Vinorelbine Side Effects

Brand Names: Navelbine

Please note - some side effects for Vinorelbine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Vinorelbine - for the Consumer

Vinorelbine

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Vinorelbine:

Diarrhea; hair loss; nausea; vomiting; weakness.

Seek medical attention right away if any of these SEVERE side effects occur when using Vinorelbine:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; constipation; cough; numbness or tingling of your fingers or toes; pain, redness, or swelling at the injection site; shortness of breath; stomach pain; unusual bleeding or bruising.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Vinorelbine Side Effects - for the Professional

Vinorelbine

The pattern of adverse reactions is similar whether Vinorelbine is used as a single agent or in combination. Adverse reactions from studies with single-agent and combination use of Vinorelbine are summarized in Tables 2–4.

Single-Agent Vinorelbine

Data in the following table are based on the experience of 365 patients (143 patients with NSCLC; 222 patients with advanced breast cancer) treated with IV Vinorelbine as a single agent in 3 clinical studies. The dosing schedule in each study was 30 mg/m2 Vinorelbine on a weekly basis.

Table 2 Summary of Adverse Events in 365 Patients Receiving Single-Agent Vinorelbine Tartrate Injection*†

Adverse Event			All Patients (n = 365)		NSCLC (n = 143)
* None of the reported toxicities were influenced by age. Grade based on modified criteria from the National Cancer Institute. † Patients with NSCLC had not received prior chemotherapy. The majority of the remaining patients had received prior chemotherapy. ‡ Incidence of paresthesia plus hypesthesia.
Bone Marrow
Granulocytopenia	<2000 cells/mm3		90%		80%
	<500 cells/mm3		36%		29%
Leukopenia	<4000 cells/mm3		92%		81%
	<1000 cells/mm3		15%		12%
Thrombocytopenia	<100,000 cells/mm3		5%		4%
	<50,000 cells/mm3		1%		1%
Anemia	<11 g/dL		83%		77%
	<8 g/dL		9%		1%
Hospitalizations due to granulocytopenic complications			9%		8%
Adverse Event	All Grades		Grade 3		Grade 4
	All Patients	NSCLC	All Patients	NSCLC	All Patients	NSCLC
Clinical Chemistry Elevations
Total Bilirubin (n = 351)	13%	9%	4%	3%	3%	2%
SGOT (n = 346)	67%	54%	5%	2%	1%	1%
General
Asthenia	36%	27%	7%	5%	0%	0%
Injection Site Reactions	28%	38%	2%	5%	0%	0%
Injection Site Pain	16%	13%	2%	1%	0%	0%
Phlebitis	7%	10%	<1%	1%	0%	0%
Digestive
Nausea	44%	34%	2%	1%	0%	0%
Vomiting	20%	15%	2%	1%	0%	0%
Constipation	35%	29%	3%	2%	0%	0%
Diarrhea	17%	13%	1%	1%	0%	0%
Peripheral Neuropathy‡	25%	20%	1%	1%	<1%	0%
Dyspnea	7%	3%	2%	2%	1%	0%
Alopecia	12%	12%	≤1%	1%	0%	0%

Hematologic

Granulocytopenia is the major dose-limiting toxicity with Vinorelbine. Dose adjustments are required for hematologic toxicity and hepatic insufficiency. Granulocytopenia was generally reversible and not cumulative over time. Granulocyte nadirs occurred 7 to 10 days after the dose, with granulocyte recovery usually within the following 7 to 14 days. Granulocytopenia resulted in hospitalizations for fever and/or sepsis in 8% of patients. Septic deaths occurred in approximately 1% of patients. Prophylactic hematologic growth factors have not been routinely used with Vinorelbine. If medically necessary, growth factors may be administered at recommended doses no earlier than 24 hours after the administration of cytotoxic chemotherapy. Growth factors should not be administered in the period 24 hours before the administration of chemotherapy.

Whole blood and/or packed red blood cells were administered to 18% of patients who received Vinorelbine.

Neurologic

Loss of deep tendon reflexes occurred in less than 5% of patients. The development of severe peripheral neuropathy was infrequent (1%) and generally reversible.

Skin

Like other anticancer vinca alkaloids, Vinorelbine is a moderate vesicant. Injection site reactions, including erythema, pain at injection site, and vein discoloration, occurred in approximately one third of patients; 5% were severe. Chemical phlebitis along the vein proximal to the site of injection was reported in 10% of patients.

Gastrointestinal

Prophylactic administration of antiemetics was not routine in patients treated with single-agent Vinorelbine. Due to the low incidence of severe nausea and vomiting with single-agent Vinorelbine, the use of serotonin antagonists is generally not required.

Hepatic

Transient elevations of liver enzymes were reported without clinical symptoms.

Cardiovascular

Chest pain was reported in 5% of patients. Most reports of chest pain were in patients who had either a history of cardiovascular disease or tumor within the chest. There have been rare reports of myocardial infarction.

Pulmonary

Shortness of breath was reported in 3% of patients; it was severe in 2%. Interstitial pulmonary changes were documented.

Other

Fatigue occurred in 27% of patients. It was usually mild or moderate but tended to increase with cumulative dosing.

Other toxicities that have been reported in less than 5% of patients include jaw pain, myalgia, arthralgia, and rash. Hemorrhagic cystitis and the syndrome of inappropriate ADH secretion were each reported in <1% of patients.

Combination Use

Adverse events for combination use are summarized in Tables 3 and 4.

Vinorelbine in Combination with Cisplatin

Vinorelbine plus Cisplatin versus Single-Agent Cisplatin (Table 3)

Myelosuppression was the predominant toxicity in patients receiving combination therapy, Grade 3 and 4 granulocytopenia of 82% compared to 5% in the single-agent cisplatin arm. Fever and/or sepsis related to granulocytopenia occurred in 11% of patients on Vinorelbine and cisplatin compared to 0% on the cisplatin arm.

Four patients on the combination died of granulocytopenia-related sepsis. During this study, the use of granulocyte colony-stimulating factor ([G-CSF] filgrastim) was permitted, but not mandated, after the first course of treatment for patients who experienced Grade 3 or 4 granulocytopenia (≤1000 cells/mm3) or in those who developed neutropenic fever between cycles of chemotherapy. Beginning 24 hours after completion of chemotherapy, G-CSF was started at a dose of 5 mcg/kg per day and continued until the total granulocyte count was >1000 cells/mm3 on 2 successive determinations. G-CSF was not administered on the day of treatment.

Grade 3 and 4 anemia occurred more frequently in the combination arm compared to control, 24% vs. 8%, respectively. Thrombocytopenia occurred in 6% of patients treated with Vinorelbine plus cisplatin compared to 2% of patients treated with cisplatin.

The incidence of severe non-hematologic toxicity was similar among the patients in both treatment groups. Patients receiving Vinorelbine plus cisplatin compared to single-agent cisplatin experienced more Grade 3 and/or 4 peripheral numbness (2% vs. <1%), phlebitis/thrombosis/embolism (3% vs. <1%), and infection (6% vs. <1%). Grade 3–4-constipation and/or ileus occurred in 3% of patients treated with combination therapy and in 1% of patients treated with cisplatin.

Seven deaths were reported on the combination arm; 2 were related to cardiac ischemia, 1 massive cerebrovascular accident, 1 multisystem failure due to an overdose of Vinorelbine, and 3 from febrile neutropenia. One death, secondary to respiratory infection unrelated to granulocytopenia, occurred with single-agent cisplatin.

Vinorelbine plus Cisplatin versus Vindesine plus Cisplatin versus Single-Agent Vinorelbine (Table 4)

Myelosuppression, specifically Grade 3 and 4 granulocytopenia, was significantly greater with the combination of Vinorelbine plus cisplatin (79%) than with either single-agent Vinorelbine (53%) or vindesine plus cisplatin (48%), P<0.0001. Hospitalization due to documented sepsis occurred in 4.4% of patients treated with Vinorelbine plus cisplatin; 2% of patients treated with vindesine and cisplatin, and 4% of patients treated with single-agent Vinorelbine. Grade 3 and 4 thrombocytopenia was infrequent in patients receiving combination chemotherapy and no events were reported with single-agent Vinorelbine.

The incidence of Grade 3 and/or 4 nausea and vomiting, alopecia, and renal toxicity were reported more frequently in the cisplatin-containing combinations compared to single-agent Vinorelbine. Severe local reactions occurred in 2% of patients treated with combinations containing Vinorelbine; none were observed in the vindesine plus cisplatin arm. Grade 3 and 4 neurotoxicity was significantly more frequent in patients receiving vindesine plus cisplatin (17%) compared to Vinorelbine plus cisplatin (7%) and single-agent Vinorelbine (9%) (P< 0.005). Cisplatin did not appear to increase the incidence of neurotoxicity observed with single-agent Vinorelbine.

Table 3 Selected Adverse Events From a Comparative Trial of Vinorelbine plus Cisplatin versus Single-Agent Cisplatin*

	Vinorelbine 25 mg/m2 plus Cisplatin 100 mg/m2 (n = 212)			Cisplatin 100 mg/m2 (n = 210)
Adverse Event	All Grades	Grade 3	Grade 4	All Grades	Grade 3	Grade 4
* Graded according to the standard SWOG criteria.
Bone Marrow
Granulocytopenia	89%	22%	60%	26%	4%	1%
Anemia	88%	21%	3%	72%	7%	<1%
Leukopenia	88%	39%	19%	31%	<1%	0%
Thrombocytopenia	29%	4%	1%	21%	1%	<1%
Febrile neutropenia	N/A	N/A	11%	N/A	N/A	0%
Hepatic
Elevated transaminase	1%	0%	0%	<1%	<1%	0%
Renal
Elevated creatinine	37%	2%	2%	28%	4%	<1%
Non-Laboratory
Malaise/fatigue/lethargy	67%	12%	0%	49%	8%	0%
Vomiting	60%	7%	6%	60%	10%	4%
Nausea	58%	14%	0%	57%	12%	0%
Anorexia	46%	0%	0%	37%	0%	0%
Constipation	35%	3%	0%	16%	1%	0%
Alopecia	34%	0%	0%	14%	0%	0%
Weight loss	34%	1%	0%	21%	<1%	0%
Fever without infection	20%	2%	0%	4%	0%	0%
Hearing	18%	4%	0%	18%	3%	<1%
Local (injection site reactions)	17%	<1%	0%	1%	0%	0%
Diarrhea	17%	2%	<1%	11%	1%	<1%
Paresthesias	17%	<1%	0%	10%	<1%	0%
Taste alterations	17%	0%	0%	15%	0%	0%
Peripheral numbness	11%	2%	0%	7%	<1%	0%
Myalgia/arthralgia	12%	<1%	0%	3%	<1%	0%
Phlebitis/thrombosis/embolism	10%	3%	0%	<1%	0%	<1%
Weakness	12%	2%	<1%	7%	2%	0%
Dizziness/vertigo	9%	<1%	0%	3%	<1%	0%
Infection	11%	5%	<1%	<1%	<1%	0%
Respiratory infection	10%	4%	<1%	3%	3%	0%

Table 4 Selected Adverse Events From a Comparative Trial of Vinorelbine Plus Cisplatin versus Vindesine Plus Cisplatin versus Single-Agent Vinorelbine*

	Vinorelbine/Cisplatin†			Vindesine/Cisplatin‡			Vinorelbine §
Adverse Event	All Grades	Grade 3	Grade 4	All Grades	Grade 3	Grade 4	All Grades	Grade 3	Grade 4
* Grade based on criteria from the World Health Organization (WHO). † n =194 to 207; all patients receiving Vinorelbine/cisplatin with laboratory and non-laboratory data. ‡ n =173 to 192; all patients receiving vindesine/cisplatin with laboratory and non-laboratory data. § n=165 to 201; all patients receiving Vinorelbine with laboratory and non-laboratory data. ¶ Categorical toxicity grade not specified. # Neurotoxicity includes peripheral neuropathy and constipation.
Bone Marrow
Neutropenia	95%	20%	58%	79%	26%	22%	85%	25%	28%
Leukopenia	94%	40%	17%	82%	24%	3%	83%	26%	6%
Thrombocytopenia	15%	3%	1%	10%	3%	0.5%	3%	0%	0%
Febrile neutropenia	N/A	N/A	4%	N/A	N/A	2%	N/A	N/A	4%
Hepatic
Elevated bilirubin ¶	6%	N/A	N/A	5%	N/A	N/A	5%	N/A	N/A
Renal
Elevated creatinine ¶	46%	N/A	N/A	37%	N/A	N/A	13%	N/A	N/A
Non-Laboratory
Nausea/vomiting	74%	27%	3%	72%	24%	1%	31%	1%	1%
Alopecia	51%	7%	0.5%	56%	14%	0%	30%	2%	0%
Ototoxicity	10%	1%	1%	14%	1%	0%	1%	0%	0%
Local reactions	17%	2%	0.5%	7%	0%	0%	22%	2%	0%
Diarrhea	25%	1.5%	0%	24%	1%	0%	12%	0%	0.5%
Neurotoxicity#	44%	7%	0%	58%	16%	1%	44%	8%	0.5%

Observed During Clinical Practice

In addition to the adverse events reported from clinical trials, the following events have been identified during post-approval 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 a combination of their seriousness, frequency of reporting, or potential causal connection to Vinorelbine.

Body as a Whole: Systemic allergic reactions reported as anaphylaxis, pruritus, urticaria, and angioedema; flushing; and radiation recall events such as dermatitis and esophagitis 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.

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. There may be increased potential for neurotoxicity in patients with pre-existing neuropathy, regardless of etiology, who receive Vinorelbine. Vestibular and auditory deficits have been observed with Vinorelbine, usually when used in combination with cisplatin.

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.

Gastrointestinal: Dysphagia, mucositis, and pancreatitis have been reported.

Cardiovascular: Hypertension, hypotension, vasodilation, tachycardia, and pulmonary edema have been reported.

Pulmonary: Pneumonia has been reported.

Musculoskeletal: Headache has been reported, with and without other musculoskeletal aches and pains.

Other: Pain in tumor-containing tissue, back pain, and abdominal pain have been reported. Electrolyte abnormalities, including hyponatremia with or without the syndrome of inappropriate ADH secretion, have been reported in seriously ill and debilitated patients.

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.

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Side Effects by Body System - for Healthcare Professionals

Hematologic

Pulmonary embolus and deep venous thrombosis have primarily been reported in seriously ill and debilitated patients with known predisposing risk factors for these events.

Hematologic side effects have included granulocytopenia, which has been the major dose-limiting toxicity with the use of vinorelbine. Granulocytopenia has been reported at a frequency of 90% of patients with less than 2,000 cells/mm3 and 36% of patients with less than 500 cells/mm3. Leukopenia has been reported at a frequency of 92% of patients with less than 4,000 cells/mm3 and 5% of patients with less than 1,000 cells/mm3. Thrombocytopenia has been reported at a frequency of 5% of patients with less than 100,000 cells/mm3 and 1% of patients with less than 50,000 cells/mm3. And finally, anemia has been reported at a frequency of 83% of patients with less than 11 g/dL and 9% of patients with less than 8 g/dL. Pulmonary embolus and deep venous thrombosis have also been reported.

Hepatic

Hepatic side effects including an increase in SGOT (67%) and an increase in total bilirubin (13%) have been reported.

Gastrointestinal

Gastrointestinal side effects including nausea (44%), constipation (35%), vomiting (20%), diarrhea (17%), dysphagia, and mucositis have been reported. A case of typhlitis (neutropenic enterocolitis) has also been reported.

General

General side effects including asthenia (36%), fatigue (27%), back pain, abdominal pain, and pain in tumor containing tissues have been reported.

Fatigue was usually mild or moderate and tended to increase with increased cumulative dosing.

Local

Local side effects including injection site reactions (28%) and injection site pain (16%) have been reported.

Nervous system

Nervous system side effects including peripheral neuropathy (paresthesia and hypesthesia) (25%) and headache have been reported.

Dermatologic

Some of these dermatologic reactions have been delayed in their occurrence.

Dermatologic side effects including alopecia (12%), rash (<5%), pruritus, blister formation, skin sloughing, and urticaria have been reported.

Cardiovascular

Most of the chest pain has been reported to have occurred in patients who had either a history of cardiovascular disease or tumor within the chest.

Cardiovascular side effects including phlebitis (7%), chest pain (5%), myocardial infarction, angioedema, hypertension, hypotension, vasodilation, tachycardia, and flushing have been reported.

Respiratory

Respiratory side effects including dyspnea (7%), shortness of breath (3%), severe shortness of breath (2%), pulmonary edema, and pneumonia have been reported.

Musculoskeletal

Musculoskeletal side effects including jaw pain, myalgia, and arthralgia have been reported in less than 5% of patients.

Genitourinary

Genitourinary side effects including hemorrhagic cystitis (<1%) have been reported.

Metabolic

Metabolic side effects including the syndrome of inappropriate antidiuretic hormone (<1%) have been reported.

Hypersensitivity

Hypersensitivity side effects including anaphylaxis have been reported.

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