Ondansetron 4 Mg/2 Ml/8 Mg/4 Ml Injection

ONDANSETRON BIOTECH is indicated for

• the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy.
• the prevention and treatment of post-operative nausea and vomiting (PONV). Routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and vomiting will occur. The study population in all trials, thus far, consisted of mainly women undergoing laparoscopic procedures. While some men were included in some trials with similar results, clearance of the agent is more rapid in men and insufficient numbers of men have been clinically studied to ensure certainty that efficacy and safety have been established. Few patients undergoing major abdominal surgery have been studied.

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: For most patients receiving emetogenic chemotherapy or radiotherapy, ONDANSETRON 8 mg/4 ml BIOTECH should be administered as a slow IV infusion (not less than 2-3 minutes) or IM injection in not less than 30 seconds, immediately before treatment.

Highly Emetogenic Chemotherapy: A single dose of ONDANSETRON 8 mg/4 ml BIOTECH by slow IV infusion (not less than 2-3 minutes) or IM injection in not less than 30 seconds, immediately before chemotherapy has been shown to be effective in many patients. Higher doses may be required in some patients, particularly those on high dose cisplatin, and the doses should be adjusted according to the severity of the emetogenic challenge. In these patients, the following dose schedules have been shown to be effective: A dose of 8 mg by slow IV infusion or IM injection immediately before chemotherapy, followed by two further IV or IM doses of 8 mg four hours apart, or by a constant infusion of 1 mg/hour for up to 24 hours. OR ALTERNATIVELY: A maximum single IV dose of 16 mg diluted in 50 - 100 ml of saline (0,9 % NaCl) or other compatible infusion fluid and infused over not less than 15 minutes immediately before chemotherapy. A single dose greater than 16 mg should not be given due to dose-dependent increased risk of QT prolongation (see sections 4.4). The efficacy of ONDANSETRON BIOTECH in highly emetogenic chemotherapy may be enhanced by the addition of a single intravenous dose of dexamethasone phosphate 20 mg administered 30 - 45 minutes prior to the first ONDANSETRON BIOTECH dose prior to chemotherapy.

Children: Experience is currently limited, but ONDANSETRON BIOTECH was effective and well tolerated in children over the age of 4 years, when given intravenously at a dose of 5 mg/m2 over 15 minutes, immediately before cancer chemotherapy.

Elderly patients: Based on more recent ondansetron plasma concentrations and exposure-response modelling, a greater effect on QTcF is predicted in patients u2265 75 years of age compared to young adults. Specific dosing information for intravenous dosing is provided for patients over 65 years of age and over 75 years of age. Elderly patients aged 75 years or older: A single dose of intravenous ONDANSETRON BIOTECH given for the prevention of chemotherapy-induced nausea and vomiting (CINV) must not exceed 8 mg (infused over at least 15 minutes). Adult patients aged less than 75 years: A single dose of intravenous ONDANSETRON BIOTECH given for the prevention of CINV in adults (aged less than 75 years) must not exceed 16 mg (infused over at least 5 minutes). Elderly patients aged 65 years or older: All intravenous doses should be diluted in 50 - 100 ml saline or other compatible fluid and infused over at least 15 minutes. Repeat intravenous doses of ONDANSETRON BIOTECH should be given no less than 4 hours apart.

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 BIOTECH 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 and therefore parenteral or oral administration is recommended.

Prevention and Treatment of Post-Operative Nausea and Vomiting: Adults: Immediately before induction of anaesthesia, or post-operatively if the patient experiences nausea and/or vomiting occurring shortly after surgery, administer 4 mg ONDANSETRON BIOTECH undiluted intramuscularly, or if given intravenously, it must be administered by IV infusion over not less than 2 - 5 minutes or longer. For treatment of established PONV, administration by injection is recommended. Repeat dosing for patients who continue to experience nausea and/or vomiting post-operatively has not been studied. While recommended as a fixed dose for all, few patients above 80 kg or below 40 kg have been studied.

Children: For prevention of post-operative nausea and vomiting in paediatric patients two years and older having surgery performed under general anaesthesia, ONDANSETRON BIOTECH may be administered by slow intravenous infusion over 2 to 5 minutes or longer at a dose of 0,1 mg/kg up to a maximum of 4 mg either prior to, at or after induction of anaesthesia. For the treatment of established post-operative nausea and vomiting in paediatric patients two years and older, ONDANSETRON BIOTECH may be administered by slow intravenous infusion at a dose of 0,1 mg/kg up to maximum of 4 mg over not less than 2-5 minutes or preferably longer. Repeat dosing for paediatric patients who continue to experience nausea and/or vomiting has not been studied, and should thus not be given.

Elderly: Based on more recent ondansetron plasma concentrations and exposure-response modelling, a greater effect on QTcF is predicted in patients u2265 75 years of age compared to young adults. Specific dosing information for intravenous dosing is provided for patients over 65 years of age and over 75 years of age. A slight age-related decrease in clearance, and an increase in the half-life of ONDANSETRON BIOTECH is predicted, presenting as slight, clinically insignificant age-related increases in both oral bioavailability (65 %) and a prolonged elimination half-life (5 hours) of ONDANSETRON BIOTECH.

Hypersensitivity to ondansetron or to any components of ONDANSETRON BIOTECH (see section 6.1). Concomitant use with apomorphine (see section 4.5). ONDANSETRON BIOTECH use is contraindicated during the first 12 weeks of pregnancy irrespective of the indication, due to an increased risk of developing oral cleft palate and/or lip to the foetus (see section 4.4). The use of ONDANSETRON BIOTECH for post-operative nausea and vomiting is contraindicated in pregnancy (see section 4.6). Congenital long QT syndrome.

Cross-hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5HT3 receptor antagonists. Respiratory events should be treated symptomatically and clinicians should pay particular attention to them as precursors of hypersensitivity reactions. ONDANSETRON BIOTECH 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 BIOTECH. Avoid ONDANSETRON BIOTECH in patients with congenital long QT syndrome (see section 4.3). ONDANSETRON BIOTECH should be administered with caution to patients who have or may develop prolongation of QTc, including patients with electrolyte abnormalities, congestive heart failure, bradydysrhythmias or patients taking other medicinal products that lead to QT prolongation or electrolyte abnormalities. Cases of myocardial ischaemia have been reported in patients treated with ondansetron. In some patients, especially in the case of intravenous administration, symptoms appeared immediately after administration of ondansetron. Patients should be alerted to the signs and symptoms of myocardial ischaemia. Hypokalaemia and hypomagnesaemia should be corrected prior to ONDANSETRON BIOTECH administration. Post-marketing reports describe patients with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the concomitant use of ONDANSETRON BIOTECH and other serotonergic medicines (including selective serotonin reuptake inhibitors (SSRI) and serotonin noradrenaline reuptake inhibitors (SNRIs)). If concomitant treatment with ONDANSETRON BIOTECH and other serotonergic medicines is clinically warranted, appropriate close observation of the patient is advised. As ONDANSETRON BIOTECH is known to increase large bowel transit time, patients with signs of intestinal obstructions should be closely monitored following administration. In patients with adeno-tonsillar surgery, prevention of nausea and vomiting with ONDANSETRON BIOTECH may mask occult bleeding. Therefore, such patients should be carefully monitored after ONDANSETRON BIOTECH. The use of ONDANSETRON BIOTECH during the first 12 weeks of pregnancy increases the risk of developing oral cleft palate and/or lip to the foetus (see section 4.3). Patients with hepatic impairment: Clearance of ONDANSETRON BIOTECH 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. The daily dose for children should not exceed 4 mg. Paediatric patients receiving ONDANSETRON BIOTECH with hepatotoxic chemotherapeutic agents should be closely monitored for impaired hepatic function. ONDANSETRON BIOTECH contains less than 1 mmol sodium (23 mg) per 4 ml ampoule (3,56 mg per ml), that is to say essentially u201csodium freeu201d.

There is no evidence that ONDANSETRON BIOTECH either induces or inhibits the metabolism of other medicines commonly co-administered with it. Specific studies have shown that there are no interactions when ONDANSETRON BIOTECH is administered with alcohol, temazepam, furosemide, alfentanil, morphine, lidocaine, thiopental, or propofol. Ondansetron is metabolised by multiple hepatic cytochrome P-450 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 BIOTECH is co-administered with other medicines that prolong the QT interval and/or cause electrolyte abnormalities (see section 4.4). Co-administration of ONDANSETRON BIOTECH with QT prolonging medicines may result in additional QT prolongation. Concomitant use of ONDANSETRON BIOTECH with cardiotoxic medicines (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 dysrhythmias (see section 4.4). Serotonergic Medicines (e.g., SSRIs and 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 BIOTECH and other serotonergic medicines (including SSRIs and SNRIs) (see section 4.4) Apomorphine: Based on reports of profound hypotension and loss of consciousness when ONDANSETRON BIOTECH was administered with apomorphine hydrochloride, concomitant use with apomorphine is contraindicated (see section 4.3). Tramadol: ONDANSETRON BIOTECH may reduce the analgesic effect of tramadol.

Women of childbearing potential: Women of childbearing potential being treated with ONDANSETRON BIOTECH should not become pregnant as ONDANSETRON BIOTECH is contraindicated in the first 12 weeks of pregnancy, irrespective of the cause of the nausea and vomiting (see section 4.3).

Pregnancy: ONDANSETRON BIOTECH is contraindicated for post-operative nausea and vomiting during pregnancy, as well as during the first 12 weeks of pregnancy irrespective of the indication due to the risk of developing oral cleft palate and/or lip to the foetus (see section 4.3). Women of childbearing potential to use contraception while taking ONDANSETRON BIOTECH and for 2 days after stopping treatment.

Breastfeeding: ONDANSETRON BIOTECH passes into the milk of lactating animals. Mothers receiving ONDANSETRON BIOTECH should not breastfeed their babies.

Fertility: There is no information on the effects of ONDANSETRON BIOTECH on human fertility.

ONDANSETRON BIOTECH causes nervous system and eye disorders which may adversely affect the ability of patients to drive or operate machines. Patients on treatment with ONDANSETRON BIOTECH should therefore not drive or use machines until the effects of ONDANSETRON BIOTECH treatment are known (see section 4.8).

Adverse events are listed below by system organ class and frequency. The following frequencies are estimated at the standard recommended doses of ONDANSETRON BIOTECH. The adverse event profiles in children and adolescents were comparable to those seen in adults.

Immune system disorders: Less frequent: Immediate hypersensitivity, including cross-sensitivity reactions sometimes severe, including anaphylaxis, bronchospasm, shortness of breath, hypotension, shock, angioedema, urticaria.

Nervous system disorders: Frequent: Headache. Less frequent: Seizures, movement disorders (including extrapyramidal reactions such as dystonic reactions, oculogyric crisis and dyskinesia have been observed without definitive evidence of persistent clinical sequelae). Dizziness during rapid intravenous administration.

Eye disorders: Less frequent: Transient visual disturbances (e.g., blurred vision) predominantly during intravenous administration. Transient blindness predominantly during intravenous administration. The majority of the blindness cases reported resolved within 20 minutes. Most patients had received chemotherapeutic medicines which included cisplatin. Some cases of transient blindness were reported as cortical in origin.

Cardiac disorders: Less frequent: Dysrhythmias, chest pain with or without ST segment depression, bradycardia, QTc prolongation (including Torsade de Pointes). Frequency unknown: Myocardial ischemia (see section 4.4).

Vascular disorders: Frequent: Sensation of warmth or flushing. Less frequent: Hypotension.

Respiratory, thoracic and mediastinal disorders: Less frequent: Hiccups. Respiratory events: should be treated symptomatically and medical practitioners should pay particular attention to them as precursors of hypersensitivity reactions.

Gastrointestinal disorders: Frequent: Constipation, increased bowel transit time.

Hepato-biliary disorders: Less frequent: Asymptomatic increases in liver function tests. These events were frequently observed in patients receiving cancer chemotherapy with cisplatin.

General disorders and administration site conditions: Frequent: Local IV injection site reactions.

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Symptoms and Signs: In the majority of cases, symptoms were similar to or an extension of those already reported in patients receiving the recommended doses (see section 4.8). 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 manner. ECG monitoring is recommended in cases of overdose.

Treatment: There is no specific antidote for ondansetron. In all cases of suspected overdose, treatment is symptomatic and supportive as appropriate. Further management should be as clinically indicated or as recommended by the national poisons centre, where available.