Navoban

Quite a few diseases or therapeutic methods of treatment have such negative manifestations as vomiting and nausea in their symptoms. In this case, the patient experiences both physical and psychological discomfort. The serotonergic, antiemetic drug Navoban was developed and introduced to the pharmacological market by the leading international pharmaceutical company Novartis, which has its own production facilities in Switzerland and Spain.

Probably, at least once, every person has encountered such symptoms as vomiting and nausea, what discomfort it brings. And if we consider that these symptoms appear against the background of antitumor chemotherapy, when the patient already suffers multiple sufferings, their appearance is especially undesirable. In such a situation, drugs designed to relieve these side effects of anticancer therapy become extremely relevant. And one of such drugs is Navoban - a highly effective antiemetic drug.

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Indications Navoban

The active substance of Navoban is the chemical compound tropisetron, whose pharmacodynamic and pharmacokinetic characteristics provide the basis for determining the indications for the use of Navoban.

• Preventive measures to prevent the occurrence of nausea and vomiting reflexes, which invariably arise as a result of antitumor chemotherapy.
• Relief of similar symptoms that appear after surgical treatment.

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Release form

The antiemetic, serotonergic drug is presented on the pharmacological market in the form of a solution used for intravenous injections. The content of the active compound tropisetron hydrochloride in the solution is 1 mg. Ampoules with a dosage of 2 ml and 5 ml are produced.

The second form of release is capsules with a capacity of 5 mg, the released packages of Navoban contain five units of this capacity.

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Pharmacodynamics

The main focus of Navoban is its antiemetic effect. Hence the pharmacodynamics of Navoban, selected by pharmacists in such a way that it meets the necessary requirements. Surgical treatment and the use of some antitumor drugs during chemotherapy can provoke the removal of serotonin (5-HT) from enterochromaffin-like cells, which are located in the mucous tissues of the gastrointestinal tract. This factor initiates a signal that manifests itself in increased nausea and a reflex vomiting reaction.

The basic chemical compound tropisetron is a highly selective (i.e., targeted), potent substance that weakens the action of a subclass of serotonin receptor - presynaptic 5-HT3 - chemoreceptors. These protein molecules are located in the central nervous system (CNS) and on peripheral neurons. It is they, when excited, that send a signal to the area postrema (the hypothalamus) and provoke the vomiting reflex.

Navoban very effectively blocks such signals, which is the basis of the action of the antiemetic manifestation of the active substance. The duration of physical and chemical stability of Novoban is determined to be 24 hours, which makes it possible to introduce it into the body once a day. The use of the drug in question in treatment protocols does not cause extrapyramidal side effects.

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Pharmacokinetics

The active substance of the antiemetic drug is almost completely absorbed from the gastrointestinal tract. Its component exceeds 96%. On average, about twenty minutes pass for half of Navoban to be absorbed by the mucous membrane. The maximum amount of the active chemical compound tropisetron (C _max ) in the blood plasma is achieved after three hours (on average).
Pharmacokinetics Navoban when it is associated with blood protein shows about 71% of the compound, in most cases, the interaction occurs with such a protein as alpha1-glycoprotein. In many ways, the bioavailability of tropisetron is determined by the amount of the drug introduced into the patient's body. About 60% of bioavailability is provided by the intake of 5 mg of Navoban, if the dose is increased to 45 mg, then the indicator tends to 100%.

It is noted that the pharmacokinetics of Navoban in children is similar to the corresponding characteristics of adult patients. Tropisetron is metabolized into glucuronide or sulfates and excreted from the body through the urinary tract together with urine and bile. A small fraction (about 20%) leaves the patient's body together with feces.

The activity of the active substance derivatives in relation to 5-HT3 receptors is significantly reduced. As a result, the metabolites do not participate in the pharmacological processes of the drug.

In case of repeated daily administration of Navoban in doses higher than 10 mg, oversaturation of the liver enzyme system, which takes an active part in the metabolism of tropisetron, may be observed. Such an action can provoke an increase in the quantitative component of the active substance in the blood. However, even in patients with weak metabolic processes (in case of administration of such doses of the drug), there is no increase in the concentration of tropisetron in the serum, more than the permissible level of tolerated indicators. Therefore, if necessary, it is quite safe to prescribe Navoban 5 mg, taken once a day for six days. In this case, the accumulation of the active substance in the patient's blood does not reach critical values.

The half-life of the drug and its metabolites (T1/2) in patients with high metabolic activity is approximately eight hours. In individuals with low metabolic activity of tropisetron, this indicator can extend to 45 hours.

The total rate of elimination of tropisetron and its metabolites is equal to 1 l/min on average. At the same time, renal clearance during utilization takes only 10% of this factor. If the patient has a weak indicator of metabolism of the active substance, then its total clearance drops to 0.1 to 0.2 l/min, while the percentage component of renal excretion of the product remains unchanged. A decrease in the extrarenal method of excretion of metabolic products contributes to an increase in the half-life by approximately four to five times. In this case, the area on the concentration-time diagram (AUC), located below the curve, increases five to seven times. The maximum concentration of the active drug (C _max ) in the blood of such a patient and the quantitative distribution of the product do not deviate from the parameters shown by patients with a high level of metabolism of the active substance Navoban. The difference can be observed in the amount of unmetabolized tropisetron excreted by the body with urine. In patients with low metabolic rate it is higher.

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Dosing and administration

Special precautions should be taken if the patient has uncontrolled hypertension. Persons who are professionally associated with work on potentially dangerous mechanisms or driving vehicles should take into account that taking Navoban dulls attention and reduces reaction speed.

The method of administration and dosage vary depending on the direction of therapy:

For preventive measures aimed at relieving nausea and vomiting caused by anti-cancer treatment, therapy lasts six days.

In case of adult patients, the daily dose of the drug administered is 5 mg. The schedule of administration: on the first day of treatment, immediately before the course of chemotherapy, Navoban is administered intravenously. The next five days, the drug is administered orally, one capsule at a time.

For teenagers and children over two years of age, the daily dosage is calculated using the formula 0.2 mg per kilogram of the child's weight, but the resulting amount should not exceed 5 mg. The schedule of administration is similar to the sequence of administration for an adult patient: the first day - intravenously, the next five orally: open the ampoule and add its contents to orange juice or some other natural drink.

When preventing or stopping vomiting and nausea as a reaction after surgery, the amount of the drug administered is determined by a dosage of 2 mg, administered intravenously, shortly before the use of anesthesia. Doctors note good tolerance of tropisetron by children over two years of age.

Navoban should be administered slowly (the required volume as an infusion should be administered over at least one minute). It is advisable to take the medicine in capsule form in the morning, approximately one hour before meals. Drink plenty of liquid.

If the therapeutic effect does not occur during treatment with tropisetron, it is worth prescribing parallel administration of dexamethasone to obtain the desired result.

The method of administration and dosage for patients of retirement age are not adjusted.

To obtain the solution required for intravenous therapy, it must be diluted with one of the following drugs:

• 5% dextrose solution.
• 0.9% sodium chloride solution.
• Ringer's solution.
• 0.3% potassium chloride solution at a concentration of 1 mg/20 ml.
• 10% mannitol solution.

It should be noted that in individuals suffering from arterial hypertension before treatment, the introduction of Navoban in an amount exceeding the therapeutic dosage (more than 10 mg) may provoke a further increase in pressure. In this case, constant monitoring of the patient's blood pressure by the attending physician is necessary.

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Use Navoban during pregnancy

The pharmacokinetics and pharmacodynamics of the drug do not allow the use of Navoban during pregnancy. An exception may be a situation when an abortion is planned - termination of pregnancy at an early stage. If, according to medical indications, the necessary course of treatment falls during the period of breastfeeding of a newborn baby, breastfeeding must be stopped.

Contraindications

When Navoban is indicated for inclusion in the treatment schedule, it is worth knowing the contraindications to the use of Navoban:

• Individual intolerance of the patient's body to tropisetron and other 5-HT3 receptor antagonists.
• Hypersensitivity to other components of the drug.
• Children under two years of age.
• Time of bearing a baby.
• The period of breastfeeding newborns.
• Particular caution should be exercised when prescribing Navoban to patients with pathological abnormalities in the functioning of the heart (rhythm or conduction disturbances).
• Use with caution in patients who are scheduled to include beta-blockers and antiarrhythmic drugs in their treatment protocol.

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Side effects Navoban

In case of using the drug in question in standard therapeutic doses, side effects of Navoban are observed quite a limited number of times. With an increase in the amount of the administered drug to 2 mg, and especially a dosage of 5 mg Navoban can cause some side effects in the patient's body.

• Painful symptoms may appear in the abdomen and head.
• Various manifestations of allergies:

• Hyperemia of the skin.
• Itching.
• Skin rashes.

• Fainting or pre-fainting condition.
• There is a disruption in the functioning of the intestines:

• Constipation.
• Diarrhea.

• Dizziness may occur.
• Decreased overall vitality, weakness throughout the body.
• Isolated cases of circulatory shock and collapse were recorded.
• Heart failure.
• A single type I hypersensitivity reaction occurred:

• Generalized urticaria.
• Heaviness behind the chest.
• A feeling of blood rushing to the skin of the face.
• A sudden attack of bronchospasm with its acute manifestation.
• Shortness of breath.
• A sharp drop in blood pressure.

But the unambiguous connection of these manifestations with the intake of Navoban has not been confirmed to date, and the causes of these phenomena have not been clarified. Some manifestations of these symptoms could be the consequences of other diseases in the patient's medical history, or concomitant therapy drugs.

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Overdose

If the patient has been repeatedly administered a large amount of tropisetron, an overdose of the drug may be observed, expressed by visual hallucinations. If the patient has a history of previous persistent high blood pressure (arterial hypertension), a rapid increase in blood pressure is observed.

In this case, symptomatic therapy, constant monitoring of the general condition of the patient and the functioning of all vital organs of the patient are necessary.

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Interactions with other drugs

Based on the fact that the basic component of the drug in question is the tropisetron component, the interactions of Navoban with other drugs directly depend on the pharmadynamic and pharmakinetic characteristics of this particular chemical compound.

Inhibitors of the cytochrome P450 enzyme system do not have any significant effect on the dynamic parameters of tropisetron. Therefore, it is not necessary to adjust the administered amount of one or the other drug. Global studies of the interaction of the active substance Navoban with anesthetic drugs have not been conducted.

Parallel use of the drug in question with rifampicin significantly reduces the quantitative component of tropisetron in the blood. A similar situation is with other drugs that stimulate the liver to produce enzymes (for example, with phenobarbital). In this situation, the doctor looks at the patient's metabolic rate. If it is high, the amount of Navoban administered must be increased. If low metabolism is detected, the dose of the drug is not adjusted.

Cardiological monitoring of the combined use of tropisetron with drugs designed to increase the QT period on the cardiogram shows an even greater prolongation. At the same time, when with monotherapy of Navoban (administered in therapeutic quantities), an increase in QT was not observed. But in this situation, special caution is still necessary when using these two drugs in tandem.

It has been noted that the introduction of tropisetron into the patient’s body together with food products allows for an increase in the bioavailability of Navoban (this figure can rise from 60% to 80%).

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Storage conditions

The diluted tropisetron is chemically and physically stable for the next 24 hours. And from the point of view of biology (the possibility of contamination by microorganisms), it is advisable to use the drug immediately after preparing the solution. The remainder of the drug can be stored for another 24 hours after dilution, in a cool place with a temperature of two to eight degrees above zero. Storage conditions for Navoban include the following requirements:

• The drug must not be frozen under any circumstances.
• The storage location should not be accessible to teenagers and children.
• The room temperature should not exceed +30 °C.

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Shelf life

The production date and the expiration date of the medicine must be indicated on the packaging. The use of Navoban beyond the expiration date is strictly prohibited. The shelf life of Navoban is five years. It is available in pharmacies upon prescription.

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