How does Zofran work to prevent nausea and vomiting. What are the recommended dosages for Zofran in adults and children. Is Zofran safe to use during pregnancy and breastfeeding. What are the most common side effects of taking ondansetron.

What is Zofran (Ondansetron) and How Does it Work?

Zofran, also known by its generic name ondansetron, is a medication primarily used to prevent and treat nausea and vomiting. It belongs to a class of drugs called serotonin 5-HT3 receptor antagonists. Ondansetron works by blocking the action of serotonin, a natural substance in the body that can trigger nausea and vomiting.

Ondansetron is commonly prescribed for:

• Preventing nausea and vomiting caused by chemotherapy
• Preventing nausea and vomiting after surgery
• Treating severe nausea and vomiting in pregnancy (hyperemesis gravidarum)
• Managing nausea and vomiting associated with radiotherapy

How quickly does Zofran take effect? Ondansetron typically starts working within 30 minutes to 2 hours after taking a dose. The duration of action can last for several hours, depending on the dosage form and individual patient factors.

Zofran Dosage Forms and Administration

Zofran is available in several dosage forms to accommodate different patient needs and situations:

• Oral tablets (4 mg, 8 mg, 24 mg)
• Orally disintegrating tablets (ODT) (4 mg, 8 mg)
• Oral solution (4 mg/5 mL)
• Injection for intravenous (IV) use

Can Zofran be taken on an empty stomach? Yes, ondansetron can be taken with or without food. However, taking it with food may help reduce the risk of stomach upset.

Dosing Guidelines for Adults

The typical dosing regimens for adults may vary based on the specific condition being treated:

• For chemotherapy-induced nausea and vomiting: 8 mg taken orally 30 minutes before chemotherapy, followed by 8 mg 8 hours later, then 8 mg twice daily for 1-2 days after chemotherapy
• For postoperative nausea and vomiting: 16 mg taken orally 1 hour before anesthesia
• For radiation-induced nausea and vomiting: 8 mg taken orally 1-2 hours before radiation therapy

Dosing for Children

Pediatric dosing of ondansetron is typically based on the child’s weight or body surface area. For children receiving chemotherapy, the usual dose is 0.15 mg/kg given intravenously, up to a maximum of 16 mg per dose.

How should Zofran be administered to children? For children who cannot swallow pills, the orally disintegrating tablets (ODT) or liquid formulation may be preferred. The ODT should be placed on the tongue and allowed to dissolve without chewing.

Safety of Zofran During Pregnancy and Breastfeeding

The use of ondansetron during pregnancy is a topic of ongoing research and debate in the medical community.

Pregnancy

According to the FDA pregnancy category, Zofran is classified as Category B, which means:

• Animal studies have not shown evidence of harm to the fetus
• There are no adequate and well-controlled studies in pregnant women

Is Zofran safe for use during the first trimester of pregnancy? While some studies have suggested a small increased risk of birth defects, particularly cleft palate, with first-trimester use, other large-scale studies have not found a significant association. The decision to use ondansetron during pregnancy should be made in consultation with a healthcare provider, weighing the potential benefits against the risks.

Breastfeeding

Limited data are available on the use of ondansetron during breastfeeding. Small amounts of the drug may pass into breast milk, but the effects on nursing infants are not well established. Caution is advised, and breastfeeding mothers should consult their healthcare provider before using ondansetron.

Common Side Effects and Precautions

While Zofran is generally well-tolerated, it can cause side effects in some individuals. The most common side effects include:

• Headache
• Constipation
• Fatigue
• Dizziness
• Diarrhea

Are there any serious side effects associated with Zofran? Rarely, ondansetron can cause more serious side effects such as:

• Irregular heartbeat or QT interval prolongation
• Serotonin syndrome (when used with other medications that increase serotonin levels)
• Allergic reactions

Patients should seek immediate medical attention if they experience symptoms such as chest pain, severe dizziness, fainting, or signs of an allergic reaction like rash, itching, or difficulty breathing.

Drug Interactions and Contraindications

Ondansetron can interact with various medications, potentially affecting its efficacy or increasing the risk of side effects. Some important drug interactions include:

• Apomorphine: Can cause severe hypotension and loss of consciousness
• Tramadol: May reduce the pain-relieving effects of tramadol
• QT-prolonging medications: Can increase the risk of irregular heartbeat
• Serotonergic drugs: May increase the risk of serotonin syndrome

What medical conditions may contraindicate the use of Zofran? Ondansetron should be used with caution or avoided in patients with:

• Long QT syndrome
• Liver disease
• Electrolyte imbalances (especially low potassium or magnesium levels)

Patients should always inform their healthcare provider about all medications, supplements, and medical conditions before starting ondansetron.

Zofran vs. Other Antiemetic Medications

Ondansetron is one of several antiemetic medications available for treating nausea and vomiting. How does it compare to other options?

Zofran vs. Promethazine

Promethazine (Phenergan) is an older antihistamine with antiemetic properties. While both medications can be effective for nausea and vomiting:

• Zofran tends to cause less sedation
• Promethazine may be more effective for motion sickness
• Zofran is often preferred for chemotherapy-induced nausea and vomiting

Zofran vs. Metoclopramide

Metoclopramide (Reglan) is a prokinetic agent that also has antiemetic effects. Comparing the two:

• Zofran is generally more effective for chemotherapy-induced nausea
• Metoclopramide may be preferred for gastroparesis or diabetic stomach issues
• Metoclopramide carries a higher risk of neurological side effects

Which antiemetic is most appropriate for a given situation? The choice between ondansetron and other antiemetics depends on the specific cause of nausea, patient characteristics, and potential side effects. Healthcare providers will consider these factors when prescribing the most suitable medication.

Cost and Availability of Zofran

Ondansetron is available as both brand-name Zofran and in generic forms. The cost can vary significantly depending on the formulation, dosage, and whether a generic version is used.

Is generic ondansetron as effective as brand-name Zofran? Generic ondansetron is required by law to be bioequivalent to the brand-name version, meaning it should have the same efficacy and safety profile. Many patients find generic ondansetron to be a more cost-effective option.

Insurance Coverage

Most health insurance plans cover ondansetron, especially when prescribed for chemotherapy-induced nausea and vomiting. However, coverage may vary for other indications. Patients should check with their insurance provider to understand their specific coverage and any potential out-of-pocket costs.

Patient Assistance Programs

For patients who have difficulty affording their medication, several options may be available:

• Manufacturer patient assistance programs
• Prescription discount cards
• State-specific medication assistance programs

Patients should discuss cost concerns with their healthcare provider or pharmacist, who may be able to suggest more affordable alternatives or assistance programs.

Future Developments and Research

Research on ondansetron and related antiemetics continues to evolve. Some areas of ongoing investigation include:

• Long-term safety data, particularly in pregnancy
• New formulations for improved efficacy or convenience
• Combination therapies for enhanced antiemetic effect
• Potential uses in other conditions, such as irritable bowel syndrome

What new developments are on the horizon for antiemetic therapy? Researchers are exploring novel drug targets and delivery methods to improve the management of nausea and vomiting. These efforts may lead to more effective and personalized treatment options in the future.

As our understanding of the mechanisms behind nausea and vomiting grows, so too does the potential for more targeted and effective therapies. Patients and healthcare providers should stay informed about the latest developments in this field to ensure optimal management of these challenging symptoms.

Ondansetron Use During Pregnancy | Drugs.com

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Medically reviewed by Drugs.com. Last updated on Oct 3, 2022.

Ondansetron is also known as: Zofran, Zofran ODT, Zuplenz

Ondansetron Pregnancy Warnings

Use is not recommended (AU, UK)
This drug should be used during pregnancy only if clearly needed (US)

AU TGA pregnancy category: B1
US FDA pregnancy category: B

Comment:
-If use is absolutely necessary, caution should be exercised, especially during the first trimester.

Animal studies have failed to reveal evidence of harm to the embryo, fetus, gestation period, perinatal/postnatal development, and/or fertility. There are no controlled data in human pregnancy.

AU TGA pregnancy category B1: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage.

US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

See references

Ondansetron Breastfeeding Warnings

Breastfeeding is not recommended during use of this drug (AU, UK)
Use with caution (US)

Excreted into human milk: Unknown
Excreted into animal milk: Yes

Comments: The effects in the nursing infant are unknown.

See references

See also

• Ondansetron use while Breastfeeding (in more detail)
• Ondansetron Consumer Information
• Pregnancy Support Group
• FDA Pregnancy Categories
• Medicine use during Pregnancy
• Medicine use while Breastfeeding
• Safe Medications during Breastfeeding

References for pregnancy information

1. Product Information. Zofran (ondansetron). GlaxoSmithKline. 2001.
2. Cerner Multum, Inc. UK Summary of Product Characteristics.
3. Cerner Multum, Inc. Australian Product Information.
4. Product Information. Zuplenz (ondansetron). Strativa Pharmaceuticals, a Division of Par Pharmaceuticals, Inc. 2010.

References for breastfeeding information

1. Product Information. Zofran (ondansetron). GlaxoSmithKline. 2001.
2. Cerner Multum, Inc. UK Summary of Product Characteristics.
3. Cerner Multum, Inc. Australian Product Information.
4. Product Information. Zuplenz (ondansetron). Strativa Pharmaceuticals, a Division of Par Pharmaceuticals, Inc. 2010.
5. United States National Library of Medicine. Toxnet. Toxicology Data Network. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT 2013.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

Ondansetron (Zofran)

How does this medicine work?

Ondansetron (on-dan-se-tron) is a medicine used to treat and prevent nausea and vomiting.

How should I give it?

Ondansetron may be given by mouth as a liquid, pill, or tablet; or in a vein (IV). It may be given in one of these ways:

• as needed
• at regular times
• continuously through an IV

Your child should be awake and alert when taking any medicine by mouth. Follow the checked instructions below:

___ If using the liquid form, draw up the correct amount in the medicine dropper or oral syringe. Give a small squirt of the medicine inside the cheek. To avoid choking, let your child swallow each squirt before giving more.

___ For babies, you may want to mix the medicine with a small amount of formula or breast milk and give it with a bottle nipple before feeding. Do not add the medicine to a whole bottle because if your baby does not finish it, you will not know how much of the medicine was taken.

___ For older children who cannot swallow pills, a special tablet called Zofran ODT (oral disintegrating tablet) is available. Place it under the tongue and it will dissolve.

Other instructions:

Are there any precautions about food or other medicines?

This medicine may be given with or without food.

Check with the doctor, nurse practitioner, or pharmacist before giving any other prescription or non-prescription medicines, herbs, or vitamins.

What should I do if a dose is missed?

If a dose is missed, give it as soon as you remember. Never give a double dose.

If your child vomits a regular dose (not of the ODT type) within 30 minutes after receiving it, give it again. If your child vomits the second dose, do not repeat it again. If your child vomits an ODT dose, do not repeat it. Ondansetron ODT is absorbed into the body right away.

If your child misses or vomits two doses in a row, please call the clinic.

What are the side effects?

Common

• headache
• constipation

Occasional

• fatigue
• change in liver tests (with long-term use)
• diarrhea
• feeling dizzy

When should I call the clinic?

• continued vomiting after 2 doses
• signs of allergic reaction:
  • fever or chills
  • rash or hives
  • wheezing
  • trouble breathing – call 911

What else do I need to know?

You and your child should know the names and doses of all medicines he or she is taking. Share this information with anyone involved in your child’s care. Please remember to bring the medicine container when your child comes to the clinic or emergency department.

Always make sure you have enough medicine on hand. Each time you refill the prescription, check to see how many refills are left. If no refills are left, the pharmacy will need 2 or 3 days to contact the clinic to renew the prescription.

Check the label and the expiration date before giving each dose. Ask your pharmacist what to do with outdated or unused medications. Empty them into the trash if there is no “take-back” program.

Store all medicines in their original containers and away from direct sunlight or heat. Do not store in humid places such as the bathroom. Keep them out of children’s reach; lock up if possible.

If too much or the wrong kind of medicine is taken, call the Poison Control Center toll-free at 1-800-222-1222. If your child is unconscious or has a seizure, call 911.

Questions?

This sheet is not specific to your child but provides general information. If you have any questions, please call the clinic or pharmacy.

Children’s Hospitals and Clinics of Minnesota
Patient/Family Education
2525 Chicago Avenue South
Minneapolis, MN 55404
Last reviewed 8/2015 ©Copyright

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Zofran instructions, price in pharmacies of Ukraine The drug contains the active component ondansetron, a selective blocker of serotonin 5HT3 receptors. The drug may show an anti-diabetic effect. The mechanism of drug administration until the end of the term, it is therapeutically effective for the drug due to the influence of serotonin 5HT3 receptors in the central and peripheral nervous system, stimulation of these receptors during chemotherapy, which improves serotonin.

The drug does not have a sedative effect and does not affect plasma prolactin levels.

After oral administration, the drug is well absorbed in the intestinal tract. For ondansetron, the characteristic effect is the first passage through the liver. The peak plasma concentration of the active ingredient is observed 1.5 years after oral ingestion of the drug and 6 years after rectal ingestion. When taking the drug at once, the bioavailability of ondansetron is increased.

Metabolized in the liver, excreted most importantly in the presence of metabolites, about 5% of the drug is excreted in the unchanged form.

The period of administration of the drug is 3 years, in patients with a frail age – 5 years, after rectal ingestion of the drug – close to 6 years (as a result of greater absorption of the drug in the rectum). In patients with severe impairment of function, the period of drinking increases to 15-20 years.

The pharmacokinetics of the drug is the same for single and repeated doses.

In patients with impaired function, the systemic clearance and volume of distribution of the active ingredient are reduced. The period of administration in patients with impaired blood function and creatinine clearance of 15 to 60 ml / hv reaches 5. 4 years.

In patients who are on hemodialysis, the pharmacokinetics of the drug are similar to those in patients with normal functioning of the drug.

In patients with severely impaired liver function, a decrease in systemic clearance of the active component of the drug, an increase in the period of administration (15-32 years) and oral bioavailability (100%) are indicated.

In women, systemic clearance and volume of ondansetron was lower, lower in humans.

Indication before congestion:

The drug is indicated for the treatment and prevention of vomiting in patients who are undergoing a course of cytostatic chemotherapy or radiotherapy.

The drug is also prescribed for the prevention and treatment of nausea and vomiting in patients who have undergone surgery. For the therapy of patients in the postoperative period, do not stop the drug Zofran in the form of suppositories.

Injection method:

Injection retailer

Prescription drug for parenteral infusion. The ampoule with the preparation should be taken out without delay before the infusion, in case, even though not all of the varieties are broken, I decide to dispose of it. Ready rozchin for infusion introduction is allowed to be taken at a temperature of 2 to 8 degrees Celsius for a duration of not more than 24 years. The drug in a dose of 8 mg and less is allowed to be administered intravenously, intravenously and at the same time as intravenous infusion. If the dose is higher than 8 mg, then the drug should be administered only in case of intravenous infusion. Intravenously, the drug should be injected regularly at the upper upper quadrant of the sydnychny m’yaza.

For the preparation of a brand for internal infusion as a retailer, a variety is allowed:

• 0.9% sodium chloride brand;
• Rozchin Ringer;
• 10% manitol;
• 5% glucose solution;
• 0.3% potassium chloride and 0.9% sodium chloride;
• 0.3% potassium chloride and 5% glucose. 0.9% sodium chloride, as well as the drug in other total sizes for intravenous administration is stable in polypropylene syringes.

  One-hour injection of a drug with a concentration of 16 to 160 µg / ml (8 mg / 500 ml and 8 mg / 50 ml) through a Y-shaped injector is allowed:

  • ia 0.48 mg / ml) for 1-8 years;
  • 5-fluorouracil (concentration 0.8 mg/ml) with a dose not exceeding 20 ml per year;
  • Carboplatin (concentration 0.18-9.9 mg / ml) with a stretch of 10-60 strands;
  • Etoposide (concentration 0.14-0.25 mg/ml) 30-60 strands;
  • Ceftazidime (dose 250-2000mg), administered in water for injection according to the recommended instructions, stretching 5 strands at a time of intravenous bolus injection;
  • Cyclophosphamide (dose 100-1000mg) is varied in water for injections according to the recommended instructions, with a stretch of 5 strands at the same time as an internal bolus injection;
  • Doxorubicin (dose 10-100mg) is administered in water for injections according to the recommended instructions, with a stretch of 5 strands at a glance for internal bolus injections;
  • The drug can also be mixed in a single urticaria with dexamethasone phosphate sodium sill (dose of ondansetron in a range of 8 µg/ml up to 1 mg/ml, dose of dexamethasone phosphate in a range of 32 µg/ml up to 2. 5 g/ml) entry hour 50- 100 ml rozchin not less than 15 quills.

  The validity of the course of treatment and the dose of the drug is determined by the drug individually for the skin patient.

  Older, if you are going to undergo a course of chemotherapy or radiotherapy, with nausea and vomiting, prescribe a proper injection of 8 mg of the drug before the start of therapy. In times like nudota or vomit, try for more than 24 years after the start of therapy, patients are prescribed the drug Zofran in medicinal forms for oral or rectal congestion.

  Let’s grow up, if you want to avoid therapy with highly methogenic drugs, in case of nausea and vomiting, prescribe a proper injection of 8 mg of the drug before chemotherapy. The dose of the drug should be increased as a fallow drug (maximum dose 32 mg) and administered as an intravenous infusion.

  In addition, during therapy with highly methogenic drugs, patients may be given the administration of ondansetron according to the regimen: 8 mg intravenously before chemotherapy, after which 2 repeated administrations of 8 mg of the drug with an interval of 2-4 godini. It is also possible to recognize ondansetron for intravenous infusion of 1 mg/year for 24 years.

  To improve the effectiveness of the drug, a single intravenous injection of 20 mg of dexamethasone phosphate sodium salt is given to current patients before chemotherapy on the cob.

  In times of nausea or vomiting, try for more than 24 years after the beginning of therapy, patients are prescribed the drug Zofran in medicinal forms for oral or rectal congestion.

  Children should be given an intravenous dose of 5 mg/m2 before chemotherapy. After 12 years after parenteral administration, the drug should be administered orally 4 mg of ondansetron 2 times a day. The oral form of the drug should be taken for 5 days after completion of the course of chemotherapy.

  Let’s grow up before the operative intervention for the prevention of nausea and vomit, administer 4 mg of the drug intravenously properly or internally during the period of induction anesthesia.

  For the treatment of vomiting in the postoperative period, it is necessary to prescribe a one-time intravenous injection of 4 mg of the drug.

  For children before surgery to prevent nausea and vomiting, prescribe the drug at a dose of 0.1 mg/kg of body weight intravenously properly during the period of induction anesthesia (it is also possible to introduce the drug before or after induction anesthesia).

  For the treatment of vomiting in the post-operative period, children should be given a one-time intravenous administration of the drug at a dose of 0.1 mg/kg body weight.

  The maximum dose of the drug for children with postoperative vomiting should be 4 mg of ondansetron.

  The maximum additional dose for the drug for patients who suffer from impaired liver function is 8 mg.

  Syrup, coated tablets, lingual tablets:

  Indication for oral administration. Tablets, covered with a shell, are recommended to be taken in whole, not rotting and not sagging, drinking down the necessary amount of water. Lingual tablets are recommended to be taken in the mouth empty until they are full (1-2 quills) after which they are swallowed. The syrup is recommended to be taken in an undiluted form, dosing the drug in the form of a syrup is carried out with the help of a special spoon, which is put into the pack at once with the bottle. The validity of the course of treatment and the dose of the drug depends on the drug individually for the skin patient.

  Older, if you want to take a course of chemotherapy or radiotherapy, with nausea and vomiting, prescribe 8 mg of the drug 1-2 years before the start of therapy. After which the drug is taken again after 12 years at a dose of 8 mg. For the prevention of piznyoї vomit, we grow up to sound, prescribe 8 mg of the drug 2 times a day. The drug should be taken for 5 days after completion of the course of chemotherapy or radiotherapy.

  Doroslimy, yakі otrimuyut therapy with highly methogenic drugs, with nausea and vomiting, prescribe 24 mg of the drug in combination with 12 mg of dexamethasone sodium sill phosphate 1-2 years before chemotherapy on the cob. For the prevention of vomit in 24 years after the first drug taken, you should prescribe 8 mg of ondansetron 2 times a day. The drug should be taken for 5 days after completion of the course of chemotherapy.

  Children should be given a parenteral drug before chemotherapy. After 12 years after parenteral administration, the drug should be administered orally 4 mg of ondansetron 2 times a day. The drug should be taken for 5 days after completion of the course of chemotherapy.

  Let’s grow up before the operative intervention for the prevention of nudity and vomit, you should prescribe 16 mg of the drug once 60 minutes before the ear of general anesthesia. For the treatment of vomiting in the postoperative period, it is recommended to stop the drug in the form of parenteral administration.

  Rectal suppositories:

  Prescription drug for rectal infusion. The validity of the course of treatment and the dose of the drug depends on the drug individually for the skin patient.

  Older, if you want to take a course of chemotherapy or radiotherapy, with nausea and vomiting, prescribe 1 suppository of the drug 1-2 years before the start of therapy. For the prevention of bloating in adulthood, prescribe 1 suppository of the drug 1 time per day.

  The preparation should be given for 5 days after completion of the course of chemotherapy or radiotherapy.

  As soon as possible, if you want to avoid therapy with highly methogenic drugs, in case of nausea and vomiting, prescribe 1 suppository of the drug 1-2 years before the start of chemotherapy. To enhance the therapeutic effect of the drug, a single intravenous injection of 20 mg of dexamethasone phosphate sodium salt is prescribed before chemotherapy on the cob.

  Let’s grow up for the prevention of vomiting in 24 years after the first drug taken, prescribe 1 suppository of the drug 1 time per day. The preparation should be taken for 5 days after completion of the course of chemotherapy.

  Probe-4 4 mg No. 10 tablets

  Trade name

  Probe-4

  International nonproprietary name

  Ondansetron

  Dosage form

  Film-coated tablets.

  Composition

  Each film-coated tablet contains

  Active substance :

  Ondansetron hydrochloride dihydrate equivalent to ondansetron 4 mg;

  Excipients: Aerosil (anhydrous colloidal silica), corn starch, microcrystalline cellulose, sodium methylparaben, sodium propylparaben, sodium lauryl sulfate, purified talc, magnesium stearate, sodium starch glycolate.

  Film jacket: AF jacket, isopropyl alcohol, methylene chloride, titanium dioxide

  Description

  Off-white to white, round, biconvex film-coated tablets scored on one side.

  Pharmacotherapeutic group

  Antiemetic drug blocker – serotonin receptors.

  ATX code A04AA01

  Pharmacological properties

  Probe-4 highly selectively blocks central (chemoreceptors of the trigger zone, vomiting center) and peripheral serotonin 5-HT3 receptors. By blocking 5-HT3 receptors, ondansetron prevents the occurrence of a gag reflex. In addition, ondansetron inhibits the central links of the gag reflex by blocking 5-HT3 receptors in the bottom of the IV ventricle.

  The drug prevents or eliminates nausea and vomiting caused by cytostatic (suppressing cell division), antitumor chemotherapy and / or radiation therapy, as well as in the postoperative period. Drugs for cytostatic chemotherapy and radiotherapy can cause an increase in the level of serotonin, which, by activating vagal afferent fibers containing 5-HT3 receptors, causes a gag reflex. Probe-4 inhibits the appearance of a gag reflex by blocking 5-HT3 receptors at the level of neurons of both the central nervous system and the peripheral nervous system.

  Probe-4 does not reduce the patient’s psychomotor activity, does not cause a sedative effect, and does not impair working capacity. Does not disturb the coordination of movements. Does not change the concentration of prolactin in plasma.

  Pharmacokinetics

  Ondansetron is completely absorbed from the gastrointestinal tract after oral administration and undergoes first-pass metabolism through the liver. With _{, max} in plasma reaches approximately 1.5 hours after ingestion at a dose of 8 mg. The distribution of ondansetron is the same for oral, IM and IM administration. With i.m. administration, the peak concentration (C _max ) in plasma is achieved within 10 minutes. Bioavailability is about 60%. Plasma protein binding is 70-76%. The volume of distribution is 140 liters. The half-life (T _½ ) is 3 hours, in elderly patients it can reach 5 hours. And with severe liver failure – 15-20 hours. It is eliminated from the systemic circulation mainly as a result of metabolism in the liver, which occurs with the participation of several microsomal liver enzymes (CYP1A2, CYP2D6, CYP3A4). The absence of the CYP2D6 isoenzyme does not affect the pharmacokinetics of Zond-4. Less than 5% of the administered dose is excreted unchanged in the urine. The pharmacokinetic parameters of Zond-4 do not change when it is taken repeatedly. In patients with moderate renal insufficiency (creatinine clearance 15-60 ml / min), both systemic clearance and volume of distribution of Zond-4 are reduced, resulting in a small and clinically insignificant increase in T _½ (up to 5.4 hours). The pharmacokinetics of Zond-4 practically does not change in patients with severe renal impairment who are on chronic hemodialysis. In patients with severe liver dysfunction, the systemic clearance of Zond-4 is sharply reduced, resulting in an increase in its half-life (up to 15-32 hours), and oral bioavailability reaches 100% due to a decrease in first-pass metabolism.

  Indications for use

  • Prevention and treatment of nausea and vomiting in the postoperative period of general surgery: eliminates vomiting in the syndrome of gastric dyspepsia, surgery to correct strabismus, laparoscopy, maxillofacial surgery, orthopedic surgery, neurosurgery.
  • Prevention and relief of vomiting after cholecystectomy, tonsillectomy, removal of adenoids and vomiting in the surgical treatment of inguinal hernia and stem cell transplantation.
  • Treatment of nausea and vomiting in case of poisoning of various origins and infectious diseases (acute gastroenteritis, meningitis, hepatitis).
  • Prevention and treatment of nausea and vomiting caused by cytostatic chemotherapy and radiotherapy.
  • Prevention and relief of nausea and vomiting in pregnancy.

  Contraindications

  Hypersensitivity to the drug.

  Restrictions for use

  Pregnancy in the first trimester, lactation, severe liver failure.

  Children under 1 month of age (safety and efficacy have not been studied).

  Dosage and administration

  The choice of dosing regimen is determined by the emetogenicity of chemotherapy.

  For adults, the daily dose of is usually 8-32 mg.

  Tablet should be swallowed whole without chewing, drinking with plenty of liquid.

  For moderate emetogenic chemotherapy or radiotherapy: The recommended dose is 8 mg of ondansetron 1–2 hours before the start of primary therapy followed by another 8 mg orally 12 hours later;

  For highly emetogenic chemotherapy: The recommended dose is ondansetron 24 mg concomitantly with dexamethasone 12 mg 1-2 hours before chemotherapy.

  To prevent late or prolonged vomiting occurring after 24 hours, ondansetron should be continued by mouth at a dose of 8 mg 2 times a day for 5 days.

  Prevention and treatment of postoperative nausea and vomiting: to prevent nausea and vomiting in the postoperative period, ondansetron 16 mg orally is recommended 1 hour before anesthesia.

  Children aged ≥ 6 months

  To prevent nausea and vomiting in children associated with chemotherapy, Zond-4 is usually given as a single intravenous injection at a dose of 5 mg/m ^{2 in the form of tablets or syrup at a dose of 4 mg (1 tablet 4 mg or 10 ml of syrup) after 12 hours. After the end of the course of chemotherapy, it is necessary to continue taking the drug orally at 4 mg 2 times / day for 5 days.}

  Dosing regimen based on body surface area:

  Body surface* (m 2 )	First day	2-6 days
  < 0.6 m 2	5 mg/m 2 i.v. 2 mg solution after 12 hours	2 mg syrup every 12 hours
  ≥ 0.6 m 2	5 mg/m 2 i.v. 4 mg solution or tablet after 12 hours	4 mg syrup or tablet every 12 hours

  * – body surface (BSA) is determined by the formula:

  BSA ² \u003d Ht (cm) x Wt (kg) , (m ² ), where Ht is height, Wt is body weight.

  3600

  Dosing regimen based on body weight:

  Weight	First day	2-6 days
  ≤10 kg	Up to 3 doses of 0.15 mg/kg IV every 4 hours	2 mg syrup every 12 hours
  >10 kg	Up to 3 doses of 0.15 mg/kg IV every 4 hours	4 mg syrup or tablet every 12 hours

  intravenous dose should not exceed 8 mg

  Elderly patients: Dosage adjustment is not required.

  Patients with impaired renal function: In case of kidney damage, it is not necessary to change the usual daily dose and frequency of administration of the drug.

  Patients with hepatic impairment: In moderate or severe hepatic impairment, the clearance of Zond-4 is significantly reduced, while its plasma half-life is increased, so it is not recommended to prescribe more than 8 mg of Zond-4 in such patients in day.

  Solution for intravenous and intramuscular administration

  For moderate emetogenic chemotherapy or radiotherapy:

  8 mg IV bolus slowly or intramuscularly immediately before starting therapy.

  For highly emetogenic chemotherapy:

  – 8 mg IV bolus slowly immediately before starting chemotherapy, followed by two more IV injections of 8 mg each 2-4 hours later;

  – continuous 24-hour infusion of the drug at a dose of 24 mg at a rate of 1 mg/hour;

  -16-32 mg, diluted in 50-100 ml of the appropriate infusion solution, as a 15-minute infusion, immediately before the start of chemotherapy.

  The effectiveness of Zond-4 can be increased by a single intravenous administration of a glucocorticoid (eg, 20 mg dexamethasone) prior to starting chemotherapy.

  Prevention and treatment of postoperative nausea and vomiting

  Adults administer a single dose of 4 mg intramuscularly or intravenously by stream, slowly at the beginning of anesthesia.

  For the relief of nausea and vomiting it is recommended to / m or slow / in the introduction of 4 mg of the drug. In / m in the same part of the body, Zond-4 can be injected at a dose not exceeding 4 mg!

  Children to prevent postoperative nausea and vomiting Probe-4 is used exclusively parenterally in a single dose of 0.1 mg/kg (up to a maximum of 4 mg) as a slow intravenous injection up to / during or after anesthesia.

  There is insufficient experience in the prevention and treatment of postoperative nausea and vomiting in children under 2 years of age.

  For the treatment of developed postoperative nausea and vomiting in children, a slow intravenous administration of a single dose of the drug 0.1 mg / kg (up to a maximum of 4 mg) is recommended.

  Special instructions

  It is not recommended to inject in the same syringe with other drugs.
  Patients with a history of allergic reactions to other selective serotonin 5HT3 receptor blockers are at an increased risk of developing them while taking ondansetron. Ondansetron can slow down the motility of the large intestine, and therefore, its administration to patients with symptoms of intestinal obstruction requires special monitoring.

  In elderly patients, there is limited experience with ondansetron for the prevention and treatment of nausea and vomiting in the postoperative period. Patients over 65 receiving chemotherapy tolerate ondansetron well; special changes in the dose, frequency of administration or route of administration of the drug are not required.

  There are currently limited data on the use of ondansetron in children under 1 month of age.

  Patients with impaired renal function and slow metabolism of sparteine/debrizoquine do not require adjustment of the daily dose, frequency or route of administration of ondansetron. Patients with impaired liver function, the daily dose of ondansetron should not exceed 8 mg per day! The safety of ondansetron during pregnancy has not been established. In experimental studies found that ondansetron does not have a direct or indirect adverse effect on the development of the embryo and fetus, the course of pregnancy, as well as perinatal and postnatal development. Ondansetron is excreted in breast milk, therefore, if it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.

  Overdose

  Symptoms: in most cases are similar to adverse reactions when using the drug at recommended doses.

  Treatment: No specific antidote. In cases of suspected overdose, symptomatic and supportive therapy is indicated.

  Side effects

  From the side of the central nervous system: headaches; rarely transient visual disturbances and dizziness (with rapid on / in the introduction), involuntary movements.

  From the side of the cardiovascular system: rarely, chest pain, arrhythmias, bradycardia, arterial hypotension.

  From the digestive system: constipation, diarrhea, abdominal pain, transient increase in serum transaminase levels.

  Allergic reactions: rarely bronchospasm, angioedema, urticaria; in some cases, anaphylactic reactions.

  Other: sensation of warmth and rush of blood to the head and epigastric region.

  Interaction with other drugs

  When used simultaneously with drugs that are inducers (barbiturates, carbamazepine, rifampicin, phenytoin, phenylbutazone) or inhibitors (cimetidine, allopurinol, disulfiram) of liver microsomal enzymes – cytochrome P 9 isoenzymes0203 450 , it is possible to change the clearance of Zond-4.

  Probe-4 solution for injection is compatible with the following infusion solutions: 0.9% sodium chloride solution, 5% glucose solution, 10% mannitol solution, Ringer’s solution, 0.3% potassium chloride solution.

  Zond-4 solution is compatible with dexamethasone phosphate solution and they can be administered through one dropper, while in the solution the concentration of dexamethasone phosphate (in the form of sodium salt) can be from 32 µg to 2.5 g per 1 ml, Zond-4 – from 8 mcg to 1 mg in 1 ml.

  Fertility, pregnancy and lactation

  Women of childbearing potential

  Women of childbearing age should consider contraception

  Pregnancy

  Based on human epidemiological data, ondansetron use during the first trimester of pregnancy is expected to cause orofacial malformations.

  In a cohort study of 1.8 million pregnant women, ondansetron use in the first trimester was associated with an increased risk of developing cleft lip and/or palate (three additional cases per 10,000 women treated; adjusted relative risk 1.24 (95% CI 1 .03-1.43).

  Data from available epidemiological studies of heart disease show conflicting results.

  Animal studies do not support direct or indirect adverse effects on reproductive toxicity.

  Ondansetron should not be used during the first trimester of pregnancy.

  FDA fetal category B.

  Lactation

  If necessary, the appointment of the drug during lactation should stop breastfeeding.

  Influence on the ability to drive a car and other mechanisms

  Probe-4 does not have a sedative effect and does not affect the ability of patients to drive vehicles or engage in other potentially hazardous activities that require increased concentration and psychomotor speed.