Navoban

A lot of diseases or therapeutic methods of treatment in their symptoms have such negative manifestations as vomiting and nausea. In this case, the patient experiences both physical and psychological discomfort. Serotonergic, antiemetic Navoban has been developed and introduced into the pharmacological market by the leading international pharmaceutical company Novartis, which has its production facilities in Switzerland and Spain.

Probably, at least once, each person faced with such symptoms as vomiting and nausea, what discomfort it brings. And if you consider that this symptomatology appears against the background of antitumor chemotherapy, when the patient already suffers multiple sufferings, its appearance is especially not desirable. In such a situation, medicines are urgently needed to remove these side effects of anticancer therapy. And one of these drugs is Navoban - a highly effective antiemetic drug. 

[1], [2], [3], [4]

Indications Navoban

The active substance of Navoban is a chemical compound tropisetron, whose pharmacodynamic and pharmacokinetic characteristics give grounds to determine indications for the use of Navoban.

• Preventative measures to prevent the occurrence of nausea and vomitive reflexes, invariably arising from the conduct of antitumor chemotherapy.
• Kupirovanie similar symptoms, which appears after the surgical treatment.

[5], [6]

Release form

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

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

[7]

Pharmacodynamics

The main thrust of Navoban is its anti-emetic effect. Hence the pharmacodynamics of Navoban, selected by pharmacists in such a way that it meets the necessary requirements. Operative treatment and use of some antitumor drugs, in the course of chemotherapy, can provoke excretion from enterochromaffin-like cells that are located in the mucous tissues of the gastrointestinal tract, serotonin (5-HT). This factor initiates a signal, manifested by increased nausea and reflex vomiting.

The basic chemical compound, troposisetron, is highly selective (ie, directed), with a strong level of exposure to the substance, which weakens the action of the subclass serotonin receptor-presynaptic 5-HTZ-chemoreceptors. These protein molecules are in the central nervous system (CNS) and peripheral neurons. They, in the case of their excitation, send a signal to the area postrema (in the hypothalamus) and provoke a vomit reflex.

Navoban very effectively blocks such signals, which is the basis of the antiemetic effect of the active substance. The duration of physical and chemical stability of Novoban is determined by 24 hours, which makes it possible to inject it into the body once during the day. The use of the drug in question in the treatment protocols does not give rise to extrapyramidal side effects.

[8], [9], [10], [11], [12], [13]

Pharmacokinetics

The active substance of an anti-emetic drug is almost completely absorbed from the gastrointestinal tract. Its component exceeds 96%. On average, it takes about twenty minutes for half of Navoban to suck in the mucosa. The maximum amount of active chemical compound troposetron (C _max ) in blood plasma is reached after three hours (on average).
The pharmacokinetics of Navoban when it binds to a blood protein shows about 71% of the compound, in most cases, the interaction occurs with a protein such as alpha1-glycoprotein. In many respects, the bioavailability of troposetron is determined by the amount of the drug administered to the body. About 60% of the bioavailability gives 5 mg of Navoban, if the dose is increased to 45 mg, then the rate tends to 100%.

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

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

In the case of repeated daily administration of Navoban in doses above 10 mg, supersaturation of the enzymatic hepatic system, which takes an active part in troposetron metabolism, can 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 the case of administration of such doses of the drug), there is no increase in serum tropisetron concentration, more than the tolerable level of tolerable indicators. Therefore, if necessary, it is quite easy to prescribe Navoban 5 mg, taken once a day for six days. In this case, the cumulation 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 persons with low metabolic activity of tropospira, this indicator can stretch for 45 hours.

The total removal rate of tropospeter and its metabolites is on average 1 l / min. At the same time, kidney clearance in the process of utilization occupies only 10% of this factor. If the patient has a weak metabolic rate of the active substance, then the total clearance drops to 0.1 to 0.2 l / min, while the percentage of renal excretion remains unchanged. Reducing the same extracellular way of release of metabolic products contributes to an increase in half-life approximately four to five times. In this case, the area in the "concentration-time" diagram (AUC), located below the curve, increases five to seven times. The maximum concentration of the active drug ( _Cmax ) in the blood of such a patient and the quantitative distribution of the product do not deviate from the parameters indicated by patients with a high level of metabolism of the active substance Navoban. The difference can be observed in the amount of unmetabolized troposetron, excreted by the body together with urine. In patients with a low level of metabolism, it is higher.

[14], [15], [16],

Dosing and administration

It is necessary to observe special precautions in case the patient develops uncontrolled hypertension. Persons who are professionally associated with work on potentially traumatic mechanisms or driving vehicles should take into account that taking Navoban dulls attention and reduces the reaction speed.

The way of application and dose vary in connection with the orientation of therapy:

With preventive measures designed to stop nausea and vomiting, caused by anti-cancer treatment, therapy lasts six days.

In the case of adult patients, the daily amount of the drug administered is 5 mg. Schedule of input: on the first day of treatment, immediately before the course of chemotherapy, Navoban is administered intravenously. For the next five days, the preparation is administered orally per capsule.

Adolescents and children older than two years, the daily dosage is calculated by the formula of 0.2 mg per kilogram of the child's weight, but the resulting amount should not exceed 5 mg. The input schedule is similar to the admission sequence for an adult patient: the first day is intravenous, five subsequent orally: open the ampoule and add its contents to orange juice or some other natural beverage.

In the prevention or control of vomiting and nausea, as reactions after the operation, the amount of drug administered is determined by a dosage of 2 mg administered intravenously, shortly before the application of anesthesia. Physicians note a good tolerability of tropospeter infants, older than two years of age.

Navoban should enter the body slowly (the required volume in the form of infusion should be entered at least one minute). The drug in the form of capsules is preferably taken in the morning, about one hour before meals. Drink plenty of fluids.

If the therapeutic effect does not occur during the treatment of troprissetron, a parallel reception of dexamethasone should be prescribed to obtain the desired result.

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

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

• 5% solution of dextrose.
• 0.9% solution of sodium chloride.
• 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 patients before the treatment of patients suffering from hypertension, the administration 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 by the attending physician of the patient's BP indices is necessary.

[24], [25], [26], [27], [28]

Use Navoban during pregnancy

The pharmacokinetics and pharmacodynamics of the therapeutic drug do not allow the use of Navoban during pregnancy. An exception may be a situation where abortion is contemplated - interruption of the child's bearing in the early stages. If for medical reasons the necessary course of treatment falls on the period of feeding the newborn baby with a breast, the feeding should be stopped. 

Contraindications

With the indications of the introduction of Navoban in the schedule of the treatment course, it is worth knowing the contraindications to the use of Navoban:

• Individual intolerance of the patient's body tropisetron and other antagonists of 5-HTs receptors.
• Hypersensitivity to other components of the drug.
• Age of children under two years.
• Time of bearing a baby.
• Feeding period of newborns.
• It is necessary to exercise special care in the case of the appointment of Navoban to patients with pathological abnormalities in the work of the heart (rhythm or conduction disorder).
• Caution should be attributed to patients who are prescribed an introduction to the protocol for the therapy of beta-blockers and antiarrhythmic drugs. 

[17], [18], [19], [20],

Side effects Navoban

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

• There may be pain symptoms in the abdomen and head.
• Different manifestations of allergy:

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

• An unconscious or pre-staining condition.
• There is a failure in the intestine:

• Constipation.
• Diarrhea.

• Dizziness may occur.
• Decreased general vitality, weakness in the whole body.
• Single cases of circulatory shock, collapse have been reported.
• Heart failure.
• A hypersensitivity reaction of the first type appeared alone:

• Generalized urticaria.
• Heavy weight.
• Feeling of a flush of blood to the skin of the face.
• Rapid attack of bronchospasm with acute manifestation of it.
• The respite.
• A sharp drop in blood pressure.

But the unambiguous connection of these manifestations with the reception of Navoban has not been confirmed to date, and the causes of these phenomena have not been clarified. Some manifestations of this symptomatology could be the consequences of other illnesses that are in the patient's anamnesis, or medication concomitant therapy.

[21], [22], [23],

Overdose

If a large number of troposetron is reintroduced to the patient, an overdose of the drug, expressed by visual hallucinations, may be observed. If a history of the patient was diagnosed with a previous persistent high blood pressure (arterial hypertension), there is a rapid increase in blood pressure.

In this case, symptomatic therapy is needed, constant monitoring of the patient's general condition and the work of all the vital organs of the patient. 

[29]

Interactions with other drugs

Proceeding from the fact that the base component of the medicament in question is the troposetron component, the interactions of Navoban with other drugs directly depend on the pharmodynamic and pharmacokinetic characteristics of this chemical compound. 

Do not have any significant effect on the dynamic parameters of troposetron inhibitors of the enzymatic system of cytochrome P450. Therefore, there is no need to adjust the amount of one or the other drug administered. Global studies of the interaction of the active substance Navoban with anesthetic preparations were not carried out.

The concurrent use of the drug in question with rifampicin significantly reduces the quantitative component of troposetron in the blood. A similar situation with other drugs that stimulate the production of liver enzymes (for example, with phenobarbital). In this situation, the doctor looks at the level of metabolism of the patient. If it is high, then the amount of Navoban introduced should be increased. If there is a low metabolism, then the dose of the medicine is not corrected.

Cardiac monitoring of the joint use of troposetron with drugs designed to increase the QT period on a cardiogram shows even more of its lengthening. At a time when the monotherapy of Navoban (administered in a therapeutic amount), no increase in QT was observed. But in this situation, nevertheless, it is necessary to adhere to special caution in the tandem use of these two drugs.

It is noticed that the introduction of tropospitron into the patient's body in conjunction with foodstuffs, allows increasing the bioavailability of Navoban (this figure from 60% is able to rise to 80%).

[30], [31], [32], [33], [34],

Storage conditions

The diluted drug 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 desirable to use the drug immediately immediately after the preparation of the solution. The remainder of the drug can be stored another day after breeding, in a cool place with a temperature of two to eight degrees above zero. The storage conditions for Navoban include the following:

• The drug should not be frozen.
• The storage location should not be accessible to adolescents and children.
• The temperature in the room should not exceed +30 ° C.

[35], [36], [37], [38], [39],

Shelf life

The date of production and the final term for the sale of the medicinal product must be specified on the packaging. The use of Navoban beyond the date of use is strictly unacceptable. The period of validity Navoban - five years. In pharmacies is released on the availability of a prescription.

[40],