Zofran Dosage Guide – Drugs.com

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Generic name: ONDANSETRON HYDROCHLORIDE 4mg
Dosage form: tablet
Drug class: 5HT3 receptor antagonists

Medically reviewed by Drugs.com. Last updated on Feb 8, 2022.

Dosage

The recommended dosage regimens for adult and pediatric patients are described in Table 1 and Table 2, respectively.

Corresponding doses of ZOFRAN tablets, ZOFRAN ODT® orally disintegrating tablets and ZOFRAN oral solution may be used interchangeably.

Dosage in Hepatic Impairment

In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), do not exceed a total daily dose of 8 mg [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

Administration Instructions for ZOFRAN ODT Orally Disintegrating Tablets

Do not attempt to push ZOFRAN ODT orally disintegrating tablets through the foil backing. With dry hands, PEEL BACK the foil backing of 1 blister and GENTLY remove the tablet. IMMEDIATELY place the ZOFRAN ODT orally disintegrating tablet on top of the tongue where it will dissolve in seconds, then swallow with saliva. Administration with liquid is not necessary.

Frequently asked questions

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Related treatment guides

• Nausea/Vomiting
• Nausea/Vomiting, Chemotherapy Induced
• Nausea/Vomiting, Postoperative
• Nausea/Vomiting, Radiation Induced

Further information

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

Medical Disclaimer

How Often Can I Take Zofran (Ondansetron) When Nauseous?

Written by
Juhi Modi

Medically reviewed by
HaVy Ngo-Hamilton, Pharm.D.
| Jun 13, 2023

If you are experiencing nausea and vomiting after surgery or cancer treatment, such as chemotherapy and radiation, your doctor may prescribe a medication called ondansetron (brand name: Zofran). Please continue reading to learn more about this medicine, including its uses, dosage, frequency of use, drug interactions, and tips on safe use. 

What is ondansetron (Zofran)?

Ondansetron (Zofran, Zofran ODT) is a prescription medication used to prevent nausea and vomiting for cancer patients after chemotherapy and radiation treatment. This medication is also used to treat nausea after surgery. It is available in various dosage forms, including oral tablets (4 mg, 8 mg, and 24 mg), orally disintegrating tablets and oral films (4 mg and 8 mg), oral solution (4 mg/5 mL), and injection vials (2 mg/mL).

These different dosage forms, such as the orally disintegrating tablets, the oral liquid, and the oral film, help lessen the nauseating feeling that may be caused by swallowing a tablet. Some of the uses of ondansetron (Zofran) may not be listed in this article.

How does Zofran work?

Zofran is an antiemetic that belongs to a group of drugs called 5-HT3 receptor antagonists. It works by blocking the action of serotonin, a natural substance in the body that can trigger nausea and initiate a vomiting reflex.

What is the usual dose of Zofran?

The usual dose of ondansetron (Zofran) in adults and children is as follows: 

Adults

• Severe nausea and vomiting due to chemotherapy: a single 24-mg dose to be taken 30 minutes before the start of a single day of highly emetogenic (vomiting-inducing) chemotherapy.  
• Moderate nausea and vomiting due to chemotherapy: An 8-mg dose is administered 30 minutes before the start of chemotherapy, followed by another 8-mg dose 8 hours later. After the completion of chemotherapy, 8 mg of Zofran should be taken every 12 hours for 1 to 2 days.
• Radiation therapy: An 8-mg ondansetron is taken 1-2 hours before radiation therapy. After the first dose, the regimen of 8 mg every 8 hours is recommended depending on the type and the location of radiation.
• Post-operative (after-surgery) nausea and vomiting: 16 mg of ondansetron is to be administered 1 hour before anesthesia.

  Children:

• Age 4 to 11: For moderate nausea and vomiting due to chemotherapy, take 4 mg of ondansetron (Zofran) 30 minutes before the start of chemotherapy, followed by another 4 mg dose given at 4 and 8 hours after the first dose. After the completion of chemotherapy, take 4 mg of ondansetron (Zofran) every 8 hours for 1 to 2 days.
   
• Age 12 to 17: For moderate nausea and vomiting due to chemotherapy, take 8 mg of ondansetron (Zofran) 30 minutes before the start of chemotherapy, followed by another 8 mg dose given 8 hours after the first dose. After the completion of chemotherapy, take 8 mg of ondansetron (Zofran) every 12 hours for 1 to 2 days.

Precautions:

• People with severe liver disease should not take more than 8 mg of ondansetron in a day.
• Zofran is not approved by the FDA to be used during pregnancy. However, there are studies that show Zofran’s safety in treating morning sickness during the first trimester. You should discuss with your doctor if you are pregnant or breastfeeding. 
• Do not give Zofran to children younger than 4 years old. 

Can I take Zofran again after 4 hours?

In some cases, you may take Zofran again after 4 hours. For example, in children, 4 mg or 8 mg of Zofran is given 30 minutes before the start of chemotherapy. (The dose is 4 mg in children between 4 and 11 years of age and 8 mg in children between 12 and 17 years of age.) This is followed by another dose 4 hours later and then one more dose 8 hours after the first dose. The child is then given one dose every 8 hours for 1-2 days after completion of chemotherapy.

Can you take Zofran every 6 hours?

The usual frequency of Zofran dosing in adults is an 8 mg tablet every 8-12 hours or 2-3 times a day. A scenario where you could take it more frequently would be if the dose taken was less than 8mg. Nevertheless, the sum of the doses taken cannot exceed 8 mg within that time frame. You should not take this medicine more often than prescribed, so leave it to your provider to determine your dose frequency. Talk to your doctor or pharmacist if your nausea and vomiting are not controlled with the prescribed dose and frequency of Zofran. 

Why can you only take Zofran every 8 hours? 

You can only take Zofran every 8 hours because clinical trials have shown that ondansetron (Zofran) increases the risk of QT prolongation. This is an abnormality in the heart’s electrical system. The risk of QT prolongation appears to be dose related. For this reason, doctors do not give intravenous (IV) doses of more than 16 mg or advise taking Zofran more often than every 8 hours when at home and without proper monitoring of a patient’s vitals.

What are the risks associated with Zofran use?

Severe allergic reactions

In a small number of people, Zofran can cause severe allergic reactions with signs and symptoms such as difficulty breathing, swelling of the throat, skin rash, and other effects. Stop taking ondansetron (Zofran) and seek immediate medical attention if you experience symptoms while on this medication to control nausea and vomiting after cancer treatment or surgery.

Serotonin syndrome

Patients taking too much ondansetron (Zofran) can develop a serious and potentially life-threatening condition called serotonin syndrome. This occurs due to high serotonin levels in the body. The risk is higher in people taking other drugs that affect serotonin levels, such as lithium, antidepressants, and migraine medications. Symptoms of serotonin syndrome may include sweating, fast heartbeat, nausea and vomiting, muscle spasms, muscle stiffness, blurred vision, confusion, and fever. Seek emergency medical attention immediately if you develop any of these symptoms while on Zofran.

Heart rhythm problems

High doses of ondansetron (Zofran) can increase the risk of heart rhythm problems, also known as arrhythmias. The risk is higher in people with congenital long QT syndrome or a history of QT prolongation. Taking other medications that cause heart rhythm problems, congestive heart failure, and low potassium or magnesium can also lead to an increased risk. Tell your healthcare provider if you have any heart rhythm abnormalities before starting ondansetron. Contact your doctor if you notice signs and symptoms such as chest pain, palpitations, slow heartbeat, or irregular heartbeat.

Masking of intestinal blockage symptoms

When you take ondansetron to treat nausea and vomiting after abdominal surgery or chemotherapy, the medicine can mask some of the symptoms of intestinal blockage and abdominal bloating, which happen to be nausea and vomiting. Tell your healthcare provider if you are not passing gas or stools. 

Risk to people with phenylketonuria

People with a rare disorder called phenylketonuria cannot break down an amino acid called phenylalanine. High levels of phenylalanine in the body can cause serious health problems. The orally disintegrating tablet of ondansetron (Zofran ODT) contains phenylalanine. Needless to say, consult your doctor before starting Zofran ODT if you have phenylketonuria.

Tips on the safe use of ondansetron (Zofran)

• Give your doctor or pharmacist a complete list of your medications, including prescription drugs, over-the-counter medicines, dietary supplements, and herbal remedies. This can help avoid dangerous drug interactions between ondansetron and another OTC product or prescription medication.
• You can take ondansetron with or without food.
• If you are taking the disintegrating tablet of Zofran, remove the foil backing with dry hands and immediately place the tablet under your tongue.
• Besides common side effects of ondansetron, like headache, tiredness, diarrhea, and constipation, this medicine can also cause dizziness. Do not drive or operate machinery until you know how ondansetron affects you. Drinking alcohol can make these side effects worse.
• In case of a missed dose, take your Zofran dose as soon as you remember. If it is time for the next dose, however, skip the missed dose and take the next dose according to the prescribed schedule. Do not take two doses to make up for a missed dose.

References:

1. https://medlineplus.gov/druginfo/meds/a601209.html
2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020103s035_020605s019_020781s019lbl.pdf
3. https://journals.lww.com/ajnonline/Abstract/2012/10000/The_FDA_Limits_Maximum_IV_Dose_of_Ondansetron. 27.aspx

Zofran: instruction, price, analogues | solution for injection Novartis

• Pharmacological properties
• Indications Zofran
• Application of Zofran
• Contraindications
• Side effects
• Special instructions
• Interactions
• Overdose
• Storage conditions
• Diagnosis
• Recommended alternatives
• Trade names

ondansetron is a potent highly selective 5HT antagonist ₃ (serotonin) receptors.

The drug prevents and eliminates nausea and vomiting caused by cytotoxic chemotherapy and / or radiation therapy, as well as postoperative nausea and vomiting. The mechanism of action of ondansetron has not been fully elucidated. It is possible that the drug blocks the occurrence of a gag reflex, exerting an antagonistic effect on 5HT ₃ receptors localized in both peripheral and CNS neurons. The drug does not reduce the psychomotor activity of the patient and does not have a sedative effect.

Pharmacokinetics. After oral administration, bioavailability is 60%, and the time to reach C _max in plasma is 1.5 hours (after taking 8 g).

With intravenous administration C _max in blood plasma is reached within 10 minutes.

Most of the dose taken is metabolized in the liver. Less than 5% of the drug is excreted unchanged in the urine. T _½ ≈3 hours (in elderly patients – 5 hours). Binding to plasma proteins – 70-76%.

Based on clinical studies in children aged 1–24 months, clearance according to body weight in this group of patients was 30% less than in children aged 5–24 months, but comparable to that in children at the age of 3–12 years. T _½ in children aged 1-4 months, according to studies, averaged 6.7 hours compared with 2.9 hours in children aged 5-24 months and 3-12 years. There is no need to adjust the dose in children aged 1-4 months, since only a single dose for intravenous administration of the drug is recommended for the treatment of postoperative nausea and vomiting. Differences in pharmacokinetic parameters can be explained in part by a larger volume of distribution of the drug in children aged 1-4 months. In clinical studies involving children aged 3–12 years, the absolute values ​​of clearance and volume of distribution of ondansetron after a single intravenous dose of 2 mg (for children aged 3–7 years) and 4 mg (aged 8–12 years) were reduced compared with those doses in adults. Both of these parameters increased linearly depending on body weight, by the age of 12 they reached the corresponding level of adults and subsequently were the same for different age groups. Based on a population analysis, pharmacokinetic parameters in patients aged 1–48 months at an intravenous dose of 0.15 mg/kg body weight every 4 hours 3 times a day will be comparable to those in patients aged 5–24 months and previous studies involving children aged 4–18 and 3–12 years.

nausea and vomiting induced by cytotoxic chemotherapy or radiotherapy; prevention and treatment of postoperative nausea and vomiting.

nausea and vomiting caused by chemotherapy or radiation therapy

Adults

The emetogenic potential of cancer therapy varies depending on the dose and combination of chemotherapy and radiotherapy regimens used.

Children . Applied in children aged 6 months with chemotherapy and aged 1 month – for the prevention and elimination of postoperative nausea and vomiting.

Emethogenic chemotherapy and radiotherapy

The recommended IM or IV dose of Zofran is 8 mg as a slow injection immediately before treatment.

Oral or rectal administration is recommended to prevent delayed or prolonged emesis after the first 24 hours.

Highly emetogenic therapy

Zofran can be given as a single dose of 8 mg IV or IM immediately prior to chemotherapy. Doses >8 mg (up to 16 mg) can only be used as a 50–100 ml IV infusion 0.9% solution of sodium chloride or other solvent; infusion should last at least 15 minutes. The maximum single dose is 16 mg.

For highly emetogenic chemotherapy, Zofran 8 mg can be given by slow IV (at least 30 seconds) or IM injection immediately prior to chemotherapy, followed by 8 mg IV or IM twice 2 or 4 hours later or by continuous infusion 1 mg/h for 24 hours.

The effectiveness of Zofran can be increased by additional administration of dexamethasone sodium phosphate at a dose of 20 mg before chemotherapy once.

Children and adolescents (aged 6 months to 17 years)

The dose of the drug can be calculated by body surface area or by weight of the child.

Dose calculation based on the child’s body surface area.

Zofran must be administered immediately before chemotherapy by a single intravenous injection at a dose of 5 mg/m ² body surface. In / in the dose can not exceed 8 mg. After 12 hours, oral administration of the drug can be started, which can be continued for another 5 days.

Dose calculation based on the child’s body weight.

Zofran must be administered immediately before chemotherapy by a single intravenous injection at a dose of 0.15 mg/kg. In / in the dose can not exceed 8 mg. On Day 1, two more IV doses can be given 4 hours apart. After 12 hours, you can start oral administration of the drug, which can last 5 days.

Elderly patients

Zofran is well tolerated by patients over 65 years of age. Changes in dose, frequency or route of administration are not required.

Postoperative nausea and vomiting

Adults

For the prevention of postoperative nausea and vomiting, the recommended dose of Zofran is 4 mg as a single IM injection or slow IV infusion during anesthesia.

For postoperative nausea and vomiting, the recommended single dose of Zofran is 4 mg IM or slow IV injection.

Children and adolescents (ages 1 month to 17 years)

For the prevention and management of postoperative nausea and vomiting in children operated on under general anesthesia, Zofran can be administered at a dose of 0. 1 mg/kg body weight (up to a maximum of 4 mg) by slow IV infusion (at least 30 c) before, during, after anesthesia or after surgery.

Elderly patients

Experience with the use of Zofran for the prevention and management of postoperative nausea and vomiting in the elderly is limited, but Zofran is well tolerated by patients over the age of 65 receiving chemotherapy.

Patients with renal insufficiency

There is no need to change the dosing regimen or route of administration of the drug in patients with impaired renal function.

Patients with hepatic insufficiency

In patients with moderate and severe hepatic impairment, the clearance of Zofran is significantly reduced, and T _½ from blood plasma increases. For such patients, the maximum daily dose of the drug should not exceed 8 mg.

Patients with impaired metabolism of sparteine/debrisoquine

T _½ of ondansetron in subjects with impaired metabolism of sparteine ​​and debrisoquine does not change. In such patients, repeated administration results in the same concentration of the drug as with undisturbed metabolism. Therefore, changes in dosage or frequency of administration of the drug are not required.

hypersensitivity to any component of the preparation. It is contraindicated to use simultaneously with apomorphine hydrochloride due to cases of severe hypertension and loss of consciousness.

are classified according to organs and systems and the frequency of their occurrence. The frequency is divided into the following categories: very often (≥1/10), often (≥1/100, but <1/10), infrequently (≥1/1000, but <1/100), rare (≥1/10,000 but <1/1000), very rare (<1/10,000, including isolated cases).

Immune system: rarely – immediate hypersensitivity reactions, sometimes severe, up to anaphylaxis.

Nervous system: very common – headache, common – movement disorders (including extrapyramidal disorders such as oculogeric crisis, dystonic reactions) and dyskinesia without persistent clinical consequences, convulsions, rare — dizziness during rapid intravenous administration of the drug.

Organ of vision: rarely – transient visual disturbances (blurred vision), most often with rapid intravenous administration, very rare – transient blindness, mainly with intravenous administration. In most cases, blindness resolves within 20 minutes after the end of the drug administration. As a rule, most patients receive chemotherapy with cisplatin. In some reports, cases of transient blindness were considered to be of cortical origin.

Cardiovascular system: infrequently – arrhythmia, pain in the heart (with segment 9 depression0037 ST or without), bradycardia, hypotension, often – sensation of warmth or flushing of the face.

Respiratory system and organs of the chest cavity: infrequently – hiccups.

Gastrointestinal: often – constipation.

Hepatobiliary system: infrequently – transient asymptomatic increase in plasma transaminase activity. These cases are observed mainly in patients receiving chemotherapy with cisplatin.

General disorders: often – local reactions at the injection site.

Postoperatively, these adverse reactions have been reported.

From the side of the cardiovascular system: chest pain and discomfort, extrasystoles, tachycardia, including ventricular and supraventricular tachycardia, atrial fibrillation, palpitations, syncope, ECG changes.

Hypersensitivity reactions: anaphylactic reactions, angioedema, bronchospasm, anaphylactic shock, itching, skin rashes, urticaria.

From the nervous system: gait disturbance, chorea, myoclonus, agitation, burning sensation, tongue protrusion, diplopia, paresthesia.

General disorders and local reactions: fever, pain, redness, burning in the injection area.

in the treatment of patients with manifestations of hypersensitivity to other selective 5HT antagonists ₃ receptors, hypersensitivity reactions have been noted. Ondansetron dose-dependently increases the interval Q-T . Additionally, according to the post-marketing study, there were reports of cases of ventricular fibrillation / flutter (Torsade de Pointes). The use of ondansetron should be avoided in patients with congenital long QT interval syndrome . Ondansetron should be used with caution in patients who have, or may develop, interval prolongation Q-T , including those with electrolyte imbalance, congestive heart failure, bradyarrhythmia, and in patients treated with other drugs that can increase Q-T or disturb electrolyte balance. Before starting treatment, it is necessary to correct hypokalemia and hypomagnesemia.

Since ondansetron impairs intestinal motility, patients with signs of subacute ileus should be carefully monitored during the use of Zofran.

Zofran ampoules do not contain preservatives and should be used immediately after opening; the remaining unused solution should be destroyed.

Zofran ampoules cannot be autoclaved.

Compatible with other IV solutions.

IV solutions should be prepared immediately prior to infusion. However, it has been established that the ondansetron solution remains stable for 7 days at temperatures up to 25 ° C in daylight or in a refrigerator when dissolved in such media: sodium chloride solution 0.9%; solution of glucose 5%; solution of manitol 10%; rr Ringer; solution of potassium chloride 0.3%; solution of sodium chloride 0.9%; solution of potassium chloride 0.3%. A study was made of the compatibility of the drug with polyvinyl chloride vials and infusion systems. It has been established that ondansetron remains stable also when using polyethylene and glass vials. It has been shown that ondansetron in 0.9% sodium chloride solution or 5% glucose solution remains stable in polypropylene syringes. It has also been proven that stability in polypropylene syringes is maintained when ondansetron is diluted with other recommended solutions.

If long-term storage of the drug is required, reconstitution should be carried out under appropriate aseptic conditions.

Compatibility with other drugs

Zofran can be administered as an IV infusion at a rate of 1 mg/hour. Through an X-shaped injector, together with Zofran at a concentration of ondansetron from 16 to 160 μg / ml (i.e. 8 mg / 500 ml or 8 mg / 50 ml, respectively), you can enter:

• cisplatin at a concentration of up to 0.48 mg / ml for 1-8 hours;
• fluorouracil at concentrations up to 0.8 mg/ml at a rate not exceeding 20 ml/h (higher concentrations of fluorouracil may cause precipitation of ondansetron). Fluorouracil infusion solution may contain up to 0.045% magnesium chloride in addition to other excipients that are compatible;
• carboplatin at a concentration of 0.18-9.9 mg / ml for 10-60 minutes;
• etoposide at a concentration of 0.14-0.25 mg / ml for 30-60 minutes;
• ceftazidime at a dose of 250 mg to 2 g, dissolved in water for injection (for example, 2. 5 ml per 250 mg or 10 ml per 2 g of ceftazidime), as an IV bolus injection over 5 minutes;
• cyclophosphamide at a dose of 100 mg to 1 g, dissolved in water for injection (5 ml per 100 mg of cyclophosphamide), as an IV bolus injection over 5 minutes;
• doxorubicin 10–100 mg dissolved in water for injection (5 ml per 10 mg doxorubicin) as an IV bolus over 5 minutes;
• dexamethasone at a dose of 20 mg as a slow intravenous injection over 2-5 minutes (with simultaneous administration of 8 mg or 32 mg of ondansetron dissolved in 50-100 ml of injection solution) for about 15 minutes.

Special warning

Hypersensitivity reactions have been observed in the treatment of patients with manifestations of hypersensitivity to other selective 5HT ₃ receptor antagonists.

Very rarely and mainly with intravenous administration of Zofran, temporary changes in the ECG are noted, including prolongation of the interval Q-T .

Since ondansetron impairs intestinal motility, patients with signs of subacute ileus should be carefully monitored during the use of Zofran.

The period of pregnancy and lactation. The safety of Zofran during pregnancy in humans has not been established.

In experimental animal studies, Zofran did not interfere with the development of the embryo or fetus and did not affect the course of pregnancy, pre- and postnatal development. However, since animal studies are not always predictive in humans, Zofran is not recommended for use during pregnancy. Experimental studies have shown that ondansetron is excreted in the breast milk of animals. If necessary, the appointment of the drug during lactation should stop breastfeeding.

Influence on the ability to drive vehicles and work with mechanisms. In psychomotor tests, ondansetron does not affect driving or operating machinery and does not have a sedative effect.

Ondansetron does not accelerate or inhibit the metabolism of other drugs when used concomitantly. Special studies have shown that ondansetron does not interact with alcohol, temazepam, furosemide, tramadol and propofol.

Ondansetron is metabolized by various hepatic cytochrome P459 enzymes: CYP 3A4, CYP 2D6 and CYP 1A2. Due to the diversity of ondansetron metabolism enzymes, inhibition or a decrease in the activity of one of them (for example, a genetic deficiency of CYP 2D6) is normally compensated by other enzymes and will not affect or its effect on total creatinine clearance will be insignificant.

Phenytoin, carbamazepine and rifampicin

In patients receiving therapy with drugs that are potential inducers of CYP 3A4 (for example, phenytoin, carbamazepine and rifampicin), the clearance of ondansetron increases and its concentration in the blood decreases.

Tramadol

A small number of clinical studies have shown that ondansetron may reduce the analgesic effect of tramadol.

insufficient data. In most cases, the symptoms are similar to those listed above (see SIDE EFFECTS). Ondansetron dose-dependently increases the interval Q-T . In case of overdose, ECG monitoring should be carried out.

Symptoms of overdose have been reported as visual disturbances, severe constipation, hypotension, vasovagal disorders with transient second degree AV block. In all cases, the phenomena were completely resolved. There is no specific antidote, symptomatic and supportive therapy is used.

The use of ipecac is not recommended for ondansetron overdosage because it is not effective due to the anti-emetic effect of Zofran.

Store in a dark place below 30°C.

GNRL/11/UA/27.09.2013/7916

Acetonuria	ICD R82.4
Hallux valgus	ICD M21.0
Congenital absence of hand and finger(s)	ICD Q71.3
DN (benign neoplasm) of long bones of the lower limb	ICD D16. 2
Other malformations of the musculoskeletal system	ICD Q79.8
MN (malignant neoplasm) of ribs, sternum and collarbone	ICD C41.3
MN (malignant neoplasm) of the brain stem	ICD C71.7
Pancreatic cyst	ICD K86.2
Equine-varus clubfoot	ICD Q66.0
Incomplete osteogenesis	ICD Q78.0
Complications of the central nervous system due to anesthesia during labor and delivery	ICD O74.3
Fracture of the upper end of the humerus	ICD S42.2
Webbed fingers	ICD Q70.1
Elective caesarean section	ICD O82. 0
Calcaneovalgus clubfoot	ICD Q66.4
Second-degree perineal tear during delivery	ICD O70.1
Mild or moderate vomiting of pregnancy	ICD O21.0
Spondyloepiphyseal dysplasia	ICD Q77.7
Traumatic brain injury	ICD S06.0
Excessive or severe vomiting of pregnant women with metabolic disorders	ICD O21.1

Medicines :: Gastrointestinal tract :: Antiemetics :: Probe-4 30 ml drops

Trade name

Probe-4

International nonproprietary name

Ondansetron

Dosage form

Oral solution.

Composition

Each 5 ml contains

Active substance :

Ondansetron hydrochloride is equivalent to ondansetron 2 mg.

Excipients: sugar (refined sugar), sodium benzoate, methyl paraben, propyl paraben, bronopol, glycerin, citric acid monohydrate, aspartame, sodium chloride, propylene glycol, dye: tartrazine, essence: mango, essence: pineapple, purified water

Description

Yellow solution.

Pharmacotherapeutic group

Antiemetic serotonin receptor blocker.

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, intramuscular and intravenous 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 of pregnant women.

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.

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.

IM or slow IV injection of 4 mg is recommended to relieve nausea and vomiting. 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.

Tablets and oral solution

Tablet should be swallowed whole without chewing, washing down with plenty of liquid. Oral solution is recommended to be taken undiluted.

Adults: 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 24 mg of ondansetron concomitantly with dexamethasone 12 mg 1-2 hours before starting 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 1 hour before anesthesia is recommended.

Children aged ≥ 6 months

For the prevention of 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 immediately prior to chemotherapy, followed by Zond-4 orally 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 (BSA) is determined by the formula:

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

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Dosing regimen based on body weight:

intravenous dose should not exceed 8 mg

Elderly patients: Dosage changes are 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 impaired liver function: In moderate or severe hepatic impairment, the clearance of Zond-4 is significantly reduced, while its half-life from plasma increases, therefore, such patients are not recommended to prescribe more than 8 mg per day.

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 less than 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. AT experimental studies established that ondansetron has no direct or indirect adverse effect on the development of the embryo and fetus, the course of pregnancy, as well as on 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 isoenzymes0029 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.