Ondavell

Ondansetron.

Film, rectangle, white.
Each ODF contains Ondansetron 8 mg.
Excipients/Inactive Ingredients: Hypromellose, purified water, polyethylene glycol 400, glycerol, sodium carbonate anhydrous, sodium sulfite, sucralose, Lychee Flavour, Titanium dioxide.

Pharmacology: Pharmacodynamic: Ondansetron is a potent, highly selective 5HT₃ receptor antagonist. Its precise mode of action in the control of nausea and vomiting is not known.
Chemotherapeutic agents and radiotherapy may cause release of 5HT in the small intestine initiating a vomiting reflex by activating vagal afferents via 5HT₃ receptors. Ondansetron blocks the initiation of this reflex.
Activation of vagal afferents may also cause a release of 5HT in the area postrema, located on the floor of the fourth ventricle, and this may also promote emesis through a central mechanism.
Thus, the effect of ondansetron in the management of the nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy is probably due to antagonism of 5HT₃ receptors on neurons located both in the peripheral and central nervous system.
The mechanisms of action in post-operative nausea and vomiting are not known but there may be common pathways with cytotoxic induced nausea and vomiting.
Ondansetron does not alter plasma prolactin concentrations.
Clinical Studies: ONDAVELL 4 mg ODF: The bioequivalence study shared that ONDAVELL 4 mg ODF is bioequivalent to comparator drugs. Pharmacokinetic parameters of ONDAVELL 4 mg ODF shown the area under the plasma concentration-time curve (AUC_0-t) is 104.65 ± 46.26 ngxh/mL, the AUC_0-∞ values is 108.91 ± 48.87 ngxh/mL, maximum concentration (C_max) is 14.82 ± 5.30 ng/mL, elimination half life (t_1/2) is 4.61 ± 0.98 h, and time to maximum concentration (t_max) is 2.06 ± 0.46 h.
ONDAVELL 8 mg ODF: The bioequivalence study shared that ONDAVELL 8 mg ODF is bioequivalent to comparator drugs. Pharmacokinetic parameters of ONDAVELL 8 mg ODF shown the area under the plasma concentration-time curve (AUC_0-t) is 272.76 ± 96.33 ngxh/mL, the AUC_0-∞ values is 281.78 ± 99.80 ngxh/mL, maximum concentration (C_max) is 41.13 ± 15.81 ng/mL, elimination half life (t_1/2) is 4.73 ± 0.81 h, and time to maximum concentration (t_max) is 1.80 ± 0.62 h.

ONDAVELL ODF is indicated for management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy.
ONDAVELL ODF is also indicated for preventing of post-operative nausea and vomiting.

ONDAVELL is available for oral use to allow the route of administration and dosing to be flexible.
Place the ODF on top of the tongue, where it will disperse within seconds, then swallow.
Chemotherapy and radiotherapy induced nausea and vomiting: The emetogenic potential of cancer treatment varies according to the doses and combinations of chemotherapy and radiotherapy regimens used. The selection of dose regimen should be determined by the severity of the emetogenic challenge.
Adults: Emetogenic chemotherapy and radiotherapy: The recommended dose for oral administration is 8 mg 1-2 hours before treatment, followed by 8 mg orally 12 hours later. To protect against delayed or prolonged emesis after the first 24 hours, oral treatment with ONDAVELL should be continued for up to 5 days after a course of treatment. The recommended oral dose is 8 mg to be taken twice daily.
Highly emetogenic chemotherapy (e.g. high dose cisplatin): ONDAVELL can be given by oral.
The recommended oral dose is 24 mg taken together with oral dexamethasone sodium phosphate 12 mg, 1-2 hours before treatment.
To protect against delayed or prolonged emesis after the first 24 hours, oral treatment with ONDAVELL should be continued for up to 5 days after a course of treatment. The recommended dose for oral administration is 8 mg twice daily.
Children: In children ONDAVELL is administered as a single dose of 5 mg/m² immediately before chemotherapy, followed by 4 mg orally 12 hours later. 4 mg orally twice daily should be continued for up to 5 days after a course of treatment. Adult doses must not be exceeded.
Elderly: ONDAVELL is well tolerated by patients over 65 years and no alteration of dosage, dosing frequency or route of administration are required.
Patients with renal impairment: No alteration of daily dosage or frequency of dosing, or route of administration are required.
Patients with hepatic impairment: Clearance of ondansetron is significantly reduced and serum half-life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8 mg oral should not be exceeded.
Post operative nausea and vomiting: Adults: For prevention of post-operative nausea and vomiting, ONDAVELL may be administered orally at a dose of 8 mg given 1 hour prior to anaesthesia. Followed by further dosage of 8 mg at 8 hours intervals, alternatively single dose of 4 mg may be given at induction on anaesthesia. For treatment of established post-operative nausea and vomiting a single dose for 4 mg ONDAVELL recommended.
Children: No studies have been conducted on the use of ondansetron in the prevention of treatment of post- operative nausea and vomiting.
Patients with renal impairment: No alteration of daily dosage or frequency of dosing, or route of administration are required.
Patients with hepatic impairment: Clearance of ondansetron is significantly reduced and serum half-life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8 mg oral should not be exceeded.

Symptoms and signs: There is limited experience of ONDAVELL overdose. In the majority of cases symptoms were similar to those already reported in patients receiving recommended doses.
Treatment: There is no specific antidote for ONDAVELL therefore in cases of suspected overdose ONDAVELL, supportive therapy and symptomatic should be given as appropriate.
The use of ipecacuanha to treat overdose with ONDAVELL is not recommended as patients are unlikely to respond due to the anti-emetic action of ondansetron itself.

Hypersensitivity to any component of the preparation.

Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5HT₃ receptor antagonists. Very rarely predominantly with ondansetron, transient ECG changes including Qt interval prolongation have been prolonged.
As ONDAVELL is known to increase large bowel transit time, patients with signs of subacute intestinal obstruction should be monitored following administration.
Effects on Ability to Drive and Use Machines: Ondansetron does not impair performance nor cause sedation.

Use in Pregnancy: The safety of ondansetron for use in human pregnancy has not been established. However, the use of ondansetron in pregnancy is not recommended.
Use in Lactation: Test have shown that ondansetron passer into milk lactating animals. It is therefore recommended that mothers receiving ONDAVELL should not breast-feed their babies.

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common, common, uncommon, rare, and very rare.
The following frequencies are estimated at the standard recommended doses of ONDAVELL according to indication and formulation.
Immune system disorders: Rare: Immediate hypersensitivity reactions sometimes severe, including anaphylaxis.
Nervous system disorders: Very common: Headache.
Uncommon: Extrapyramidal reactions (such as oculogyric crisis/dystonic reactions dyskinesia) have been observed without definitive evidence of persistent clinical sequelae, seizures.
Rare: Dizziness during rapid intravenous administration.
Eye disorders: Rare: Transient visual disturbances (e.g. blurred vision) predominantly during intravenous administration.
Very rare: Transient blindness predominantly during intravenous administration.
The majority of the blindness cases reported resolved within 20 minutes. Most patients had received chemotherapeutic agents which included cisplatin. Some cases of transient blindness were reported as cortical in origin.
Cardiac disorders: Uncommon: Arrhythmias, chest pain with or without ST segment depression, bradycardia.
Vascular disorders: Common: Sensation of warmth or flushing.
Uncommon: Hypotension.
Respiratory, thoracic and, mediastinal disorders: Uncommon: Hiccups.
Gastrointestinal disorders: Common: Constipation.
Local burning sensation following insertion of suppositories.
Hepatobiliary disorders: Uncommon: Asymptomatic increases in liver function tests*.
*These events were observed commonly in patients receiving chemotherapy with cisplatin.
General disorders and administration site conditions: Common: Local intravenous injection site reactions.

There is no evidence that ONDAVELL either induces or inhibits the metabolism of other drugs commonly coadministered with it.
Specific studies have shown that there are no pharmacokinetic interactions when ONDAVELL is administered with alcohol, temazepam, furosemide, tramadol and propofol. Ondansetron is metabolised by multiple hepatic cytochrome P-450 enzymes: CYP3A4, CYP2D6 and CYP1A2. Due to the multiplicity of metabolic enzymes capable of metabolizing ondansetron, enzyme inhibition or reduced activity of one enzyme (e.g. CYP2D6 genetic deficiency) is normally compensated by other enzymes and should result in little or no significant change in overall ondansetron clearance or dose requirement.
Phenytoin, Carbamazepine and Rifampicin: In patients treated with potent inducers of CYP3A4 (i.e. phenytoin, carbamazepine and rifampicin), the oral clearance of ondansetron was increased and ondansetron blood concentrations were decreased.
Tramadol: Ondansetron may reduce the analgesic effect of tramadol.

Incompatibility: Not reported.
Instructions for Use/Handling: Place the ODF on top of the tongue, where it will disperse within seconds, then swallow.

Store below 30°C.
Shelf Life: 2 years.

Antiemetics / Supportive Care Therapy

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

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