Ondansetron 4 mg/8 mg

ONDANSETRON ODF PHARMA-Q is indicated for:

• the management of nausea and vomiting induced by cytotoxic cancer 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.

Posology

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 ODF PHARMA-Q can be taken orally 1 u2013 2 hours before treatment, followed by 8 mg orally twelve hourly. In circumstances where delayed or prolonged emesis is expected after the first 24 hours, ONDANSETRON ODF PHARMA-Q may be continued orally, 8 mg twice daily for up to five days after a course of treatment. Highly emetogenic chemotherapy: To protect against delayed or prolonged emesis after the first 24 hours, treatment with ONDANSETRON ODF PHARMA-Q may be continued orally, with 8 mg twice daily for up to 5 days after a course of treatment.

Children: Experience is currently limited, but ondansetron 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, followed by oral therapy at doses of ONDANSETRON ODF PHARMA-Q every 12 hours for up to 5 days.

Elderly patients: Based on more recent ondansetron, as in ONDANSETRON ODF PHARMA-Q, plasma concentrations and exposure-response modelling, a greater effect on QTcF is predicted in patients u2265 75 years of age compared to young adults.

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 ODF PHARMA-Q 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: For treatment of established PONV, administration by injection is recommended. Alternatively, for the prevention of post-operative nausea and vomiting, 16 mg may be given orally one hour prior to induction of anaesthesia.

Elderly: Based on more recent ondansetron, as in ONDANSETRON ODF PHARMA-Q, plasma concentrations and exposure-response modelling, a greater effect on QTcF is predicted in patients u2265 75 years of age compared to young adults. A slight age-related decrease in clearance, and an increase in the half-life of ondansetron, as in ONDANSETRON ODF PHARMA-Q, 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.

Patients with renal impairment: No alteration of daily dosage or frequency of dosing, or route of administration are required for mild or moderate renal impairment. There is limited information available for daily dosage or frequency of dosing, or route of administration for severe renal impairment.

Patients with hepatic impairment: Clearance of ONDANSETRON ODF PHARMA-Q 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.

Method of administration: Oral. Place ONDANSETRON ODF PHARMA-Q on top of the tongue, where it will disperse within seconds, then swallow.

• Hypersensitivity to ondansetron or to any of the excipients listed in section 6.1.
• Concomitant use with apomorphine (see section 4.5).
• ONDANSETRON ODF PHARMA-Q 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 ODF PHARMA-Q 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 medical practitioners should pay particular attention to them as precursors of hypersensitivity reactions. Ondansetron, as in ONDANSETRON ODF PHARMA-Q prolongs the QT interval in a dose-dependent manner (see section 5.1). In addition, post-marketing cases of torsades de pointes have been reported in patients using ONDANSETRON ODF PHARMA-Q. Avoid ONDANSETRON ODF PHARMA-Q in patients with congenital long QT syndrome (see section 4.3). ONDANSETRON ODF PHARMA-Q 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 medicines that lead to QT prolongation or electrolyte abnormalities. Myocardial ischemia has been reported in patients treated with ondansetron, as in ONDANSETRON ODF PHARMA-Q. In some patients, especially in the case of intravenous administration, symptoms appeared immediately after administration of ondansetron, as in ONDANSETRON ODF PHARMA-Q. Patients should be alerted to the signs and symptoms of myocardial ischaemia. Hypokalaemia and hypomagnesaemia should be corrected prior to ONDANSETRON ODF PHARMA-Q administration. 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 ODF PHARMA-Q and other serotonergic medicines (including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs)). If concomitant treatment with ONDANSETRON ODF PHARMA-Q and buprenorphine/opioids or other serotonergic medicines is clinically warranted, appropriate close observation of the patient is advised, particularly during treatment initiation and dose increases. If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be considered depending on the severity of the symptoms. As ONDANSETRON ODF PHARMA-Q 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 ODF PHARMA-Q may mask occult bleeding. Therefore, such patients should be carefully monitored after ONDANSETRON ODF PHARMA-Q. The use of ONDANSETRON ODF PHARMA-Q during the first 12 weeks of pregnancy increases the risk of developing oral cleft palate and or lip to the fetus (see section 4.3).

Special populations: Patients with hepatic impairment: Adult: Clearance of ONDANSETRON ODF PHARMA-Q 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. Paediatric population: The daily dose for children should not exceed 4 mg. Paediatric patients receiving ondansetron, as in ONDANSETRON ODF PHARMA-Q with hepatotoxic chemo-therapeutic medicines should be monitored closely for impaired hepatic function.

The concomitant use with apomorphine is contraindicated (see section 4.3). Profound hypotension and loss of consciousness was reported when ONDANSETRON ODF PHARMA-Q was taken concomitantly with apomorphine hydrochloride. There is no evidence that ONDANSETRON ODF PHARMA-Q 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 ODF PHARMA-Q is taken with alcohol, temazepam, furosemide, alfentanil, morphine, lidocaine, thiopental, or propofol. Ondansetron, as in ONDANSETRON ODF PHARMA-Q is metabolised by multiple hepatic cytochrome P450 enzymes CYP3A4, CYP2D6 and CYP1A2. Due to the multiplicity of metabolic enzymes capable of metabolising ondansetron, as in ONDANSETRON ODF PHARMA-Q, enzyme inhibition or reduced activity of one enzyme (e.g. CYP2D6 genetic deficiency) is normally compensated for by other enzymes and should result in little or no significant change in overall ONDANSETRON ODF PHARMA-Q clearance or dose requirement. Caution must be exercised when ONDANSETRON ODF PHARMA-Q is co-administered with other medicines that prolong the QT interval and/or cause electrolyte abnormalities (see section 4.4). Use of ONDANSETRON ODF PHARMA-Q with QT prolonging medicines may result in additional QT prolongation. Concomitant use of ONDANSETRON ODF PHARMA-Q with cardiotoxic medicines (e.g. anthracyclines [e.g. doxorubicin, daunorubicin] or trastuzumab), antibiotics (e.g. erythromycin), antifungals (e.g. ketoconazole), antidysrhythmics (e.g. amiodarone) and beta-blockers (e.g. 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 ODF PHARMA-Q and buprenorphine/opioids or other serotonergic medicines (including SSRIs and SNRIs) (see section 4.4).

Phenytoin, carbamazepine and rifampicin: In patients treated with potent inducers of CYP3A4 (i.e. phenytoin, carbamazepine and rifampicin), the clearance of ONDANSETRON ODF PHARMA-Q was increased and blood concentrations of ondansetron were decreased causing a reduced antiemetic efficacy. Tramadol: ONDANSETRON ODF PHARMA-Q may reduce the analgesic effect of tramadol.

Women of childbearing potential: Women of childbearing potential being treated with ONDANSETRON ODF PHARMA-Q should not become pregnant and should consider the use of contraception while taking ONDANSETRON ODF PHARMA-Q, as well as for two days after stopping treatment with ONDANSETRON ODF PHARMA-Q.

Pregnancy: ONDANSETRON ODF PHARMA-Q 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 (see section 4.3). Use during the first 12 weeks of pregnancy can be associated with an increased risk of developing oral cleft palate and/or lip to the fetus.

Breastfeeding: Mothers receiving ONDANSETRON ODF PHARMA-Q should not breastfeed their babies.

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

ONDANSETRON ODF PHARMA-Q causes nervous system and eye disorders which may adversely affect the ability of patients to drive a vehicle or operate machines. Patients taking ONDANSETRON ODF PHARMA-Q should therefore not drive a vehicle or use machines until the effects of ONDANSETRON ODF PHARMA-Q treatment are known (see section 4.8).

Summary of adverse reactions:

Immune system disorders: Less frequent: Immediate hypersensitivity reactions, including cross-sensitivity reactions which are sometimes severe (e.g. anaphylaxis, bronchospasm, shortness of breath, hypotension, shock, angioedema, urticaria) have been reported.

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

Eye disorders: Less frequent: Transient visual disturbances (e.g. blurred vision) 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, bradycardia and chest pains with or without ST segment depression, QTc prolongation (including torsades de pointes), myocardial ischaemia.

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: Increase in large bowel transit time is known to be caused by ONDANSETRON ODF PHARMA-Q which cause constipation in some patients.

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

Skin and subcutaneous tissue disorders: Less frequent: Toxic skin eruption, including toxic epidermal necrolysis.

Paediatric Population: The adverse event profile in children and adolescents was comparable to that seen in adults.

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of ONDANSETRON ODF PHARMA-Q is important. It allows continued monitoring of the benefit/risk balance of ONDANSETRON ODF PHARMA-Q. Health care providers are asked to report any suspected adverse reactions via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

Symptoms: 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 atrioventricular (AV) block. Ondansetron prolongs the QT interval in a dose-dependent manner. Electrocardiogram (ECG) monitoring is recommended in cases of overdose.

Paediatric population: Paediatric cases consistent with serotonin syndrome have been reported after inadvertent oral overdoses of ondansetron (exceeded estimated ingestion of 4 mg/kg) in infants and children aged 12 months to 2 years.

Treatment: There is no specific antidote for ondansetron, as in ONDANSETRON ODF PHARMA-Q. Therefore, 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.