Ondansetron vs Zofran: A Comprehensive Comparison
What is the difference between ondansetron and zofran? What are the uses, side effects and ratings of these two anti-nausea medications? Find the answers here.
Introducing Ondansetron and Zofran
Ondansetron and Zofran are two popular anti-nausea medications used to prevent and treat nausea and vomiting caused by various medical conditions and treatments. Both drugs belong to the class of serotonin 5-HT3 receptor antagonists and are considered effective in managing nausea and vomiting. However, there are some key differences between the two that are important to understand.
Ondansetron: An Overview
Ondansetron is a prescription-only medication primarily used for the prevention and treatment of nausea and vomiting associated with chemotherapy, radiation therapy, and post-operative conditions. It works by blocking the action of serotonin, a chemical in the body that can trigger the vomiting reflex.
Ondansetron is approved for use in both adults and children over the age of 4. It is available in various formulations, including tablets, orally disintegrating tablets, and injectable solutions. The most common side effects of ondansetron include constipation, headache, and dizziness.
Zofran: An Overview
Zofran, also known by its generic name ondansetron, is another prescription-only medication used for the treatment and prevention of nausea and vomiting caused by cancer chemotherapy, radiation therapy, and surgery. Like ondansetron, Zofran works by blocking the action of serotonin in the body.
Zofran is approved for use in adults and children over the age of 4. It is available in tablet, orally disintegrating tablet, and injectable formulations. The most commonly reported side effects of Zofran include headache, hypoxia (low oxygen levels), and fever.
Comparing Ondansetron and Zofran
While ondansetron and Zofran are both effective in managing nausea and vomiting, there are some key differences between the two:
- Approved uses: Both medications are approved for the treatment and prevention of nausea and vomiting associated with chemotherapy, radiation therapy, and post-operative conditions. However, Zofran may also be used off-label for other conditions, such as gastroenteritis, alcohol use disorder, and obsessive-compulsive disorder.
- Formulations: Ondansetron is available in tablet, orally disintegrating tablet, and injectable formulations, while Zofran is available in the same formulations, as well as an oral solution.
- Side effects: The most common side effects of ondansetron include constipation and headache, while the most common side effects of Zofran include headache, hypoxia, and fever.
- Ratings: Ondansetron has an average rating of 7.7 out of 10 from 473 user ratings, while Zofran has not been rated by users on the Drugs.com website.
Choosing Between Ondansetron and Zofran
When choosing between ondansetron and Zofran, healthcare providers will consider factors such as the patient’s medical history, the underlying cause of the nausea and vomiting, and the potential side effects of each medication. In some cases, one medication may be more appropriate than the other based on the specific needs and circumstances of the patient.
It’s important to note that both ondansetron and Zofran are prescription-only medications and should only be taken under the guidance of a healthcare provider. Patients should always follow the instructions provided by their healthcare provider and report any adverse effects or concerns to their doctor.
Frequently Asked Questions
What is the difference between ondansetron and Zofran?
Ondansetron and Zofran are both prescription-only medications used to prevent and treat nausea and vomiting, but they have some key differences in their approved uses, formulations, and side effects.
Can Zofran be used for purposes other than nausea and vomiting?
Yes, Zofran may be used off-label for other conditions, such as gastroenteritis, alcohol use disorder, and obsessive-compulsive disorder, although these uses are not approved by the FDA.
What are the common side effects of ondansetron and Zofran?
The most common side effects of ondansetron include constipation and headache, while the most common side effects of Zofran include headache, hypoxia (low oxygen levels), and fever.
How do the ratings of ondansetron and Zofran compare?
Ondansetron has an average rating of 7.7 out of 10 from 473 user ratings, while Zofran has not been rated by users on the Drugs.com website.
Conclusion
In summary, ondansetron and Zofran are both effective anti-nausea medications that can be used to prevent and treat nausea and vomiting caused by various medical conditions and treatments. While they have some similarities, there are also key differences in their approved uses, formulations, and side effects that healthcare providers must consider when prescribing these medications. Patients should always consult with their healthcare provider to determine the most appropriate treatment option for their individual needs.
Ondansetron vs Zofran Comparison – Drugs.com
Ondansetron vs Zofran Comparison – Drugs.com
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Related suggestions Nausea/Vomiting
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| More about Ondansetron | More about Zofran (ondansetron) | ||||||||
| Generic Status | |||||||||
Lower-cost generic is available | Lower-cost generic is available | ||||||||
| Ratings & Reviews | |||||||||
Ondansetron has an average rating of | Zofran has an average rating of | ||||||||
View all 473 reviews | View all 261 reviews | ||||||||
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| Side Effects | |||||||||
See also: ondansetron side effects in more detail. | See also: Zofran side effects in more detail. | ||||||||
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View all | We could not find an exact match for this medicine. Try searching the Price Guide directly. | ||||||||
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| Half Life The half-life of a drug is the time taken for the plasma concentration of a drug to reduce to half its original value.  | |||||||||
4 hours | 4 hours | ||||||||
| CSA Schedule ** View glossary of terms | |||||||||
Is not subject to the Controlled Substances Act. | Is not subject to the Controlled Substances Act. | ||||||||
| Pregnancy Category | |||||||||
See the full pregnancy warnings document. | See the full pregnancy warnings document. | ||||||||
| Drug Interactions | |||||||||
A total of 338 drugs are known to interact with ondansetron:
| A total of 338 drugs are known to interact with Zofran:
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| Alcohol/Food/Lifestyle Interactions | |||||||||
No known alcohol/food interactions. | No known alcohol/food interactions. This does not necessarily mean no interactions exist. Always consult your healthcare provider. | ||||||||
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January 04, 1991 | December 31, 1992 | ||||||||
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It is approved for use in adults and children over the age of 4. A headache, hypoxia, and fever are some of the more commonly reported side effects.</p>
<p>
Prescribed for Nausea/Vomiting, Nausea/Vomiting – Postoperative, Nausea/Vomiting – Chemotherapy Induced, Nausea/Vomiting – Radiation Induced.
</p>
<p>
Zofran may also be used for purposes not listed in this comparison guide.
</p>
”>
It is approved for use in adults and children over the age of 4. A…
7 out of 10 from a total of
This does not necessarily mean no interactions exist. Always consult your healthcare provider.** The Controlled Substances Act (CSA) schedule information displayed applies to substances regulated under federal law.
There may be variations in CSA schedules between individual states.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Medical Disclaimer
Ondansetron vs Zofran ODT Comparison
Ondansetron vs Zofran ODT Comparison – Drugs.com
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| Prescription only Prescribed for Nausea/Vomiting, Nausea/Vomiting – Postoperative, Nausea/Vomiting – Chemotherapy Induced, Nausea/Vomiting – Radiation Induced. | Related suggestions Nausea/Vomiting
Nausea/Vomiting, Chemotherapy Induced
Nausea/Vomiting, Postoperative
Nausea/Vomiting, Radiation Induced
Popular comparisons
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| More about Ondansetron | More about Zofran ODT (ondansetron) | ||||||||
| Generic Status | |||||||||
Lower-cost generic is available | Lower-cost generic is available | ||||||||
| Ratings & Reviews | |||||||||
Ondansetron has an average rating of | Zofran ODT has an average rating of | ||||||||
View all 473 reviews | View all 58 reviews | ||||||||
| Drug Class | |||||||||
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| Side Effects | |||||||||
See also: ondansetron side effects in more detail. | See also: Zofran ODT side effects in more detail. | ||||||||
| Pricing and Coupons * Prices are without insurance | |||||||||
View all | We could not find an exact match for this medicine. Try searching the Price Guide directly. | ||||||||
Get free Discount Card | Get free Discount Card | ||||||||
| Dosage Form(s) Available | |||||||||
|
| ||||||||
| Half Life The half-life of a drug is the time taken for the plasma concentration of a drug to reduce to half its original value.  | |||||||||
4 hours | 4 hours | ||||||||
| CSA Schedule ** View glossary of terms | |||||||||
Is not subject to the Controlled Substances Act. | Is not subject to the Controlled Substances Act. | ||||||||
| Pregnancy Category | |||||||||
See the full pregnancy warnings document. | See the full pregnancy warnings document. | ||||||||
| Drug Interactions | |||||||||
A total of 338 drugs are known to interact with ondansetron:
| A total of 338 drugs are known to interact with Zofran ODT:
| ||||||||
| Alcohol/Food/Lifestyle Interactions | |||||||||
No known alcohol/food interactions. | No known alcohol/food interactions. This does not necessarily mean no interactions exist. Always consult your healthcare provider. | ||||||||
| Disease Interactions | |||||||||
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| First Approval Date | |||||||||
January 04, 1991 | January 27, 1999 | ||||||||
| WADA Class View World Anti-Doping Agency classifications. | |||||||||
N/A | N/A | ||||||||
| More Information | |||||||||
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| Patient resources | |||||||||
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</p>
<p>
Prescribed for Nausea/Vomiting, Nausea/Vomiting – Postoperative, Nausea/Vomiting – Chemotherapy Induced, Nausea/Vomiting – Radiation Induced.
</p>
<p>
May also be
prescribed off label for Gastroenteritis, Alcohol Use Disorder, Obsessive Compulsive Disorder, Postanesthetic Shivering, Pruritus.
</p>
”>
..
Zofran ODT may also be used for purposes not listed in…
7 out of 10 from a total of
This does not necessarily mean no interactions exist. Always consult your healthcare provider.** The Controlled Substances Act (CSA) schedule information displayed applies to substances regulated under federal law.
There may be variations in CSA schedules between individual states.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Medical Disclaimer
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.
Fluorouracil infusion solution may contain up to 0.045% magnesium chloride in addition to other excipients that are compatible;
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 |
Zofran in the treatment of complications of cytostatic therapy | Abramov M.E., Lichinitser M.R.
Significant advances in chemotherapy in recent years are based on the development of supportive or concomitant therapy, which has made it possible to make the treatment of patients with cancer more effective.
Almost the entire spectrum of cytostatic drugs has a number of pronounced side effects. Nausea and vomiting are among the most common complications of chemotherapy. More recently, about 10% of patients refused chemotherapy or interrupted it prematurely due to the development of intolerable nausea and vomiting. Complications in the form of uncontrolled nausea and vomiting can force the postponement of chemotherapy and significantly worsen the patient’s quality of life. These complications include refusal to eat, malnutrition, dehydration, water and electrolyte imbalance and, as a result, damage to the cardiovascular and other body systems. These side effects of chemotherapy lead to depression of the emotional status, the development of depression that is difficult to stop. The length of hospitalization is extended, which leads to an increase in the cost of treatment. Overcoming these symptoms is an important task of effective treatment of cancer patients, aimed at improving the quality of life of patients.
Nausea and vomiting induced by chemotherapy are divided into 3 groups: acute (within 24 hours after the start of treatment), delayed (occurring 24 hours or more after treatment), and preliminary (occurs before the start of chemotherapy).
A key role in the development of acute nausea and vomiting is played by the neurotransmitter serotonin (5-HT), the release of which occurs when exposed to radiation therapy or the introduction of cytotoxic drugs from enterochromaffin cells of the small intestine mucosa. Serotonin acts on the 5-HT3 receptors of the trigger zone, impulses from which are transmitted to the center of vomiting in the CNS, which leads to the development of nausea and vomiting. Most 5-HT3-receptors are localized in the central structures of the brain, on the vagus nerve and neurons of the gastrointestinal tract. The effect of 5-HT3 receptor antagonists on 5-HT4 receptors is also important, which affects the mechanism of serotonin release when cytostatics are administered.
Another decisive mechanism for the development of nausea and vomiting is the stimulation of substance P neurokinin receptors (NK-1) [2,3,18].
In addition to cytotoxic drugs and radiation therapy, the cause of nausea and vomiting can also be brain metastases, metabolic disorders, ulcerative lesions of the gastrointestinal mucosa, non-steroidal anti-inflammatory drugs, opiates, digoxin, anticoagulants, anticholinergics, etc. The level of emetogenicity of cytostatics also depends on dose and route of administration. It has been shown that the intravenous drip route of administration reduces the emetogenicity of drugs (in contrast to bolus administration) [9]. Nausea and vomiting also depend on the characteristics of the patients themselves. It has been noted that the risk of nausea and vomiting increases with insufficient control of previous chemotherapy, it is most susceptible to women and patients under 65 years of age, as well as patients who rarely drink alcohol [4,10].
A full understanding of the neuropathophysiology of nausea and vomiting in the future will require a large number of scientific studies.
The neuropharmacological mechanism for the development of delayed nausea and vomiting is still unclear and requires further study, but, most likely, the leading role belongs to the mechanism of action of serotonin on 5-HT3 receptors.
Inadequate control of acute and delayed nausea and vomiting in the first courses (stages) of treatment often leads to nausea and vomiting before the next administration of the chemotherapy drug – nausea and vomiting of waiting. The risk of waiting nausea and vomiting has been shown to increase in the absence of adequate control in previous courses of chemotherapy [6].
All chemotherapy drugs are divided into 4 groups depending on the development and intensity of nausea and vomiting. This classification was developed based on the consensus of the International Association for Supportive Care in Oncology (MASCC) in September 2005 (Tables 1 and 2).
However, the presented classifications show the emetogenic potential of drugs when used in monotherapy.
Currently, the most commonly used combination chemotherapy (2, 3 or more cytotoxic drugs). To determine the emetogenicity of combinations, an algorithm was developed, presented in Table 3 [20].
Table 3 illustrates the algorithm for correctly assessing the emetogenicity of ongoing chemotherapy. The algorithm starts by identifying the most emetogenic drug in a given combination. Next, the degree of emetogenicity of other drugs included in the combination is assessed. When combined with a minimally emetogenic drug, the degree of emetogenicity of the combination is not enhanced. When combined with drugs from the group of low emetogenicity, the overall emetogenicity of the combination is increased by 1 level more than the most emetogenic drug from this combination. When adding level 3 or 4 drugs to the treatment regimen, the emetogenicity of the combination is increased by the level of each agent.
A retrospective analysis of a large number of studies on the emetogenicity of total body irradiation (TBI) showed high efficacy of 5-HT3 receptor antagonists.
According to the literature, the use of ondansetron (Zofran) at a dose of 8 mg allows 75–97% to achieve complete control of nausea and vomiting [9,12,14,15,19]. Table 4 presents data on emetogenicity depending on body areas during radiation therapy [6].
Based on a large number of studies and NCCN consensus, recommendations were made in 2004 for the prevention of nausea and vomiting during radiotherapy (Table 5).
Emetogenic potential may be high during total body or abdominal radiotherapy. In these cases, according to clinical studies, oral forms of ondansetron – Zofran (including a new unique form of the drug – lozenges) can be successfully used to prevent nausea and vomiting.
The level of emetogenicity of combined radiation and chemotherapy is determined by the emetogenicity of cytostatics with recommendations, as in chemotherapy regimens.
More than 40 years ago, Borison and Wang’s work [9] on animals initiated the study of the neuropathophysiology of nausea and vomiting.
Prior to the use of 5-HT3 receptor antagonists, various groups of drugs (phenothiazines, butyrophenones, corticosteroids, cannabinoids, benzodiazepines, etc.) were widely used over the past 30 years with minimal success [1]. For the first time in 1963, the Mayo Clinic demonstrated the effectiveness of prochlorperazine and thiopropazate in comparison with placebo in reducing nausea and vomiting when using drugs of 1-3 levels of emetogenicity [9]. But when using highly emetogenic regimens, unfortunately, the drugs of the above groups did not differ in effectiveness from placebo. Pronounced side effects when using these drugs in therapeutic doses severely limited their use. The development and introduction into wide practice at the beginning of 1990 of 5-HT3 receptor antagonists made it possible to radically reduce nausea and vomiting during chemotherapy. Due to the selective action, these drugs almost completely stop nausea and vomiting, while having minimal side effects [8,13].
The most common drugs from the group of 5-HT3 receptor antagonists – ondansetron (Zofran), tropisetron (Navoban), granisetron (Kitril) – differ slightly in pharmacokinetics.
The most studied and most commonly used is Zofran.
According to the literature, drugs from the group of 5-HT3 receptor blockers are metabolized by liver cytochrome P450 (CYP) [1,4,16].
Table 6 summarizes the 2004 NCCN recommendations for the prevention of acute nausea and vomiting when using highly emetogenic chemotherapy [5].
The 2004 NCCN recommendations for the prevention of acute and delayed nausea and vomiting when using low emetogenic chemotherapy are shown in Table 7.
The 2004 NCCN recommendations for the prevention of acute and delayed nausea and vomiting when using low emetogenic chemotherapy.
• Dexamethasone 12 mg orally or IV
or
• Prochlorperazine 10 mg orally or IV every 6 hours
or
• Metoclopramide 20–40 mg orally every 6 hours or 1–2 mg/kg IV 3 times daily ± diphenhydratamine 25 –50 mg orally or IV every 6 hours
• ± Lorazepam 0.5–2 mg orally or IV every 6 hours.
According to the 2004 NCCN guidelines, prevention of acute and delayed nausea and vomiting is not required with minimally emetogenic chemotherapy.
According to various authors, it is not always possible to achieve complete relief of nausea. In the case of incomplete relief of NCCN nausea in 2004, the following treatment regimen was proposed [5].
• Prochlorperazine 25 mg suppositories per rectum every 12 hours or 10 mg orally or 10 mg IV every 6 hours
or
• Metoclopramide 20–40 mg orally every 6 hours or 1–2 mg/kg IV 3 times a day ± Diphenhydratamine 25–50 mg orally or IV every 6 hours
or
• Lorazepam 0.5–2 mg orally every 6 hours
or
• Ondansetron 8 mg orally or IV daily
or
• Granisetron 1–2 mg orally or 1 mg twice daily orally or 0.01 mg/kg (maximum 1 mg) IV
or
• Dolasetron 100 mg orally or 1.8 mg/kg or 100 mg IV
or
• Haloperidol 1–2 mg orally every 6 hours or 1–3 mg intravenously every 6 hours
or
• Dronabinol 5–10 mg orally 3 times a day
or
• Dexamethasone 12 mg orally or intravenously if not previously given.
Many authors note that special attention should be paid to patients who receive high-dose chemotherapy, including as a conditioning agent before hematopoietic stem cell transplantation.
In this context, the causes of nausea and vomiting, in addition to chemotherapy, can be antibiotics, opioid analgesics, without which the management of pain in mucositis is indispensable, and also (in some cases) radiation. Meta-analysis of different antiemetic regimens is difficult due to the diversity of high-dose chemotherapy regimens and the heterogeneity of patient groups.
Three randomized trials of 5HT3 antagonists have been published in which ondansetron was more effective than metoclopramide and droperidol, granisetron showed the same efficacy as this therapy, and chlorpromazine in the form of a long-term infusion was comparable in efficacy to ondansetron, but more toxic. Thus, the standard approach for the prevention of nausea and vomiting in patients receiving high-dose chemotherapy, in particular in the context of hematopoietic stem cell transplantation, is ondansetron (if necessary, in combination with dexamethasone). Neither palonosetron nor aprepitant have been studied in this patient population.
Since the mid-1980s, great progress has been made in the development of antiemetics. Until that time, metoclopramide was used in highly emetogenic chemotherapy. Its effectiveness did not exceed 30-60%, with the development of side effects in the form of extrapyramidal disorders in 5% of cases. The development of antiemetics from among the blockers of serotonin type 3 receptors – 5-HT3 receptor antagonists, determined a breakthrough in chemotherapy.
Zofran (ondansetron) was first made available for general use on January 1991 g. A distinctive feature of this drug is its affinity not only for 5-HT3 receptors, but also for 5-HT1B, 5-HT1C, a1-adrenergic receptors, m-opioid receptors. This feature of Zofran to some extent can determine its effectiveness [1].
Zofran is currently considered the reference drug in antiemetic therapy. Recommended doses by the International Association for Supportive Care in Oncology (MASCC, see Annals of Oncology 17: 20-28, 2006) are 16-24 mg orally or 8 mg (0.
15 mg/kg) intravenously for acute vomiting or 8 mg 2 times a day orally – for delayed.
A distinctive feature of Zofran is its equal effectiveness when using low doses (8 mg) and high doses (32 mg) (the latter are recommended in the USA for highly emetogenic chemotherapy). These data were first published in 1992 by Seynaeve C. [1,3]. The 8 mg dose of Zofran in combination with corticosteroids is as effective as the 32 mg dose of Zofran in emetogenic therapy [8].
According to the literature, the combination of corticosteroids with 5-HT3 receptor antagonists is significantly more effective than combinations of corticosteroids with other drugs. Roila F. [1] at 1993 published data on the effectiveness of 79% (complete protection against nausea and vomiting) of a combination of 5-HT3 receptor antagonists in combination with corticosteroids, in contrast to 59% – in a combination of corticosteroids with other drugs, but without 5-HT3-antagonists receptors.
T.M. Beck et al published data on the use of oral Zofran (at various doses) in moderately emetogenic chemotherapy [7].
A double-blind, placebo-controlled study included 349 chemotherapy-naive patients. Compared to placebo (19% efficiency), the effectiveness of three oral doses of Zofran at a dose of 1 mg, 4 mg, 8 mg was 57, 65 and 66%, respectively.
It should be noted that most chemotherapy regimens currently in use do not require hospitalization of the patient and can be administered on an outpatient basis. In these cases, with acute and delayed nausea and vomiting, it is convenient to use oral forms of Zofran. In some cases, when oral administration of drugs is difficult, it is possible to use syrup, suppositories, and lozenges, which are not inferior in effectiveness to intravenous administration of Zofran [12,17]. These dosage forms make an invaluable contribution to the prevention of delayed nausea and vomiting, and are also successfully used in multi-day, oral regimens using highly emetogenic drugs. In addition, an additional convenience of Zofran lozenges is that they can be administered to patients with severe mucositis when other drugs are difficult to take.
As mentioned earlier, ondansetron is the most studied drug from the group of 5-HT3 receptor antagonists, with a favorable safety profile. The main side effects of 5-HT3 receptor antagonists are headache, dry mouth, abdominal pain, diarrhea, asthenia, and drowsiness. As a rule, these side effects do not require medical correction and are not clinically significant [8].
It should also be noted that odinsetron is the only drug approved for the prevention of postoperative nausea and vomiting [11]. Ondansetron at a dose of 4 mg can be recommended in the preoperative and postoperative period in order to relieve nausea and vomiting.
The development of antiemetics and combined regimens in combination with 5-HT3 receptor antagonists, steroids, NK1 receptor antagonists and other drugs has significantly reduced the emetogenicity of ongoing chemotherapy, making chemotherapy treatment outpatient and economical in many cases.
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