Zofetron

Zofetron is a medicine with antiemetic effect. Its active element is ondansetron hydrochloride, an antagonist of the serotonin endings of the 5HT3 subspecies.

Reliably establish the mechanisms of development of antiemetic activity of the drug has not yet succeeded. There is information confirming that the use of chemotherapy of a cytotoxic or radiation type causes the release of serotonin (a subtype of 5HT) from particular enterochromaphin cells located inside the small intestine.

Indications Zofetrona

It is used for vomiting with nausea, manifested due to radiation or cytotoxic chemotherapy.

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

Release form

The release of the drug is implemented in the form of tablets, 5 pieces inside the cellular packaging. Inside the pack - 2 such packages.

Pharmacodynamics

The development of the gag reflex arises from the interaction of serotonin and the endings of 5HT3, which are located in the region of the vagus nerve (its afferent endings). After activation of the latter, serotonin release can occur within the central nervous system (from the trigger chemoreceptor region located in the bottom zone of the 4th cerebral ventricle). It is believed that ondansetron is capable of blocking the activation of the gag reflex both in the zone of afferent endings of the vagus nerve and inside the serotonin endings located inside the central regions of the NA.

Ondansetron has a sedative activity, but it does not lead to a change in plasma parameters of prolactin 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 of drugs is 60%. Inside the body, the substance undergoes active metabolic processes, metabolic components are excreted in the feces and urine. From the moment of taking the medication until reaching the Cmax values, it takes 1.5 hours. Intlasma protein synthesis is approximately 73%. The main part of the accepted portion is involved in intrahepatic metabolism.

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

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

Dosing and administration

The drug should be taken orally.

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

Moderate types of emethogenic radiotherapy or chemotherapy procedures.

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

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

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

Procedures for highly chemotherapy.

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

To prevent late vomiting, it is necessary after the first 24 hours to use the drug at 8 mg 2 times a day (throughout the treatment cycle, and then another 5 days after its completion).

Dosages for a child older than 4 years of age are selected, taking into account its weight or area of the body surface. If you need the introduction of a portion of 2 mg of ondansetron, use the medication with the appropriate size of dosages.

Selection of portions, taking into account the physical area.

Before the start of treatment procedures, ondansetron in the form of injection fluid is administered 1-fold in a dose of 5 mg / m ² (the size of the intravenous dose is not more than 8 mg). Taking the medicine inside start after 12 hours and continue for the next 5 days. In general, no more than 32 mg of the drug can be administered per day.

Selection of dosages based on weight.

The size of a single injection of a drug before chemotherapy procedures is 0.15 mg / kg body weight (the maximum intravenous dose of drugs is 8 mg). Next allowed the introduction of 2 / injections with 4-hour breaks. For the whole day, you can apply a maximum of 32 mg. Zofetron can be taken inside after 12 hours and continue for up to 5 days.

With a weight of> 10 kg, for the first day intravenously up to 3 portions of 0.15 mg / kg is administered at a 4-hour interval. On 2-6th days the drug is taken orally - 4 mg with 12-hour intervals.

Postoperative vomiting with nausea.

To prevent the development of the above disorders in an adult, the drug is administered orally at a dosage of 16 mg 60 minutes before administering anesthesia. For a day, a maximum of 32 mg of ondansetron is allowed.

The child in such cases, you need to enter the substance through the injection.

Persons with liver failure in moderate form.

In people with similar disorders, a significant decrease in the clearance of the drug occurs, 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 Zofetrona during pregnancy

Ondansetron is forbidden to enter pregnant women. There is no information regarding the excretion of substances with mother's milk, which is why breastfeeding should be abandoned at the time of therapy.

Contraindications

The main contraindications:

• strong personal sensitivity towards drug elements and other selective antagonists of serotonin endings 5HT3;
• disorders of liver activity in severe severity;
• performing operations in the peritoneal zone.

Side effects Zofetrona

Clinical testing revealed that most often from side effects were observed constipation, headaches, hot flashes, or a feeling of warmth. Of the other violations:

• immune lesions: occasionally there are immediate signs of allergies. Perhaps the development of severe disorders - bronchial spasms, anaphylaxis and vascular puffiness;
• problems associated with the work of the central nervous system: seizures or movement disorders are often noted (among them extrapyramidal symptoms - dystonic signs, ocular crisis, as well as dyskinesia, which do not have sustained clinical complications). Occasionally, paresthesias occur or CNS suppression occurs;
• lesions of the visual organs: occasionally some visual disturbances (ocular clouding) occur;
• Dysfunction of the cardiovascular system: sometimes there is bradycardia, tachycardia with arrhythmia or pain in the heart zone (accompanied by ST-segment depression or not), and the level of blood pressure decreases or increases;
• disorders of respiratory activity and the work of the organs of the sternum: sometimes there is a cough or hiccups;
• problems with the work of the digestive tract: often dry mouth mucous membranes or diarrhea;
• manifestations associated with hepatobiliary function: sometimes there is an asymptomatic increase in the values of liver activity or a disorder of its work;
• systemic signs: fainting or weakness. Such violations mainly occur in individuals using chemotherapeutic drugs, which contain cisplatin.

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Overdose

Signs of intoxication: constipation, a decrease in blood pressure values, visual impairment and vasovagus disorders with transient AV-blockade.

It is necessary to cancel the use of drugs and to appoint supporting and symptomatic measures. Antiemetic procedures should not be carried out, because the medicine itself has this effect. The antidote is missing.

Interactions with other drugs

The ondansetron's metabolic processes are realized with the participation of the hemoprotein P450 enzyme structure; therefore, substances that induce or slow down the microsome enzymes can alter the clearance indicators and the term half-life of drugs.

Because of this, Zofetron is carefully combined with enzyme inducers (carbamazepine, tolbutamide, and marshalls with lithimethymide, carbamazepine, phenytoin and carisoprodol with griseofulvin, rifampicin and papaverine, and also nitric oxide and phenylbutazone) and with the help of the synthesis systems and the tampon-remover; disulfiram, allopurinol, diltiazem, MAOI, ketoconazole and chloramphenicol with fluoroquinolones, and in addition, valproate Na, quinidine, estrogen-containing contraception, omeprazole with valproic acid, verapamil with fluconazole and metroni azole, and isoniazid, quinine and lovastatin with propranolol).

The drug has no interaction with furosemide, alcoholic drinks, propofol, tamazepam, and tramadol. Pharmacokinetic parameters of drugs do not change under the action of etoposide, carmustine and cisplatin.

The drug can weaken the analgesic activity of tramadol.

The use of drugs in combination with substances prolonging the QT-segment may cause its additional extension.

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

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Storage conditions

Zofetron must be stored in a place closed to children. The temperature level is no more than 30 ° С.

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Shelf life

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

Application for children

This form of release of Zofetron is not appointed to persons younger than 4 years.

Analogs

Analogs of drugs are Granitron, Osetron, Emtron and Domegan with Emeset, and in addition Zoltem, Emetron, Omstron and Zofran with Setronon, Tropisetron with Isotron, as well as Emesetron, Navoban and Ondansetron.