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Information for Healthcare Professionals

Revised: 17 June 2015

Data Sheet

NAVELBINE® ORAL

Vinorelbine 20 mg and 30 mg soft capsules.

Description

Vinorelbine tartrate is a semi-synthetic vinca alkaloid with antitumor activity. The chemical name is 3',4'-didehydro-4'-deoxy-C'-norvincaleukoblastine [ R-(R*,R*) -2,3 dihydroxybutanedioate (1:2)(salt)].

Vinorelbine tartrate has the following structure:

Vinorelbine chemical structure.

CAS No: 125317-39-7

Vinorelbine tartrate is a white to yellow or light brown amorphous powder with the molecular formula C45H54N4O8.2C4H6O6 and molecular weight of 1079.12. The aqueous solubility is > 1000 mg/mL in distilled water.

NAVELBINE® soft capsules also contains the following excipients: ethanol, water - purified, glycerol, macrogol 400, gelatin, sorbitol, sorbitan, medium-chain triglycerides, phosphatidyl choline, glycerides, hypromellose, propylene glycol, edible printing ink E120, titanium dixoide, iron oxide yellow CI77492 and / or iron oxide red CI77491.

Pharmacology

Vinorelbine is an antineoplastic drug. It is a semi-synthetic member of the vinca alkaloid family that interferes with microtubule assembly. The vinca alkaloids are structurally similar compounds comprised of two multiringed units, vindoline and catharanthine. Unlike other vinca alkaloids, the catharanthine unit is the site of structural modification for vinorelbine. The antitumor activity of vinorelbine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. In intact tectal plates from mouse embryos, vinorelbine, vincristine, and vinblastine inhibited mitotic microtubule formation at the same concentration (2µM), including a blockade of cells at metaphase. Vincristine produced depolymerisation of axonal tubules at 5µM, but vinblastine and vinorelbine did not have this effect until concentrations of 30µM and 40µM respectively. These data suggest relative selectivity of vinorelbine for mitotic microtubules.

Pharmacokinetics

Following oral administration, NAVELBINE® is promptly absorbed and the Tmax is reached within 1.5 to 3 hours with a blood concentration peak (Cmax) of approximately 130 ng/mL after dosing at 80 mg/m². The absolute bioavailability is about 40% and simultaneous intake of a low fat standard meal does not modify the area-under the concentration-time curve (AUC). The effect of a high fat meal on absorption has not been studied.

NAVELBINE® Oral 60 and 80 mg/m² leads to a comparable AUC to that obtained from 25 and 30 mg/m² of the IV formulation respectively. Interindividual variability of the AUC is similar after administration by both the IV and oral routes. There is a proportional increase between the AUC and dose. The mean pharmacokinetic parameters were evaluated in blood. After intravenous administration, the terminal half-life averaged 38 hours. Blood clearance was high, approached liver blood flow and averaged 0.72 L/hr/kg (range: 0.32 - 1.26 L/hr/kg), while steady state volume of distribution was large, averaged 21.2 L/kg (range: 7.5 - 39.7 L/kg), and indicated extensive tissue distribution.

Vinorelbine binds extensively to blood cells and especially platelets (70-80%), but less extansively (about 15%) to plasma proteins. There is a significant uptake of NAVELBINE® in lungs, as assessed by pulmonary surgical biopsies showing up to a 300 fold greater concentration than in serum. NAVELBINE® has not been detected in the central nervous system.

NAVELBINE® is mostly metabolised by the CYP 3A4 isoform of the cytochrome P450. All the metabolites have been identified, and none are active except 4-O-deacetylvinorelbine, which is the main metabolite in blood. No sulfo or glucurono conjugates are observed. Renal elimination is low (<20% of the dose) and consists mostly of the parent compound. Biliary excretion is the predominant elimination route of both metabolites and unchanged NAVELBINE®, which is the main recovered compound. The effect of renal dysfunction on NAVELBINE® disposition has not been assessed, however dose reduction in the presence of renal insufficiency is not indicated with NAVELBINE® due to its low renal elimination.

Vinorelbine is cleared from the circulation primarily by the liver, and therefore elevated blood concentrations may be expected in patients with hepatic impairment. In a Phase I pharmacokinetic study, 6 subjects with severe hepatic impairment were treated with 20 mg/m² intravenously. Plasma concentrations were elevated compared to historical data from patients with normal hepatic function. Vinorelbine is contraindicated in patients with severe hepatic insufficiency. There is limited experience in patients with mild or moderate hepatic impairment, however available data suggests that dose modification is not required. Haematological toxicity should be closely monitored.

A strong relationship was demonstrated between AUC and leucocyte or PMN decreases.

Clinical Trials:

NAVELBINE® IV:

Advanced breast cancer

Non-small cell lung cancer
The activity of vinorelbine was investigated in a series of phase II trials. The overall response rate to vinorelbine single agent in NSCLC patients ranged from 8% to 33% in previously untreated patients. In the two major phase II trials with more than 60 evaluable patients, the overall response rate was over 30% in chemotherapy-naive patients. The high activity of vinorelbine as single agent in non-small cell lung cancer which was observed in non-controlled phase II studies has also been confirmed in three randomised phase III trials. In one prospective randomised study with 216 stage IV patients, vinorelbine was compared to 5-fluorouracil with leucovorin (considered equivalent to best supportive care for the purposes of the study). The median survival time of patients who received vinorelbine was 30 weeks compared to 22 weeks for those on the 5-fluorouracil/leucovorin arm (log-rank p=0.03). The response rates were 12% for the vinorelbine arm and 3% for the fluorouracil/leucovorin arm.

The activity of vinorelbine in combination with cisplatin has been investigated in two randomised phase III trials in a total of 782 patients. In a two arm trial, vinorelbine was compared to vinorelbine with cisplatin. The overall response rate to vinorelbine as single agent was 16% while that of the combination vinorelbine/cisplatin was 43%. The median survival time for patients receiving vinorelbine as single agent was similar to that observed with vinorelbine and cisplatin.

In a large European clinical trial, 612 patients with Stage III or IV non-small cell lung cancer, no prior chemotherapy and WHO performance Status of 0, 1 or 2 were randomised to treatment with single-agent vinorelbine (30 mg/m²/week), vinorelbine (30 mg/m²/week) cisplatin (120 mg/m² days 1 and 29 then every 6 weeks), and vindesine (3 mg/m²/week for 7 weeks, then every second week) plus cisplatin (120 mg/m² days 1 and 29 then every 6 weeks). Vinorelbine plus cisplatin produced longer survival times than vindesine plus cisplatin (median survival 40 weeks vs 32 weeks, p=0.03). The median survival time for patients receiving single-agent vinorelbine was similar to that observed with vindesine plus cisplatin (31 weeks vs 32 weeks). The 1-year survival rates were 36% for vinorelbine plus cisplatin, 27% for vindesine plus cisplatin, and 30% for single-agent vinorelbine. The overall objective response rate (all partial responses) was significantly higher in patients treated with vinorelbine plus cisplatin (28%) than in those treated with vindesine plus cisplatin (19%, p=0.03) and in those treated with single-agent vinorelbine (14%, p<0.001). The response rates reported for vindesine plus cisplatin and single-agent vinorelbine were not significantly different. Significantly, less nausea, vomiting, alopecia, and neurotoxicity were observed in patients receiving single-agent vinorelbine compared to those receiving the combination of vindesine and cisplatin.

NAVELBINE® Oral

Oral vinorelbine has been developed as a line extension of the IV dosage form. Hence the primary objective of the clinical program was to demonstrate bioequivalence between the oral and intravenous formulations on the basis of pharmacokinetic studies. An oral dose of 80 mg/m² was demonstrated to correspond to 30 mg/m² of the IV formulation and 60 mg/m² orally to 25 mg/m² given by the IV route.

Subsequent phase II studies, were conducted to examine the efficacy and tolerance of oral vinorelbine

Non-small cell lung cancer
One randomised Phase II study with the recommended oral dose regimen was conducted, comparing oral and IV vinorelbine in patients with advanced or metastatic NSCLC who had not been previously treated with cytotoxic chemotherapy. Results are summarised in thefollowing table:

  Oral vinorelbine IV vinorelbine
Study I - CA 205    
No of subjects 77 38
Response rate (ITT population) 11.7% 10.5%
Response rate (Evaluable population) 14.1% 11.8%
Median duration of response 7.7 months 5.5 months
Median progression-free survival 3.3 months 2.1 months
Median Survival 9.4 months 7.9 months

In a multicentre, phase II study of 56 patients in combination with cisplatin 100 mg/m² (day 1 q 4 weeks), the weekly administration of vinorelbine (IV vinorelbine 25 mg/m² day 1, oral vinorelbine 60 mg/m² days 8, 15 and 22) produced a response rate of 30% for all registered patients and 33% for evaluable patients in the first line treatment of unresectable, localised or metastatic NSCLC. Median progression-free survival and survival were 5.5 and 8.9 months, respectively.

Indications

NAVELBINE® is indicated as a single agent or in combination for the treatment of non small cell lung cancer (NSCLC).

Contraindications

Known hypersensitivity to vinorelbine or other vinca alkaloids.

Disease significantly affecting absorption.

Previous significant surgical resection of stomach or small bowel.

Neutrophil counts < 1500 cells/mm³, or current or recent severe infection due to neutropenia (within 2 weeks).

Pregnancy.

Lactation.

Patients requiring long-term oxygen therapy.

Severe hepatic insufficiency.

Precautions

Administration

NAVELBINE® soft capsule should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. If the patient chews or sucks the capsule by mistake, rinse mouth with water or preferably a normal saline solution.

In the event of the capsule being cut or damaged, the liquid content is an irritant, and so may cause damage if in contact with skin, mucosa or eyes. Damaged capsules should not be swallowed and should be returned to the pharmacy or to the physician in order to be properly destroyed. If any contact occurs, immediate thorough washing with water or preferably with normal saline solution should be undertaken.

If vomiting occurs within a few hours of drug intake, administration of the dose should not be repeated. Prophylactic treatment with metoclopramide or oral antiemetics may reduce the incidence. It is recommended that the capsule be taken with food.

Myelosuppression

Neutropenia is dose-limiting. Complete blood counts with differentials should be performed and results reviewed prior to administering each dose of NAVELBINE®. Patients treated with NAVELBINE® should be frequently monitored for myelosuppression both during and after therapy. NAVELBINE® should not be administered to patients with neutrophil counts < 1500 cells/mm³.

Patients developing severe neutropenia should be monitored carefully for evidence of infection and/or fever. If patients present signs or symptoms suggestive of infection, a prompt investigation should be carried out. (See DOSAGE AND ADMINISTRATION for recommended dose adjustments for neutropenia).

NAVELBINE® 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 (see DOSAGE AND ADMINISTRATION).

During clinical trials where treatment was initiated at a weekly dose of 80 mg/m² (corresponding to an IV dose of 30 mg/m² in terms of systemic exposure), febrile neutropenia, in some cases fatal, was encountered in about 15% of patients. Therefore, it is recommended that the starting dose should be 60 mg/m² and increased to 80 mg/m² only if the dose is tolerated (see DOSAGE AND ADMINISTRATION).Laboratory tests

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 and reviewed on the day of treatment prior to each dose of NAVELBINE®. If the neutrophil count is below 1500 / mm³ and/or the platelet count is between 75,000 and 100,000 / mm³, then treatment should be delayed until recovery.

General

Most drug-related adverse events of NAVELBINE® are reversible. If severe adverse events occur, NAVELBINE® should be reduced in dosage or discontinued and appropriate corrective measures taken. Reinstitution of therapy with NAVELBINE® should be carried out with caution and alertness as to possible recurrence of toxicity.

Patients presenting with ischaemic cardiac disease should be carefully monitored (see ADVERSE REACTIONS).

Acute shortness of breath and severe bronchospasm have been reported infrequently along with rare cases of interstitial pneumopathy following the administration of NAVELBINE® and other vinca alkaloids, most commonly when the vinca alkaloid was used in combination with mitomycin. These adverse events may require treatment with supplemental oxygen, bronchodilators, and/or corticosteroids, particularly when there is a pre-existing pulmonary dysfunction.

Vinorelbine is contraindicated in patients with severe hepatic insufficiency. There is limited experience in patients with mild or moderate hepatic impairment, however available data suggest that dose modification is not required. Haematological toxicity should be closely monitored.NAVELBINE® should not be given concomitantly with radiotherapy if the treatment field includes the liver.

Because of the low level of renal excretion, no dose modification is necessary in patients with renal impairment.

Due to the presence of sorbitol, patients with the rare hereditary problem of fructose intolerance should not take this medicine

Carcinogenicity/Mutagenicity

Vinorelbine tartrate has been shown to affect chromosome number and possibly structure in vivo (polyploidy in bone marrow cells from Chinese hamsters and a positive micronucleus test in mice).

It was not mutagenic or cytotoxic in a reverse histidine mutation (Ames) test but showed mutagenic potential in a mouse forward mutation (TK locus) test. Carcinogenicity studies in mice and rats showed no tumourigenic activity at dose levels up to 2.4 mg/m² given by IV injection every two weeks for 18 months or two years respectively. However, the positive findings in genetic toxicity assays suggest that the drug may have carcinogenic potential at the higher dose level used in humans.

Effects on fertility

Adverse effects on the male reproductive system were observed in repeat-dose toxicity studies in animals, including decreased spermatogenesis in rats dosed twice weekly at 2.1 - 7.2 mg/m² for 13 weeks, reduced prostate/seminal vesicle secretion in rats dosed twice weekly at 3 mg/m² for 26 weeks, reduced testicular weight in mice dosed at 19 mg/m²/day for three 5-day cycles, and reduced epididymal weight in dogs dosed at 5 mg/m² for 26 weeks. Vinorelbine tartrate did not affect fertility when administered to male and female rats prior to and during mating; however, the doses used in these studies (9 mg/m² once weekly or up to 4.2 mg/m² at 3-day intervals) were lower than the human dose.

Use in pregnancy

Category D
NAVELBINE® may cause fetal harm if administered to a pregnant woman. When given every three days during organogenesis, vinorelbine tartrate has been shown to be teratogenic in rats and rabbits at doses of 3 and 7.7 mg/m² respectively. A single 9 mg/m² dose of vinorelbine tartrate caused embryonic deaths in mice. Doses causing adverse fetal effects in animals were lower than the human dose. There are no studies in pregnant women. If NAVELBINE® is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the foetus. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with NAVELBINE®.

Use in lactation

It is not known whether vinorelbine is excreted in milk of animals or humans. A study in rats showed that growth of the offspring was suppressed when vinorelbine tartrate was administered to lactating dams at 6 mg/m² every three days. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from NAVELBINE®, it is recommended that nursing be discontinued in women who are receiving therapy with NAVELBINE®.

Interaction with other drugs

Acute pulmonary reactions have been reported with NAVELBINE® and other vinca alkaloids used in conjunction with mitomycin. NAVELBINE® should be administered with caution in combination with mitomycin.

The combination of NAVELBINE® soft capsules and other drugs with known bone marrow toxicity is likely to exacerbate the myelosuppressive adverse effects.

In the absence of specific studies evaluating drug-drug interaction with warfarin, the patient should be cautiously monitored when vinorelbine is given in combination with warfarin.

Although the pharmacokinetics of vinorelbine are not influenced by the concurrent administration of cisplatin, the incidence of toxicities, specifically granulocytopenia, with the combination of NAVELBINE® and cisplatin is significantly higher than with single-agent NAVELBINE®.

In studies with rats, the anticoagulant effect of phenindione was potentiated when given in combination with high dose of vinorelbine (30 mg/m²/day for 4 consecutive days or 15 mg/m²/day for 5 consecutive days) but combination treatment with sodium valproate did not cause any increase in anticonvulsant activity.

Vinorelbine is metabolised by cytochrome CYP3A4. Although interaction studies have not been performed, it is expected that inhibitors of CYP3A4 such as ketoconazole, itraconazole, ritinovir etc, would result in elevated blood concentrations of vinorelbine. Inducers of CYP3A4 such as rifampicin and phenytoin may reduce concentrations of vinorelbine. Since the magnitude of the inducing or inhibiting effects is unknown, such drug combinations should be avoided.

Food

Simultaneous intake of a low fat standard meal does not modify exposure to vinorelbine.

Paediatric use

Safety and effectiveness have not been established.

Geriatric Use

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.

Adverse Reactions

The reported incidence of undesirable effects with NAVELBINE® Oral was determined from clinical studies in 210 patients.

Haematological

Neutropenia is the dose-limiting toxicity with NAVELBINE®. Neutropenia (Grade 1-2:

24%, Grade 3: 19%, Grade 4: 23.8%) was rapidly reversible and non-cumulative. Grade 4 neutropenia was associated with a fever over 38°C in 2.9% of patients. Further treatment may be given after recovery of the neutrophil count. Infections were observed in 15.2% of patients but were severe in 5.2%.

Anaemia was very common but usually mild to moderate (Grade 3: 4.3%, Grade 4: 0.5%). Thrombocytopenia may also occur but was seldom severe (Grade 1 to 2: 12.9%). Dose adjustments are required for haematologic toxicity (see DOSAGE AND ADMINISTRATION).

Neurological

Neurosensory disorders were generally limited to loss of deep tendon reflexes (Grades 1 to 2: 12.4%) and infrequently severe. One patient presented partially reversible grade 3 ataxia. Neuromotor disorders were seen in 10.0% of patients (Grade 3: 1.0%).

Neuroconstipation was seen in 11.3% of patients (Grades 1 to 2: 10%) and rarely progressed to paralytic ileus (1.4%). One episode of fatal paralytic ileus was reported. Use of prescription laxatives may be appropriate in patients with prior history of constipation and/or who received concomitant treatment with opioid analgesics.

Mild to moderate peripheral neuropathy manifested by paraesthesia and loss of deep tendon reflexes (Grade 3: 2.5%, Grade 4: 0.2%) and hyperesthesia have been reported with IV administration. After prolonged treatment, weakness of the lower extremities has also been reported. The effects are dose dependent but usually reversible when treatment is discontinued.

Gastrointestinal

Gastrointestinal adverse events occur more commonly with oral vinorelbine than with intravenous administration. Gastrointestinal adverse events reported included: nausea (Grades 1 to 2: 70.5%, Grade 3: 8.6%, Grade 4: 0.5%), vomiting (Grades 1 to 2: 52.9%, Grade 3: 4.3%, Grade 4: 3.3%), diarrhoea (Grades 1 to 2: 41.9%, Grade 3: 2.9%, Grade 4: 2.4%), and anorexia (Grades 1 to 2: 26.7%, Grade 3: 4.8%, Grade 4: 1.0%). Concomitant supportive treatment with metoclopramide or 5HT3 antagonists may reduce the occurrence of nausea and vomiting.

Stomatitis usually mild to moderate occurred (Grades 1-2: 8.7%). Oesophagitis was seen in 4.8% of patients (Grade 3: 0.5%). Pancreatitis has been reported very rarely when vinorelbine is given intravenously.

Other

Fatigue (Grades 1-2: 19.5%, Grade 3: 6.7%), fever (Grades 1-2: 12.4%), arthralgia including jaw pain, myalgia (Grades 1-2: 9.0%), pain including pain at the tumour site (Grades 1-2: 5.2%) have been experienced by patients receiving NAVELBINE® Oral. Haemorrhagic cystitis and the syndrome of inappropriate ADH secretions were each reported in < 1% of patients given Navelbine® IV. Rare cases of severe hyponatraemia have been reported with Navelbine® IV.

In addition, it cannot be ruled out that the following effects may also be experienced with use of NAVELBINE® Oral, as they have been observed with intravenous administration, and with other vinca alkaloids.

Cardiovascular

There have been rare reports of ischemic cardiac disease (angina pectoris, myocardial infarction). In very rare cases, cardiac failure and pulmonary oedema have been reported during treatment with Navelbine® IV, however a causal relationship has not been established.

Hepatic

Transient elevations of liver enzymes were reported without clinical symptoms.

Respiratory

As with other vinca alkaloids, the intravenous administration of NAVELBINE® has been associated with dyspnea, bronchospasm and rare cases of interstitial pneumopathy in particular in patients treated with NAVELBINE® in combination with mitomycin.

Dermatological

Alopecia is usually mild (Grades 1-2: 27.1%) and may appear progressively with extended courses of treatment. Rarely vinca alkaloids may produce generalised cutaneous reactions.

Adverse Reactions from post-marketing surveillance

Frequencies are defined as: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1,000, <1/100), rare (>1/10,000, <1/1,000), very rare (<1/10,000).

System organ class
(MedDRA classification)
Very common
(>10%)
Common
(>1% and ≤10%)
Uncommon
(>0.1% and ≤1%)
Blood and lymphatic system disorders Neutropenia
(grades 1 to 4)
Anaemia
(grades 1 to 4)
Thrombocytopenia (grades 1 to 2)
Anaemia (grade 3) Anaemia (grade 4)
Gastrointestinal disorders Nausea
(grades 1 to 2)
Vomiting
(grades 1 to 2)
Diarrhoea
(grades 1 to 2)
Anorexia
(grades 1 to 2)
Nausea (grade 3)
Vomiting
(grades 3 to 4)
Stomatitis
(grades 1 to 2)
Diarrhoea
(grades 3 to 4)
Oesophagitis
(grades 1 to 2)
Anorexia (grade 3)
Nausea (grade 4)
Oesophagitis
(grade 3)
Anorexia (grade 4)
Peripheral autonomic and central nervous system disorders Loss of Tendon reflexes
(grades 1 to 2)
Neuromotor disorders (grades 1 to 2)
Neuro-comstipation (grades 1 to 2)
Paralytic ileus
Neuromotor disorders (grade 3)
Ataxia (grade 3)
Skin and subcutaneous tissue disorders Alopecia
(grades 1 to 2)
   
General disorders and administration site conditions Fatigue
(grades 1 to 2)
Fever (grades 1 to 2)
Fatigue (grade 3)
Pain (grades 1 to 2)
 
Musculoskeletal and connective tissue disorders   Arthralgia
(grades 1 to 2)
Myalgia
(grades 1 to 2)

Dosage and Administration

NAVELBINE® soft capsules must be given strictly via the oral route. They should be swallowed whole with water and should not be chewed or sucked. It is recommended that the capsule be taken with food.

Dosage in adults

Single agent
The recommended regimen is:

Dose modifications according to haematological status

If the neutrophil count is below 1500 / mm³ and/or the platelet count is between 75,000 and 100,000 / mm³, then treatment should be delayed until recovery.

Neutrophil count during the first 3 administrations at 60 mg/m²/week Neutrophils
>1000
Neutrophils
≥ 500 and < 1000
(1 episode)
Neutrophils
≥ 500 and < 1000
(2 episodes)
Neutrophils
<500
Recommended dose for 4th and subsequent administrations 80 80 60 60


For any administration planned at the 80 mg/m²/week dose, if the neutrophil count falls below 500 / mm³, the dose must be delayed until recovery and reduced from 80 to 60 mg/m² per week during the 3 subsequent administrations.

Neutrophil count beyond the 4th administration at 80 mg/m²/week Neutrophils
>1000
Neutrophils
≥ 500 and < 1000 (1 episode)
Neutrophils
≥ 500 and < 1000 (2 episodes)
Neutrophils
<500
Recommended dose for the next administration 80 60


It is possible to re-escalate the dose from 60 to 80 mg/m²/week if the neutrophil count does not drop below 500/mm³, or more than once between 500 and 1000 / mm³, during the three administrations given at the 60 mg/m² dose.

Dose modifications for hepatic insufficiency

Vinorelbine is contraindicated in patients with severe hepatic insufficiency. There is limited experience in patients with mild or moderate hepatic impairment, however available data suggests that dose modification is not required. Haematological toxicity should be closely monitored.

Combination chemotherapy

The use of oral vinorelbine in combination regimens has not been extensively studied. However, based on pharmacokinetic studies, the oral dose of 80 mg/m² was demonstrated to correspond to 30 mg/m² of the IV form and 60 mg/m² orally to 25 mg/m² IV.

In combination regimens, intravenous vinorelbine dosing may be replaced with oral vinorelbine therapy. The recommended dose is 60 mg/m². The safety of higher doses of oral vinorelbine (eg 80 mg/m²) in combination regimens has not been established.

The following table gives the dose required for appropriate ranges of body surface area (BSA).

  60 mg/m² 80 mg/m²
BSA (m²) Dose (mg) Dose (mg)
0.95 to 1 60 80
1.05 to 1.14 70 90
1.15 to 1.24 70 100
1.25 to 1.34 80 100
1.35 to 1.44 80 110
1.45 to 1.54 90 120
1.55 to 1.64 100 130
1.65 to 1.74 100 140
1.75 to 1.84 110 140
1.85 to 1.94 110 150
≥ 1.95 120 160


Even patients with a body surface area (BSA) ≥ 2 m² the dose should never exceed 120 mg per week at 60 mg/m² and 160 mg per week at 80 mg/m².

Procedures for proper handling and disposal of anticancer drugs should be used. Several guidelines on this subject have been published.

Overdose

There is no known antidote for overdoses of NAVELBINE®. No case of overdosage has been reported with NAVELBINE® oral, however the primary anticipated complications of overdosage would consist of bone marrow suppression and peripheral neurotoxicity. If overdosage occurs, general supportive measures together with appropriate blood transfusions and antibiotics should be instituted as deemed necessary by the physician.

Presentation

20 mg soft capsule: light brown soft capsule printed N20,

30 mg soft capsule: pink soft capsule printed N30,

Pack size: 1 capsule

Shelf life

Store at 2 to 8° C (Refrigerate. Do not freeze) in the original container.

Protect from light.

Medicine Classification

Prescription Medicine

Name and Address

New Zealand Medical & Scientific Limited
PO Box 24-138,
Royal Oak
AUCKLAND

Date of Preparation

6 November 2006

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