Relubin

Vinorelbine.

Each mL contains: Vinorelbine Tartrate equivalent to Vinorelbine 10 mg.

Pharmacology: Vinorelbine Tartrate is a cytostatic antineoplastic of theVinca Alkaloids group. The molecular target of its activity is tubulin/microtubule dynamic equilibrium. Vinorelbine Tartrate inhibits the polymerization of tubulin. lt acts preferentially on mitotic microtubules and affects axonal microtubules only at high concentration. The effects on tubulin spiralization are lower than with Vincristine. Vinorelbine Tartrate blocks mitosis in phase G2+M and induces cell death at interphase or at the following mitosis.

Non small cell lung cancer.
Advanced breast cancer in combination with standard chemotherapy.

No dose adjustments are required for renal insufficiency. lf moderate or severe neurotoxicity develops, RELUBIN should be discontinued. The dosage should be adjusted according to hematologic toxicity or hepatic insufficiency, whichever results in the lower dose.
Dose modifications for Hematologic Toxicity: Granulocyte counts should be ≥ 1,500 cells/mm³ prior to the administration of RELUBIN. Adjustments in the dosage of RELUBIN should be based on granulocyte counts obtained on the day of treatment according to Table 1 as follows: see Table 1.


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Note: For patients during treatment with RELUBIN who have experienced fever and/or sepsis while granulocytopenia or had 2 consecutive weekly doses held due to granulocytopenia, subsequent doses of RELUBIN should be: 22.5 mg/m², for granulocytes >1,500 cells/mm³.
Dose modification for Hepatic lnsufficiency: RELUBIN should be administered with caution to patients with hepatic insufficiency. ln patients who develop hyperbilirubinemia during treatment with RELUBIN, the dose should be adjusted for total bilirubin according to Table 2 as follows: see Table 2.


Click on icon to see table/diagram/image


Dose modification for concurrent hematological toxicity and hepatic insufficiency: In patients with both hematological toxicity and hepatic insufficiency, the lower of the doses determined from Table 1 and 2 should be administered.
Administration: Strictly by intravenous administration after appropriate dilution. The use of intrathecal route is contraindicated. It is recommended to infuse RELUBIN over 6-10 minutes after dilution in 20-50 mL of normal saline solution or 5% Dextrose solution. Administration should always be followed with at least 250 mL of an isotonic solution infusion to flush the vein.
In monotherapy, the usual dose given is 25-30 mg/m² once weekly.
ln combination chemotherapy the dose may be the same while the frequency of administration reduced, i.e.: day 1 and 5 every 3 week or day 1 and 8 every 3 weeks according to treatment protocol.

Accidental acute overdose have been reported in human: they may produce bone marrow hypoplasia sometimes associated with infection, fever, and paralytic ileus. General supportive measures together with blood transfusion and broad spectrum antibiotic therapy should be instituted as deemed necessary by the physician. There is no known antidote for overdose of Vinorelbine Tartrate.

Vinorelbine Tartrate is contraindicated in pregnancy, lactation, known hypersensitivity to Vinorelbine Tartrate or other Vinca Alkaloids, neutrophil count < 1,500/mm³ or severe infection current or recent (within 2 weeks).

Vinorelbine Tartrate injection should be administered under the supervision of a physician experienced in the use of cancer chemotherapy agents. The product is for intravenous (i.v.) use only. lntrathecal administration of other Vinca Alkaloids has resulted in death.
Severe granulocytopenia resulting in increased susceptibility to infection may occur. Granulocyte counts should be > 1,500 cells/mm³. Prior to the administration of Vinorelbine Tartrate, the dosage should be adjusted according to complete blood counts with differentials obtained on the day of treatment.
Caution: lt is extremely important that the intravenous needle or catheter be properly positioned before Vinorelbine Tartrate is injected. Administration of Vinorelbine Tartrate may result in extravasation causing rarely local tissue necrosis and/or thrombophlebitis.

Vinorelbine Tartrate must only be administered by the intravenous route.
lt is extremely important that the intravenous needle or catheter be properly positioned before any Vinorelbine Tartrate is injected. Leakage into surrounding tissue during intravenous administration of Vinorelbine Tartrate may cause considerable irritation, local tissue necrosis, and/or thrombophlebitis. If extravasations occur, the injection should be discontinued immediately, and any remaining of the dose should then be introduced into another vein. Since there are no established guidelines for the treatment of extravasations injuries with Vinorelbine, institutional guidelines may be used. The ONS chemotherapy guidelines provide additional recommendations for the prevention of extravasations injuries.
Treatment should be undertaken with close haematological monitoring (determination of haemoglobin level and number of leukocytes, granulocytes and platelets before each new injection); if the neutrophil count is below 1,500/mm³ and/or the platelet count is below 75,000/mm³, then the treatment should be delayed until recovery.
If there is severe hepatic impairment the dose should be reduced.
In case of renal impairment, no dose modification is necessary because of the low level of renal excretion.
Vinorelbine Tartrate should not be given concomitantly with radiotherapy if the treatment field includes the liver.
All contact with the eyes should be strictly avoided: risk of severe irritation and even corneal ulceration if the drug is sprayed under pressure. Immediate abundant rinsing of the eye with normal saline solution is recommended in case of contact.
Special core should be taken for patients with history of ischemic cardiac disease.
lf patients present signs or symptoms suggestive of infection, a prompt investigation should be carried out.
Patients treated with Vinorelbine Tartrate should be frequently monitored for myelosuppression both during and after therapy.
Reported cases of interstitial pulmonary changes and ARDS occurred in patients treated with Vinorelbine Tartrate, in combination with Mitomycin. The meantime to onset of these symptoms after Vinorelbine Tartrate administration was 1 week (range 3 to 8 days). Patients with alterations in their baseline pulmonary symptoms or with new onset of dyspnoea, cough, hypoxia, or other symptoms should be evaluated promptly.
Vinorelbine Tartrate has been reported to cause severe constipation (e.g. grade 3-4) such as paralytic ileus.
If severe adverse events occur, Vinorelbine Tartrate should be reduced in dosage or discontinued and appropriate corrective measures taken. Reinstitution of therapy with Vinorelbine Tartrate should be carried out with caution and alertness as to possible recurrence of toxicity.
Vinorelbine Tartrate 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 the effects of previous chemotherapy.
Patients with a prior history or pre-existing neuropathy, regardless of etiology, should be monitored for new or worsening signs and symptoms of neuropathy while receiving Vinorelbine Tartrate.
Effects on ability to drive and use machines: Vinorelbine Tartrate is unlikely to impair the ability of patients to drive or to operate machinery. Nevertheless patients should be advised that their ability to drive and operate machinery may be affected.

Haematological tolerance: The limiting toxicity is bone marrow depression resulting mainly neutropenia which is reversible within 5 to 7 days and non cumulative over time; neutrophil nadir occurs usually between 7 to 14 days after administration.
Anaemia and thrombocytopenia may occur, but are seldom severe.
Neurological tolerance: Mild to moderate peripheral neuropathy manifested by paresthesia and hyperesthesia were the most frequently reported neurologic toxicities. The development of severe peripheral neuropathy was infrequent and generally reversible.
Gastrointestinal tolerance: Constipation is the main symptom which rarely progresses to paralytic ileus. Treatment may be resumed after recovery of normal bowel mobility. Stomatitis and diarrhea usually mild to moderate may occur.
Nausea and vomiting may occur. The incidence of severe effects is low. Antiemetic therapy may reduce their occurrence.
Rare cases of pancreatitis have been reported.
Liver: Transient elevations of liver function tests without clinical symptoms were reported.
Skin: Alopecia usually mild in nature may occur.
Rarely Vinorelbine Tartrate may produce generalized cutaneous reactions.
Respiratory system: As with other Vinca Alkoloid, Vinorelbine Tartrate may occasionally produce acute shortness of breath, dyspnea and severe bronchospasm. These adverse events may require treatment with supplemental oxygen, bronchodilators, and/or corticosteroids, particularly when there is pre-existing pulmonary dysfunction.
Rare cases of interstitial pneumopathy have been reported in patients treated with Vinorelbine Tartrate in combination with mitomycin.
Cardiovascular system: There have been rare reports of ischemic cardiac disease (angina pectoris, myocardial infarction).
Most reports of chest pain were in patients who had either a history of cardiovascular disease or tumor within the chest.
Local reaction: Like with other Vinca Alkaloid, Vinorelbine Tartrate is a moderate vesicant. lnjection site reactions including erythema, vein discoloration, burning pain and local phlebitis.
Chemical phlebitis along the vein proximal to the site of injection. Bolus injection followed by abundant flushing of the vein can limit this effect. Insertion of a central venous line may be necessary.
Other undesirable effects: Fever, fatigue, arthralgia including jaw pain, myalgia, chest pain and pain at the tumor site have been experienced by patients receiving Vinorelbine Tartrate therapy.
Any extravasations may induce local reactions which rarely progress to necrosis (see Warnings and Precautions).
Rare cases of severe hyponatraemia have been reported.

Acute pulmonary reaction have been reported with Vinorelbine Tartrate and other anticancer Vinca Alkaloids use in conjunction with Mitomycin. Although the pharmacokinetics of Vinorelbine Tartrate are not influenced by the concurrent administration of Cisplatin, the incidence of granulocytopenia with Vinorelbine Tartrate used in combination with Cisplatin is significantly higher than with single agent Vinorelbine Tartrate. Patients who receive Vinorelbine Tartrate and Paclitaxel, either concomitantly or sequentially, should be monitored for signs and symptoms of neuropathy. Administration of Vinorelbine Tartrate to patients with prior or concomitant radiation therapy may result in radiosensitizing effect.
Based on the available limited information, it is conceivable that interaction may occur with other drugs which are metabolised via the cytochrome CYP3A4. Concurrent administration of Vinorelbine with an inhibitor of this metabolic pathway may cause an earlier onset and/or increased severity of side effects.

Instructions for Use/Handling: Handling guidelines: The preparation and administration of Vinorelbine Tartrate should be carried out by trained staff; suitable eye protection, disposable gloves, face mask and disposable apron should be worn. Eventual spillage or leakage should be mopped up.
As with other toxic compounds, caution should be exercised in handling and preparing the solution of VinorelbineTartrate. Skin reactions may occur with accidental exposure. The use of gloves is recommended. If the solution of Vinorelbine Tartrate contact the skin or mucosa, immediately wash the skin or mucosa thoroughly with soap and water. It is recommended to infuse Vinorelbine Tartrate over 6-10 minutes after dilution in 20-50 mL of normal saline or 5% Dextrose solution. After administration, the vein should be thoroughly flushed with at least 250 mL of isotonic solution.
Vinorelbine Tartrate must be given strictly intravenously: it is very important to make sure that the cannula is accurately placed in the vein before starting to infuse Vinorelbine Tartrate. If Vinorelbine Tartrate extravasates into the surrounding tissue during the administration, considerable local irritation may occur. In this case, the administration should be stopped, the vein flushed with normal saline and the remaining dose administered in another vein.
In case of extravasations, to reduce the risk of phlebitis, I.V glucocorticoids could be administered immediately.

Store at temperature 2°C - 8°C. Away from light. Do not freeze.
RELUBIN is a clear colourless to pale yellow solution. These slight differences in colour do not affect the quality of the product.
RELUBIN must not be used after the expiry date stated on the package.
RELUBIN should not be diluted in alkaline solutions (risk of precipitation). In case of polychemotherapy, RELUBIN should not be mixed with other agents.
RELUBIN is not adsorbed or affected by either PVC or clear neutral glass.
Storage after dilution: After diluted in Dextrose 5% or Normal Saline, store the medicine at temperature of 22°C - 25°C. The product is stable to be used within 24 hours after diluted.

Cytotoxic Chemotherapy

L01CA04 - vinorelbine ; Belongs to the class of plant alkaloids and other natural products, vinca alkaloids and analogues. Used in the treatment of cancer.

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