Ondansetron-Teva

Ondansetron (as hydrochloride dihydrate).

Each tablet contains ondansetron 8 mg (as hydrochloride dihydrate).
The 8 mg tablets should not be divided.
Excipients with known effect: Contains lactose monohydrate 177.6 mg (see Precautions).
Excipients/Inactive Ingredients: Lactose monohydrate, sodium starch glycolate, microcrystalline cellulose, pre-gelatinised starch, magnesium stearate, Opadry 02G22211 yellow (hypromellose E464, titanium dioxide E171, macrogol and yellow iron oxide E172).

Adults: Ondansetron-Teva tablets are indicated for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy.
Ondansetron-Teva tablets are indicated for the prevention of post-operative nausea and vomiting (PONV).

Chemotherapy- and radiotherapy-induced nausea and vomiting (CINV and RINV): Adults: 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.
Emetogenic Chemotherapy and Radiotherapy: Ondansetron can be given by oral administration.
The recommended oral dose is 8 mg taken 1 to 2 hours before chemotherapy or radiation treatment, followed by 8 mg every 12 hours for a maximum of 5 days to protect against delayed or prolonged emesis.
For highly emetogenic chemotherapy, a single dose of up to 24 mg ondansetron taken with 12 mg oral dexamethasone sodium phosphate, 1 to 2 hours before chemotherapy, may be used.
To protect against delayed or prolonged emesis after the first 24 hours, oral treatment with ondansetron may be continued for up to 5 days after a course of treatment.
The recommended dose for oral administration is 8 mg to be taken twice daily.
Elderly: No alteration of oral dose or frequency of administration is 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 should not be exceeded.
Patients with Poor Sparteine/Debrisoquine Metabolism: The elimination half-life of ondansetron is not altered in subjects classified as poor metabolisers of sparteine and debrisoquine. Consequently in such patients, repeat dosing will give drug exposure levels no different from those of the general population. No alteration of daily dosage or frequency of dosing is required.
Post-operative nausea and vomiting (PONV): Adults: For the prevention of PONV, ondansetron can be administered orally. The recommended oral dose is 16 mg taken one hour prior to anaesthesia.
Elderly: There is limited experience in the use of ondansetron in the prevention and treatment of post-operative nausea and vomiting in the elderly, however, ondansetron is well tolerated in patients over 65 years receiving chemotherapy.
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 should not be exceeded.
Patients with Poor Sparteine/Debrisoquine Metabolism: The elimination half-life of ondansetron is not altered in subjects classified as poor metabolisers of sparteine and debrisoquine. Consequently in such patients, repeat dosing will give drug exposure levels no different from those of the general population. No alteration of daily dosage or frequency of dosing is required.
Method of Administration: The tablets should be swallowed whole with liquid.

Symptoms and Signs: There is limited experience of ondansetron overdose. In the majority of cases, symptoms were similar to those already reported in patients receiving recommended doses (see Adverse Reactions). Manifestations that have been reported include visual disturbances, severe constipation, hypotension and a vasovagal episode with transient second degree AV block. Ondansetron prolongs the QT interval in a dose-dependent fashion. ECG monitoring is recommended in cases of overdose.
Management: There is no specific antidote for ondansetron, therefore, in all cases of suspected overdose, symptomatic and supportive therapy should be given as appropriate.
Further management should be as clinically indicated or as recommended by hospitals, where available.
The use of ipecacuanha to treat overdose with ondansetron is not recommended, as patients are unlikely to respond due to the antiemetic action of ondansetron itself.

Hypersensitivity to the active substance or to any of the excipients listed.
Concomitant use with apomorphine is contraindicated (see Interactions).

Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT₃ receptor antagonists. Respiratory events should be treated symptomatically and clinicians should pay particular attention to them as precursors of hypersensitivity reactions.
Ondansetron prolongs the QT interval in a dose-dependent manner. In addition, post-marketing cases of torsade de pointes have been reported in patients using ondansetron. Avoid ondansetron in patients with congenital long QT syndrome. Ondansetron should be administered with caution to patients who have or may develop prolongation of QTc, including patients with electrolyte abnormalities, congestive heart failure, bradyarrhythmias or patients taking other medicinal products that lead to QT prolongation or electrolyte abnormalities.
Rarely, transient ECG changes including QT interval prolongation have been reported in patients receiving ondansetron. In addition, post-marketing cases of torsade de pointes have been reported in patients using ondansetron. Ondansetron should be administered with caution to patients who have or may develop prolongation of QTc. These conditions include patients with electrolyte abnormalities, with congenital long QT syndrome, or patients taking other medicinal products that lead to QT prolongation.
Hypokalaemia and hypomagnesaemia should be corrected prior to ondansetron administration.
Cases of life-threatening serotonin syndrome have been reported with 5-HT₃ receptor antagonist antiemetics, particularly when given in combination with other serotonergic and/or neuroleptic drugs. Treatment should be discontinued if such events occur and supportive symptomatic treatment should be initiated. If concomitant treatment of Ondansetron-Teva tablets with a drug affecting the serotonergic neurotransmitter system is clinically warranted, careful observations of the patient is advised, particularly during treatment initiation and dose increases.
As ondansetron is known to increase large bowel transit time, patients with signs of subacute intestinal obstruction should be monitored following administration.
In patients with adenotonsillar surgery, prevention of nausea and vomiting with ondansetron may mask occult bleeding. Therefore, such patients should be followed carefully after ondansetron.
Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on ability to drive and use machines: Ondansetron has no or negligible influence on the ability to drive and use machines.
In psychomotor testing, ondansetron does not impair performance nor cause sedation. No detrimental effects on such activities are predicted from the pharmacology of ondansetron.

Women of childbearing potential: Women of childbearing potential should consider the use of contraception.
Pregnancy: Based on human experience from epidemiological studies, ondansetron is suspected to cause orofacial malformations when administered during the first trimester of pregnancy.
In one cohort study including 1.8 million pregnancies, first trimester ondansetron use was associated with an increased risk of oral clefts (3 additional cases per 10,000 women treated; adjusted relative risk, 1.24 (95% CI 1.03-1.48)).
The available epidemiological studies on cardiac malformations show conflicting results.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.
Ondansetron should not be used during the first trimester of pregnancy.
Breast-feeding: Tests have shown that ondansetron passes into the milk of lactating animals. It is, therefore, recommended that mothers receiving ondansetron should not breast-feed their babies.
Fertility: There is no information on the effects of ondansetron on human fertility.

Tabulated list of adverse reactions: Adverse events are listed as follows by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), and very rare (<1/10,000). Very common, common and uncommon events were generally determined from clinical trial data. The incidence in placebo was taken into account. Rare and very rare events were generally determined from post-marketing spontaneous data.
The following frequencies are estimated at the standard recommended doses of ondansetron. The adverse event profiles in children and adolescents were comparable to that seen in adults.
Immune system disorders: Rare: Immediate hypersensitivity reactions sometimes severe, including anaphylaxis.
Nervous system disorders: Very common: Headache.
Uncommon: Seizures, movement disorders (including extrapyramidal reactions such as dystonic reactions, oculogyric crisis and dyskinesia)⁽¹⁾.
Rare: Dizziness predominantly during rapid IV administration.
Eye disorders: Rare: Transient visual disturbances (e.g. blurred vision) predominantly during IV administration.
Very rare: Transient blindness predominantly during IV administration⁽²⁾.
Cardiac disorders: Uncommon: Arrhythmias, chest pain with or without ST segment depression, bradycardia.
Rare: QTc prolongation (including torsade de pointes).
Vascular disorders: Common: Sensation of warmth or flushing.
Uncommon: Hypotension.
Respiratory, thoracic and mediastinal disorders: Uncommon: Hiccups.
Gastrointestinal disorders: Common: Constipation.
Hepatobiliary disorders: Uncommon: Asymptomatic increases in liver function tests⁽³⁾.
⁽¹⁾ Observed without definitive evidence of persistent clinical sequelae.
⁽²⁾ 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.
⁽³⁾ These events were observed commonly in patients receiving chemotherapy with cisplatin.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.

There is no evidence that ondansetron either induces or inhibits the metabolism of other drugs commonly co-administered with it. Specific studies have shown that there are no interactions when ondansetron is administered with alcohol, temazepam, furosemide, alfentanil, tramadol, morphine, lidocaine, thiopental, or propofol.
Ondansetron is metabolised by multiple hepatic cytochrome P450 enzymes: CYP3A4, CYP2D6 and CYP1A2. Due to the multiplicity of metabolic enzymes capable of metabolising 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.
Caution should be exercised when ondansetron is co-administered with drugs that prolong the QT interval and/or cause electrolyte abnormalities (see Precautions).
Use of ondansetron with QT-prolonging drugs may result in additional QT prolongation. Concomitant use of ondansetron with cardiotoxic drugs (e.g. anthracyclines (such as doxorubicin, daunorubicin) or trastuzumab), antibiotics (such as erythromycin), antifungals (such as ketoconazole), antiarrhythmics (such as amiodarone) and beta-blockers (such as atenolol or timolol) may increase the risk of arrhythmias. (See Precautions.)
Serotonergic Drugs (e.g. Selective Serotonin Reuptake Inhibitors [SSRIs] and Serotonin Noradrenaline Reuptake Inhibitors [SNRIs]): There have been post-marketing reports describing patients with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the concomitant use of ondansetron and other serotonergic drugs (including SSRIs and SNRIs) (see Precautions).
Apomorphine: Based on reports of profound hypotension and loss of consciousness when ondansetron was administered with apomorphine hydrochloride, concomitant use with apomorphine is contraindicated.
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: Data from small studies indicate that ondansetron may reduce the analgesic effect of tramadol.

Antiemetics / Supportive Care Therapy

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

P₁S₁S₃