post-title portfolio-title Ondansetron Hydrochloride Tablets 4mg Taj Pharma 2020-01-23 13:47:22 no no
  1. NAME OF THE MEDICINAL PRODUCT

Ondansetron Hydrochloride Tablets 4mg Taj Pharma
Ondansetron Hydrochloride Tablets 8mg Taj Pharma

  1. QUALITATIVE AND QUANTITATIVE COMPOSITION

a) Ondansetron Hydrochloride Tablets USP 4mg Taj Pharma
Each film-coated tablet contains: 5 mg Ondansetron Hydrochloride USP Equivalent to 4mg of? Ondansetron

b) Ondansetron Hydrochloride Tablets USP 8mg Taj Pharma
Each film-coated tablet contains: 10 mg Ondansetron hydrochloride, USP Equivalent to 8mg of? Ondansetron

For a full list of excipients, see section 6.1.

  1. PHARMACEUTICAL FORM

Oral lyophilisate.

White, round, plano-convex, freeze dried, fast dispersing oral dosage form.

  1. CLINICAL PARTICULARS

4.1 Therapeutic indications

Adults:

Ondansetron HCL Melt is indicated for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy.

Ondansetron HCL Melt is indicated for the prevention of post-operative nausea and vomiting (PONV).

For treatment of established PONV, administration by injection is recommended.

Paediatric Population:

Ondansetron HCL is indicated for the management of chemotherapy-induced nausea and vomiting in children aged ?6 months

No studies have been conducted on the use of orally administered ondansetron in the prevention and treatment of PONV in children aged ?1 month, administration by IV injection is recommended for this purpose.

4.2 Posology and method of administration

Place the Melt on top of the tongue, where it will disperse within seconds, then swallow.

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 selection of dose regimen should be determined by the severity of the emetogenic challenge.

Emetogenic chemotherapy and radiotherapy:?Ondansetron HCL can be given either by rectal, oral (as Melt, tablets or syrup) intravenous or intramuscular administration.

For oral administration: 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 HCL 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 or rectal treatment with Ondansetron HCL 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.

Paediatric Population:

CINV in children aged ? 6 months and adolescents

The dose for CINV can be calculated based on body surface area (BSA) or weight ? see below. In paediatric clinical studies, ondansetron was given by IV infusion diluted in 25 to 50 mL of saline or other compatible infusion fluid and infused over not less than 15 minutes. Weight-based dosing results in higher total daily doses compared to BSA-based dosing (see section 4.4).

There are no data from controlled clinical trials on the use of Ondansetron HCL in the prevention of delayed or prolonged CINV. There are no data from controlled clinical trials on the use of Ondansetron HCL for radiotherapy-induced nausea and vomiting in children.

Dosing by BSA:

Ondansetron HCL should be administered immediately before chemotherapy as a single intravenous dose of 5 mg/m2. The single intravenous dose must not exceed 8 mg.

Oral dosing can commence 12 hours later and may be continued for up to 5 days (Table 1).

The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg.

Table 1: BSA-based dosing for Chemotherapy – Children aged ?6 months and adolescents

BSA Day 1?(a,b) Days 2-6(b)
< 0.6 m2 5 mg/m2?IV. plus

2 mg syrup after 12 hours

2 mg syrup every 12 hours
? 0.6 m2?to ?1.2 m2 5 mg/m2?IV plus

4 mg syrup or tablet after 12 hours

4 mg syrup or tablet every 12 hours
>1.2 m2 5 mg/m2?or 8 mg IV plus

8 mg syrup or tablet after 12 hours

8 mg syrup or tablet every 12 hours

a The intravenous dose must not exceed 8 mg.

b The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg

Dosing by bodyweight:

Weight-based dosing results in higher total daily doses compared to BSA-based dosing (see sections 4.4 and 5.1).

Ondansetron HCL should be administered immediately before chemotherapy as a single intravenous dose of 0.15 mg/kg. The single intravenous dose must not exceed 8 mg. Two further intravenous doses may be given in 4-hourly intervals.

Oral dosing can commence 12 hours later and may be continued for up to 5 days (Table 2).

The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg.

Table 2: Weight-based dosing for Chemotherapy – Children aged ?6 months and adolescents

Weight Day 1?(a,b) Days 2-6(b)
? 10 kg Up to 3 doses of 0.15 mg/kg IV every 4 hours 2 mg syrup every 12 hours
> 10 kg Up to 3 doses of 0.15 mg/kg IV every 4 hours 4 mg syrup or tablet every 12 hours

a The intravenous dose must not exceed 8 mg.

b The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg.

Elderly:

No alteration of oral dose or frequency of administration is required.

Post operative nausea and vomiting (PONV)

Adults:

For the prevention of PONV:?Ondansetron HCL may be administered either orally (as Melt, tablets or syrup) or by intravenous or intramuscular injection.

For oral administration: 16 mg taken one hour prior to anaesthesia.

For the treatment of established PONV:?Intravenous or intramuscular administration is recommended.

Paediatric population:

PONV in children aged ? 1 month and adolescents

Oral formulation:

No studies have been conducted on the use of orally administered ondansetron in the prevention or treatment of post-operative nausea and vomiting; slow IV injection (not less than 30 seconds) is recommended for this purpose.

Injection:

For prevention of PONV in paediatric patients having surgery performed under general anaesthesia, a single dose of ondansetron may 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 either prior to, at or after induction of anaesthesia.

For the treatment of PONV after surgery in paediatric patients having surgery performed under general anaesthesia, a single dose of Ondansetron HCL may 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 HCL in the treatment of PONV in children below 2 years of age.

Elderly:

There is limited experience in the use of Ondansetron HCL in the prevention and treatment of PONV in the elderly, however Ondansetron HCL is well tolerated in patients over 65 years receiving chemotherapy.

For both indications

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 HCL 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.

4.3 Contraindications

Concomitant use with apomorphine (see section 4.5)

Hypersensitivity to any component of the preparation.

4.4 Special warnings and 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 clinicians should pay particular attention to them as precursors of hypersensitivity reactions.

Ondansetron prolongs the QT interval in a dose-dependent manner (see section 5.1). 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.

Hypokalaemia and hypomagnesaemia should be corrected prior to ondansetron 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 and other serotonergic drugs (including selective serotonin reuptake inhibitors (SSRI) and serotonin noradrenaline reuptake inhibitors (SNRIs)). If concomitant treatment with ondansetron and other serotonergic drugs is clinically warranted, appropriate observation of the patient is advised.

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.

Ondansetron HCL Melt formulation contains aspartame and therefore should be taken with caution in patients with phenylketonuria.

Paediatric Population:

Paediatric patients receiving ondansetron with hepatotoxic chemotherapeutic agents should be monitored closely for impaired hepatic function.

CINV:?When calculating the dose on an mg/kg basis and administering three doses at 4-hour intervals, the total daily dose will be higher than if one single dose of 5 mg/m2?followed by an oral dose is given. The comparative efficacy of these two different dosing regimens has not been investigated in clinical trials. Cross-trial comparison indicates similar efficacy for both regimens (see section 5.1).

4.5 Interaction with other medicinal products and other forms of interaction

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 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 is coadministered with drugs that prolong the QT interval and/or cause electrolyte abnormalities. (See section 4.4)

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 section 4.4).

Serotonergic Drugs (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 and other serotonergic drugs (including SSRIs and SNRIs). (See section 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 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.

4.6 Fertility, pregnancy and lactation

Pregnancy

The safety of ondansetron for use in human pregnancy has not been established. Evaluation of experimental animal studies does not indicate direct or indirect harmful effects with respect to the development of the embryo, or the foetus, the course of gestation and peri- and post-natal development. However, as animal studies are not always predictive of human response the use of ondansetron in pregnancy is not recommended.

Breast-feeding

Tests have shown that ondansetron passes into the milk of lactating animals. It is therefore recommended that mothers receiving Ondansetron HCL should not breast-feed their babies.

Fertility

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

4.7 Effects on 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

4.8 Undesirable effects

Adverse events are listed below 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.
  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.

4.9 Overdose

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 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 fashion. 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, 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 the national poisons centre, where available.

The use of ipecacuanha to treat overdose with ondansetron is not recommended, as patients are unlikely to respond due to the anti-emetic action of ondansetron itself.

  1. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Mechanism of Action

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.

The role of ondansetron in opiate-induced emesis is not yet established.

QT Prolongation

The effect of ondansetron on the QTc interval was evaluated in a double blind, randomized, placebo and positive (moxifloxacin) controlled, crossover study in 58 healthy adult men and women. Ondansetron doses included 8 mg and 32 mg infused intravenously over 15 minutes. At the highest tested dose of 32 mg, the maximum mean (upper limit of 90% CI) difference in QTcF from placebo after baseline-correction was 19.6 (21.5) msec. At the lower tested dose of 8 mg, the maximum mean (upper limit of 90% CI) difference in QTcF from placebo after baseline-correction was 5.8 (7.8) msec. In this study, there were no QTcF measurements greater than 480 msec and no QTcF prolongation was greater than 60 msec.

Paediatric population:

CINV

The efficacy of ondansetron in the control of emesis and nausea induced by cancer chemotherapy was assessed in a double-blind randomised trial in 415 patients aged 1 to 18 years (S3AB3006). On the days of chemotherapy, patients received either ondansetron 5 mg/m2?intravenous and ondansetron 4 mg orally after 8-12 hours or ondansetron 0.45 mg/kg intravenous and placebo orally after 8 to 12 hours. Post-chemotherapy both groups received 4 mg ondansetron syrup twice daily for 3 days. Complete control of emesis on worst day of chemotherapy was 49% (5 mg/m2?intravenous and ondansetron 4 mg orally) and 41% (0.45 mg/kg intravenous and placebo orally). Post-chemotherapy both groups received 4 mg ondansetron syrup twice daily for 3 days. There was no difference in the overall incidence or nature of adverse events between the two treatment groups.

A double-blind randomised placebo-controlled trial (S3AB4003) in 438 patients aged 1 to 17 years demonstrated complete control of emesis on worst day of chemotherapy in:

  • 73% of patients when ondansetron was administered intravenously at a dose of 5 mg/m2intravenous together with 2 to 4 mg dexamethasone orally
  • 71% of patients when ondansetron was administered as syrup at a dose of 8 mg together with 2 to 4 mg dexamethasone orally on the days of chemotherapy.

Post-chemotherapy both groups received 4 mg ondansetron syrup twice daily for 2 days. There was no difference in the overall incidence or nature of adverse events between the two treatment groups.

The efficacy of ondansetron in 75 children aged 6 to 48 months was investigated in an open-label, non-comparative, single-arm study (S3A40320). All children received three 0.15 mg/kg doses of intravenous ondansetron, administered 30 minutes before the start of chemotherapy and then at 4 and 8 hours after the first dose. Complete control of emesis was achieved in 56% of patients.

Another open-label, non-comparative, single-arm study (S3A239) investigated the efficacy of one intravenous dose of 0.15 mg/kg ondansetron followed by two oral ondansetron doses of 4 mg for children aged < 12 years and 8 mg for children aged ? 12 years (total no. of children n = 28). Complete control of emesis was achieved in 42% of patients.

PONV

The efficacy of a single dose of ondansetron in the prevention of post-operative nausea and vomiting was investigated in a randomised, double-blind, placebo-controlled study in 670 children aged 1 to 24 months (post-conceptual age ?44 weeks, weight ? 3 kg). Included subjects were scheduled to undergo elective surgery under general anaesthesia and had an ASA status ? III. A single dose of ondansetron 0.1 mg/kg was administered within five minutes following induction of anaesthesia. The proportion of subjects who experienced at least one emetic episode during the 24-hour assessment period (ITT) was greater for patients on placebo than those receiving ondansetron (28% vs. 11%, p <0.0001).

Four double-blind, placebo-controlled studies have been performed in 1469 male and female patients (2 to 12 years of age) undergoing general anaesthesia. Patients were randomised to either single intravenous doses of ondansetron (0.1 mg/kg for paediatric patients weighing 40 kg or less, 4 mg for paediatric patients weighing more than 40 kg; number of patients = 735) or placebo (number of patients = 734). Study drug was administered over at least 30 seconds, immediately prior to or following anaesthesia induction. Ondansetron was significantly more effective than placebo in preventing nausea and vomiting. The results of these studies are summarised in Table 3.

Table 3: Prevention and treatment of PONV in Paediatric Patients ? Treatment response over 24 hours

Study Endpoint Ondansetron % Placebo % p value
S3A380 CR 68 39 ?0.001
S3GT09 CR 61 35 ?0.001
S3A381 CR 53 17 ?0.001
S3GT11 no nausea 64 51 0.004
S3GT11 no emesis 60 47 0.004

CR = no emetic episodes, rescue or withdrawal

5.2 Pharmacokinetic properties

Following oral administration of ondansetron, absorption is rapid with maximum peak plasma concentrations of about 30 ng/mL being attained and achieved in approximately 1.5 hours after an 8 mg dose. The syrup and tablet formulations are bioequivalent and have an absolute oral bioavailability of 60%. The disposition of ondansetron following oral, intravenous and intramuscular dosing is similar with a terminal elimination half-life of approximately 3 hours and a steady-state volume of distribution of about 140 L. Ondansetron is not highly protein bound (70-76%) and is cleared from the systemic circulation predominantly by hepatic metabolism through multiple enzymatic pathways. Less than 5% of the absorbed dose is excreted unchanged in the urine. The absence of the enzyme CYP2D6 (the debrisoquine polymorphism) has no effect on the pharmacokinetics of ondansetron. The pharmacokinetic properties of ondansetron are unchanged on repeat dosing.

Special Patient Populations

Gender

Gender differences were shown in the disposition of ondansetron, with females having a greater rate and extent of absorption following an oral dose and reduced systemic clearance and volume of distribution (adjusted for weight).

Children and Adolescents (aged 1 month to 17 years)

In paediatric patients aged 1 to 4 months (n=19) undergoing surgery, weight normalised clearance was approximately 30% slower than in patients aged 5 to 24 months (n=22) but comparable to the patients aged 3 to 12 years. The half-life in the patient population aged 1 to 4 month was reported to average 6.7 hours compared to 2.9 hours for patients in the 5 to 24 month and 3 to 12 year age range. The differences in pharmacokinetic parameters in the 1 to 4 month patient population can be explained in part by the higher percentage of total body water in neonates and infants and a higher volume of distribution for water soluble drugs like ondansetron.

In paediatric patients aged 3 to 12 years undergoing elective surgery with general anaesthesia, the absolute values for both the clearance and volume of distribution of ondansetron were reduced in comparison to values with adult patients. Both parameters increased in a linear fashion with weight and by 12 years of age, the values were approaching those of young adults. When clearance and volume of distribution values were normalised by body weight, the values for these parameters were similar between the different age group populations. Use of weight-based dosing compensates for age-related changes and is effective in normalising systemic exposure in paediatric patients.

Population pharmacokinetic analysis was performed on 428 subjects (cancer patients, surgery patients and healthy volunteers) aged 1 month to 44 years following intravenous administration of ondansetron. Based on this analysis, systemic exposure (AUC) of ondansetron following oral or IV dosing in children and adolescents was comparable to adults, with the exception of infants aged 1 to 4 months. Volume was related to age and was lower in adults than in infants and children. Clearance was related to weight but not to age with the exception of infants aged 1 to 4 months. It is difficult to conclude whether there was an additional reduction in clearance related to age 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 will only receive a single dose in PONV a decreased clearance is not likely to be clinically relevant.

Elderly

Early Phase I studies in healthy elderly volunteers showed a slight age-related decrease in clearance, and an increase in half-life of ondansetron. However, wide inter-subject variability resulted in considerable overlap in pharmacokinetic parameters between young (< 65 years of age) and elderly subjects (? 65 years of age) and there were no overall differences in safety or efficacy observed between young and elderly cancer patients enrolled in CINV clinical trials to support a different dosing recommendation for the elderly.

Based on more recent ondansetron plasma concentrations and exposure-response modelling, a greater effect on QTcF is predicted in patients ?75 years of age compared to young adults. Specific dosing information is provided for patients over 65 years of age and over 75 years of age for intravenous dosing.

Renal impairment

In patients with renal impairment (creatinine clearance 15-60 mL/min), systemic clearance and volume of distribution are reduced, resulting in a slight, but clinically insignificant increase in elimination half-life (5.4 hours). A study in patients with severe renal impairment who required regular haemodialysis (studied between dialyses) showed ondansetron’s pharmacokinetics to be essentially unchanged.

Hepatic impairment

In patients with severe hepatic impairment, systemic clearance is markedly reduced with prolonged elimination half-lives (15-32 hours) and an oral bioavailability approaching 100% because of reduced pre-systemic metabolism.

5.3 Preclinical safety data

No additional data of relevance.

  1. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Gelatin, Mannitol, Aspartame

Sodium methyl para-hydroxybenzoate

Sodium propyl para-hydroxybenzoate

Strawberry flavour

6.2 Incompatibilities

None reported.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Store below 30?C.

6.5 Nature and contents of container

Double aluminium foil blister strip containing 10 tablets

6.6 Special precautions for disposal and other handling

Do not attempt to push Ondansetron HCL Melt through the lidding foil.

Peel back the lidding foil of one blister and gently remove the Ondansetron HCL Melt.

Place the Melt on top of the tongue, where it will disperse within seconds then swallow.

7. Manufactured in India By:
TAJ PHARMACEUTICALS LIMITED
at SURVEY NO.188/1 TO 189/1,190/1 TO 4,
ATHIYAWAD, DABHEL, DAMAN- 396210 (INDIA)

Ondansetron Hydrochloride Tablets USP 4mg Taj Pharma

Package Leaflet: Information for the User?

(Ondansetron)

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions about your illness or your medicine, ask your doctor, nurse or pharmacist.
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
  • If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, nurse or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet?

  • What Ondansetron Hydrochloride is and what it is used for
  • What you need to know before you take Ondansetron Hydrochloride
  • How to take Ondansetron Hydrochloride
  • Possible side effects
  • How to store Ondansetron Hydrochloride
  • Contents of the pack and other information

 

 

  1. WHAT ONDANSETRON HYDROCHLORIDE IS AND WHAT IT IS USED FOR

Ondansetron Hydrochloride contains a medicine called ondansetron. This belongs to a group of medicines called anti- emetics. Ondansetron Hydrochloride is a special type of Ondansetron Hydrochloride tablet that dissolves very quickly when put on top of the tongue.

Ondansetron Hydrochloride is used for:

  • preventing nausea and vomiting caused by chemotherapy (in adults and children) or radiotherapy for cancer (adults only)
  • preventing nausea and vomiting after surgery (adults only).

Ask your doctor, nurse or pharmacist if you would like any further explanation about these uses.

  1. WHAT YOU NEED TO KNOW BEFORE YOU TAKE ONDANSETRON HYDROCHLORIDE DO NOT TAKE ONDANSETRON Hydrochloride if:
  • you are taking apomorphine (used to treat Parkinson?s disease)
  • you are allergic (hypersensitive) to ondansetron or any of the other ingredients in Ondansetron Hydrochloride (listed in Section 6).

If you are not sure, talk to your doctor, nurse or pharmacist before taking Ondansetron Hydrochloride.

Warnings and precautions

Check with your doctor, nurse or pharmacist before taking Ondansetron Hydrochloride if:

  • you have ever had heart problems (e.g. congestive heart failure which causes shortness of breath and swollen ankles)
  • you have an uneven heart beat (arrhythmias)
  • you are allergic to medicines similar to ondansetron, such as granisetron or palonosetron
  • you have liver problems
  • you have a blockage in your gut
  • you have problems with the levels of salts in your blood, such as potassium, sodium and magnesium.

If you are not sure if any of the above apply to you, talk to your doctor, nurse or pharmacist before taking Ondansetron Hydrochloride .

Other medicines and Ondansetron Hydrochloride

Please tell your doctor, nurse or pharmacist if you are taking or have recently taken or might take other medicines. This includes medicines that you buy without a prescription and herbal medicines. This is because Ondansetron Hydrochloride can affect the way some medicines work. Also some other medicines can affect the way Ondansetron Hydrochloride works.

In particular, tell your doctor, nurse or pharmacist if you are taking any of the following medicines:

  • carbamazepine or phenytoin used to treat epilepsy
  • rifampicin used to treat infections such as tuberculosis (TB)
  • antibiotics such as erythromycin or ketoconazole
  • anti-arrhythmic medicines used to treat an uneven heart beat
  • beta-blocker medicines used to treat certain heart or eye problems, anxiety or prevent migraines
  • tramadol, a pain killer.
  • medicines that affect the heart (such as haloperidol or methadone)
  • cancer medicines (especially anthracyclines and trastuzumab)
  • SSRIs (selective serotonin reuptake inhibitors) used to treat depression and/or anxiety including fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram
  • SNRIs (serotonin noradrenaline reuptake inhibitors) used to treat depression and/or anxiety including venlafaxine, duloxetine.

If you are not sure if any of the above applies to you, talk to your doctor, nurse or pharmacist before having Ondansetron Hydrochloride .

Pregnancy and breast-feeding

It is not known if Ondansetron Hydrochloride is safe during pregnancy. If you are pregnant, think you are pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking Ondansetron Hydrochloride .

Do not breast-feed if you are taking Ondansetron Hydrochloride . This is because small amounts pass into the mother?s milk. Ask your doctor or midwife for advice.

Important information about some of the ingredients of Ondansetron Hydrochloride

  • This medicine contains aspartame (which is a source of phenylalanine). If you have an inherited illness called phenylketonuria speak to your doctor before taking this medicine.
  • This medicine contains sodium methyl para-hydroxybenzoate and sodium propyl para-hydroxybenzoate. This may cause allergic reactions (which could be delayed).

3. HOW TO TAKE ONDANSETRON HYDROCHLORIDE

Always take Ondansetron Hydrochloride exactly as your doctor has told you. You should check with your doctor, nurse or pharmacist if you are not sure. The dose you have been prescribed will depend on the treatment you are having.

To prevent nausea and vomiting from chemotherapy or radiotherapy

?

On the day of chemotherapy or radiotherapy

  • the usual adult dose is 8 mg taken one or two hours before treatment and another 8 mg twelve hours after.

On the following days

  • the usual adult dose is 8 mg twice a day
  • this may be given for up to 5 days.

Children aged over 6 months and adolescents:

The doctor will decide the dose depending on the child?s size (body surface area) or weight. Look at the label for more information.

  • the usual dose for a child is up to 4 mg twice a day
  • this can be given for up to 5 days.

To prevent nausea and vomiting after an operation

The usual adult dose is 16 mg before your operation.

Children aged over 1 month and adolescents:

It is recommended that Ondansetron Hydrochloride is given as an injection.

Patients with moderate or severe liver problems

The total daily dose should not be more than 8 mg.

If you are sick (vomit) within one hour of taking a dose

  • take the same dose again
  • otherwise, do not take more Ondansetron Hydrochloride than the label says. If you continue to feel sick, tell your doctor or nurse.

If you take more Ondansetron Hydrochloride than you should

If you or your child take more Ondansetron Hydrochloride than you should, talk to a doctor or go to a hospital straight away. Take the medicine pack with you.

If you forget to take Ondansetron Hydrochloride

If you miss a dose and feel sick or vomit:

  • take an Ondansetron Hydrochloride as soon as possible, then
  • take your next tablet at the usual time (as shown on the label)
  • do not take a double dose to make up for a forgotten dose.

If you miss a dose but do not feel sick

  • take the next dose as shown on the label
  • do not take a double dose to make up for a forgotten dose.
  1. POSSIBLE SIDE EFFECTS

Like all medicines, Ondansetron Hydrochloride can cause side effects, although not everybody gets them.

Allergic reactions

If you have an allergic reaction, stop taking it and see a doctor straight away. The signs may include:

  • sudden wheezing and chest pain or chest tightness
  • swelling of your eyelids, face, lips, mouth or tongue
  • skin rash – red spots or lumps under your skin (hives) anywhere on your body

Common (may affect up to 1 in 10 people)

  • a feeling of warmth or flushing
  • constipation
  • changes to liver function test results (if you take Ondansetron Hydrochloride with a medicine called cisplatin, otherwise this side effect is uncommon).

Uncommon (may affect up to 1 in 100 people)

  • hiccups
  • low blood pressure, which can make you feel faint or dizzy
  • uneven heart beat
  • chest pain
  • fits
  • unusual body movements or shaking.

Rare (may affect up to 1 in 1,000 people)

  • feeling dizzy or light headed
  • blurred vision
  • disturbance in heart rhythm (sometimes causing a sudden loss of consciousness)

Very rare (may affect up to 1 in 10,000 people)

  • poor vision or temporary loss of eyesight, which usually comes back within 20 minutes.
  1. HOW TO STORE ONDANSETRON HYDROCHLORIDE
  • Keep this medicine out of the sight and reach of children.
  • Do not use Ondansetron Hydrochloride after the expiry date which is stated on the pack after ?Exp?. The expiry date refers to the last day of that month.
  • Store Ondansetron Hydrochloride below 30?C.
  • Ondansetron Hydrochloride should only be taken out of the blister immediately before taking it.
  • Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
  1. CONTENTS OF THE PACK AND OTHER INFORMATION WHAT ONDANSETRON HYDROCHLORIDE CONTAINS

a) Ondansetron Hydrochloride Tablets USP 4mg Taj Pharma
Each film-coated tablet contains: 5 mg Ondansetron Hydrochloride USP Equivalent to 4mg of? Ondansetron

b) Ondansetron Hydrochloride Tablets USP 8mg Taj Pharma
Each film-coated tablet contains: 10 mg Ondansetron hydrochloride, USP Equivalent to 8mg of? Ondansetron

What Ondansetron Hydrochloride looks like and contents of the pack

Tablets are packed in blisters

Pack Size of: 7, 14, 28, 30, 50, 90, 100 or 200 tablets.

Not all pack sizes may be marketed.

7. Manufactured in India By:
TAJ PHARMACEUTICALS LIMITED
at SURVEY NO.188/1 TO 189/1,190/1 TO 4,
ATHIYAWAD, DABHEL, DAMAN- 396210 (INDIA)

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