Vinorelbin “Ebewe” 10 mg/ml

/ Novartis

Vinorelbine should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents.
This product is for Intravenous use only, after appropriate dilution. Intrathecal administration is contraindicated.
It is extremely important that the intravenous needle be correctly positioned before vinorelbine is administered.
Extravasation into surrounding tissue during intravenous administration may cause local reactions (irritation, local tissue necrosis and/or thrombophlebitis). Should extravasation occur, the administration should be discontinued immediately and the remaining dose should then be introduced into another vein.
The usual weekly monotherapy dose is 25 mg to 30 mg/m².
When given in combination with other antineoplastics, dose and frequency should be adjusted according to accepted protocol.
Vinorelbine can be given as a slow bolus (5-10 minutes) after dilution in 20-50 ml physiological saline solution, or by perfusion (20-30 minutes) after dilution in 125 ml physiological saline solution. Administration should be followed by a thorough flush of the vein with at least 250 ml of physiological saline solution.
Clinical experience has not identified relevant differences in the elderly, but greater sensitivity of some older individuals cannot be ruled out.

For the treatment of non-small cell lung cancer.
For the treatment of advanced breast cancer.
Hormone-refractory prostate cancer, especially in combination with low dose oral corticoid therapy or estramustine.

Known hypersensitivity to vinorelbine or other vinca alkaloids, or to any of the constituents.
As with other cytostatic drugs, vinorelbine is contraindicated in pregnancy, lactation and in patients with severe hepatic insufficiency.
Neutrophil count <2000/mm³ or severe infection, current or recent (within 2 weeks).

Vinorelbine should be administered under the supervision of a physician experienced in the use of chemotherapy.
Since inhibition of the hematopoietic system is the main risk associated with vinorelbine, close hematological monitoring should be undertaken during treatment (determination of hemoglobin level and the leukocyte, granulocyte and platelet counts on the day of each new administration).
The dose limiting adverse reaction is mainly neutropenia. This effect is non-cumulative, having its nadir between 7 and 14 days after the administration, and is rapidly reversible within 5 to 7 days. If the neutrophil count is below 2000/mm³ and/or the platelet count is below 75000/mm³, the treatment
should be delayed until recovery.
If patients present signs or symptoms suggestive of infection, a prompt investigation should be carried out.
Special care should be taken when prescribing for patients with history of ischemic heart disease.
Pediatric Use: Vinorelbine at doses similar to those used in adults is usually well tolerated with similar toxicity to that reported in adults.
Hepatic Impairment: Caution should be exercised when administering vinorelbine to patients with severe hepatic insufficiency and the dosage adjusted accordingly.
Vinorelbine should not be prescribed in combination with liver radiotherapy.
Renal Impairment: Caution should be exercised when administering vinorelbine to patients with renal insufficiency and the dosage adjusted accordingly.
In case of accidental contact with the eyes, rinse the eyes immediately and thoroughly.

Hematologic: Granulocytopenia is the major dose limiting toxicity with vinorelbine (see Warnings and Precautions).
Neurologic: Usually limited to the loss of deep tendon reflexes. The development of severe peripheral neuropathy is rare. After prolonged treatment with vinorelbine, fatigue of the lower extremities might be observed.
Cases of paralytic ileus have been reported.
Pulmonary: Shortness of breath, dyspnea and bronchospasms have been reported.
Skin: Leakage into surrounding tissue during IV administration of vinorelbine may cause local reaction including erythema, pain at injection site, vein discoloration. Chemical phlebitis along the vein proximal to the site of injection has also been reported.
Other: Alopecia (progressive and moderate), sensation of pain in the jaws.
Gastrointestinal: Constipation, diarrhea (severe diarrhea is uncommon), nausea/vomiting: severe nausea and vomiting may occasionally occur. Conventional anti-emetic therapy reduces these undesirable effects.

As CYP 3A4 is mainly involved in the metabolism of vinorelbine, combination with inducers or inhibitors of this isoenzyme might modify the pharmacokinetics of vinorelbine.
There are no known drug interactions.

Pregnancy: In animal reproductive studies vinorelbine was embryo-feto-lethal and teratogenic. Therefore, vinorelbine should not be used during pregnancy. If pregnancy occurs during treatment genetic counselling should be offered.
Women of Childbearing Potential: Women of childbearing potential have to use effective contraception during treatment.
Lactation: It is not known whether vinorelbine passes into the breast milk. Breast-feeding must be discontinued prior to starting vinorelbine treatment.

Overdoses involving quantities up to 10 times the recommended dose (30 mg/m²) have been reported.
The toxicities reported are in line with those mentioned in the section Undesirable Effects.
If overdosage occurs, general supportive measures together with appropriate blood transfusions, growth factors and antibiotics should be instituted according to the decision of the physician.