Zofsetron
Zofsetron Uses, Dosage, Side Effects, Food Interaction and all others data.
Zofsetron is a selective 5-HT3 receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT3 type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. It is not certain whether ondansetron's antiemetic action is mediated centrally, peripherally, or in both sites. However, cytotoxic chemotherapy appears to be associated with release of serotonin from the enterochromaffin cells of the small intestine.
Zofsetron is a highly specific and selective serotonin 5-HT3 receptor antagonist, not shown to have activity at other known serotonin receptors and with low affinity for dopamine receptors , . The serotonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema , . The temporal relationship between the emetogenic action of emetogenic drugs and the release of serotonin, as well as the efficacy of antiemetic agents, suggest that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract , . The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting , .
Moreover, the effect of ondansetron on the QTc interval was evaluated in a double-blind, randomized, placebo and positive (moxifloxacin) controlled, crossover study in 58 healthy adult men and women . Zofsetron was tested at single doses of 8 mg and 32 mg infused intravenously over 15 minutes . At the highest tested dose of 32 mg, prolongation of the Fridericia-corrected QTc interval (QT/RR0.33=QTcF) was observed from 15 min to 4 h after the start of the 15 min infusion, with a maximum mean (upper limit of 90% CI) difference in QTcF from placebo after baseline-correction of 19.6 (21.5) msec at 20 min . At the lower tested dose of 8 mg, QTc prolongation was observed from 15 min to 1 h after the start of the 15-minute infusion, with a maximum mean (upper limit of 90% CI) difference in QTcF from placebo after baseline-correction of 5.8 (7.8) msec at 15 min . The magnitude of QTc prolongation with ondansetron is expected to be greater if the infusion rate is faster than 15 minutes . The 32 mg intravenous dose of ondansetron must not be administered . No treatment-related effects on the QRS duration or the PR interval were observed at either the 8 or 32 mg dose .
An ECG assessment study has not been performed for orally administered ondansetron . On the basis of pharmacokinetic-pharmacodynamic modelling, an 8 mg oral dose of ondansetron is predicted to cause a mean QTcF increase of 0.7 ms (90% CI -2.1, 3.3) at steady-state, assuming a mean maximal plasma concentration of 24.7 ng/mL (95% CI 21.1, 29.0) . The magnitude of QTc prolongation at the recommended 5 mg/m2 dose in pediatrics has not been studied, but pharmacokinetic-pharmacodynamic modeling predicts a mean increase of 6.6 ms (90% CI 2.8, 10.7) at maximal plasma concentrations .
Trade Name | Zofsetron |
Availability | Prescription only |
Generic | Ondansetron |
Ondansetron Other Names | Ondansetron |
Related Drugs | hydroxyzine, lorazepam, Zofran, dexamethasone, meclizine, promethazine, diphenhydramine, Ativan, metoclopramide, Decadron |
Type | |
Formula | C18H19N3O |
Weight | Average: 293.363 Monoisotopic: 293.152812245 |
Protein binding | The plasma protein binding associated with ondansetron was documented as approximately 73% . |
Groups | Approved |
Therapeutic Class | Anti-emetic drugs |
Manufacturer | |
Available Country | Belgium |
Last Updated: | September 19, 2023 at 7:00 am |
![Zofsetron Zofsetron](https://www.medicinesfaq.com/media/png/zofsetron.png)
Uses
Zofsetron is used for:
- Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy
- Prevention of nausea and vomiting associated with radiotherapy
- Prevention of post operative nausea and vomiting
Zofsetron is also used to associated treatment for these conditions: Chemotherapy-Induced Nausea and Vomiting (CINV), Cholestatic pruritus, Post Operative Nausea and Vomiting (PONV), Uremic Pruritus, Radiation therapy induced nausea and vomiting, Severe Hyperemesis gravidarum
How Zofsetron works
Zofsetron is a selective antagonist of the serotonin receptor subtype, 5-HT3 .
Cytotoxic chemotherapy and radiotherapy are associated with the release of serotonin (5-HT) from enterochromaffin cells of the small intestine, presumably initiating a vomiting reflex through stimulation of 5-HT3 receptors located on vagal afferents . Zofsetron may block the initiation of this reflex. Activation of vagal afferents may also cause a central release of serotonin from the chemoreceptor trigger zone of the area postrema, located on the floor of the fourth ventricle . Thus, the antiemetic effect of ondansetron is probably due to the selective antagonism of 5-HT3 receptors on neurons located in either the peripheral or central nervous systems, or both .
Although the mechanisms of action of ondansetron in treating postoperative nausea and vomiting and cytotoxic induced nausea and vomiting may share similar pathways, the role of ondansetron in opiate-induced emesis has not yet been formally established .
Dosage
Zofsetron dosage
Prevention of chemotherapy induced nausea & vomiting (CINV):
Adult-
- Tablet and oral solution: The recommended adult oral dosage of Zofsetron is 24 mg given as three 8 mg tablets in highly emetogenic chemotherapy. In case of moderately emetogenic chemotherapy the oral dose is one 8 mg Zofsetron tablet or 10 ml of Zofsetron oral solution given twice daily.
- Injection: The recommended i.v. dose of Zofsetron is a single 32 mg dose or three 0.15 mg/kg doses. A single 32 mg dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. Subsequent doses (0.15 mg/kg) are administered 4 and 8 hours after the first dose of Zofsetron.
- Suppository: The recommended adult dose is one 16 mg suppository 1-2 hours before treatment. Zofsetron should be continued for upto 5 days after a course of treatment.The recommended dose is one suppository daily.
Pediatric patients-
- Tablet and oral solution:for pediatric patients 4 through 11 years of age the dosage is one 4 mg Zofsetron tablet or 5ml of Zofsetron solution should be administered 3 times a day for 1 to 2 days after completion of chemotherapy.
- Injection: the dosage in pediatric patients 4 to 18 years of age should three 0.15-mg/kg doses.
- Suppository:Not recommended.
Radiotherapy induced nausea and vomiting:
Adult-
- Tablet and oral solution: the recommended oral dosage is one 8mg Zofsetron tablet or 10ml of Zofsetron oral solution given 3 times daily.
Post operative nausea & vomiting (PONV):
Adult-
- Tablet and oral solution: The recommended dosage is 16 mg given as two 8 mg Zofsetron tablets or 20 ml of Zofsetron oral solution 1hour before induction of anesthesia.
- Injection: The recommended I.V. dosage of Zofsetron for adults is 4 mg undiluted administered intravenously in not less than 30 seconds, preferably over 2 to 5 minutes, immediately before induction of anesthesia, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery. Alternatively, 4 mg undiluted may be administered intramuscularly as a single injection for adults. In patients who do not achieve adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, I.V. dose of Zofsetron 4 mg, administration of a second I.V. dose of 4 mg Zofsetron postoperatively does not provide additional control of nausea and vomiting.
- Suppository: The recommended adult dose is one 16 mg suppository 1-2 hours before treatment. Zofsetron should be continued for upto 5 days after a course of treatment.The recommended dose is one suppository daily.
Pediatric patients-
- Injection: The recommended I.V. dosage of Zofsetron for pediatric patients (2 to 12 years of age) isa single 0.1-mg/kg dose for pediatric patients weighing 40 kg or less, or a single 4 mg dose for pediatric patients weighing more than 40 kg. The rate of administration should not be less than 30 seconds, preferably over 2 to 5 minutes. Little information is available about dosage in pediatric patients younger than 2 years of age.
- Suppository: Not recommended.
Prior to IV infusion, dilute in 50 ml dextrose 5% inj or normal saline.
Side Effects
The most common adverse effects include headache, constipation, diarrhea. In chemotherapy induced nausea and vomiting rash has occurred in approximately 1% of patients receiving Zofsetron. Blurred vision, chest pain with or without ST segment depression, cardiac arrhythmias, hypotension and bradycardia have been rarely reported.
Toxicity
At present, there is little information concerning overdosage with ondansetron . Nevertheless, there have been certain cases of somewhat idiosyncratic adverse effects associated with particular dosages of ondansetron used .
“Sudden blindness” (amaurosis) of 2 to 3 minutes duration plus severe constipation occurred in one patient that was administered 72 mg of ondansetron intravenously as a single dose . Hypotension (and faintness) occurred in another patient that took 48 mg of oral ondansetron . Following infusion of 32 mg over only a 4-minute period, a vasovagal episode with transient second-degree heart block was observed . Neuromuscular abnormalities, autonomic instability, somnolence, and a brief generalized tonic-clonic seizure (which resolved after a dose of benzodiazepine) were observed in a 12-month-old infant who ingested seven or eight 8-mg ondansetron tablets (approximately forty times the recommended 0.1-0.15 mg/kg dose for a pediatric patient) . In all instances, however, the events resolved completely .
The safety of ondansetron for use in human pregnancy has not been established . Zofsetron is not teratogenic in animals . However, as animal studies are not always predictive of human response, the use of ondansetron in pregnancy is not recommended .
Zofsetron is excreted in the milk of lactating rats . It is not known if it is excreted in human milk, however, nursing is not recommended during treatment with ondansetron .
Insufficient information is available to provide dosage recommendations for children 3 years of age or younger .
Precaution
Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other 5-HT3 receptor antagonists. Zofsetron is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction. The use of Zofsetron in patients following abdominal surgery or in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus and/or gastric distension.
Interaction
In patients treated with potent inducers of CYP3A4 (i.e Phenytoin, Carbamazepine or Rifampicin), the oral clearance of Zofsetron was increased and Zofsetron blood concentrations were decreased. Data from small studies indicate that Zofsetron may reduce the analgesic effect of tramadol.
Food Interaction
- Take with or without food. The absorption is unaffected by food.
Zofsetron Drug Interaction
Major: duloxetineModerate: polyethylene glycol 3350, acetaminophen / hydrocodone, albuterolUnknown: amphetamine / dextroamphetamine, diphenhydramine, omega-3 polyunsaturated fatty acids, fluticasone nasal, pregabalin, metoprolol, metoprolol, acetaminophen, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, ergocalciferol, cholecalciferol, alprazolam, cetirizine
Zofsetron Disease Interaction
Volume of Distribution
The volume of distribution of ondansetron has been recorded as being approximately 160L .
Elimination Route
Zofsetron is absorbed from the gastrointestinal tract and undergoes some limited first-pass metabolism . Mean bioavailability in healthy subjects, following administration of a single 8-mg tablet, was recorded as being approximately 56% to 60% . Bioavailability is also slightly enhanced by the presence of food .
Zofsetron systemic exposure does not increase proportionately to dose . The AUC from a 16-mg tablet was 24% greater than predicted from an 8-mg tablet dose . This may reflect some reduction of first-pass metabolism at higher oral doses .
Half Life
The half-life of ondansetron after either an 8 mg oral dose or intravenous dose was approximately 3-4 hours and could be extended to 6-8 hours in the elderly .
Clearance
The clearance values determined for ondansetron in various patient age groups were recorded as approximately 0.38 L/h/kg in normal adult volunteers aged 19-40 yrs, 0.32 L/h/kg in normal adult volunteers aged 61-74 yrs, 0.26 L/h/kg in normal adult volunteers aged >=75 yrs .
Elimination Route
Following oral or IV administration, ondansetron is extensively metabolised and excreted in the urine and faeces .
Pregnancy & Breastfeeding use
In pregnancy: Pregnancy category B. Reproduction studies at daily oral dose up to 10 and 30 mg/kg/day have been performed in animals and have revealed no evidence of impaired fertility harm to the fetus due to Zofsetron. There are, however, no adequate and well-controlled studies in pregnant women. So the drug should be used in pregnancy only if clearly needed.
In lactation: Zofsetron excretes in milk of lactating animals. Caution should be exercised when Zofsetron is administered to nursing mother.
Contraindication
Zofsetron is contraindicated in patients with known hypersensitivity to the drug.
Special Warning
Pediatric use: Can be given in children 1 month of age and above.
Geriatric use: No dosage adjustment is necessary in the elderly.Dosage adjustment for patients with impaired hepatic function:
- Tablet and Oral Solution: The total daily dose of 8 mg should not be exceeded.
- Injection: A single maximal dose of 8 mg to be infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended.
- Suppository: Not recommended
Acute Overdose
There is no specific antidote for Zofsetron overdose. In addition to the adverse events, hypotension (and faintness) occurred in a patient that took 48 mg of AVONA tablets. In all instances, the events resolved completely.
Storage Condition
Store in a cool and dry place, protected from light and moisture. For suppository- Store below 25º c.
Innovators Monograph
You find simplified version here Zofsetron
Zofsetron contains Ondansetron see full prescribing information from innovator Zofsetron Monograph, Zofsetron MSDS, Zofsetron FDA label
FAQ
What is Zofsetron used for?
Zofsetron is used to prevent nausea and vomiting that may be caused by surgery, cancer chemotherapy, or radiation treatment.
How safe is Zofsetron?
Zofsetron may increase the risk of developing abnormal changes in the electrical activity of the heart, which can result in a potentially fatal abnormal heart rhythm.
How does Zofsetron work?
Zofsetron works by blocking the action of serotonin, a natural substance that may cause nausea and vomiting.
What are the common side effects of Zofsetron?
Common side effects of Zofsetron are include :
- headache.
- constipation.
- weakness.
- tiredness.
- chills.
- drowsiness.
Is Zofsetron safe during pregnancy?
Zofsetron is safe to use during the first trimester when most women experience morning sickness.
Is Zofsetron safe during breastfeeding?
Zofsetron appears to be compatible with breastfeeding and has limited adverse effects in normal use.
Can I drink alcohol with Zofsetron?
Zofsetron and alcohol do not directly interact, Zofsetron has many common side effects that could be worsened by alcohol, such as drowsiness or dizziness.
Can I drive after taking Zofsetron ?
Zofsetron may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely.
When should be taken of Zofsetron?
The first dose of Zofsetron is usually taken 30 minutes before the start of chemotherapy, 1 to 2 hours before the start of radiation therapy, or 1 hour before surgery. Additional doses are sometimes taken one to three times a day during chemotherapy or radiation therapy and for 1 to 2 days after the end of treatment.
How often should Zofsetron be taken?
Zofsetron may be taken up to 3 times a day for 1 to 2 days after your chemotherapy or radiation treatment is finished. If you are taking this medication on a prescribed schedule, take it regularly in order to get the most benefit from it. To help you remember, take it at the same times each day.
How long does it take for Zofsetron to start working?
Zofsetron should start to work within 30 minutes to an hour.
Does barnd work better on an empty stomach?
Medicines generally work faster on an empty stomach, an hour before food or 2 hours after.
How long does Zofsetron stay in my system?
Zofsetron has a half-life of three to four hours in healthy adults, but this may be increased to six to eight hours in older adults.
Does Zofsetron build up in my system?
Taking Zofsetron while you are using certain other medicines can cause high levels of serotonin to build up in your body, a condition called serotonin syndrome which can be fatal.
How long can I take Zofsetron?
Zofsetron may be taken up to 3 times a day for 1 to 2 days after your chemotherapy or radiation treatment is finished. If you are taking this medication on a prescribed schedule, take it regularly in order to get the most benefit from it.
Who should not take Zofsetron?
You should not use Zofsetron if you are also using apomorphine or you are allergic to Zofsetron or similar medicines.
What happens if I miss a dose of Zofsetron?
Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
What happens if I overdose of Zofsetron?
Seek emergency medical attention.Overdose symptoms may include sudden loss of vision, severe constipation, feeling light-headed, or fainting.
What happen If I stop taking Zofsetron?
If you stop taking the drug suddenly or don't take it at all.You could have nausea and vomiting that's not controlled.
Does Zofsetron stop stomach pain?
Zofsetron taken at higher doses might also relieve pain.
Does Zofsetron stop vomiting?
Zofsetron is used to prevent nausea and vomiting that may be caused by surgery, cancer chemotherapy, or radiation treatment.
Does Zofsetron cause heart palpitations?
Zofsetron can cause erratic heartbeats and high serotonin levels, which may be life-threatening.