Onsia

Ondansetron hydrochloride dihydrate.

ONSIA (4 MG TABLET): Each tablet contains Ondansetron (as hydrochloride dihydrate) 4 mg.
ONSIA (8 MG TABLET): Each tablet contains Ondansetron (as hydrochloride dihydrate) 8 mg.
ONSIA INJECTION: Each mL contains Ondansetron (as hydrochloride dihydrate) 2 mg.

Pharmacology: Pharmacodynamics: Ondansetron is a competitive, highly selective 5-HT₃ receptor antagonist, acting on both central and peripheral nervous systems.
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. Chemotherapeutic agents and radiotherapy may cause release of 5-HT₃ in the small intestine initiating a vomiting reflex by activating vagal afferents via 5-HT₃ receptors. Thus, Ondansetron is used for the management of the nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy.
Pharmacokinetics: After oral administration, Ondansetron is well absorbed via GI tract. The absolute bioavailability is only about 60%, mainly because of hepatic first-pass metabolism. Ondansetron is extensively distributed into the body and about 70-75% plasma protein bound. It is metabolized in the liver through cytochrome P450 isoenzymes, primarily CYP3A4, partially CYP1A2 and CYP2D6. Less than 5% of a dose is excreted 95% unchanged in the urine.

For the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy.
For the prevention and treatment of post-operative nausea and vomiting.

Film-coated tablet: Dosage: Prevention of chemotherapy and/or radiotherapy-induced nausea and vomiting: Adult: For highly emetogenic chemotherapy: Administer 24 mg orally as a single dose 1-2 hours before the start of single-day chemotherapy and/or radiotherapy.
For emetogenic chemotherapy and/or radiotherapy: Administer 8 mg orally up to 1-2 hours before chemotherapy and/or radiotherapy, and subsequent dose of 8 mg is administered 8-12 hours after the first dose.
To protect against delayed emesis, 24 hours after chemotherapy and/or radiotherapy, Ondansetron 8 mg should be administered orally every 12 hours for up to 5 days after the end of chemotherapy and/or radiotherapy.
Children (4-11 years): For emetogenic chemotherapy and/or radiotherapy: Administer 4 mg orally 1-2 hours before chemotherapy and/or radiotherapy, subsequent doses of 4 mg are administered 4 and 8 hours after the first dose.
To protect against delayed emesis 24 hours after chemotherapy and/or radiotherapy Ondansetron 4 mg should be administered orally every 8 hours for 1-2 days after the end of chemotherapy and/or radiotherapy.
Prevention of post-operative nausea and vomiting: Adult: Administer 16 mg orally as a single dose 1 hour before anesthesia.
Dosage in children: Little information currently is available regarding dosage for children younger than 4 years of age.
Dosage in elderly: Dosage adjustment is not required.
Dosage in renal function impairment: Dosage adjustment is not required.
Plasma clearance is reduced to 50% in patients with severe renal function impairment (creatinine clearance less than 30 mL/min).
Dosage in hepatic function impairment: In patient with mild to moderate hepatic function impairment drug clearance is reduced 50% compared to patients with normal hepatic function and half-life is increased to 11.6 hours compared to 5.7 hours in patients with normal hepatic function.
The total daily dose in patient with moderate or severe liver disease should not exceed 8 mg.
Injection: Mode of Administration: ONSIA INJECTION is given by intravenous bolus injection (IV bolus injection) or intravenous infusion (IV infusion) as the hydrochloride dihydrate or IM injection.
IV bolus injection: The undiluted drug is administered by IV injection at least 2-5 minutes.
IV infusion: The drug should be diluted in 50 mL of compatible solutions such as dextrose 5% injection or sodium chloride 0.9% injection and infused IV over at least 15-30 minutes. Should be infused via IV infusion equipment.
Although Ondansetron injection is chemically and physically stable when diluted as recommended, sterile precautions should be observed because diluents generally do not contain preservative. Do not store any unused portion of the IV infusion solution for reuse.
Parenteral drug product should be inspected visually for particulate matter and discoloration before administration.
Recommended Dose: Management of chemotherapy and/or radiotherapy-induced nausea and vomiting: Dose regimen of Ondansetron should be determined by the severity of emetic response caused by different chemotherapy and/or radiotherapy, and individual-patient assessment, or under the prescription.
Adult: Administered as a single 8 mg by slow IV or IM immediately before chemotherapy and/or radiotherapy.
For highly emetogenic chemotherapy: Administered as a single 8 mg by slow IV or IM immediately before chemotherapy as diluted in 50 mL of compatible solutions such as dextrose 5% injection or sodium chloride 0.9% injection over 15 minutes, beginning 30 minutes before chemotherapy; Or alternatively administered as a single 8 mg by slow IV or IM immediately before chemotherapy, followed by IV or IM 2 further doses of 8 mg 2-4 hours apart, or by a constant infusion of 1 mg/hour for up to 24 hours.
The efficacy of Ondansetron in highly emetogenic chemotherapy may be enhanced by giving IV dexamethasone sodium phosphate 20 mg before chemotherapy.
To protect against delayed emesis, followed by Ondansetron 8 mg orally twice daily for up to 5 days after the end of a course of chemotherapy.
Children (6 months to 17 years): Administered 5 mg/m² dose of Ondansetron by single IV dose immediately before chemotherapy and/or radiotherapy, followed by oral Ondansetron 4 mg 12 hours later, may be continued for up to 5 days after the end of a course of chemotherapy; Or administered as a single 8 mg by IV before chemotherapy followed by oral Ondansetron 8 mg 12 hours later, oral Ondansetron 8 mg can be given twice daily for up to 5 days after the end of a course of chemotherapy.
Children over 6 months of age administered single IV dose 0.15 mg/kg/dose (Not to excess 8 mg) before chemotherapy, subsequent doses are administered 4 and 8 hours after the first dose.
Prevention of post-operative nausea and vomiting: Adult: The recommended dose is 4 mg as a single by IV bolus injection or IM before induction of anesthesia.
Children (1 month to 17 years): weight less than 40 kg: Administered 0.1 mg/kg as a single dose by IV bolus injection at induction of anesthesia; weight more than 40 kg: Administered 4 mg as a single dose by IV bolus injection at induction of anesthesia.
Treatment of Post-operative nausea and vomiting: Adult: The recommended dose is 4 mg as a single dose by IV bolus injection or IM.
Children (1 month to 17 years): weight less than 40 kg: Administered 0.1 mg/kg as a single dose by IV bolus injection; weight more than 40 kg: Administered 4 mg as a single dose by IV bolus injection.
Dosage in children: Little information currently is available regarding dosages for children younger than 4 years of age.
Dosage in elderly: In elderly patients do not require Ondansetron dosage adjustment.
Dosage in renal function impairment: In patient with renal function impairment do not require Ondansetron dosage adjustment.
In patient with severe renal function impairment (creatinine clearance less than 30 mL/min) mean plasma clearance has been decreased by about 50%.
Dosage in hepatic function impairment: In patient with mild to moderate hepatic function impairment, clearance is reduced 2-fold and mean half-life is increased to 11.6 hours, compared with 5.7 hours in healthy patients.
In patient with severe hepatic function impairment, a single maximal daily dose of 8 mg to be infused over 15 minutes before chemotherapy and/or radiation 30 minutes.

Symptoms: labored respiration, subdued behavior, ataxia, tremors, convulsion, hypotension, dizziness, headache, transient second-degree heart block, gasping, pallor, cyanosis, sudden blindness, collapse and death.
Treatment: There is no specific antidote for Ondansetron overdose. Manage patients with appropriate supportive therapy.

Hypersensitivity to Ondansetron, other selective 5-HT₃ antagonist or any component of the formulation.

Ondansetron may mask a progressive ileus and/or gastric distension in patients undergoing abdominal surgery or in patients with chemotherapy and/or radiotherapy-induced nausea and vomiting.
Ondansetron does not stimulate gastric or intestinal peristalsis so should not be used as a substitute for nasogastric suction.
The drug should be used with caution and at reduced dosage in patients with moderate to severe hepatic impairment.
Ondansetron may cause serious hypersensitivity reactions. Patients should be advised to monitor these reactions including urticaria, angioedema, hypotension, bronchospasm and labored respiration. If rash or any reactions occur, discontinue drug use and consult physicians. In addition, hypersensitivity can occur in patients who are allergic to other selective 5-HT₃ receptor antagonists.
Injection: Transient ECG changes (including QT interval prolongation) have been reported (rarely) with IV use.
Ondansetron injection should not be mixed with solutions for which physical and chemical compatibility have not been established. In particular, this applies to alkaline solutions, as a precipitate may form.
Use in the Elderly: Dose selection for elderly patients should be cautious, usually starting at the low dose, and it may be useful to monitor closely. Because they are more likely to have decreased hepatic, renal or cardiac function.

Pregnancy category: B: There are no adequate safety data in pregnant women. Use during pregnancy only if the potential benefit justifies is superior to the potential risk to the fetus.
It is not known whether Ondansetron is distributed into human milk; therefore, the drug should be used with caution in nursing women.

Central nervous system: headache, malaise/fatigue, drowsiness, fever, dizziness, anxiety, cold sensation, insomnia.
Gastrointestinal: constipation, diarrhea, dyspepsia, heartburn, thirst, flatulence, abdominal cramp, abnormal taste, anorexia, intestinal obstruction.
Dermatologic: pruritus, rash, injection site reaction (pain, erythema, swelling, and burning), urticaria.
Genitourinary: gynecological disorder, urinary retention.
Neuromuscular and skeletal: paresthesia.
Respiratory: hypoxia, hiccups.
Cardiovascular system: hypotension, hypertension.
Hepatic: ALT/AST increased, hepatosplenomegaly, jaundice, liver failure, bilirubin increased, γ-glutamyltransferase increased.
Ocular (predominantly during IV administration): transient blurred vision, blindness, oculogyric crisis.
Limited to important or life-threatening: anaphylactoid reactions, anaphylaxis (for injection: swelling, low blood pressure, bronchospasm, laryngeal edema, shortness of breath, raspy voice), flushing, angina, angioedema, arrhythmia, bradycardia, bronchospasm, cardiopulmonary arrest, ECG changes, electrocardiographic alterations (second degree heart block and ST-segment depression), extrapyramidal symptoms, laryngeal edema, laryngospasm, QT interval increased, shock, stridor, supraventricular tachycardia, syncope, tachycardia, vascular occlusive events, ventricular arrhythmia.
Film-coated tablet: dyspnea, dystonic reaction, grand mal seizure, hypokalemia, palpitation, premature ventricular contractions (PVC).

Concomitant use with carbamazepine may cause an increase in Ondansetron clearance resulted in decreasing Ondansetron blood level.
Concomitant use with phenytoin may cause an increase in Ondansetron clearance resulted in decreasing Ondansetron blood level.
Concomitant use with rifamycins may cause a decrease in Ondansetron plasma concentration.
Concomitant use with cisplatin may cause a decrease in cisplatin plasma concentration which may reduce its therapeutic effect. Therefore, it may be necessary to increase cisplatin dose when used in combination.
Concomitant use with cyclophosphamide may cause a decrease in cyclophosphamide plasma concentration which may reduce its therapeutic effect. Therefore, it may be necessary to increase cyclophosphamide dose when used in combination.
Concomitant use with apomorphine may enhance hypotensive effect of apomorphine. Concurrent use is contraindicated.

Stability: ONSIA INJECTION when diluted in a compatible one as 5% dextrose in water or 0.9% sodium chloride injection are stable for 7 days when stored at 25°C, protected from light.

Store below 30°C, protect package from light.

Supportive Care Therapy / Antiemetics

A04AA01 - ondansetron ; Belongs to the class of serotonin (5HT3) antagonists. Used for the prevention of nausea and vomiting.

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