Zofran

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Zofran: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Drug interactions
11. Analogs
12. Terms and conditions of storage
13. Terms of dispensing from pharmacies
14. Reviews
15. Price in pharmacies

Latin name: Zofran

ATX code: A04AA01

Active ingredient: Ondansetron (Ondansetron)

Producer: GLAXO WELLCOME PRODUCTION (France), GlaxoSmithKline Trading (Russia)

Description and photo update: 2019-12-08

Zofran is a drug with antiemetic action.

Release form and composition

Solution for intravenous and intramuscular administration: colorless transparent liquid, practically free of foreign inclusions (in ampoules of 2 or 4 ml, 5 ampoules in contour plastic packages (pallets), 1 pallet in a cardboard box);
Syrup: clear liquid from light yellow color to colorless with a characteristic strawberry smell (in dark glass bottles of 50 ml, 1 bottle in a cardboard box with a measuring spoon included);
Rectal suppositories: white, homogeneous, smooth, in the form of a cylinder with a pointed end (in strips of 1 suppository, 1 or 2 strips in a cardboard box);
Lozenges: white, round, convex on one side, on the other - flat (in blisters of 10 pcs., 1 blister in a cardboard box).

The composition of 1 ml solution for intravenous and intramuscular administration includes:

Active ingredient: ondansetron - 2.5 mg (in the form of dihydrate hydrochloride), in terms of ondansetron - 2 mg;
Auxiliary components: citric acid monohydrate, sodium citrate, sodium chloride, water for injection.

The composition of 1 lozenge contains:

Active substance: ondansetron - 4 or 8 mg;
Auxiliary components: aspartame, gelatin, mannitol, sodium methyl hydroxybenzoate, strawberry flavor, sodium propyl hydroxybenzoate, purified water.

The composition of 5 ml of syrup includes:

Active ingredient: ondansetron - 5 mg (in the form of dihydrate hydrochloride), in terms of ondansetron - 4 mg;
Auxiliary components: anhydrous citric acid, sodium citrate dihydrate, sodium benzoate, sorbitol solution, strawberry flavor, purified water.

The composition of 1 rectal suppository includes:

Active ingredient: ondansetron - 16 mg;
Auxiliary component: witepsol S58.

Pharmacological properties

Pharmacodynamics

Ondansetron, the active component of Zofran, is a potent highly selective 5HT ₃ receptor antagonist. The mechanism for preventing symptoms such as nausea and vomiting is not precisely defined. With the use of cytostatic drugs and radiation therapy, serotonin (5HT) is presumably released in the small intestine, which causes the gag reflex by stimulating the endings of the afferent fibers of the vagus nerve and activating 5HT ₃ receptors. Ondansetron provides an initial blockage of this reflex.

In turn, the activation of the afferent endings of the vagus nerve can lead to the triggering of the central mechanism of the emetic reflex and the release of 5HT in the posterior field of the fundus of the fourth ventricle. Therefore, suppression by Zofran of nausea and vomiting caused by radiation therapy and the use of cytostatic drugs as chemotherapy is most likely feasible due to the antagonistic effect on 5HT ₃ receptors of neurons located both in the central nervous system and in the periphery.

The mechanism of action of Zofran in the prevention of nausea and vomiting as postoperative complications is unknown, but generally corresponds to that in the relief of nausea and vomiting triggered by sessions of radiation therapy and chemotherapy.

Taking ondansetron does not affect the plasma prolactin content.

Pharmacokinetics

Pharmacokinetic parameters of ondansetron remain unchanged when it is repeatedly administered into the body. This compound is characterized by identical systemic effects when administered intramuscularly and intravenously. The protein-binding capacity of ondansetron is insignificant and amounts to 70–76%.

Both when taken orally, and with intramuscular and intravenous administration, the distribution of the active component of Zofran in adults is similar. The volume of distribution at steady state is approximately 140 liters.

Ondansetron is excreted from the systemic circulation, mainly metabolized in the liver. Less than 5% of the administered dose is excreted through the kidneys unchanged. The distribution of this substance with intramuscular and intravenous administration, as well as oral administration, is identical to the half-life and is approximately 3 hours.

The pharmacokinetics of ondansetron is determined by the sex of the patient. In women, a greater degree of absorption and speed and a lower volume of distribution and systemic clearance are observed (parameters are adjusted taking into account body weight) than in male patients.

In children aged 1–4 months who underwent surgery, clearance was approximately 30% slower than in patients aged 5–24 months. A similar trend was observed when comparing groups of newborns and children aged 3–12 years. The half-life of ondansetron in patients aged 1-4 months averages 6.7 hours, while in patients aged 5-24 months and 3-12 years, it is approximately 2.9 hours.

The differences in pharmacokinetic parameters are explained by the increased percentage of fluid in the body in newborns and infants, as well as by the large volume of distribution of ondansetron, which is a water-soluble substance, in children aged 1–4 months.

In children aged 3–12 years, who were assigned elective operations under general anesthesia, the absolute values of the volume of distribution and clearance of ondansetron decrease compared with these indicators in adults. Correction of the values of the volume of distribution and clearance depending on the body weight leads to almost the identity of these indicators in different age groups. Calculation of the dose in accordance with body weight fully compensates for the systemic exposure of ondansetron and age-related changes in children.

The data on the content of ondansetron in the blood plasma, as well as the results of modeling the dependence of the clinical response on exposure, suggest a more noticeable effect of the drug on the QTcF interval in patients aged 75 and older than in patients of younger age.

In patients with moderate renal insufficiency (CC 15-60 ml / min), the volume of distribution and systemic clearance decrease after intravenous administration of Zofran, the consequence of which is an increase in the half-life of almost no clinical significance to 5.4 hours. Studies in which patients participated with severe renal failure, requiring constant hemodialysis, did not reveal changes in the pharmacokinetics of ondansetron after infusion.

In patients with severe liver dysfunctions, the systemic clearance of the active substance Zofran sharply decreases, and the half-life increases to 15–32 hours. Oral bioavailability is almost 100% due to inhibition of presystemic metabolism.

Indications for use

Zofran is prescribed to prevent and eliminate vomiting and nausea, which are caused by the following reasons:

Cytostatic chemotherapy or radiotherapy;
Surgical interventions (tablets for resorption, solution for intravenous and intramuscular administration, syrup).

Contraindications

Pregnancy and lactation;
Hypersensitivity to drug components.

Zofran in the form of suppositories is contraindicated in childhood, syrup and lozenges can be taken from 2 years of age (the effectiveness and safety of the drug for young children has not been studied).

The solution for intravenous and intramuscular administration should be used with caution simultaneously with antiarrhythmics and beta-blockers, as well as in patients with cardiac arrhythmias and conduction disorders and with significant electrolyte disturbances (in very rare cases, intravenous administration of the drug may develop transient ECG changes, including lengthening QT interval).

Instructions for use of Zofran: method and dosage

Zofran tablets should be placed on the tip of the tongue and swallowed after dissolution, the syrup should be taken orally.

The scheme of using the drug for the prevention and elimination of vomiting and nausea caused by radiotherapy or cytostatic chemotherapy is due to the emetogenicity of anticancer therapy.

Typically, the adult daily oral dose is 8-32 mg.

It is recommended to use the following modes:

Moderate emetogenic chemotherapy and radiotherapy: 8 mg 1-2 hours before the start of the main therapy, again after 12 hours take the same dose;
Highly emetogenic chemotherapy: ondansetron 24 mg concurrently with dexamethasone 12 mg 1-2 hours before the start of chemotherapy.

For the prevention of prolonged or late vomiting that occurs after 24 hours, for 5 days it is necessary to continue taking Zofran orally 2 times a day, 8 mg.

To children, immediately before the start of chemotherapy, Zofran is injected once in the form of a solution for injection intravenously at a dose of 5 mg / m². After 12 hours, the drug is taken orally (syrup, tablets for resorption) at a dose of 4 mg. After the end of the course of chemotherapy, treatment should be continued for 5 days, 2 times a day, 4 mg.

To prevent and eliminate vomiting and nausea in the postoperative period, adults are shown taking Zofran in the form of a syrup or tablets for resorption at a dose of 16 mg 1 hour before anesthesia.

For relief of postoperative vomiting and nausea, Zofran's solution for injection is used.

To prevent and arrest the development of postoperative vomiting and nausea in children, the drug is administered intravenously.

No dosage change is required for elderly patients and patients with renal insufficiency and slow metabolism of sparteine / debrisoquine. The daily dose of ondansetron for patients with functional impairment of the liver should not exceed 8 mg.

Zofran in the form of suppositories is used rectally.

The scheme of using the drug for the prevention and elimination of vomiting and nausea caused by radiotherapy or cytostatic chemotherapy is due to the emetogenicity of anticancer therapy. With moderate emetogenic chemotherapy or radiotherapy, 1 suppository (16 mg of ondansetron) is prescribed 1-2 hours before the start of the main therapy. For highly emetogenic chemotherapy, the drug is used in the same dose simultaneously with intravenous administration of 20 mg of dexamethasone.

To prevent prolonged or late vomiting that develops 24 hours after the end of radiotherapy or chemotherapy, it is necessary to continue therapy for 5 days, 1 suppository per day (it is also possible to take the drug orally in the form of lozenges or syrup).

It is not recommended to use Zofran in the form of suppositories for children and patients with functional disorders of the liver. No dosage change is required for elderly patients and patients with renal insufficiency and slow metabolism of sparteine / debrisoquine.

The dosage regimen of the drug in the form of a solution for injection for the prevention and elimination of vomiting and nausea caused by radiotherapy or cytostatic chemotherapy depends on the emetogenicity of the antitumor treatment.

The following regimens are recommended for adults:

Emetogenic radiotherapy and chemotherapy: before starting therapy, 8 mg of Zofran is administered intramuscularly or slowly intravenously;
Highly emetogenic chemotherapy: immediately before the start of therapy, 8 mg of Zofran is administered once intravenously or intramuscularly. The use of higher doses (8-32 mg) is possible by intravenous infusion after dissolving Zofran in 50-100 ml of 0.9% sodium chloride solution or other compatible infusion solution for 15 minutes or more. It is possible to use the drug in another way: 8 mg of the solution is injected slowly intravenously or intramuscularly immediately before chemotherapy, then 2 more intravenous or intramuscular injections are prescribed at the same dose with an interval of 2-4 hours, or for 24 hours, a continuous infusion of the drug is used at a rate of 1 mg per hour. The efficacy of Zofran can be enhanced by an additional single intravenous administration of 20 mg of dexamethasone sodium phosphate before chemotherapy.

For children from 6 months to 17 years old, Zofran is prescribed based on the surface area of the body (the drug is administered intravenously immediately before chemotherapy):

Less than 0.6 m²: initial dose - 5 mg / m²; after 12 hours, 2 mg of syrup is taken orally;
0.6-1.2 m²: initial dose - 5 mg / m²; after 12 hours, 4 mg of syrup is taken orally;
More than 1.2 m²: initial dose - 8 mg; after 12 hours, 8 mg of syrup is taken orally.

For 5 days after the end of the course of treatment, the syrup is continued 2 times a day at the same dose (2, 4 or 8 mg, respectively).

As an alternative to children, Zofran can be administered immediately before chemotherapy as a single intravenous dose of 0.15 mg / kg (up to 8 mg). This dose can be re-administered every 4 hours (in total, no more than three doses). Taking Zofran orally 2 times a day at 4 mg can be continued for another 5 days after the completion of the course of chemotherapy. Doses should not be higher than those recommended for adults.

To prevent and eliminate vomiting and nausea in the postoperative period, a single intramuscular or slow intravenous injection of 4 mg of Zofran is recommended for adults during induction of anesthesia. For the treatment of vomiting and nausea in the postoperative period, 4 mg of the solution is administered once intramuscularly or slowly intravenously.

To prevent and eliminate vomiting and nausea in the postoperative period (after surgery under general anesthesia), children from 1 month to 17 years old are prescribed 0.1 mg / kg (maximum up to 4 mg) in the form of a slow intravenous injection. The drug can be administered after surgery or before, during or after induction of anesthesia. The same dose is indicated for the relief of vomiting and nausea that developed in the postoperative period.

Experience with the use of Zofran for the prevention and relief of postoperative vomiting and nausea in elderly patients is limited, although the drug is generally well tolerated by patients over 65 years of age receiving chemotherapy.

No dosage change is required for patients with functional impairment of the kidneys and slow metabolism of sparteine / debrisoquine. The daily dose of ondansetron for patients with functional impairment of the liver should not exceed 8 mg.

When diluting Zofran's injection solution, the following solutions can be used:

5% dextrose solution;
0.9% sodium chloride solution;
10% mannitol solution;
Ringer's solution;
0.9% sodium chloride solution and 0.3% potassium chloride solution;
5% dextrose solution and 0.3% potassium chloride solution.

The infusion solution should not be prepared in advance. If necessary, the ready-made solution can be stored for 24 hours under natural light or normal light at a temperature of 2-8 ° C.

Side effects

According to the instructions, Zofran in the form of lozenges, syrup and suppositories can lead to the development of the following side effects:

Cardiovascular system: chest pain (sometimes with ST segment depression), bradycardia, arrhythmia, lowering blood pressure;
Digestive system: dry mouth, hiccups, diarrhea or constipation, burning sensation in the rectum and anus (after the administration of suppositories); sometimes - an asymptomatic transient increase in the activity of liver tests;
Nervous system: dizziness, headache, seizures and spontaneous movement disorders;
Allergic reactions: bronchospasm, urticaria, laryngospasm, anaphylaxis, angioedema;
Others: a feeling of heat, flushing of the face, temporary impairment of visual acuity, hypercreatininemia, hypokalemia.

When using the drug in the form of a solution for intravenous and intramuscular administration, the following disorders may develop:

Cardiovascular system: sometimes - arrhythmia, chest pain (may be accompanied by a decrease in the ST segment), a decrease in blood pressure, bradycardia; often hot flashes or hot flashes; very rarely - transient ECG changes, including prolongation of the QT interval (usually with intravenous administration);
Nervous system: very often - headache; sometimes - convulsions, movement disorders (including such extrapyramidal symptoms as oculogyric crisis, dyskinesia and dystonia) without persistent clinical consequences; rarely - dizziness associated with rapid intravenous administration;
Immune system: rarely - immediate-type hypersensitivity reactions (sometimes with severe course, including anaphylaxis);
Gastrointestinal tract: often - constipation;
Respiratory system, mediastinal and chest organs: sometimes - hiccups;
Liver and biliary tract: sometimes - an asymptomatic increase in liver function tests (more often observed in patients receiving chemotherapy with cisplatin);
Organ of vision: rarely - transient visual disturbances (in the form of blurred vision), as a rule, with intravenous administration; very rarely - transient blindness, usually with intravenous administration (in most cases, the blindness disappeared within 20 minutes; many patients were prescribed chemotherapy drugs containing cisplatin; in some cases, transient blindness was of cortical origin);
Local and general reactions: often - local reactions at the sites of intravenous administration.

Overdose

At the moment, information on overdose is scarce. Mostly its symptoms are similar to the side effects that appear in some patients who received the drug in the recommended doses.

The use of Zofran can lead to a dose-dependent prolongation of the QT interval. In case of possible overdose, regular ECG monitoring is recommended. Overdose in children when taking the drug by mouth is often accompanied by symptoms resembling serotonin syndrome.

The specific antidote for the drug is unknown, so when it is taken in high doses, appropriate supportive and symptomatic therapy is prescribed. For the treatment of overdose, the appointment of ipecac is not recommended, since the likelihood of a significant clinical response to therapy with ipecac is negligible due to the antiemetic action of the drug.

special instructions

In patients with a history of indications of hypersensitivity to other 5HT3 receptor antagonists, allergic reactions may develop when using Zofran.

Ondansetron increases the duration of the passage of contents through the large intestine, therefore, patients with symptoms of intestinal obstruction after using Zofran require regular monitoring.

The lozenges contain aspartame, which is why they are recommended to be taken with caution in patients with phenylketonuria.

Do not squeeze Zofran tablets out of foil in advance.

Data on the use of ondansetron in the form of a solution for injection in children under 1 month old are limited.

Do not enter Zofran in the same syringe or in the same infusion solution with other drugs.

Influence on the ability to drive vehicles and complex mechanisms

For Zofran, a sedative effect is uncharacteristic, therefore, its reception does not affect the ability of patients to drive a car or perform potentially dangerous work that requires increased concentration and concentration.

Application during pregnancy and lactation

The safety of ondansetron therapy during pregnancy in humans has not been proven. Preclinical studies do not indicate a direct or indirect negative impact on the development of the embryo, fetus, gestational processes, peri- and postnatal development. However, these results do not confirm the complete safety of Zofran treatment of pregnant women, therefore, its appointment to this category of patients is contraindicated.

Studies have shown that ondansetron passes into the breast milk of animals during lactation. Therefore, when prescribing Zofran, breastfeeding should be stopped.

Drug interactions

There is no evidence that ondansetron inhibits or induces the metabolism of other drugs often prescribed in combination with it.

Care must be taken when using the following drugs together:

Enzymatic inducers of P450 (CYP2D6 and CYP1A2), such as rifampicin, carbamazepine, barbiturates, nitrous oxide, carisoprodol, griseofulvin, glutethimide, phenylbutazone, papaverine, phenytoin (probably other hydantoins), tolbutamide;
Inhibitors of P450 enzymes (CYP2D6 and CYP1A2), such as antidepressants, monoamine oxidase inhibitors, allopurinol, cimetidine, macrolide antibiotics, chloramphenicol, estrogen-containing oral contraceptives, valproic acid, diltiazem, disulfiraminate ketoconazole, omeprazole, metronidazole, propranolol, quinine, quinidine, verapamil.

Zofran does not interact with alcohol, furosemide, temazepam, propofol (diprivan) and tramadol.

With the simultaneous use of Zofran in the form of a solution for intravenous and intramuscular administration with some drugs, undesirable effects may occur:

Phenytoin, rifampicin and carbamazepine: decrease in the concentration of ondansetron in the blood;
Tramadol: reducing its analgesic effect.

Zofran at a concentration of 0.016 mg / ml and 0.16 mg / ml (8 mg / 500 ml and 8 mg / 50 ml, respectively) is pharmaceutically compatible and can be administered via a Y-shaped injector intravenously drip simultaneously with the following drugs:

Doxorubicin: for 5 minutes (dose - 10-100 mg, as an intravenous bolus injection);
5-fluorouracil: (concentration - 0.8 mg / ml at a rate of 20 ml per hour, higher concentrations of 5-fluorouracil can lead to precipitation of Zofran);
Cisplatin: for 1-8 hours (concentration - up to 0.48 mg / ml);
Etoposide: for 30-60 minutes (concentration - 0.144-0.25 mg / ml);
Carboplatin: for 10-60 minutes (concentration - 0.18-9.9 mg / ml);
Cyclophosphamide: for 5 minutes (dose - 100-1000 mg, in the form of an intravenous bolus injection);
Ceftazidime: for 5 minutes (dose - 250-2000 mg, as an intravenous bolus injection);
Dexamethasone: intravenous administration of 20 mg of the drug is possible slowly, over 2-5 minutes. It is possible to administer drugs through one dropper, while in the solution the concentration of dexamethasone sodium phosphate can be 0.032-2.5 mg / ml, Zofran - 0.008-1 mg / ml.

Analogs

Zofran's analogues are: Latran, Ondansetron, Ondansetron-Teva, Ondansetron-Ronts, Ondansetron-Altpharm, Ondasol, Emetron, Domegan, Vero-Ondansetron, Lazaran VM, Zoltem, Ondantor, Osetron, Emeset, Setronon.

Terms and conditions of storage

Keep out of reach of children at temperatures up to 30 ° C.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Zofran

According to reviews, Zofran in most cases copes well with nausea caused by the use of general anesthesia or taking chemotherapy drugs. Many patients like the results of treatment and the wide range of dosage forms of this drug. Side effects are extremely rare.

Price for Zofran in pharmacies

The price of Zofran in tablets with a dosage of 4 mg is on average 2,400-2,600 rubles, and with a dosage of 8 mg - 4,580-4,700 rubles (10 pcs per pack). You can buy solution for intramuscular and intravenous administration in pharmacies for 1500-1600 rubles (the package includes 5 ampoules). A rectal suppository (1 pc.) Will cost about 730–905 rubles. Zofran syrup costs approximately 2,470–2690 rubles (for a 50 ml bottle).

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!