Ondansetron-Teva - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate, carboxymethyl starch sodium, type A, cellulose microcrystalline, corn starch pregelatinized, magnesium stearate, shell opadrai yellow 02G22211 (hypromellose E464, titanium dioxide E171, macrogol-6000, macrogol-400, ferric oxide yellow oxide E172).

Description:

Tablets 4 mg: oblong film-coated tablets, pale yellow with an engraving "4" on one side, on the fracture core of white color.

Tablets 8 mg: oblong film-coated tablets, pale yellow with an engraving "8" on one side and a risk on the other, on the fracture core of white.

Pharmacotherapeutic group:antiemetics, serotonin receptor antagonist

ATX: & nbsp

A.04.A.A.01 Ondansetron

Pharmacodynamics:

Ondansetron is a selective antagonist of 5-HTs receptors (serotonin). Medicines for cytostatic chemotherapy and radiotherapy can cause an increase in the concentration of serotonin, which, by activating the afferent fibers of the vagus nerve, containing 5-HTs receptors, causes a vomiting reflex.Selectively blocks serotonin 5HTs-receptors of central neurons (vomiting center) and peripheral (gastrointestinal) of the nervous system that regulate the vomiting reflex. He violates the coordination of movements, does not cause sedation and reduced efficiency. Does not change the concentration of prolactin in the plasma.

Pharmacokinetics:

After oral administration ondansetron completely absorbed in the gastrointestinal tract and subjected to the effect of "first passage" through the liver. Bioavailability is about 60%. The maximum concentration in the blood plasma is achieved after 1.5 hours and is approximately 30 ng / ml after taking the drug at a dose of 8 mg. Bioavailability of the drug increases slightly with simultaneous reception with a niche, but it does not change when taking antacids.

The distribution of ondansetron when administered orally, intravenously or intramuscularly is the same. The volume of distribution when an equilibrium state is reached is about 140 liters. Binding to blood plasma proteins - 70-76%.

Ondansetron is eliminated from the body, mainly as a result of metabolism and the liver with the participation of several microsomal enzymes (CYP1A2, CYP2D6, CYP3A4). The absence of an isomorphism CYP2D6 does not affect the pharmacokinetics of ondansetron. Less than 5% of the administered dose is excreted by the kidneys in

unchanged form. The half-life is 3 hours. The pharmacokinetic parameters of ondansetron do not change when it is repeated. Pharmacokinetics in special clinical cases

In children, the values of clearance and volume of distribution depend on age. Correction of the dose taking into account the body weight of patients (from 0.1 mg / kg to 4 mg maximum) compensates for these changes and normalizes the system exposure of ondansetron in children.

In patients with moderate renal insufficiency (clearance krsatinina 15-60 ml / min) systemic clearance and volume of distribution are reduced, which leads to a small and clinically insignificant increase in the half-life (T1 / 2 - 5.4 hours).

In patients with severe impairment of renal function on hemodialysis, the pharmacokinetics of ondansetron is virtually unchanged.

In patients with severe hepatic insufficiency significantly decreases the clearance of ondansetron, resulting in a half-life increases (up to 15-32 h). and oral bioavailability reaches 100% due to a decrease in the systemicmetabolism.

In elderly people there is a slight increase in bioavailability to 65% and a half-life of up to 5 hours.

The distribution of ondansetron depends on sex, women have a higher intake absorption, as well as a lower systemic clearance and volume of distribution.

Indications:

- Prevention and management of nausea and vomiting caused by cytotoxic chemotherapy and radiotherapy.

Prevention and relief of nausea and vomiting in the postoperative period.

Contraindications:

Hypersensitivity to ondansetron, other selective antagonists of serotonin 5HTs-receptors and other components of the drug; simultaneous application with apomorphine, children under 3 years of age (for a dosage of 4 mg) - insufficient data on efficacy and safety; children under 12 years of age (for a dosage of 8 mg); pregnancy and the period of breastfeeding.

Carefully:

If cardiac arrhythmia and conduction, simultaneous use of antiarrhythmic drugs or beta-blockers, violation electrolyte balance, hepatic insufficiency, signs of intestinal obstruction, hereditary

lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Dosing and Administration:

The drug is intended for oral administration.

The choice of the dosage regimen is determined by the severity of the emetogenic effect of the antitumor therapy.

For of adults The daily dose, as a rule, is 8-24 mg.

The following modes are recommended:

With moderate expression of the emetogenic effect of chemo- or radiotherapy:

adults and children over 12 years appoint 8 mg of ondansetron 1-2 hours before the start of the main therapy with the subsequent intake of another 8 mg orally after 12 hours; children from 4 to 11 years old appoint 4 mg of ondansetron 30 minutes before the start of the main therapy, followed by taking another 4 mg orally every 8 hours.

Application data for radiotherapy in children up to 12 years are absent.

If the emetogenic effect of chemotherapy or radiotherapy is high Recommended dose for adults (no data for use in children) is 24 mg concomitantly with dexamethasone inside at a dose of 12 mg 1-2 hours before the start of chemotherapy.

To prevent late or prolonged vomiting

Adults should continue taking the drug inside at a dose of 8 mg 2 times a day for 5 days after the end of the main therapy.

Children the drug is given in a dose of 5 mg / m² surface of the body intravenously for at least 15 minutes immediately before the start of chemotherapy, followed by ingestion of 4 mg ondansetron after 12 hours; treatment is recommended to continue at a dose of 4 mg 2 times a day inside for 5 days.

Prevention of postoperative nausea and vomiting:

adults prescribe 16 mg orally 1 hour before the onset of general anesthesia;

- children for preventing and arresting postoperative nausea and vomiting ondansetron only applied parenterally.

Elderly patients A dose change is not required.

Patients with impaired renal function

Change the usual daily dose and the frequency of taking the drug is not required.

Patients with impaired hepatic function The daily dose should not exceed 8 mg per day.

Patients with a slow metabolism of sparteine / debrisoquine Correction of a daily dose or frequency of ondansetron is not required.

Side effects:

Side effects are classified according to the following frequency: very often - not less than 10%; often - not less than 1%, but of the type, sometimes severe, including anaphylaxis.

Co side of the nervous system: headache, dizziness, convulsions, spontaneous movement disorders, including extrapyramidal disorders (dystonic reactions, oculogic crisis, dyskinesia), which are reversible and do not lead to persistent clinical consequences.

From the cardiovascular system: pain in the chest, in some cases with depression of the segment S-T, arrhythmias, bradycardia, lowering blood pressure.

From the digestive system: hiccough, dry mouth, diarrhea, constipation, asymptomatic transient increase in the activity of "liver" enzymes. Other: sensation of heat and redness of the skin of the face, hypokalemia,

hypercreatininaemia; temporary

decreased visual acuity.

less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%, including isolated cases.

Allergic reactions: rarely - urticaria, bronchospasm, laryngospasm,

angioedema, immediate-type hypersensitivity reactions, sometimes severe, including anaphylaxis.

From the central nervous system: very often - headache; infrequent - dizziness, convulsions, spontaneous movement disorders, including extrapyramidal disorders

(dystonic reactions, oculogic crisis, dyskinesia), which are reversible and do not lead to persistent clinical consequences.

From the side of the organ of vision: rarely

temporary decrease in visual acuity; very rarely - temporary blindness, mainly after intravenous administration.

From the cardiovascular system: infrequently - pain in the chest, in some cases accompanied by depression of the segment S-T, arrhythmias, bradycardia, lowering blood pressure.

From the digestive system: often constipation; infrequently - hiccough, dryness of the oral mucosa, diarrhea, transient increase in the activity of "liver" transaminases.

Other: often - a feeling of heat, "hot flashes", irritation at the injection site; rarely -redness of the facial skin, hypokalemia, hypercreatininaemia; temporary reduction of visual acuity.

Overdose:

Symptoms: visual impairment, constipation, lowering of arterial pressure and vasovagal episode with transient atrioventricular blockade of the II degree. In all cases the phenomena are completely invertible.

Treatment: conduct symptomatic and supportive therapy, a specific antidote is not known.

Interaction:

There is no evidence that ondansetron induces or inhibits the metabolism of other drugs often used in combination with it.

According to special studies, it has been established that ondansetron not

interacts with ethanol, temazepam, furosemide, alfentanil, tramadol, morphine, lidocaine, thiopental sodium and propofol.

Ondansetron is metabolized by several isoenzymes of the cytochrome P450 system

(CYP3A4, CYP2D6 and CYP1A2). In connection with the variety of isoenzymes that are able to metabolize ondansetron,

inhibition of isoenzymes or a decrease in the activity of one of the

isoenzymes (eg, with genetic deficiency CYP2D6) is usually compensated by other isoenzymes, as a result of which changes in the total clearance of ondansetron are either absent, or insignificant and practically do not require dose adjustment. Care should be taken when

simultaneous application with inhibitors of cytochrome P450 isoenzymes (isozymes CYP2D6 and CYP3A4) allopurinol, macrolide antibiotics, antidepressants (inhibitors

monoamine oxidase), chloramphenicol, propofol.

Data from special studies indicate that ondansetron can reduce the anesthetic effect of tramadol.

Special instructions:

When using ondansetron, more often with intravenous administration, there may be changes in the electrocardiogram of a transient nature, including lengthening the interval QT. Therefore, it follows from

intestines, patients with symptoms of subacute intestinal obstruction require regular monitoring by a physician. Ondansetron can not be used for prevention and treatment

postoperative nausea and vomiting in children after surgery on the abdominal organs.

Effect on the ability to drive transp. cf. and fur:

In case of adverse reactions from the nervous system, patients are advised to refrain from controlling the car and other mechanisms, as well as activities that require concentration of attention, stress of psychomotor functions.

Form release / dosage:Tablets, film-coated, 4 mg.

Packaging:

For 10 tablets in aluminum foil / PVC / PVDCH blisters.

Tablets, film-coated,

8 mg. For 10 or 15 tablets in aluminum foil / PVC / PVDCH blisters.

1 blister with instructions for use in a cardboard pack.

Storage conditions:

List B.

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

He Use at the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001138/10

Date of registration:18.02.2010

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Industries, Ltd. Israel

Representation: & nbspTeva Teva Israel

Information update date: & nbsp17.06.2011

Illustrated instructions

Instructions

Ondansetron-Teva (Ondansetron-Teva)