followed.
Vinorelbine injection is initially clear and colorless to pale yellow, but may develop a slightly darker yellow to light amber color in time. This does not indicate a change which should preclude its use. Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration whenever solution and container permit. If particulate matter is seen, vinorelbine should not be administered.
