EMITRON TABLETS

Indications

• Prevention of nausea and vomiting associated with cytotoxic chemotherapy
• Prevention of postoperative nausea and vomiting
• Management of nausea and vomiting induced by radiotherapy

Dosage

Adults: For adults, ondansetron is typically administered as 8 mg before chemotherapy or surgery, followed by an additional 8 mg dose 12 hours later if necessary. The maximum total dose should not

Mechanism of action

Ondansetron selectively antagonizes the serotonin receptor subtype 5-HT3. Cytotoxic chemotherapy and radiotherapy cause serotonin release from enterochromaffin cells in the small intestine, leading to the stimulation of 5-HT3 receptors on vagal afferents, which can initiate the vomiting reflex. By blocking these receptors, ondansetron interrupts this pathway, thus preventing nausea and vomiting. Additionally, it may influence the central nervous system by affecting the chemoreceptor trigger zone in the area postrema.

Pharmacodynamics

Ondansetron is a highly specific and selective 5-HT3 receptor antagonist with minimal activity at other serotonin receptors and low affinity for dopamine receptors. Its pharmacodynamic properties are characterized by its ability to inhibit the 5-HT3-mediated vomiting reflex, which is triggered by the release of serotonin due to the gastrointestinal effects of emetogenic drugs. The drug has a significant role in controlling nausea and vomiting without major sedative effects.

Pharmacokinetics

Ondansetron is well-absorbed after intravenous or oral administration, with peak plasma concentrations reached within 1-2 hours. It has a bioavailability of approximately 60% when taken orally. The drug is extensively metabolized in the liver, primarily by CYP3A4, CYP2D6, and CYP1A2 enzymes. Its elimination half-life ranges from 3 to 6 hours, and it is primarily excreted in urine as metabolites, with less than 5% of the dose excreted unchanged. Patients with hepatic impairment may require dose adjustments due to altered metabolism.

Adverse effects

• Extrapyramidal symptoms
• QT interval prolongation
• Serotonin syndrome
• Dystonia
• Appetite decreased
• Dry mouth
• Flushing
• Generalised oedema
• Vertigo

Interactions

• Mitotane - Unknown (decreases exposure)

Precautions

• Caution in hepatic impairment
• Avoid in pregnancy
• Avoid during breastfeeding

Pregnancy

Manufacturer advises to avoid use during pregnancy.

Breast-feeding

Avoid – no information available.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Powder for solution for infusion
• Solution for injection
• Tablets
• Transdermal patch

Indications

• Difficulty swallowing
• Dysphagia
• Pediatric use
• Elderly patients
• Patients with nausea

Dosage

Children: Refer to the BNF for Children for specific dosing guidance tailored to pediatric patients.

Adults: Refer to the prescribing information for specific dosages, as they can vary widely depending on the active ingredient and indication.

Mechanism of action

Disintegrating tablets utilize disintegrants that swell and promote rapid breakdown of the tablet upon contact with saliva. This action increases the surface area of the drug, facilitating quicker dissolution and absorption in the gastrointestinal tract. The rapid disintegration enhances the onset of action of the active pharmaceutical ingredients.

Pharmacodynamics

The pharmacodynamics of disintegrating tablets is primarily determined by the active ingredients they contain. Upon disintegration, the active drug is released into the saliva, which aids in absorption through the oral mucosa or, after swallowing, in the gastrointestinal tract. This delivery method can lead to faster onset of action compared to traditional tablets, particularly for drugs that are absorbed quickly.

Pharmacokinetics

The pharmacokinetics of disintegrating tablets vary based on the specific drug formulation and the active ingredients used. Generally, after disintegration and dissolution, the drug is absorbed in the gastrointestinal tract, with peak plasma concentrations occurring at different times depending on the drug's properties. Factors such as solubility, permeability, and presence of food can influence the absorption rate and bioavailability.

Pregnancy

Safety in pregnancy has not been established. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Use with caution. Monitor for adverse effects in the infant.

Storage

Store at room temperature, away from moisture and heat. Keep in a tightly closed container.

Dosage

Children: Refer to specific drug monographs for paediatric dosing information, as it varies widely based on the medication and condition treated.

Adults: Refer to specific drug monographs for adult dosing information, as it varies widely based on the medication and condition treated.

Mechanism of action

The mechanism of action for orally administered drugs varies widely based on the specific medication. Generally, once ingested, drugs are absorbed through the gastrointestinal tract into the bloodstream, where they interact with target receptors or enzymes to exert their therapeutic effects. The pharmacological action depends on the specific drug's chemical structure and designed therapeutic pathway.

Pharmacodynamics

Pharmacodynamics describes how a drug affects the body, including the relationship between drug concentration and effect. For orally administered drugs, factors such as absorption rate, distribution, metabolism, and excretion influence therapeutic outcomes. Drugs may act as agonists or antagonists at receptor sites, modulating physiological responses to achieve desired effects.

Pharmacokinetics

Pharmacokinetics involves the study of how the body absorbs, distributes, metabolizes, and excretes drugs taken orally. The absorption phase can be affected by factors such as gastric pH, presence of food, and gastrointestinal motility. Once absorbed, drugs are distributed via the bloodstream to various tissues. Metabolism primarily occurs in the liver, where drugs may be converted into active or inactive forms. Excretion mainly occurs through the kidneys, eliminating drugs and their metabolites from the body.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Dizziness
• Headache
• Dry mouth
• Fatigue

Precautions

• Use with caution in patients with gastrointestinal disorders
• Monitor for potential allergic reactions
• Consider renal and hepatic function when prescribing

Pregnancy

Safety during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised. The effects on nursing infants are unknown.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Mechanism of action

Ondansetron 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. Ondansetron 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.

Pharmacodynamics

Ondansetron 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. Ondansetron 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. In healthy subjects, single intravenous doses of 0.15 mg/kg of ondansetron had no effect on esophageal motility, gastric motility, lower esophageal sphincter pressure, or small intestinal transit time. Multiday administration of ondansetron has been shown to slow colonic transit in healthy subjects. Ondansetron has no effect on plasma prolactin concentrations.