Ondantor - instructions for use, doses, side effects, contraindications

for a dosage of 4 mg: tablet core composition: active ingredient: ondansetron hydrochloride dihydrate 5,000 mg (calculated on ondansetron 4 mg); auxiliary ingredients: lactose anhydrous 73.250 mg; cellulose microcrystalline 36.625 mg; starch

pregelatinized 7,500 mg; magnesium stearate 0.625 mg; tablet coating composition: opadray yellow 4,000 mg (hypromellose 1,600 mg, lactose monohydrate 1,000 mg, titanium dioxide 0,800 mg, triacetin 0.440 mg, iron oxide oxide yellow 0.160 mg).

for a dosage of 8 mg: composition of the core of the tablet: active ingredient: ondansetron hydrochloride dihydrate 10,000 mg (expressed as ondansetron 8 mg); auxiliary ingredients: lactose anhydrous 146,500 mg; cellulose microcrystalline 73.250 mg; starch

pregelatinized 15,000 mg; magnesium stearate 1,250 mg; composition of the tablet shell: opadray yellow 6,000 mg (hypromellose 2,400 mg, lactose monohydrate 1,500 mg, titanium dioxide 1,200 mg, triacetin 0,660 mg, iron oxide oxide yellow 0.240 mg).

Description:oval, flat tablets, covered with a film coating of yellow color. View of the fracture: a homogeneous mass of white color.

Pharmacotherapeutic group:antiemetic drug, serotonin receptor antagonist.

ATX: & nbsp

A.04.A.A.01 Ondansetron

Pharmacodynamics:

Ondansetron is a highly selective 5-HT antagonist₃-receptors (serotonin). Drugs (drugs) for cytostatic chemotherapy and radiotherapy can cause an increase in the concentration of serotonin, which by activation of the afferent fibers of the vagus nerve, containing 5-HT₃receptors, causes a vomitive reflex. Ondansetron selectively blocks serotonin 5HT₃-receptors of central neurons (vomiting center) and peripheral (gastrointestinal tract (GIT)) of the nervous system that regulate the gag reflex.

Does not disrupt the coordination of movements, does not cause sedation and reduced efficiency. Does not change the concentration of prolactin in the blood plasma.

Pharmacokinetics:

After oral administration ondansetron is completely absorbed in the gastrointestinal tract (GIT) and is subjected to the effect of "first passage" through the liver. Bioavailability is about 60%. The maximum concentration (C_mOh) in 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 is slightly increased with simultaneous intake with food, but 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 liver metabolism involving several microsomal isozymes (CYP1A2, CYP2D6, CYP3A4).

Less than 5% of the administered dose is excreted by the kidneys unchanged. The half-life (T1 / 2) is 3 hours. The pharmacokinetic parameters of ondansetron do not change when it is repeated.

Pharmacokinetics in special clinical cases

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 of creatinine (CK) 15-60 ml / min) systemic clearance and volume of distribution were reduced, which leads to a small and clinically insignificant increase in the half-life (T1 / 2 - 5.4 hours).

In patients with severe renal dysfunction, which are on permanent hemodialysis, the pharmacokinetics of ondansetron practically does not change.

In patients with severe hepatic insufficiency significantly decreases the clearance of ondansetron, resulting in T1 / 2 increases to 15-32 h, and bioavailability with ingestion reaches 100% due to a decrease in presystemic metabolism. In such patients, the daily dose of ondansetron should not exceed 8 mg / day.

In the elderly, there is a slight increase in bioavailability to 65% and T1 / 2 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 or radiotherapy;
prevention of nausea and vomiting in the postoperative period.

Contraindications:

- increased sensitivity to ondansetron and other auxiliary components of the drug;

- children under 3 years of age (for a dosage of 4 mg);

- children under 12 years of age (for a dosage of 8 mg);

- pregnancy and lactation;

- congenital lengthening syndrome QT;

- joint application with apomorphine (see section "Interaction with other drugs");

Carefully:

Caution should be exercised when using ondansetron in patients with hypersensitivity to other 5HT antagonists₃-receptors, with violation of heart rate and conductivity; in patients receiving antiarrhythmic drugs and beta-blockers; in patients with significant electrolyte imbalance; In patients with lengthening or the risk of lengthening the interval QTc, including patients with electrolyte imbalance, chronic heart failure, bradyarrhythmia, or in patients taking other medications that may cause lengthening of the interval QT or disturbance of the water-electrolyte balance, or a decrease in the heart rate; in patients with subacute intestinal obstruction; in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, with simultaneous use with other serotonergic drugs (see section "Interaction with other drugs").

Pregnancy and lactation:

A drug Ondantor® is contraindicated for use during pregnancy and breastfeeding.

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 dosage regimens for Ondantor® are recommended. Prevention and management of nausea and vomiting caused by cytotoxic chemotherapy or radiotherapy:

Adults

In moderately emetogenic chemotherapy or radiotherapy ondansetron 8 mg administered 1-2 hours before the start of the main therapy followed by another 8 mg every 12 hours;

When vysokoemetogennoy chemotherapy (e.g., with high doses of cisplatin), the recommended dose is 24 mg simultaneously with dexamethasone orally at a dose of 12 mg for 1-2 hours before the start of chemotherapy.

To prevent late or prolonged vomiting that occurs after 24 hours, adults Should continue taking the drug Ondantor inside at a dose of 8 mg

1 once a day for 5 days after the end of the main therapy.

Children from 3 to 18 years for the prevention of nausea and vomiting associated with chemotherapy, ondansetron usually administered as a solution for injection once intravenously (iv) at a dose of 5 mg / m² for at least 15 minutes immediately before the start of chemotherapy followed by taking Ondantor® tablets inside at a dose of 4-8 mg after 12 hours. After completing the course of chemotherapy, it is necessary to continue taking Ondantor intravenously 4-8 mg twice a day for 5 days for the prevention of late or prolonged vomiting after the first 24 hours.

Table of dose calculation based on body surface area in children aged 3 to 18 years for the prevention of nausea and vomiting caused by chemotherapy

Body surface area	Day 1	Day 2-6
> 0.6 m² and <1.2 m²	5 mg / m² intravenously, then 4 mg of ondansetron after 12 h	4 mg ondansetron every 12 hours
> 1.2 m²	5 mg / m² intravenously, then 8 mg of ondansetron after 12 hours	8 mg ondansetron every 12 hours

Calculation of the dose based on body weight in children aged 3 to 18 years for the treatment of nausea and vomiting caused by chemotherapy

The weight	Day 1	Day 2-6
> 10 kg	Up to 3 doses of 0.15 mg / kg every 4 hours	4 mg ondansetron every 12 hours

Prevention of nausea and vomiting in the postoperative period:

Adults recommend taking the drug Ondantor ® inside at a dose of 16 mg for 1 h before anesthesia.

For the relief of postoperative nausea and vomiting, ondansetron for injection is recommended.

Children from 3 to 18 years to prevent postoperative nausea and vomiting ondansetron appoint only IV, the drug should be administered slowly, for at least 30 seconds. The method of use is due to the condition of the patient in the postoperative period.

Application of Ondantor® pills in elderly patients (over 65 years of age) and in patients with impaired renal function: correction of the daily dose or the frequency of taking the drug Ondantor is not required.

Use of Ondantor® tablet in patients with impaired hepatic function: dose of the drug Ondantor® should not exceed 8 mg per day.

Patients with a slow metabolism of sparteine / debrisoquin: correction of the daily dose or the frequency of taking Ondantor ® is not required.

Side effects:

According to the World Health Organization (WHO), adverse reactions are classified according to their frequency of development as follows: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, < 1/100), rarely (> 1/10000, <1/1000) and very rarely (<1/10000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

From the immune system

rarely: urticaria, bronchospasm, laryngospasm, angioedema, immediate-type hypersensitivity reactions, sometimes severe, including anaphylaxis.

From the nervous system and the organ of vision Often: headache;

infrequently: dizziness, convulsions, spontaneous movement disorders, including extrapyramidal disorders (dystonic reactions, oculogic crisis, dyskinesia), which are reversible and do not lead to persistent clinical consequences; rarely: transient vision impairment (blurred vision).

From the side of the cardiovascular system

infrequently: pain in the chest, in some cases with depression of the segment ST, arrhythmia, bradycardia, lowering blood pressure; rarely: interval lengthening QT, arrhythmias of the "pirouette" type (torsade de pointes). From the gastrointestinal tract

often: dryness of the oral mucosa, diarrhea, constipation;

infrequently: hiccup, asymptomatic transient increase in activity

"hepatic" enzymes.

From the skin

rarely: rash, Lyell's syndrome (toxic epidermal necrolysis). Other

often: sensation of heat and redness of the skin of the face; infrequently: hypercreatininaemia; rarely: hypokalemia.

Overdose:

Symptoms: visual impairment, constipation, lowering of arterial pressure and vasovagal episode with transient atrioventricular blockade of the II degree.

In the cases studied, overdose phenomena are completely reversible. Treatment: conduct symptomatic and supportive therapy, a specific antidote is not known. As ondansetron causes dose-dependent lengthening of the interval QT in case of an overdose it is recommended to monitor the heart rate (ECG).

It is not recommended to use ipecacuanas for the treatment of an overdose of ondansetron, t. patients may not respond to treatment with ipecacuano due to the antiemetic effect of ondansetron.

Interaction:

Ondansetron is metabolized by a number of isoenzymes of the cytochrome P450 system in the liver: CYP3A4, CYP2D6, CYP1A2. In connection with the diversity of isoenzymes capable of metabolizing ondansetron, inhibition of isoenzymes or a decrease in the activity of one of them (for example, 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. Nevertheless, since ondansetron metabolized by the enzymatic system of cytochrome P450 - (CYP3A4, CYP2D6, CYP1A2) liver, caution is required when combined:

- with inducers of cytochrome P450 (isozymes CYP2D6 and CYP3A) - barbiturates, carbamazepine, carisoprodol, glutetimide, griseofulvin, dinitrogen oxide, papaverine, phenylbutazone, phenytoin (probably other hydantoins), rifampicin, tolbutamide - when combined use increases the clearance of ondansetron, and its concentration in the blood plasma is reduced, therefore, it is possible to reduce the effectiveness of the therapy.

- with inhibitors of cytochrome P450 (isozymes CYP2D6 and CYP3A) - allopurinol, macrolide antibiotics, antidepressants (monoamine oxidase inhibitors), chloramphenicol, cimetidine, estrogen-containing oral contraceptives, diltiazem, disulfiram, valproic acid and its salts, erythromycin, fluconazole, fluoroquinolones, isoniazid, ketoconazole, lovastatin, metronidazole, omeprazole, propranolol, quinidine, quinine, verapamil - The patient's condition should be carefully monitored for possible development / enhancement of the above-listed side effects.

Special studies have shown that ondansetron does not interact with ethanol, temazepam, furosemide, propofol, alfentanil, thiopental sodium, morphine, lidocaine.

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

Joint use with apomorphine can cause a marked decrease in blood pressure and loss of consciousness. Joint use is contraindicated.

Use of ondansetron with drugs that cause lengthening of the interval QT (including but not limited to: antibacterial

(grapafloxacin, sparfloxacin, erythromycin, clarithromycin, telithromycin, azithromycin, sulfamethoxazole-trimethoprim), antifungal (ketoconazole, fluconazole, voriconazole), antiprotozoal drugs (halofantrine, pentamidine), antipsychotics and antipsychotics (droperidol, ziprasidone, risperidone, quetiapine, clozapine, sulpiride, sertindole, mesoridazine, thioridazine), antidepressants (doxepin, desipramine, imipramine, amitriptyline, clomipramine), triazolam, levometadil, lidoflazin, antiarrhythmics (dofetilide, ibutilid, procainamide, quinidine, sotalol, amiodarone, disopyramide), bepridil, H1-histamine receptor blockers (misolastine, terfenadine, astemizole), cisapride, domperidone, terodiline, hypothiazide, loop diuretics (furosemide, torasemide, ethacrynic acid), arsenic trioxide) can potentiate this side effect. Joint use with cardiotoxic drugs (anthracycline antibiotics (doxorubicin, daunorubicin), trastuzumab, certain antibiotics and antifungal agents (erythromycin, ketoconazole), (amiodarone), beta-blockers may increase the risk of arrhythmia.

Some post-marketing studies describe cases of the development of serotonin syndrome (including changes in consciousness, autonomic regulation disorders and neuromuscular disorders) against the background of joint use of ondansetron and other drugs that affect serotonergic transmission (both selective and nonselective).

Special instructions:

Ondansetron in tableted dosage form should not be administered to children with a body surface area of less than 0.6 m².

As ondansetron slows the bowel motility, patients with symptoms of subacute intestinal obstruction require regular monitoring of the doctor.

Ondansetron causes lengthening of the interval QT (see section "Interaction with other drugs").

Before prescribing the drug, hypokalemia and hypomagnesemia should be adjusted.

In the course of post-marketing studies, reports of the development of serotonin syndrome including changes in consciousness, autonomic regulation disorders, and neuromuscular disorders were documented) when combined use of ondansetron and other drugs affecting serotonergic transmission (including selective serotonin reuptake inhibitors (SSRIs) and selective inhibitors re-uptake of norepinephrine and serotonin). It is necessary to conduct careful medical supervision of such patients. In patients receiving

for the prevention of nausea and vomiting after adenotomy and tonsillectomy, the drug can mask the symptoms of latent bleeding.

Special precautions for the destruction of unused medicinal product

There is no need for special precautions when destroying unused Ondantor®.

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

Ondansetron does not adversely affect psychomotor activity and does not cause sedation.

During the period of drug treatment Ondantor® care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 4 mg, 8 mg

Packaging:

For 10 tablets are placed in a blister of PVC / PVDC / aluminum foil.

One blister, along with instructions for medical use, is placed in a cardboard box.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 25^aboutFROM

Keep out of the reach of children!

Shelf life:

3 of the year.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000267

Date of registration:16.02.2011

The owner of the registration certificate:Sandoz GmbHSandoz GmbH Austria

Manufacturer: & nbsp

SANDOZ, GmbH Austria

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp18.11.2014

Illustrated instructions

Instructions

Ondantor® (Ondantor®)