Posology : מינונים

4.2 Posology and method of administration

For intravenous injection or for intravenous infusion after dilution. For instructions on dilution of the product before administration, see section 6.6.

Chemotherapy and radiotherapy induced nausea and vomiting (CINV and RINV) 
Adults

The emetogenic potential of cancer treatment varies according to the doses and combinations of chemotherapy and radiotherapy regimens used. The route of administration and dose of Ondansetron-Fresenius should be flexible in the range of 8-32 mg a day and selected as shown below.

Emetogenic chemotherapy and radiotherapy

For patients receiving emetogenic chemotherapy or radiotherapy ondansetron can be given either by intravenous or oral administration. The recommended intravenous dose of ondansetron is 8 mg administered as a slow intravenous injection in not less than 30 seconds immediately before treatment.

Oral or rectal treatment is recommended to protect against delayed or prolonged emesis after the first 24 hours. For oral or rectal administration refer to the SmPC of ondansetron tablets and suppositories, respectively.

Highly emetogenic chemotherapy e.g. high-dose cisplatin

Ondansetron-Fresenius may be administered as a single 8 mg intravenous dose immediately before chemotherapy. Doses of greater than 8 mg and up to a maximum of 16 mg of ondansetron may only be given by intravenous infusion diluted in 50 to 100 ml of saline or other compatible infusion fluid and infused over not less than 15 minutes. A single dose greater than 16 mg must not be given due to dose dependent increase of QT-prolongation risk (see sections 4.4, 4.8 and 5.1).

For management of highly emetogenic chemotherapy, a dose of 8 mg may be administered by slow intravenous injection in not less than 30 seconds, followed by two further intravenous doses of 8 mg four hours apart, or by a constant infusion of 1 mg/hour for up to 24 hours.

The efficacy of Ondansetron-Fresenius in highly emetogenic chemotherapy may be enhanced by the addition of a single intravenous dose of dexamethasone sodium phosphate, 20 mg administered prior to chemotherapy.

Oral or rectal treatment is recommended to protect against delayed or prolonged emesis after the first 24 hours. For oral or rectal administration refer to the SmPC of ondansetron tablets and suppositories, respectively.

Paediatric Population

CINV i   hild e aged       o ths a d adoles e ts:
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 intravenous infusion diluted in 25 to 50 ml of saline or other compatible infusion fluid (see section 6.6) and infused over not less than 15 minutes.

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

Ondansetron-Fresenius should be diluted in 5% dextrose or 0.9% sodium chloride or other compatible infusion fluid (see section 6.6.) and infused intravenously over not less than 15 minutes.

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

Dosing by BSA:

Ondansetron-Fresenius should be administered immediately before chemotherapy as a single intravenous dose of 5 mg/m2. The intravenous dose must not exceed 8 mg. Oral dosing can commence twelve hours later and may be continued for up to 5 days. See Table 1 below. 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 induced nausea and vomiting - Children aged o ths a d adoles e tsa

BSA                             Day 1b,c                      Days 2-6c < 0.6 m2                        5 mg/m2 i.v. plus 2 mg syrup 2 mg syrup every 12 hours after 12 hours
> 0.6 m to .
2          2
5 mg/m2 i.v. plus 4 mg syrup 4 mg syrup or tablet every or tablet after 12 hours      12 hours
2                               2
> 1.2 m                         5 mg/m or 8 mg i.v. plus 8    8 mg syrup or tablet every mg syrup or tablet after 12   12 hours hours a Not all pharmaceutical forms may be available.
b The intravenous dose must not exceed 8 mg.
c 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)

Ondansetron 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. The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg. Oral dosing can commence twelve hours later and may be continued for up to 5 days. See Table 2 below.

Table 2: Weight-based dosing for chemotherapy induced nausea and vomiting - Children aged      o ths a d adoles e tsa

Weigth                          Day 1b,c                      Days 2-6c ≤ 10 kg                         Up to 3 doses of 0.15 mg/kg 2 mg syrup every 12 hours i.v. every 4 hours
> 10 kg                         Up to 3 doses of 0.15 mg/kg 4 mg syrup or tablet every i.v. every 4 hours            12 hours a Not all pharmaceutical forms may be available.
b The intravenous dose must not exceed 8 mg.
c The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg.
Elderly:

In patients 65 to 74 years of age, the dose schedule for adults can be followed. All intravenous doses should be diluted in 50-100 ml of saline or other compatible infusion fluid (see section 6.6) and infused over 15 minutes.

In patients 75 years of age or older, the initial intravenous dose of Ondansetron-Fresenius should not exceed 8 mg. All intravenous doses should be diluted in 50-100 ml of saline or other compatible infusion fluid (see section 6.6) and infused over 15 minutes.

The initial dose of 8 mg may be followed by two further intravenous doses of 8 mg, infused over 15 minutes and given no less than four hours apart (see section 5.2).


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-Fresenius 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 are required.


Post-operative nausea and vomiting (PONV)

Adults:

Prevention of PONV
For prevention of post-operative nausea and vomiting, the recommended dose of Ondansetron-Fresenius is a single dose of 4 mg by slow intravenous injection in not less than 30 seconds administered at the induction of anaesthesia.

Treatment of established PONV

For treatment of established PONV a single dose of 4 mg given by slow intravenous injection in not less than 30 seconds is recommended.

Paediatric population:

Post-ope ati e ausea a d o iti g i      hild e aged        o th a d adoles e ts For prevention of PONV in paediatric patients having surgery performed under general anaesthesia, a single dose of Ondansetron-Fresenius may be administered by slow intravenous injection (not less than 30 seconds) at a dose 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-Fresenius 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-Fresenius for treatment of postoperative vomiting in children below 2 years of age.

Elderly:

There is limited experience in the use of Ondansetron-Fresenius in the prevention and treatment of post-operative nausea and vomiting (PONV) in older people, however ondansetron is well tolerated in patients over 65 years receiving chemotherapy.

Special Populations

Patients with renal impairment
No alteration of daily dosage or frequency of dosing, or route of administration is required.


Patients with hepatic impairment

Clearance of Ondansetron is significantly reduced and serum half life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8 mg (orally or parenterally) 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.