Active ingredients: Ondansetron
Ondansetron Mylan Generics 4 mg film-coated tablets
Ondansetron Mylan Generics 8 mg film-coated tablets
Why is Ondansetron used - Generic Drug? What is it for?
Ondansetron Mylan Generics belongs to a group of medicines called antiemetics or anti-vomiting drugs. Ondansetron inhibits the effects of the neurotransmitter serotonin in the brain. Serotonin causes nausea and vomiting.
Ondansetron Mylan Generics is used in adults for:
- control nausea and vomiting caused by chemotherapy or radiotherapy for cancer
- prevent nausea and vomiting following an operation
Ondansetron Mylan Generics is used in children for:
- control nausea and vomiting caused by chemotherapy in children aged 6 months and over
- prevent nausea and vomiting following an operation in children aged 1 month and over.
Ask your doctor, nurse or pharmacist if you would like other explanations on these uses.
Contraindications When Ondansetron - Generic Drug should not be used
Do not take Ondansetron Mylan Generics:
- if you are allergic to ondansetron, or any of the other ingredients of this medicine (listed in section 6)
- if you are allergic to other anti-vomiting medicines belonging to the group of selective serotonin (5-HT3) receptor antagonists (e.g. granisetron or dolasetron) as in these cases you may also be allergic to ondansetron
- if you are taking apomorphine (used to treat Parkinson's disease)
If you are not sure, talk to your doctor, nurse or pharmacist before taking Ondansetron Mylan Generics.
Precautions for use What you need to know before taking Generic Ondansetron
Talk to your doctor, pharmacist or nurse before taking Ondansetron Mylan Generics:
- if you have ever had heart problems or changes in your heart rhythm (arrhythmias or cardiac conduction disturbances)
- if you have problems with the levels of salts in your blood such as potassium, sodium and magnesium
- if you have intestinal problems such as intestinal blockage or if you suffer from severe constipation
- if you are about to have or have recently had your adenoids or tonsils removed, as treatment with this medicine may mask the symptoms of internal bleeding
- if you are a child with a body surface area of less than 0.6 m2
- if you have liver problems.
Children and adolescents
This medicine should not be given to children for the prevention of the treatment of nausea and vomiting after a stomach operation.
If you are not sure if any of the above apply to you, talk to your doctor, nurse or pharmacist before taking Ondansetron Mylan Generics.
Interactions Which drugs or foods may change the effect of Ondansetron - Generic Drug
Tell your doctor, nurse or pharmacist if you are taking, have recently taken or might take any other medicines. This also includes those you buy without a prescription or herbal medicines. This is because Ondansetron Mylan Generics may affect others. medicines or other medicines may affect Ondansetron Mylan Generics.
In particular, tell your doctor, nurse or pharmacist if you are taking any of the following medicines:
- apomorphine (a medicine used to treat Parkinson's disease), as significant decreases in blood pressure and loss of consciousness have been reported when apomorphine was used concomitantly with ondansetron - phenytoin or carbamazepine (medicines to treat epilepsy ) which can reduce the effect of the ondansetron
- rifampicin (an antibiotic used to treat infections such as tuberculosis) which may reduce the effects of ondansetron
- antibiotics such as erythromycin or ketoconazole - antiarrhythmic medicines such as amiodarone (used to treat irregular heartbeat)
- beta blockers such as atenolol or timolol (used to treat certain heart or eye problems, anxiety or to prevent migraines) - tramadol (a pain reliever) which can be reduced by ondansetron Mylan Generics
- medicines for cancer (especially anthracyclines and trastuzumab)
- some types of medicines used to treat depression known as SSRIs (selective serotonin reuptake inhibitors) or SNRIs (serotonin and norepinephrine reuptake inhibitors), as these can cause serotonin syndrome, a potentially life-threatening reaction if used in conjunction with ondansetron. Symptoms of serotonin syndrome can include a combination of the following: nausea (feeling sick), vomiting, agitation, diarrhea, high temperature, increased blood pressure, excessive sweating, rapid heartbeat, hallucinations, loss of coordination, overactive reflexes and coma.
If you are not sure if any of the above apply to you, talk to your doctor, nurse or pharmacist before taking Ondansetron Mylan Generics.
Warnings It is important to know that:
Pregnancy and breastfeeding
The use of Ondansetron Mylan Generics is not recommended during pregnancy.Before taking Ondansetron Mylan Generics ask your doctor or pharmacist for advice if you are pregnant or might become pregnant.
Do not breast-feed while being treated with Ondansetron Mylan Generics. This is because this medicine can pass into breast milk. Ask your doctor, pharmacist or midwife for advice.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Driving and using machines
Ondansetron Mylan Generics does not affect the ability to drive or use machines.
Ondansetron Mylan Generics contains lactose
If you have been told by your doctor that you have "intolerance to some sugars, contact your doctor before taking this medicinal product.
Dose, Method and Time of Administration How to use Ondansetron - Generic Drug: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. Ask your doctor, nurse or pharmacist for advice if you are not sure. The dose you have been prescribed will depend on the treatment you are receiving.
The recommended dose is:
Treatment and prevention of nausea and vomiting related to chemotherapy or radiotherapy for cancer treatment
Adults
Take 8 mg of ondansetron one or two hours before treatment, followed by 8 mg of ondansetron 12 hours later. An 8 mg dose of ondansetron twice daily can be taken for up to 5 days after treatment. Your doctor may decide to give you the first dose as an injection immediately before treatment.
Use in children (6 months of age and older) and adolescents
The dose is individual and depends on the weight, size / body surface of the child, however the total daily dose should not exceed 32 mg. Your doctor will decide the dose for your child. See label for more information. The recommended dose for a child is 8 mg twice a day depending on body weight. This can be given for up to 5 days.
Senior citizens
Ondansetron is well tolerated in patients over the age of 65 receiving chemotherapy. No dosage adjustment is required.
Prevention and treatment of post-operative nausea and vomiting
Adults
The usual dose is 16 mg ondansetron one "hour before your operation or 8 mg ondansetron one" hour before your operation, followed by 2 doses of 8 mg at 8 hour intervals.
Use in children (aged 1 month and over) and adolescents
It is recommended that ondansetron be given as an injection. Other pharmaceutical forms of this medicine are more suitable for use in children; ask your doctor or pharmacist.
Senior citizens
There is limited experience with the use of ondansetron in the elderly, however ondansetron is well tolerated in patients over the age of 65 receiving chemotherapy (see section above).
Patients with kidney disease or low metabolism of sparteine / debrisoquine
No dosage adjustment is required in patients with renal disease or for patients unable to metabolise sparteine / debrisoquine.
Patients with liver disease
The total daily dose should not exceed 8 mg per day if you have moderate to severe liver problems.
If you continue to feel nauseous, contact your doctor, pharmacist or nurse.
Method of administration:
- Swallow the tablets with a glass of water
- Ondasetron is also available for injection.
If you forget to take Ondansetron Mylan Generics
- If you forget to take a dose, and feel nauseous or vomit, take it as soon as you remember. After that, take your next tablet at the usual time (as shown on the label). However, if it is already time for your next dose, skip the missed dose and continue as usual.
Do not take a double dose to make up for a forgotten dose.
- If you miss a dose but do not feel nauseous, take the next dose as shown on the label.
Do not take a double dose to make up for a forgotten dose.
If you stop taking Ondansetron Mylan Generics
You should not stop taking this medicine unless your doctor tells you to. Symptoms may recur.
Overdose What to do if you have taken too much Ondansetron - Generic Drug
If you or your child takes more Ondansetron Mylan Generics than they should
Contact your doctor or the nearest emergency room immediately. Take the box of medicine and any remaining tablets with you. There is limited information on overdose with ondansetron. Signs of overdose that have been reported include visual problems, severe constipation, low blood pressure which can cause dizziness or fainting and irregular heart rhythm.
Side Effects What are the side effects of Ondansetron - Generic Drug
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following serious side effects may occur while taking this medicine. If you notice any of these side effects, stop taking the medicine and consult a doctor immediately or go to the nearest hospital.
Rare (may affect up to 1 in 1000 people)
- if you have an allergic reaction the signs include:
- sudden wheezing and chest pain or chest tightness
- swelling of the eyelids, face, lips, mouth, or tongue
- rash
- red spots or lumps under the skin (hives) anywhere on the body
- collapse
Uncommon (may affect up to 1 in 100 people)
- involuntary eye movements (oculogyric crisis)
Other possible side effects
Very common (may affect more than 1 in 10 people):
- headache.
Common (may affect up to 1 in 10 people):
- constipation
- feeling of warmth or redness
Uncommon (may affect up to 1 in 100 people):
- sobs
- low blood pressure, which can make you feel faint or dizzy
- irregular heartbeats or slow heartbeats
- chest pain with or without changes in the ECG
- seizures, unusual body movements or tremor
- muscle cramps
- changes in blood tests showing changes in the way the liver works (more often in patients receiving cisplatin chemotherapy)
Rare (may affect up to 1 in 1,000 people):
- temporary blurred vision
- heart rhythm problems called QT interval prolongation (delayed conduction of electrical signals, which can be seen on an ECG, an electrical recording of the heart). In some people this can lead to a potentially serious heart disease known as torsades de pointes. This can result in a very fast heartbeat causing loss of consciousness.
Very rare (may affect up to 1 in 10,000 people):
- poor vision or temporary loss of vision which usually resolves within 20 minutes
- abnormal fast heartbeat
Undesirable effects in children and adolescents
The side effects reported in children and adolescents were very similar to those seen in adults and reported in the above list.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov. it / it / responsible. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions. Do not use this medicine after the expiry date which is stated on the blister and carton after "EXP". The expiry date refers to the last day of that month.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Deadline "> Other information
What Ondansetron Mylan Generics contains
- The active ingredient is ondansetron.
Each tablet contains respectively 4 mg or 8 mg of the active substance ondansetron (as hydrochloride dihydrate)
- The other ingredients are: lactose monohydrate (see section 2 "Ondansetron Mylan Generics contains lactose monohydrate"), microcrystalline cellulose, pregelatinised maize starch and magnesium stearate.
The coating contains hypromellose, titanium dioxide (E 171), hydroxypropyl cellulose, macrogol, sorbitan oleate, sorbic acid, vanillin, quinoline yellow (E 104).
What Ondansetron Mylan Generics looks like and contents of the pack
4 mg tablet: Pale yellow, round and biconvex film-coated tablet, debossed with "41" on one side.
8 mg tablet: Pale yellow, round and biconvex film-coated tablet, debossed with "42" on one side.
Blister packs:
4 mg: 3, 6, 9, 10, 14, 15, 20, 30, 40, 50, 60, 90, 100, 200, 300, 500 film-coated tablets.
8 mg: 3, 6, 9, 10, 14, 15, 20, 30, 40, 50, 60, 90, 100, 200, 300, 500 film-coated tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT -
ONDANSETRONE MYLAN GENERICS TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
Ondansetron Mylan Generics 4 mg film-coated tablets.
Each film-coated tablet contains 4 mg of ondansetron (in the form of ondansetron hydrochloride dihydrate).
Excipients with known effect: each tablet contains 84.50 mg of lactose monohydrate.
Ondansetron Mylan Generics 8 mg film-coated tablets.
Each film-coated tablet contains 8 mg of ondansetron (in the form of ondansetron hydrochloride dihydrate).
Excipients with known effect: each tablet contains 169.00 mg of lactose monohydrate.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Film-coated tablet.
Each 4 mg film-coated tablet is pale yellow, round, biconvex, debossed with "41" on one side.
Each 8 mg film-coated tablet is pale yellow, round, biconvex, debossed with "42" on one side.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Adults
Ondansetron is indicated for the treatment of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy and for the prevention and treatment of post-operative nausea and vomiting (PONV).
Pediatric population
Ondansetron is indicated for the treatment of chemotherapy induced nausea and vomiting (CINV) in children aged ≥ 6 months and for the prevention and treatment of post-operative nausea and vomiting (PONV) in children aged ≥ 1 month. .
04.2 Posology and method of administration -
Dosage
Chemotherapy and radiotherapy induced nausea and vomiting.
Adults
The emetogenic potential of cancer treatment varies according to the doses and combinations of chemotherapy and radiotherapy regimens used. The route of administration and dose of ondansetron should be flexible and chosen according to the following.
Emetogenic chemotherapy and radiotherapy
In patients receiving emetogenic chemotherapy or radiotherapy, ondansetron can be administered either orally or intravenously.
For most patients receiving emetogenic chemotherapy or radiotherapy, ondansetron should initially be administered intravenously immediately prior to treatment followed by 8 mg orally every 12 hours.
For oral administration: 8 mg 1 to 2 hours before treatment, followed by 8 mg after 12 hours.
In order to protect against delayed or prolonged emesis after the first 24 hours, oral treatment with ondansetron should be continued for up to 5 days after the course of treatment.
Highly emetogenic chemotherapy
In patients receiving highly emetogenic chemotherapy, eg. high doses of cisplatin, ondansetron can be administered intravenously.
In order to protect against delayed or prolonged emesis after the first 24 hours, oral treatment with ondansetron should be continued for up to 5 days after the course of treatment.
The recommended dose for oral administration is 8 mg twice daily.
Pediatric population
CINV in children aged ≥ 6 months and adolescents:
The dose for CINV can be calculated on the basis of body surface area (BSA) or weight - see below. Weight-based dosing results in higher total daily doses than the BSA-based dose (see sections 4.4 and 5.1).
Ondansetron Mylan Generics for infusion should be diluted in 5% dextrose or 0.9% sodium chloride or other comparable infusion fluids and infused intravenously for not less than 15 minutes.
There are no data from controlled clinical trials on the use of Ondasetron Mylan Generics in the prevention of delayed or prolonged nausea and vomiting induced by chemotherapy. There are no data from controlled clinical trials on the use of Ondasetron Mylan Generics for nausea and vomiting. induced by radiotherapy in children.
Dose calculated by the BSA
Ondasetron Mylan Generics should be administered immediately prior to chemotherapy as a single intravenous dose of 5 mg / m². The intravenous dose should not exceed 8 mg.
The oral dose can be started 12 hours later and continued for up to 5 days (see table 1 below).
The total daily dose should not exceed adult dose of 32 mg.
Table 1: BSA-based Dose for Chemotherapy - Children aged ≥ 6 months and adolescents
a: the intravenous dose should not exceed 8 mg.
b: The total daily dose should not exceed adult dose of 32 mg.
Dosage calculated on body weight
Weight-based doses result in a higher total daily dose than the BSA-based dose - see sections 4.4 and 5.1.
Ondasetron Mylan Generics should be administered immediately prior to chemotherapy as a single intravenous dose of 0.15 mg / kg. The intravenous dose should not exceed 8 mg.
Two further intravenous doses can be administered over a 4 hour interval.
The total daily dose should not exceed adult dose of 32 mg.
The oral dose can be started 12 hours later and continued for up to 5 days (see table 2).
Table 2: Weight-based Dose for Chemotherapy - Children aged ≥ 6 months and adolescents
a: the intravenous dose should not exceed 8 mg.
b: The total daily dose should not exceed adult dose of 32 mg.
Senior citizens
Ondansetron is well tolerated in patients over 65 years of age and no changes in dose, frequency or route of administration are required.
See also "Special populations".
Post-operative nausea and vomiting (PONV)
Adults
Prevention of PONV
For the prevention of PONV, ondansetron can be administered orally or by intravenous injection.
Oral administration:
- 16 mg one hour before anesthesia
- alternatively 8 mg one hour before anesthesia, followed by 2 further doses of 8 mg at 8 hour intervals.
PONV treatment in place
Intravenous administration is recommended for the treatment of existing PONV.
Pediatric population
Postoperative nausea and vomiting in children aged ≥1 month and adolescents
Oral formulations
No studies have been conducted on the use of orally administered ondansetron in the prevention or treatment of post-operative nausea and vomiting; slow intravenous injection is advisable for this purpose.
Injection:
For the prevention of PONV in pediatric patients with surgery performed under general anesthesia, a single dose of ondansetron can be administered by slow intravenous injection (not less than 30 seconds) at a dose of 0.1 mg / kg up to a maximum of 4 mg. , before or after induction of anesthesia.
For the treatment of PONV after surgery in pediatric patients with surgery performed under general anesthesia, a single dose of Ondansetron Mylan Generics can be administered by slow intravenous injection (not less than 30 seconds) at a dose of 0.1 mg / kg up to a maximum of 4 mg.
There are no data on the use of ondansetron Mylan Generics in the treatment of postoperative vomiting in children under 2 years of age.
Senior citizens
The experience of the use of ondansetron in the prevention and treatment of post-operative nausea and vomiting (PONV) in the elderly is limited, however ondansetron is well tolerated in patients over the age of 65 receiving chemotherapy.
See also "Special populations".
Special populations
Patients with renal impairment
No daily changes in dose, frequency or route of administration are required.
Patients with hepatic impairment
In subjects with moderate or severe hepatic impairment, the clearance of ondansetron is significantly reduced and the serum half-life significantly prolonged. In such patients the total dose of 8 mg per day should not be exceeded and parenteral or oral administration is therefore recommended.
Patients with impaired metabolism of sparteine / debrisoquine
The elimination half-life of ondansetron is not altered in patients classified as poor metabolisers of sparteine and debrisoquine. Consequently, repeated doses in these patients will give drug exposure levels no different from those of the general population. No changes in daily dose or frequency of administration are required.
Method of administration
Oral use.
04.3 Contraindications -
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Hypersensitivity to other selective 5-HT3 receptor antagonists (e.g. granisetron, dolasetron).
Concomitant use of apomorphine (see section 4.5).
04.4 Special warnings and appropriate precautions for use -
Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5HT3 receptor antagonists.
Respiratory events should be treated symptomatically and physicians should pay particular attention to them as precursors of hypersensitivity reactions.
QT prolongation
Ondansetron prolongs the QT interval in a dose-dependent manner (see section 5.1). In addition, there have been post-marketing reports of torsade de pointes in patients receiving ondansetron. Avoid the use of ondansetron in patients with congenital long QT syndrome. Ondansetron should be administered with caution in patients who have or may develop QTc interval prolongation, including patients with electrolyte disturbances, congestive heart failure, bradyarrhythmias, disturbances. rhythm or conduction, or in patients treated with anti-arrhythmics, beta-adrenergic blocking agents or other medicines that lead to prolongation of the QT interval or to electrolyte abnormalities. Caution should also be exercised when Ondansetron Mylan Generics is administered to cardiac patients undergoing simultaneous anesthesia.
Hypokalaemia and hypomagnesaemia must be corrected prior to administration of ondansetron.
There have been post-marketing reports of patients with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following concomitant use of ondansetron and other serotonergic drugs (including selective serotonin reuptake inhibitors (SSRIs) ) and norepinephrine and serotonin reuptake inhibitors (SNRIs).) If concomitant treatment with ondansetron and other serotonergic drugs is clinically warranted, appropriate patient monitoring is recommended.
Since ondansetron is known to increase transit time in the large intestine, patients with signs of subacute intestinal obstruction should be monitored after administration.
Ondansetron is not indicated for the prophylaxis and treatment of postoperative nausea and vomiting in children following abdominal surgery.
In patients undergoing adeno-tonsillar surgery, the prevention of nausea and vomiting with ondansetron may mask occult bleeding. Therefore such patients should be followed closely after ondansetron administration.
Ondansetron Mylan Generics should be used with caution in patients with hepatic impairment.
Ondansetron Mylan Generics film-coated tablets should not be used in children with a total body surface area of less than 0.6 m².
Pediatric population
Pediatric patients receiving ondansetron with hepatotoxic chemotherapeutic agents should be closely monitored for impaired hepatic function.
Chemotherapy induced nausea and vomiting (CINV)
If the dose is calculated by weight (mg / kg) and if 3 doses are given at 4 hour intervals, the total daily dose will be higher than if a single 5 mg / m² dose were given followed by an oral dose. The comparative efficacy of these two different dosage regimens has not been verified by clinical studies.
Cross-compliance studies indicate "similar efficacy for both regimens (see section 5.1).
Excipients with known effect
Ondansetron Mylan Generics contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the lapp-lactase insufficiency or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction -
There is no evidence that ondansetron induces or inhibits the metabolism of other commonly co-administered medicinal products. 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 P-450 enzymes: CYP3A4, CYP2D6 and CYP1A2. genetic deficiency of CYP2D6), is normally compensated for by other enzymes and should lead to little or no significant changes in the overall clearance of ondansetron and its required doses.
The use of ondansetron with drugs that prolong the QT interval may cause prolongation of the supplemental QT interval. Concomitant use of ondansetron with cardiotoxic drugs (eg anthracyclines such as doxorubicin, daunorubicin or trastuzumab), antibiotics (such as erythromycin or ketoconazole), antiarrhythmics (such as amiodarone) and beta-blockers (such as atenolol or timolol) may increase the risk of arrhythmias (See section 4.4).
There have been post-marketing reports of patients with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following concomitant use of ondansetron and other serotonergic drugs (including SSRIs and SNRIs). (See paragraph 4.4)
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 CYP3A4 inducers (eg phenytoin, carbamazepine and rifampicin) the oral clearance of ondansetron is increased and the blood concentrations of ondansetron decrease.
Tramadol: Data from small studies indicate that ondansetron may reduce the analgesic effect of tramadol.
04.6 Pregnancy and breastfeeding -
Pregnancy
The safety of ondasetron use in pregnant women has not been established.
Evaluation of experimental animal studies does not indicate direct or indirect harmful effects on the development of the embryo, fetus, pregnancy and peri- and postnatal development. men, the use of ondasetron during pregnancy is not recommended.
Feeding time
Studies have shown that ondansetron is excreted in the milk of lactating animals (see section 5.3). It is therefore recommended that mothers being treated with ondansetron do not breastfeed.
04.7 Effects on ability to drive and use machines -
In psychomotor testing, ondansetron has no influence on performance and does not cause sedation. No adverse effect on these activities is expected based on the pharmacology of ondansetron.
04.8 Undesirable effects -
Undesirable effects are listed below according to system organ class and frequency.
Frequencies are defined as follows:
Very common: (≥1 / 10)
Common: (≥1 / 100 y
Uncommon: (≥1 / 1,000 y
Rare: (≥1 / 10,000 y
Very rare: (
Not known: (frequency cannot be estimated from the available data)
Very common, common and uncommon events are events generally determined during clinical trials. The incidence in placebo is taken into account. Rare and very rare events are events generally determined by spontaneous reports during the post marketing phase.
The following frequencies are estimated at the standard recommended doses for the use of ondansetron according to the indications and formulation.
¹ Observed with no definitive evidence of persistent clinical sequelae
² Most reported cases of blindness resolved within 20 minutes. Many patients were being treated with chemotherapeutic agents, which include cisplatin. Some cases of transient blindness have been reported as being cortical in origin.
³ These cases have been commonly observed in patients receiving cisplatin chemotherapy.
Pediatric population
The adverse event profile in children and adolescents is comparable to that seen in adults.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions that occur after authorization of the medicinal product is important as it allows for continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the reporting system. address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose -
Signs and Symptoms
There is limited experience with ondasetron overdose. In most cases, symptoms were similar to those already reported in patients receiving the recommended dose (see section 4.8).
Manifestations that have been reported include visual disturbances, severe constipation, hypotension and vasovagal episodes with transient second degree AV block.
Ondansetron prolongs the QT interval in a dose dependent manner. It is recommended to monitor the ECG in case of overdose
Treatment
There is no specific antidote to ondansetron, therefore appropriate symptomatic and supportive therapy should be provided in all cases of suspected overdose.
The use of ipecac for the treatment of ondansetron overdose is not recommended, as patients are likely to unresponsive due to the antiemetic effect of ondansetron itself.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: antiemetics and antinauseants, serotonin (5HT3) antagonists.
ATC code: A04AA01.
Mechanism of action
Ondansetron is a potent and highly selective 5-HT3 receptor antagonist.
Its precise mechanism of antiemetic and anti-nausea action is not known. Chemotherapeutic agents and radiotherapy can cause a release of serotonin (5-HT) from the small intestine which in turn, by activating serotonergic vagal afferents through receptors 5-HT3, can trigger the gag reflex. The ondansetron blocks the initiation of this reflex. Furthermore, the activation of the vagal afferent pathways can determine, at the level of the postrema area located in the floor of the IV ventricle, the release of serotonin and this can stimulate vomiting through a central mechanism. Therefore, the efficacy of ondansetron in the treatment of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy is probably due to its antagonistic action on the 5HT3 receptors of neurons located both in the central and peripheral nervous systems.
The mechanism of action in the control of post-operative nausea and vomiting is unknown but may be similar to the control mechanism of cytotoxic induced nausea and vomiting.
In a pharmaco-psychological study in volunteers, ondansetron did not show sedative effects.
Ondansetron does not alter plasma prolactin concentrations.
The role of ondansetron in opioid-induced emesis is still unclear.
Pediatric population
Chemotherapy induced nausea and vomiting (CINV)
The efficacy of ondansetron in the control of vomiting and nausea induced by chemotherapy for cancer was evaluated in a randomized double-blind clinical trial in 415 patients aged 1 to 18 years (S3AB3006).
On the day of chemotherapy, patients received ondansetron 5 mg / m² i.v. + ondansetron 4 mg orally after 8 or 12 hours or ondansetron 0.45 mg / kg i.v. + oral placebo after 8 or 12 hours.
After chemotherapy both groups received 4 mg ondansetron syrup 2 times a day for 3 days. Complete control of emesis on the worst day of chemotherapy was 49% (5 mg / m² i.v. + ondansetron 4 mg orally) and 41% (0.45 mg / kg i.v. + placebo orally).
After chemotherapy both groups received 4 mg ondansetron syrup 2 times a day for 3 days.
A double-blind randomized placebo-controlled clinical trial (S3AB4003) in 438 patients aged 1 to 17 years demonstrated complete control of emesis on the worst day of chemotherapy in:
• 73% ≥ of patients when ondansetron was administered intravenously at a dose of 5 mg / m² i.v. together with 2-4 mg of dexamethasone orally
• 71% of patients when ondansetron was administered as a syrup at a dose of 8 mg + 2-4 mg dexamethasone orally on chemotherapy days).
After chemotherapy both groups received 4 mg ondansetron syrup 2 times a day for 2 days.
The efficacy of ondansetron in 75 children aged 6 to 48 months was studied in an open-label, non-comparative one-arm study (S3A40320). All children received 3 doses of 0.15 mg / kg intravenous ondansetron. administered 30 minutes before the start of chemotherapy and followed 4 and 8 hours after the first dose.
Complete control of emesis was achieved in 56% of patients.
Another open-label, non-comparative one-arm study (S3A239) investigated the efficacy of a 0.15 mg / kg dose of ondansetron followed by 2 oral doses of 4 mg ondasetron for children aged
Complete control of emesis was achieved in 42% of patients.
Prevention of post-operative nausea and vomiting (PONV)
The efficacy of a single dose of ondansetron in the prevention of postoperative nausea and vomiting was investigated in a double-blind, randomized, placebo-controlled study in 670 children aged 1 to 24 months (post-conceptual age ≥ 44 weeks, weight ≥ 3 kg). The included subjects planned to perform selective surgery under general anesthesia and had an ASA level ≤ III. A single dose of ondansetron 0.1 mg / kg was administered within 5 minutes of induction. of anesthesia.The percentage of subjects who experienced at least one emetic episode during the 24-hour evaluation period (ITT) was higher for patients receiving placebo than for those receiving ondansetron (28% vs 11%, p
Four double-blind, placebo-controlled studies were performed in 1469 male and female patients (aged 2 to 12 years) undergoing general anesthesia. Patients were randomized to single intravenous doses of ondansetron (0.1 mg / kg for pediatric patients weighing 40 kg or less than 4 mg for pediatric patients weighing more than 40 kg, the number of patients = 735) or placebo (number of patients = 734). Study drug was administered over at least 30 seconds, immediately before or after induction of anesthesia. Ondansetron was significantly more effective than placebo in preventing nausea and vomiting. The results of these studies are summarized in Table 3.
Table 3: Prevention and treatment of PONV in pediatric patients - 24 hour response treatment
CR = no episode of emesis, rescue or withdrawal
05.2 "Pharmacokinetic properties -
Following oral administration, ondansetron is passively and completely absorbed via the gastrointestinal tract and undergoes first pass metabolism (bioavailability is approximately 60%). Peak plasma concentration after a dose of 8 mg , is approximately 30 ng / ml, reached approximately 1.5 hours after administration. For doses above 8 mg the increase in systemic exposure to ondansetron with increasing dose is greater than a proportional increase; may reflect some reduction in first pass metabolism at higher oral doses. Bioavailability after oral administration is slightly increased by the presence of food but is not altered by antacids. Studies in healthy elderly volunteers have shown a slight, but clinically non significant, age-related increase in both the oral bioavailability (65%) and the half-life (5 hours) of ondansetron. Gender differences have been found in the metabolism of ondansetron: women have a higher rate and degree of absorption after an oral dose and a reduction in systemic clearance and volume of distribution (adjusted for weight).
The availability of ondansetron after oral, intramuscular and intravenous doses is similar, with a terminal half-life of approximately 3 hours and a steady-state volume of distribution of approximately 140 liters. Equivalent systemic exposure is obtained after intramuscular and intravenous administration of ondansetron.
Ondansetron is not highly protein bound (70-76%). A direct relationship between plasma concentrations and antiemetic effect has not been established. Ondansetron is cleared from the systemic circulation predominantly through hepatic metabolism by multiple metabolic pathways. Less than 5% of the absorbed dose is excreted unchanged in the urine. The absence of the CYP2D6 enzyme ( debrisoquine polymorphism) it has no effect on the pharmacokinetics of ondansetron. The pharmacokinetic characteristics of ondansetron are unchanged after repeated dosing.
Special populations
Children and adolescents (1 month to 17 years)
In pediatric patients aged 1 to 4 months (n = 19) who had to undergo surgery, normalized weight, clearance was approximately 30% lower than in patients aged 5 to 24 months (n = 22) but comparable to patients aged between 3 and 12 years. The half-life in the patient population aged 1 to 4 months was reported to mean 6.7 hours compared to 2.9 hours for patients aged 5 to 24 months and 3 to 12 years.
Differences in pharmacokinetic parameters in the patient population aged 1 to 4 months can be explained in part by a higher percentage of water in infants and children and a higher volume of distribution for water-soluble medicinal products such as "ondansetron.
In pediatric patients aged 3 to 12 years undergoing selective surgery under general anesthesia, the absolute values for both clearance and volume of distribution were reduced compared to the values in adult patients.
Both parameters increased linearly with weight and by 12 years of age, the values were approaching those of young adults.
When clearance and volume of distribution values were normalized by body weight, the values of these parameters were similar across age groups in the population. Use of weight-based dosing compensates for age-related variations and is effective in normalizing systemic exposure in pediatric patients.
The population pharmacokinetic analysis was performed on 428 subjects (cancer patients, surgery patients and healthy patients) aged 1 month to 44 years following intravenous administration of ondansetron. Based on this analysis, exposure systemic (AUC) following oral or intravenous dosing ondansetron in children and adolescents was comparable to adults, with the exception of children aged 1 to 4 months. The volume was age-related and was lower in adults than in infants and children. Clearance was related to weight, but not age, with the exception of infants 1 to 4 months of age.
It is difficult to conclude whether there was a "further reduction in age-related clearance in infants 1 to 4 months or simply inherent variability due to the low number of subjects studied in this age group. Since patients less than 6 months of age" age will receive only a single dose of PONV a reduced clearance may not be clinically relevant.
Kidney failure
In patients with renal insufficiency (creatinine clearance 15-60 mL / min), both systemic clearance and volume of distribution are reduced following IV administration of ondansetron, resulting in a slight, but clinically insignificant, increase in the elimination half-life. (5.4 hours.) A study in patients with severe renal insufficiency requiring regular hemodialysis (studied between dialyses) showed the pharmacokinetics of ondansetron to be substantially unchanged after intravenous administration.
Elderly or Kidney failure
Specific studies in the elderly or in patients with renal insufficiency have been limited to IV and oral administration. However, the half-life of ondansetron after rectal administration in these populations is expected to be similar to that observed in healthy volunteers, since the rate of ondansetron elimination following rectal administration is not determined by systemic clearance.
Hepatic insufficiency
After oral, intravenous or intramuscular administration in patients with severe hepatic insufficiency, systemic clearance is markedly reduced, with a prolongation of the elimination half-life (15-32 hours) and an oral bioavailability approaching 100% due to reduced metabolism. pre-systemic. The pharmacokinetics of ondasentrone following administration as suppositories have not been evaluated in patients with hepatic insufficiency.
05.3 Preclinical safety data -
Non-clinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.
Ondansetron and its metabolites accumulate in the milk of rats. The milk / plasma ratio is 5.2.
A study in cardiac channels of cloned human ions showed that ondansetron has the potential to interfere with cardiac repolarization by blocking HERG potassium channels. The clinical relevance of this finding is unclear. QT prolongation. dose-dependent has been reported in a detailed QT study in volunteers (see section 5.1)
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Core of the tablets:
Lactose monohydrate, microcrystalline cellulose, pregelatinised maize starch, magnesium stearate.
Coating of tablets:
Hypromellose, titanium dioxide (E171), hydroxypropylcellulose, macrogol, sorbitan oleate, sorbic acid, vanillin, quinoline yellow (E104).
06.2 Incompatibility "-
Not relevant.
06.3 Period of validity "-
3 years.
06.4 Special precautions for storage -
This medicinal product does not require any special storage precautions.
06.5 Nature of the immediate packaging and contents of the package -
Blister (PVC / AL)
4 mg: 3, 6, 10, 14, 15, 20, 30, 40, 50, 60, 90, 100, 200, 300 and 500 film-coated tablets.
8 mg: 3, 6, 9,10, 14, 15, 20, 30, 40, 50, 60, 90, 100, 200, 300 and 500 film-coated tablets.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling -
No special instructions.
Unused medicines and the resulting waste must be disposed of in accordance with local regulations.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Mylan S.p.A. - Via Vittor Pisani, 20 - 20124 Milan, Italy
08.0 MARKETING AUTHORIZATION NUMBER -
4 mg film-coated tablets 3 tablets in PVC / AL blister - AIC n. 037548017
4 mg film-coated tablets 6 tablets in PVC / AL-AIC blister n. 037548029
4 mg film-coated tablets 10 tablets in PVC / AL-AIC blister n. 037548031
4 mg film-coated tablets 14 tablets in PVC / AL-AIC blister n. 037548043
4 mg film-coated tablets 15 tablets in PVC / AL blister - AIC n. 037548056
4 mg film-coated tablets 20 tablets in PVC / AL blister - AIC n. 037548068
4 mg film-coated tablets 30 tablets in PVC / AL blister - AIC n. 037548070
4 mg film-coated tablets 40 tablets in PVC / AL-AIC blister n. 037548082
4 mg film-coated tablets 50 tablets in PVC / AL-AIC blister n. 037548094
4 mg film-coated tablets 60 tablets in PVC / AL-AIC blister n. 037548106
4 mg film-coated tablets 90 tablets in PVC / AL-AIC blister n. 037548118
4 mg film-coated tablets 100 tablets in PVC / AL-AIC blister n. 037548120
4 mg film-coated tablets 200 tablets in PVC / AL-AIC blister n. 037548132
4 mg film-coated tablets 300 tablets in PVC / AL-AIC blister n. 037548144
4 mg film-coated tablets 500 tablets in PVC / AL-AIC blister n. 037548157
8 mg film-coated tablets 3 tablets in PVC / AL-AIC blister n. 037548169
8 mg film-coated tablets 6 tablets in PVC / AL-AIC blister n. 037548171
8 mg film-coated tablets 10 tablets in PVC / AL-AIC blister n. 037548183
8 mg film-coated tablets 14 tablets in PVC / AL-AIC blister n. 037548195
8 mg film-coated tablets 15 tablets in PVC / AL-AIC blister n. 037548207
8 mg film-coated tablets 20 tablets in PVC / AL-AIC blister n. 037548219
8 mg film-coated tablets 30 tablets in PVC / AL-AIC blister n. 037548221
8 mg film-coated tablets 40 tablets in PVC / AL-AIC blister n. 037548233
8 mg film-coated tablets 50 tablets in PVC / AL-AIC blister n. 037548245
8 mg film-coated tablets 60 tablets in PVC / AL-AIC blister n. 037548258
8 mg film-coated tablets 90 tablets in PVC / AL-AIC blister n. 037548260
8 mg film-coated tablets 100 tablets in PVC / AL-AIC blister n. 037548272
8 mg film-coated tablets 200 tablets in PVC / AL-AIC blister n. 037548284
8 mg film-coated tablets 300 tablets in PVC / AL-AIC blister n. 037548296
8 mg film-coated tablets 500 tablets in PVC / AL blister - AIC n. 037548308
4 mg film-coated tablets 9 tablets in PVC / AL-AIC blister n. 037548310
8 mg film-coated tablets 9 tablets in PVC / AL-AIC blister n. 037548322
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
November 2008
October 2012
10.0 DATE OF REVISION OF THE TEXT -
August 2015
