How does Zofran work to prevent nausea and vomiting. What is the recommended dosage for adults and children. How often can Zofran be taken safely. What are the potential side effects and precautions for using Zofran.

Understanding Zofran: An Effective Antiemetic Medication

Zofran, also known by its generic name ondansetron, is a powerful prescription medication used to prevent and treat nausea and vomiting. It belongs to a class of drugs called 5-HT3 receptor antagonists, which work by blocking the action of serotonin in the body. This blockade helps to reduce the triggering of nausea and the initiation of the vomiting reflex.

Zofran is commonly prescribed for patients undergoing cancer treatments such as chemotherapy and radiation therapy, as well as for those experiencing post-operative nausea and vomiting. It is available in various forms, including oral tablets, orally disintegrating tablets, oral films, oral solution, and injection vials, providing flexibility in administration based on patient needs and preferences.

Zofran Dosage Guidelines: Tailoring Treatment to Patient Needs

The dosage of Zofran varies depending on the severity of nausea, the underlying cause, and the patient’s age. Here are some general guidelines for Zofran dosing:

Adult Dosing for Chemotherapy-Induced Nausea and Vomiting

• Severe cases: A single 24 mg dose taken 30 minutes before highly emetogenic chemotherapy.
• Moderate cases: 8 mg taken 30 minutes before chemotherapy, followed by another 8 mg dose 8 hours later. After chemotherapy, 8 mg every 12 hours for 1-2 days.

Adult Dosing for Radiation Therapy

8 mg taken 1-2 hours before radiation therapy, followed by 8 mg every 8 hours as needed, depending on the type and location of radiation.

Adult Dosing for Post-Operative Nausea and Vomiting

16 mg administered 1 hour before anesthesia.

Pediatric Dosing for Chemotherapy-Induced Nausea and Vomiting

• Ages 4-11: 4 mg taken 30 minutes before chemotherapy, followed by 4 mg doses at 4 and 8 hours after the first dose. After chemotherapy, 4 mg every 8 hours for 1-2 days.
• Ages 12-17: 8 mg taken 30 minutes before chemotherapy, followed by an 8 mg dose 8 hours later. After chemotherapy, 8 mg every 12 hours for 1-2 days.

Frequency of Zofran Administration: Finding the Right Balance

The frequency of Zofran administration is crucial for maintaining its effectiveness while minimizing potential side effects. But how often can Zofran be taken safely?

For adults, the typical dosing frequency is every 8-12 hours, or 2-3 times a day, with a standard dose of 8 mg. However, in some cases, such as pediatric chemotherapy-induced nausea, doses may be given as frequently as every 4 hours initially, followed by a less frequent regimen.

It’s important to note that Zofran should not be taken more frequently than prescribed by a healthcare provider. The maximum daily dose and frequency are determined based on factors such as the severity of symptoms, the patient’s age, and any underlying health conditions.

Zofran and QT Prolongation: Understanding the 8-Hour Rule

Why is Zofran typically administered every 8 hours? The 8-hour interval between doses is primarily due to the risk of QT prolongation, a potentially serious heart rhythm disorder. Clinical trials have shown that ondansetron can increase the risk of QT prolongation, particularly at higher doses or with more frequent administration.

QT prolongation can lead to a potentially life-threatening arrhythmia called Torsades de Pointes. To minimize this risk, healthcare providers typically limit the frequency of Zofran administration to every 8 hours or less frequently, depending on the specific dosing regimen.

Special Considerations and Precautions for Zofran Use

While Zofran is generally well-tolerated, there are several important precautions and considerations to keep in mind:

• Liver Disease: Patients with severe liver disease should not exceed 8 mg of ondansetron per day.
• Pregnancy: Zofran is not FDA-approved for use during pregnancy. However, some studies have shown its safety in treating morning sickness during the first trimester. Pregnant women should consult their healthcare provider before using Zofran.
• Breastfeeding: The safety of Zofran during breastfeeding is not well-established. Nursing mothers should discuss the risks and benefits with their healthcare provider.
• Pediatric Use: Zofran is not approved for use in children younger than 4 years old.
• Drug Interactions: Zofran may interact with other medications, particularly those that affect heart rhythm or serotonin levels in the body.

Managing Side Effects and Monitoring Zofran Effectiveness

Like all medications, Zofran can cause side effects. Common side effects may include headache, constipation, and fatigue. More serious side effects, such as allergic reactions or irregular heartbeat, should be reported to a healthcare provider immediately.

It’s essential to monitor the effectiveness of Zofran in controlling nausea and vomiting. If symptoms persist or worsen despite taking Zofran as prescribed, patients should consult their healthcare provider. The dosage or frequency may need to be adjusted, or an alternative antiemetic medication may be considered.

Alternatives to Zofran: Exploring Other Antiemetic Options

While Zofran is a highly effective antiemetic medication, it’s not the only option available for managing nausea and vomiting. Depending on the underlying cause and individual patient factors, healthcare providers may consider alternative medications or complementary therapies.

Other 5-HT3 Receptor Antagonists

Zofran belongs to a class of medications called 5-HT3 receptor antagonists. Other drugs in this class include:

• Granisetron (Kytril)
• Palonosetron (Aloxi)
• Dolasetron (Anzemet)

These medications work similarly to Zofran and may be prescribed as alternatives if Zofran is not well-tolerated or ineffective.

Other Antiemetic Medications

Several other classes of medications can be used to manage nausea and vomiting, including:

• Dopamine antagonists (e.g., metoclopramide, domperidone)
• NK1 receptor antagonists (e.g., aprepitant)
• Antihistamines (e.g., promethazine)
• Cannabinoids (e.g., dronabinol)
• Benzodiazepines (e.g., lorazepam)

The choice of antiemetic medication depends on various factors, including the cause of nausea, patient characteristics, and potential drug interactions.

Non-Pharmacological Approaches

In addition to medication, several non-pharmacological approaches can help manage nausea and vomiting:

• Dietary modifications (e.g., eating small, frequent meals)
• Acupressure or acupuncture
• Ginger supplements
• Relaxation techniques
• Aromatherapy

These approaches may be used in conjunction with antiemetic medications to provide comprehensive symptom management.

The Future of Antiemetic Therapy: Emerging Treatments and Research

As our understanding of the mechanisms underlying nausea and vomiting continues to evolve, researchers are exploring new approaches to antiemetic therapy. Some areas of ongoing research include:

Combination Therapies

Combining different classes of antiemetic medications may provide more comprehensive symptom control. For example, using a 5-HT3 receptor antagonist like Zofran in combination with an NK1 receptor antagonist has shown promise in managing chemotherapy-induced nausea and vomiting.

Personalized Medicine Approaches

Genetic factors may influence an individual’s response to antiemetic medications. Research is ongoing to identify genetic markers that could predict a patient’s response to specific antiemetics, allowing for more tailored treatment approaches.

Novel Drug Targets

Scientists are investigating new molecular targets for antiemetic therapy. For example, research is being conducted on medications that target the endocannabinoid system or other neurotransmitter systems involved in nausea and vomiting.

Improved Delivery Methods

Developing new formulations and delivery methods for antiemetic medications could improve their effectiveness and reduce side effects. For instance, transdermal patches or long-acting injectable formulations could provide more consistent symptom control.

As research in these areas progresses, it’s likely that we’ll see new and improved options for managing nausea and vomiting in the coming years, potentially offering alternatives or complements to established medications like Zofran.

Patient Education: Maximizing the Benefits of Zofran Therapy

Proper patient education is crucial for ensuring the safe and effective use of Zofran. Healthcare providers should discuss the following points with patients prescribed Zofran:

Proper Administration

• Take Zofran exactly as prescribed, following the recommended dosage and frequency.
• For orally disintegrating tablets, allow the tablet to dissolve on the tongue before swallowing.
• Take Zofran with or without food, but be consistent in how you take it.

Timing of Doses

Emphasize the importance of taking Zofran at the prescribed intervals, particularly for preventing chemotherapy-induced nausea and vomiting. Explain that taking doses too close together can increase the risk of side effects.

Missed Doses

Instruct patients on what to do if they miss a dose. Generally, if it’s close to the time for the next dose, it’s best to skip the missed dose and continue with the regular schedule.

Potential Side Effects

Educate patients about common side effects and when to seek medical attention. Emphasize the importance of reporting any unusual symptoms, particularly those related to heart rhythm disturbances.

Drug Interactions

Advise patients to inform their healthcare provider about all medications they’re taking, including over-the-counter drugs and supplements, to avoid potential interactions.

Monitoring Effectiveness

Encourage patients to keep a record of their nausea and vomiting episodes and the effectiveness of Zofran in controlling these symptoms. This information can help healthcare providers adjust the treatment plan if needed.

By providing comprehensive education and support, healthcare providers can help patients maximize the benefits of Zofran therapy while minimizing potential risks and side effects.

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

Ondansetron OD Tabs / 8mg / 30 Count – Rising Pharmaceuticals

January 19, 2021/by admin8mg / 30 Count
Back to Products

Brand name: Zofran ODT®

1 Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥ 50 mg/m2.

2 Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

3 Prevention of nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen.

4 Prevention of postoperative nausea and/or vomiting. As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and/or vomiting must be avoided postoperatively, ondansetron orally disintegrating tablets, USP are recommended even where the incidence of postoperative nausea and/or vomiting is low.

For more information please see the prescribing information on DailyMed.

*The brand names listed are not owned by Rising Pharma. Rising Pharma products are generic equivalents to the respective brand names listed on this website.

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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 cytostatic 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 cytostatic drugs and radiation therapy, the cause of nausea and vomiting can also be brain metastases, metabolic disorders, ulcerative lesions of the gastrointestinal mucosa, the use of 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 the development 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).
With total body or abdominal radiotherapy, the emetogenic potential may be high. 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, the work of Borison and Wang [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 IV every 6 hours
or
• Dronabinol 5–10 mg orally 3 times a day
or
• Dexamethasone 12 mg orally or IV 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 with 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 antiemetic drugs. 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 the 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 (in 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.

Literature
1. Schnell F.M.. Chemotherapy – induced nausea and vomiting: the importance of acute antiemetic control. The Oncologist 2003, Vol. 8, No 2, 187–198.
2. Belle S.V., Lichinitser M.R. et all. Prevention of Cisplatin – Induced acute and delayed emesis by the selective Neurokinin – 1 antagonists, L–758, 298 and MK – 869. Cancer 2002; 94;3032–41.
3. Kris M.G., Hesketh P.J., et all. Consensus proposals for the prevention of acute and delayed vomiting and nausea following high-emetic-risk chemotherapy. Support Care Cancer 2005, 13:85–96.
4. By Rolf Kaiser, Orhan Sezer, Anja Papies, Steffen Bauer, Claudia Schelenz, Pierre–Benoit Tremblay, Kurt Possinger, Ivar Roots, J?rgen Brockm?ller. Patient–Tailored Antiemetic Treatment With 5–Hydroxytryptamine Type 3 Receptor Antagonists According to Cytochrome P–450 2D6 Genotypes Journal of Clinical Oncology, Vol 20, Issue 12 (June), 2002: 2805–2811
5. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology v. 1. 2004.
6. Perugia International cancer conference VII. Consensus conference on antiemetic therapy.
Multinational Association of Supportive Care in Cancer September 2005.
7. Thomas M. Beck; Arthur A. Ciociola; Stephen E. Jones; Walter H. Harvey; N. Simon Tchekmedian; Alex Chang; Daniel Galvin; Nan E. Hart, Ondansetron Study Group* Efficacy of Oral Ondansetron in the Prevention of Emesis in Outpatients Receiving Cyclophosphamide–based Chemotherapy. Annals of internal medicine, 15 March 1993, Volume 118 Issue 6, Pages 407–413
8. Goodin S., Cunningham R. 5–HT3 – receptor antagonists for the treatment of nausea and vomiting: a reappraisal of their side–effect profile.The Oncologist 2002, Vol. 7, 424–436.
9. Steven M. Grunberg, and Paul J. Hesketh. Control of Chemotherapy–Induced Emesis The New England journal of medicine, Volume 329:1790–1796, December 9, 1993, Number 24
10. Verna A. Rohodes, Eds and Roxanne W. McDaniel, Ph D. Nausea, vomiting, and retching: complex problems in palliative care. CA Cancer J. Clinical 2001, 51: 232–248.
11. Darkow T., Pharm. D., et all. Impact of antiemetic selection on postoperative nausea and vomiting and patient satisfaction. Pharmacotherapy 21(5):540-548. 2001.
12. Herrstedt J., Koeller J.M., Roila F., Warr D., et all. Acute emesis: moderately emetogenic chemotherapy. Support Care Cancer 2005, 13:97–103.
13. Herrington Jon D. Pharm. D., Peter Kwan, et all. Randomized, multicenter comparison of oral Granisetron and oral Ondansetron for emetogenic chemotherapy. Pharmacotherapy 20 (11): 1318 – 1323. 2000.
14. The Italian Group for Antiemetic Research Dexametasone alone or in combination with Ondansetron for the prevention of delayed nausea and vomiting induced by chemotherapy. The New England journal of medicine, Volume 342:1554–1559, May 25, 2000, number 21.
15. Steven M. Grunberg, Paul J. Hesketh, D. Osoba et all. Evaluation of new antiemetic agents and definition of antineoplastic agent emetogeniciti – an update. Support Care Cancer 2005, 13:80–84.
16. Pierre-Benoit Tremblay, Rolf Kaiser, Orhan Sezer, Nadja Rosler, Claudia Schelenz, Kurt Possinger, Ivar Roots, Jorgen Brockmaller Variations in the 5-Hydroxytryptamine Type 3B Receptor Gene as Predictors of the Efficacy of Antiemetic Treatment in Cancer Patients. Journal of Clinical Oncology, Vol 21, Issue 11 (June), 2003: 2147–2155
17. Marc L. Citron Placebos and Principles: A Trial of Ondansetron. Annals of internal medicine, 15 March 1993, Volume 118 Issue 6, Pages 470–471
18. Jordan K., Kasper C., Schmoll H.–J. Chemotherapy – induced nausea and vomiting: current and new standards in the antiemetic prophylaxis and treatment. European Journal of Cancer 41, 2005, 199–205.
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20. Hesketh P.J. Defining the emetogenicity of cancer chemotherapy regimens: relevance to clinical practice. The Oncologist 1999, 4, 1

Zofran instructions, price in pharmacies of Ukraine

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

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

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

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

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

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

In patients with impaired function, the systemic clearance and volume of distribution of the active ingredient are reduced. The period of administration in patients with impaired blood function and creatinine clearance of 15 to 60 ml / hv reaches 5.4 years.

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

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

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

Indication before congestion:

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

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

Injection method:

Injection retailer

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

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

• 0.9% sodium chloride brand;
• Rozchin Ringer;
• 10% manitol;
• 5% glucose solution;
• 0.3% potassium chloride and 0.9% sodium chloride;
• 0.3% potassium chloride and 5% glucose.

The drug is stable in case of congestion of polyethylene infusion bags and glass bottles type 1. The drug is made in 5% glucose or 0.9% sodium chloride, as well as the drug in other total sizes for intravenous administration is stable in polypropylene syringes.

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

• Cysplate (concentration ia 0.48 mg / ml) for 1-8 years;
• 5-fluorouracil (concentration 0.8 mg/ml) at a rate not exceeding 20 ml per year;
• Carboplatin (concentration 0.18-9.9 mg / ml) with a stretch of 10-60 strands;
• Etoposide (concentration 0. 14-0.25 mg/ml) with a draw of 30-60 strands;
• Ceftazidime (dose 250-2000mg), administered in water for injections according to the recommended instructions, stretching 5 strands at a time of intravenous bolus injection;
• Cyclophosphamide (dose 100-1000mg) is varied in water for injection according to the recommended instructions, with a stretch of 5 strands at the same time as an internal bolus injection;
• Doxorubicin (dose 10-100mg) is administered in water for injections according to the recommended instructions, stretching 5 strands at a time of internal bolus injection;
• The drug can also be mixed in a single urticaria with dexamethasone sodium phosphate phosphate (dose of ondansetron in a range of 8 µg/ml up to 1 mg/ml, dose of dexamethasone phosphate in a range of 32 µg/ml up to 2.5 g/ml) entry hour 50- 100 ml rozchin not less than 15 quills.

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

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

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

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

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

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

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

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

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

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

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

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

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

Syrup, coated tablets, lingual tablets:

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

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

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

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

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

Rectal suppositories:

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

Older, if you want to take a course of chemotherapy or radiotherapy, with nausea and vomiting, prescribe 1 suppository of the drug 1-2 years before the start of therapy.