Ondem

Ondem is a substance that prevents the development of nausea along with vomiting; it is a drug that acts antagonistically on the 5HT3 endings of serotonin.

Medicines used in radiotherapy or cytostatic treatment can increase serotonin levels in the small intestine, which causes the development of a gag reflex - the endings of 5-HT3 serotonin are activated, and excitation develops within the afferent receptors of the vagus nerve. At the same time, a serotonin release occurs in the area postrema, which through the central system triggers the development of a gag reflex.

The drug blocks the activity of the triggers responsible for the appearance of the gag reflex.

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Indications Ondema

It is used in cases of nausea and vomiting that occur due to radiation therapy or cytotoxic chemotherapy.

It is prescribed to prevent the development and relieve existing vomiting with nausea after the completion of surgical procedures.

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Release form

The release of the therapeutic substance is realized in injection liquid - inside ampoules with a volume of 2 or 4 ml; the pack contains 5 such ampoules.

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Pharmacodynamics

Ondansetron is a highly selective serotonin 5HT3 terminal antagonist with potent therapeutic effects.

The drug eliminates or prevents vomiting and nausea that develop as a result of radiation therapy or cytotoxic chemotherapeutic procedures, as well as nausea and vomiting associated with surgical operations.

The principle of ondansetron's effect has not yet been fully determined. There is a suggestion that the drug blocks the gag reflex by exerting an antagonistic effect on the 5HT3 endings located in the CNS and PNS neurons.

Ondem reduces the patient's psychomotor activity without having a sedative effect.

Pharmacokinetics

After administration of the drug, plasma Cmax values are noted after a 10-minute period. The distribution volume is 140 l. Most of the used portion is involved in intrahepatic metabolism. Up to 5% of the drug is excreted unchanged in the urine. The half-life is approximately 3 hours (in the elderly - 5 hours).

Intraplasmic protein binding is 70-76%.

In individuals with moderate renal impairment (creatinine clearance values are 15-60 ml/minute), the overall clearance and distribution volume of the drug decrease, resulting in a clinically insignificant prolongation of the half-life of the substance.

In people with chronic liver failure (in severe stages), the total clearance of ondansetron is significantly reduced, while the half-life is prolonged (up to 15-32 hours).

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Dosing and administration

Vomiting along with nausea that develops during radiation or chemotherapy.

The emetogenic potential of oncological treatment varies depending on the dosage size, as well as the combination of radiation therapy and chemotherapy regimens. The selection of the dose regimen is determined by the severity of the emetogenic effect.

Adults.

Emetogenic chemotherapy and radiation therapy.

For intramuscular and intravenous injections, 8 mg of the substance must be administered by injection, at a low speed (at least half a minute), immediately before the start of the treatment session.

To prevent prolonged or delayed vomiting (occurs after the first 24 hours), the medicine should be taken orally.

Highly emetogenic chemotherapeutic procedures (eg, high doses of ciplatin).

The drug is used in the form of a single dose of 8 mg (i.m. or i.v.), which is administered before the start of the chemotherapy session. Portions over 8 mg (up to 16 mg) are allowed to be administered exclusively through i.v. infusion (using 0.9% NaCl or another suitable solvent - 50-100 ml of the substance). The duration of the infusion is at least 15 minutes. More than 16 mg of the drug cannot be used at one time.

In highly emetogenic chemotherapeutic treatment, a dosage of 8 mg (or less) does not need to be dissolved - it is administered via IV or IM injection at a low speed (at least 0.5 minutes), immediately before the start of the procedure. Then the drug is used 2 times a day - IV or IM injection of 8 mg of the drug after 2 and 4 hours; or a constant infusion (for 24 hours) of 1 mg/hour of the substance can be used.

The drug efficacy during a highly emetogenic chemotherapy course can be increased by administering 1 additional 20 mg of dexamethasone before the start of the procedure.

Use for the age subgroup 0.5-17 years.

In pediatrics, Ondem is administered via infusion, previously dissolved in 0.9% NaCl or another suitable solvent. This procedure lasts at least 15 minutes. The dose of the medication is calculated based on the child's body surface area or weight.

Selection of a portion taking into account the patient's body surface area.

The administration is performed immediately before the start of the procedure - a single injection of a dosage of 5 mg/ ^m2; in this case, the intravenous portion should be a maximum of 8 mg. After 12 hours, oral administration of the drug begins, which can continue for another 5 days.

Selecting portions based on weight.

A single injection of the drug is 0.15 mg/kg; the intravenous dose can be a maximum of 8 mg of the substance. During the first day, 2 more intravenous administrations of the drug are allowed with a 4-hour break. After 12 hours, the transition to oral administration of the drug is made - its duration can be another 5 days.

Elderly people.

For people over 65 years of age, any IV dosage injections should be dissolved and then administered over a 15-minute period; if repeated use is required, the interval between administrations should be at least 4 hours.

For people aged 65-74 years, the initial dose of the drug is 8 or 16 mg; it must be administered via infusion (15 minutes). Therapy can be continued with a dose of 8 mg, which is administered 2 times a day. Such an infusion lasts 15 minutes, and the interval between procedures is at least 4 hours.

People over 75 years of age are initially administered a maximum of 8 mg of the drug intravenously (minimum 15-minute infusion). Later, the same 8 mg of the drug are administered twice a day (15-minute infusion with at least 4-hour intervals between them).

Persons with liver function impairment.

In people with similar disorders of a moderate or severe nature, there is a significant decrease in clearance, and the serum half-life of the component increases. Such patients can be administered a maximum of 8 mg of Ondem per day.

Postoperative vomiting with nausea.

Adults.

To prevent the occurrence of postoperative disorders (vomiting with nausea), 4 mg of the drug should be administered intramuscularly or intravenously (low rate) during the process of induction of anesthesia.

If nausea and vomiting already occur, the same dosage portion is used, which is administered slowly intravenously or intramuscularly.

In childhood (from 1 month to 17 years).

To prevent or eliminate postoperative vomiting with nausea in a child undergoing surgery under general anesthesia, 0.1 mg/kg of the drug (maximum 4 mg of the substance) is used - through a slow injection (at least half a minute) before the introduction of anesthesia, during this introduction, as well as after it or after the operation.

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Use Ondema during pregnancy

There is no information on whether the drug is safe to use during pregnancy. Animal experiments have shown that Ondem did not have a negative effect on embryonic and fetal development, as well as on the course of pregnancy, peri-, and postnatal periods. However, due to the lack of confirmation of these data regarding humans, the drug should not be prescribed to pregnant women.

Also, experimental tests have shown that ondansetron passes into the mother's milk in animals. Therefore, if it is necessary to use the drug, it is necessary to stop breastfeeding.

Contraindications

Contraindicated for use in combination with apomorphine hydrochloride due to the risk of a strong decrease in blood pressure and loss of consciousness in the case of their combination.

It is also not prescribed to people with severe sensitivity associated with the elements of the drug.

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Side effects Ondema

Main side effects:

• immune disorders: symptoms of immediate intolerance (sometimes can be severe, even leading to anaphylaxis);
• disorders of the nervous system: convulsions, headaches and movement disorders (including extrapyramidal manifestations - dystonic symptoms, oculogyric crisis, as well as dyskinesia that does not lead to persistent clinical complications), and in addition dizziness - mainly with a high rate of drug administration;
• problems with visual function: short-term visual impairment (cloudy vision), as well as temporary blindness (mainly after intravenous injections). Often the blindness disappears after 20 minutes;
• cardiac disorders: arrhythmia, bradycardia, and at the same time pain in the sternum (accompanied by depression of the ST index or not) and prolongation of the QT interval (this also includes tremors or ventricular fibrillation);
• vascular disorders: decreased blood pressure and hot flashes or a feeling of warmth;
• problems affecting the organs of the sternum and respiratory tract: hiccups;
• gastrointestinal tract lesions: constipation;
• signs from the hepatobiliary system: asymptomatic increase in liver function values. Mainly observed in people using chemotherapeutic agents containing cisplatin;
• lesions of subcutaneous tissues and epidermis: toxic rash (for example, TEN);
• systemic disorders: local manifestations in the injection area.

During post-registration observations the following violations were recorded:

• damage to the cardiovascular system: discomfort and pain in the sternum, palpitations, extrasystole, fainting, tachycardia (this includes its supraventricular and ventricular varieties), changes in ECG readings and atrial fibrillation;
• signs of intolerance: anaphylaxis and anaphylactic symptoms, rashes, bronchial spasm, urticaria, Quincke's edema and itching;
• disorders of the nervous system function: chorea, paresthesia, burning sensation, diplopia and myoclonus, as well as gait disorder, tongue protrusion and restlessness;
• systemic manifestations and local signs: pain, redness and burning sensation in the injection area, as well as an increase in temperature;
• others: development of hypokalemia.

Overdose

Ondansetron increases QT interval values depending on the dose size. In case of poisoning with the drug, ECG parameters should be monitored.

Symptoms of overdose include severe constipation, visual disturbances, decreased blood pressure, and vasovagal signs with temporary second-degree AV block. All of these manifestations resolved completely and spontaneously.

The drug has no antidote, so in case of intoxication, symptomatic and supportive measures are taken.

Ipecac should not be used to treat ondansetron poisoning because its effect will not develop due to the antiemetic effect of Ondem.

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Interactions with other drugs

Ondansetron does not slow down or speed up the metabolic processes of other medications when combined with it. The tests conducted have shown that the drug does not interact with furosemide, lignocaine, temazepam, alcoholic beverages, and also with morphine, thiopental, alfentanil, propofol and tramadol.

The drug is involved in the metabolism together with various enzymes of the liver hemoprotein P450, and also CYP3A4 together with CYP2D6, as well as CYP1A2. The diversity of metabolic enzymes allows, with standard parameters, to compensate for the slowdown or weakening of the activity of any of them (possibly with a genetic deficiency of the CYP2D6 element) by the influence of other enzymes, as a result of which no effect on systemic clearance develops (or it will be insignificant).

Ondem should be combined with caution with medications that prolong the QT interval or lead to a disturbance of salt balance.

The use of the drug in combination with apomorphine hydrochloride is prohibited, because it can lead to a strong decrease in blood pressure and loss of consciousness.

In people using potential CYP3A4 inducers (for example, carbamazepine with phenytoin, as well as rifampicin), the clearance rate of the drug increases and its blood values decrease.

The development of serotonin intoxication (with changes in mental status, neuromuscular disorders and autonomic instability) occurs in the case of combined use of the drug with other serotonergic drugs - for example, SSRIs, as well as SNRIs.

Information from some clinical trials has shown that ondansetron may reduce the pain-relieving effects of tramadol.

Administration of the drug together with substances that prolong the QT interval results in additional prolongation.

The combined use of Ondem and cardiotoxic drugs (for example, anthracyclines) leads to an increased likelihood of developing arrhythmias.

Storage conditions

Ondem can be stored in a place closed to children. Temperature indicators are not higher than 25°C.

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Shelf life

Ondem is permitted to be used for a period of 36 months from the date of sale of the therapeutic substance.

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Application for children

For chemotherapy, it is prescribed to children over six months of age, and for the prevention and elimination of postoperative vomiting with nausea - over 1 month.

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Analogues

Analogues of the drug are the drugs Zondane, Emetron and Ondansetron with Osetron.

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