Zofetron

Zofetron is a drug with an antiemetic effect. Its active ingredient is ondansetron hydrochloride, which is an antagonist of serotonin endings of the 5HT3 subtype.

It has not yet been possible to reliably establish the mechanisms of development of the antiemetic activity of the drug. There is information confirming that the use of cytotoxic or radiation chemotherapy causes the release of serotonin (a subtype of 5HT) from special enterochromaffin cells located inside the small intestine.

Indications Zofetron

It is used for vomiting with nausea caused by radiation or cytotoxic chemotherapy.

It is also prescribed to eliminate and prevent postoperative nausea and vomiting.

Release form

The drug is released in the form of tablets, 5 pieces per blister pack. There are 2 such packs inside the pack.

Pharmacodynamics

The development of the gag reflex occurs due to the interaction of serotonin and 5HT3 endings, which are located in the area of the vagus nerve (its afferent endings). After activation of the latter, serotonin release may occur inside the CNS (from the trigger chemoreceptor site located in the area of the bottom of the 4th cerebral ventricle). It is believed that ondansetron is able to block the activation of the gag reflex both in the area of the afferent endings of the vagus nerve and inside the serotonin endings located inside the central areas of the NS.

Ondansetron has a sedative effect, but does not change plasma prolactin levels and does not weaken the patient's psychomotor activity.

Regarding the principles of the antiemetic effect of ondansetron during the postoperative period, this issue has not yet been studied very well.

Pharmacokinetics

The bioavailability index of the drug is 60%. The substance undergoes active metabolic processes inside the body, metabolic components are excreted with feces and urine. From the moment of taking the drug until reaching the Cmax values, 1.5 hours pass. Intraplasmic protein synthesis is approximately 73%. The main part of the dose taken is involved in intrahepatic metabolism.

The half-life is 3-4 hours; in elderly people - about 6-8 hours. Less than 10% of the active component of the drug is excreted unchanged in the urine.

Information obtained from studies of ondansetron metabolism in vitro shows that the substance is a substrate of the enzyme structure of the human liver hemoprotein P450 (this includes CYP1A2 with CYP2D6, as well as CYP3A4). Ondansetron metabolism processes are realized mainly under the action of the enzyme CYP3A4. Since the metabolism of the active component can be carried out with the participation of several enzymes of the hemoprotein P450 structure, in case of deficiency of any of them, the total clearance of ondansetron does not change significantly, since the deficiency of one enzyme can be compensated by the others.

Dosing and administration

The medication must be taken orally.

The dosage regimen should be selected taking into account the intensity of the emetogenic effect of antitumor treatment and established individually.

Moderate types of emetogenic radiation or chemotherapy procedures.

It is necessary to take 8 mg of the drug 60-120 minutes before therapy, with subsequent use of 8 mg of the drug at 12-hour intervals.

To prevent late or prolonged vomiting with nausea, after the first 24-hour period, 8 mg of the drug should be taken at 12-hour intervals for 5 days. When selecting the dosage, it is necessary to take into account the severity of vomiting. In case of partial irradiation of the abdominal area with large portions, it is necessary to take 8 mg at 8-hour intervals.

The medicine is used throughout the entire cycle of radiation and chemotherapy, and in addition for another 1-2 days (if necessary - 3-5 days) after its completion.

Highly emetogenic chemotherapy procedures.

An adult should take 24 mg of Zophetron orally (in combination with dexamethasone phosphate) 60-120 minutes before the start of chemotherapy procedures.

To prevent late vomiting, after the first 24 hours, the drug should be taken at 8 mg 2 times a day (throughout the entire treatment cycle, and then for another 5 days after its completion).

Dosages for children over 4 years of age are selected based on their weight or body surface area. If a 2 mg dose of ondansetron is required, use a medication with the appropriate dosage size.

Selecting a portion size based on body surface area.

Before the start of treatment procedures, ondansetron in the form of an injection liquid is administered 1 time in a portion of 5 mg / m ² (the size of the intravenous portion is no more than 8 mg). Oral administration of the drug begins after 12 hours and continues for the next 5 days. In total, no more than 32 mg of the drug can be administered per day.

Selection of dosages taking into account weight.

The size of a single injection of the drug before chemotherapy procedures is 0.15 mg/kg of weight (the maximum intravenous dose of the drug is 8 mg). Then, 2 intravenous injections are allowed with 4-hour intervals. A maximum of 32 mg of the drug can be used per day. Zofetron can be taken orally after 12 hours and continued for up to 5 days.

For weights >10 kg, up to 3 portions of 0.15 mg/kg are administered intravenously on the first day at 4-hour intervals. On days 2-6, the drug is taken orally – 4 mg at 12-hour intervals.

Postoperative vomiting with nausea.

To prevent the development of the above-mentioned disorders in an adult, the medication is administered orally at a dosage of 16 mg 60 minutes before the administration of anesthesia. A maximum of 32 mg of ondansetron is allowed per day.

In such cases, the child needs to be given the substance through injections.

Persons with moderate liver dysfunction.

In people with such disorders, there is a significant decrease in drug clearance, and the term of its serum half-life, on the contrary, increases. Such patients can be administered no more than 8 mg of the drug per day.

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Use Zofetron during pregnancy

Ondansetron is prohibited for use in pregnant women. There is no information regarding the excretion of the substance in breast milk, which is why breastfeeding should be discontinued during therapy.

Contraindications

Main contraindications:

• strong personal sensitivity to the components of the drug and other selective antagonists of serotonin 5HT3 endings;
• severe liver dysfunction;
• performing operations in the peritoneum area.

Side effects Zofetron

Clinical testing revealed that the most common side effects were constipation, headaches, hot flashes, or a feeling of warmth. Other disorders included:

• immune damage: occasionally, immediate signs of allergy occur. Severe disorders may develop – bronchial spasms, anaphylaxis and vascular edema;
• problems associated with the functioning of the central nervous system: seizures or movement disorders are often observed (among them extrapyramidal symptoms - dystonic signs, oculogyric crisis, as well as dyskinesia, which do not have stable clinical complications). Occasionally, paresthesia occurs or the functioning of the central nervous system is suppressed;
• visual impairment: occasionally some visual disturbances (cloudy vision) occur;
• dysfunction of the cardiovascular system: sometimes bradycardia, tachycardia with arrhythmia or pain in the heart area (accompanied by depression of the ST segment or not) occurs, and blood pressure levels decrease or increase;
• respiratory and sternum disorders: sometimes coughing or hiccups are observed;
• problems with the gastrointestinal tract: dry mouth or diarrhea often appears;
• manifestations associated with hepatobiliary function: sometimes an asymptomatic increase in liver function values or a disorder in its functioning is observed;
• systemic symptoms: fainting or weakness. Such disorders mainly occur in people using chemotherapeutic drugs that contain cisplatin.

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Overdose

Signs of intoxication: constipation, decreased blood pressure, visual impairment and vasovagal disorders with transient atrioventricular block.

It is necessary to stop using the drug and prescribe supportive and symptomatic measures. Antiemetic procedures should not be carried out, because the drug itself has this effect. There is no antidote.

Interactions with other drugs

The metabolic processes of ondansetron are realized with the participation of the enzymatic structure of hemoprotein P450, therefore substances that induce or inhibit microsomal enzymes are capable of changing the clearance rates and half-life of the drug.

For this reason, Zofetron should be combined with caution with enzyme inducers (carbamazepine, tolbutamide, barbiturates with glutethimide, carbamazepine, phenytoin and carisoprodol with griseofulvin, rifampicin and papaverine, as well as nitric oxide and phenylbutazone) and inhibitors (including cimetidine, erythromycin, macrolides with disulfiram, allopurinol, diltiazem, MAOIs, ketoconazole and chloramphenicol with fluoroquinolones, as well as sodium valproate, quinidine, estrogen-containing contraception, omeprazole with valproic acid, verapamil with fluconazole and metronidazole, as well as isoniazid, quinine and lovastatin with propranolol).

The drug does not interact with furosemide, alcoholic beverages, propofol, tamazepam, and tramadol. The pharmacokinetic parameters of the drug do not change under the influence of etoposide, carmustine, and cisplatin.

The drug can weaken the analgesic activity of tramadol.

The use of drugs in combination with substances that prolong the QT segment may cause its further prolongation.

The combination of the drug and cardiological agents (for example, anthracyclines) may increase the likelihood of arrhythmia.

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Storage conditions

Zofetron must be stored in a place inaccessible to children. Temperature level – no more than 30°С.

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Shelf life

Zofetron can be used within a 5-year period from the date of manufacture of the medicinal substance.

Application for children

This form of Zofetron is not prescribed to persons under 4 years of age.

Analogues

Analogues of the drug are Granitron, Osetron, Emtron and Domegan with Emeset, and in addition to this, Zoltem, Emetron, Omtron and Zofran with Setronon, Tropisetron with Isotron, as well as Emesetron, Navoban and Ondansetron.