Navelbine, 20 mg capsules

How to take, the dosage

Navelbine is used both as monotherapy and in combination with other anticancer drugs. When choosing the dose and mode of administration in each individual case the special literature should be consulted.

Navelbin concentrate is administered strictly intravenously as a 6-10 minute infusion.

The capsules are taken orally whole with water without chewing or mashing them in the mouth.

In monotherapy, the usual dose of the drug for IV administration is 25-30 mg/m2 of body surface once a week. Navelbine is diluted in 0.9% sodium chloride solution or 5% dextrose solution to a concentration of 1.0-2.0 mg/ml (50 ml on average). After the drug is injected, the vein should be flushed with at least 250 ml of additional 0.9% sodium chloride solution or 5% dextrose solution.

In patients with a body surface area of 2 m2 or more, a single dose of Navelbine for IV administration should not exceed 60 mg.

The recommended starting single dose of Navelbine for oral administration is 60 mg/m2 body surface area once a week. After the third dose, the dose should be increased to 80 mg/m2.

A dose increase from 60 mg/m2 to 80 mg/m2 may be implemented if there has been no grade 4 neutropenia (less than 500/µL) for three weeks of Navelbine administration or there has been one episode of grade 3 neutropenia (less than 1000/µL but greater than 500/µL) and the neutrophil count before the next intake is at least 1500/µL.

The minimum neutrophil count (cells/μL) recorded in the first 3 weeks of oral administration of Navelbine at a dose of 60 mg/m2 per week

The minimum neutrophil count (cells/μL) recorded in the first 3 weeks of oral administration of Navelbine at a dose of 60 mg/m2 per week

>1000

≥ 500 and

≥ 500 and

Recommended dose starting on the 4th dose

80 mg/m2

/p>

60 mg/m2

If a dose of 80 mg/m2 of Navelbin causes grade 4 neutropenia (less than 500/mL) or 2 cases of grade 3 neutropenia (less than 1000/mL but more than 500/mL), the dose of Navelbin should be reduced from 80 to 60 mg/m2 per week at the next 3 doses.

The minimum neutrophil count (cells/μL) recorded in the first 3 weeks of oral administration of Navelbine at a dose of 80 mg/m2 per week

>1000

≥ 500 and

≥ 500 and

< 500

Recommended dose starting on the 4th dose

80 mg/m2

60 mg/m2

/p>

If the neutrophil count has not decreased below 500/mL, or more than one decrease in neutrophil count between 500 and 1000/mL has not been observed over three weeks of a 60 mg/m2 dose of Navelbine (as recommended above), the dose can be increased again from 60 to 80 mg/m2 per week.

The recommended oral doses of Navelbine as a function of patient body surface area (BSA) are shown in the following table.

Body surface area (m2)

60 mg/m2

80 mg/m2

Dose (mg) per week

0.95 to 1.0

60

1.05 to 1.14

70

1.15 to 1.24

70

1.25 to 1.34

80

1.35 to 1.44

80

1.44 to 1.54

90

1.55 to 1.64

p> 100

1.65 to 1.74

100

1.75 to 1.84

110/p>

1.85 to 1.94

110

1.95 or more

120

For patients with a BSA of 2 m2 or more, the total single oral dose of Navelbine should never exceed 120 mg per week at a dose of 60 mg/m2 and 160 mg per week at a dose of 80 mg/m2.

The oral administration of Navelbine at doses of 60 mg/m2 and 80 mg/m2 is consistent with the intravenous administration of Navelbine at doses of 25 mg/m2 and 30 mg/m2.

In polychemotherapy, the dose and frequency of administration of Navelbine (both IV and oral) depends on the specific antitumor therapy program.

If the neutrophil count is less than 1,500/μL or platelet count is less than 75,000/μL (IV) or less than 100,000/μL (oral), the next dose or oral administration of Navelbin should be delayed for 1 week. If 3 weekly injections or ingestions of Navelebin have to be withheld because of hematologic toxicity, it is recommended that Navelebin be discontinued.

In patients with severe hepatic impairment, Navelbine should be administered with caution, at a dose reduced by 33%.

The safety and effectiveness of Navelbine in children has not been studied.

Particular adjustments to the dosing regimen of Navelbine in the elderly are not necessary.

Interaction

When co-administered with other cytostatics there may be mutual exacerbation of side effects, primarily myelosuppression.

In co-administration with mitomycin C acute respiratory failure may occur.

In co-administration with paclitaxel the risk of neurotoxicity increases.

The use against a background of radiation therapy leads to radiosensitization. The use of Navelbine after radiation therapy may lead to the reappearance of radiation reactions.

The concomitant use of the drug with inducers and inhibitors of cytochrome P450 isoenzymes may lead to changes in pharmacokinetics of vinorelbine.

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Special Instructions

Treatment with Navelbine should be done under the supervision of a physician experienced in the use of antitumor drugs.

The dose of Navelbine should be reduced by 33% if liver function is severely impaired.

In case of impaired renal function, the patient’s condition should be monitored.

In case of signs of neurotoxicity of grade 2 or higher, the use of Navelbine should be discontinued. If dyspnea, cough, or hypoxia of unknown etiology occur, the patient should be evaluated to rule out pulmonary toxicity.

If extravasation occurs, the drug infusion should be stopped immediately and the remaining dose administered in another vein.

If nausea or vomiting occurs after taking Navelbine capsules, the same dose should not be taken again.

During and for at least three months after discontinuation of therapy, reliable contraceptive methods should be used.

If the active ingredient comes into contact with the oral cavity, it is recommended to rinse the mouth with water or any saline solution.

In case of contact of Navelbine with the eyes, they should be rinsed abundantly and thoroughly with water.

Because the drug contains sorbitol, Navelbine should not be used in patients with hereditary fructose intolerance.

Laboratory monitoring

The drug is monitored under close hematologic control, with the number of white blood cells, neutrophils, platelets and hemoglobin determined before each repeated injection or oral administration. In case the number of neutrophils is less than 1500/μl and/or the number of platelets is less than 75 000/μl (for intravenous injection) or less than 100 000/μl (for oral intake) the next dose of the preparation is delayed until the normalization of these parameters and the patient’s state is controlled simultaneously.

Contraindications

• Neutrophil count less than 1,500/µL;
• platelet count less than 75,000/µL (for IV administration) and less than 100,000/µL (for oral administration);
• severe hepatic insufficiency not related to the tumor process;
• requirement for continuous oxygen therapy in patients with a lung tumor;
• diseases and conditions resulting in reduced absorption from the GI tract (for oral administration);
• pregnancy;
• lactation (breastfeeding) period;
• high sensitivity to the drug and to other vincaalkaloids.

With caution: the drug is used in case of respiratory insufficiency, suppression of medullary hematopoiesis (including after previous chemotherapy or radiation therapy), constipation or bowel obstruction in anamnesis, neuropathy in anamnesis.

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Side effects

The following adverse events occurred more frequently than in isolated cases. The following criteria were used to assess the frequency of adverse events:

• very frequently ( > 1/10);
• often ( > 1/100,1/10);
• sometimes ( > 1/1000, 1/100);
• often ( > 1/10,000, 1/1000);
• extremely rarely (1/10,000).

With the hematopoietic system: very often – neutropenia, anemia, thrombocytopenia, accession of secondary infections against the background of inhibition of medullary hematopoiesis; often – fever (38°C) against the background of neutropenia; sometimes – sepsis, septicemia; extremely rare – complicated septicemia, in some cases leading to death. The lowest number of neutrophils is observed on days 7-10 from the start of therapy, recovery occurs in the next 5-7 days. No cumulation of hematotoxicity has been observed.

Peripheral nervous system disorders: very often – paresthesias, hyperesthesia, decrease or loss of deep tendon reflexes; often – weakness in legs; sometimes – severe paresthesias with sensory and motor symptoms, usually of reversible nature.

The cardiovascular system: sometimes – increase or decrease of BP, hot flashes and coldness of the extremities; rarely – CHD (angina, myocardial infarction), marked hypotension, collapse; very rarely – tachycardia, palpitation, cardiac pacing.

Respiratory system: sometimes – dyspnea, bronchospasm; rarely – interstitial pneumonia (in combined therapy with mitomycin), acute respiratory distress syndrome.

Digestive system disorders: very frequently – nausea, vomiting, stomatitis, constipation, diarrhea, transient increase of liver function tests (ALT, ACT); rarely – pancreatitis, increased bilirubin level, paresis of bowels.

Intrinsic system disorders: rarely – anaphylactic shock and angioedema.

Dermatological reactions: often – alopecia; rarely – skin rash.

Local reactions: often – pain/burning or redness at the injection site, discoloration of the vein, phlebitis; in extravasation – cellulitis; possibly – necrosis of the surrounding tissues.

Others: often – fatigue, myalgia, arthralgia, fever, pain of different localization, including chest pain, pain in the lower jaw and in the area of tumors; rarely – hyponatremia; very rare – hemorrhagic cystitis and syndrome of inadequate secretion of ADH.

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Overdose

Symptoms: suppression of bone marrow function, neurotoxic reactions.

Treatment: in case of overdose the patient should be hospitalized; symptomatic therapy with careful monitoring of the functions of vital organs is carried out. A specific antidote is not known.

Pregnancy use

Navelbin is contraindicated in pregnancy and during lactation (breastfeeding).

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