Palonosetron Hospira

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Palonosetron Hospira250 micrograms solution for injection.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml of solution contains 50 micrograms palonosetron (as hydrochloride). 
Each vial of 5 ml of solution contains 250 micrograms palonosetron (as hydrochloride). 

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection. 
Clear, colourless solution.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Palonosetron Hospira is indicated in adults for: 
• the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy, 
• the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy. 

Palonosetron Hospira is indicated in paediatric patients 1 month of age and older for: 
• the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy 

and prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.

4.2 Posology and method of administration

Palonosetron Hospira should be used only before chemotherapy administration. This medicinal product 
should be administered by a healthcare professional under appropriate medical supervision. 

Posology

Adults 
250 micrograms palonosetron administered as a single intravenous bolus approximately 30 minutes before 
the start of chemotherapy. Palonosetron Hospira should be injected over 30 seconds. 

The efficacy of Palonosetron Hospira in the prevention of nausea and vomiting induced by highly 
emetogenic chemotherapy may be enhanced by the addition of a corticosteroid administered prior to 
chemotherapy. 

Elderly population 

No dose adjustment is necessary for the elderly. 



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Paediatric population 

Children and Adolescents (aged 1 month to 17 years): 

20 micrograms/kg (the maximum total dose should not exceed 1500 micrograms) palonosetron administered 
as a single 15 minute intravenous infusion beginning approximately 30 minutes before the start of 
chemotherapy. 

The safety and efficacy of palonosetron in children aged less than 1 month have not been established. No 
data are available. There are limited data on the use of palonosetron in the prevention of nausea and 
vomiting in children under 2 years of age.

Hepatic impairment 

No dose adjustment is necessary for patients with impaired hepatic function.

Renal impairment 

No dose adjustment is necessary for patients with impaired renal function. 
No data are available for patients with end stage renal disease undergoing haemodialysis.

Method of administration 

For intravenous use.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

As palonosetron may increase large bowel transit time, patients with a history of constipation or signs of 
subacute intestinal obstruction should be monitored following administration. Two cases of constipation with 
faecal impaction requiring hospitalisation have been reported in association with palonosetron 
750 micrograms. 

At all dose levels tested, palonosetron did not induce clinically relevant prolongation of the QTc interval. A 
specific thorough QT/QTc study was conducted in healthy volunteers for definitive data demonstrating the 
effect of palonosetron on QT/QTc (see section 5.1). 

However, as for other 5-HT3 antagonists, caution should be exercised in the use of palonosetron in patients 
who have or are likely to develop prolongation of the QT interval. These conditions include patients with a 
personal or family history of QT prolongation, electrolyte abnormalities, congestive heart failure, 
bradyarrhythmias, conduction disturbances and in patients taking anti-arrhythmic agents or other medicinal 
products that lead to QT prolongation or electrolyte abnormalities. Hypokalemia and hypomagnesemia 
should be corrected prior to 5-HT3 -antagonist administration. 

There have been reports of serotonin syndrome with the use of 5-HT3 antagonists either alone or in 
combination with other serotonergic drugs (including selective serotonin reuptake inhibitors (SSRI) and 
serotonin noradrenaline reuptake inhibitors (SNRIs). Appropriate observation of patients for serotonin
syndrome-like symptoms is advised. 

Palonosetron Hospira should not be used to prevent or treat nausea and vomiting in the days following 
chemotherapy if not associated with another chemotherapy administration. 

This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially ‘sodium-free’.



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4.5 Interaction with other medicinal products and other forms of interaction

Palonosetron is mainly metabolised by CYP2D6, with minor contribution by CYP3A4 and CYP1A2 
isoenzymes. Based on in vitro studies, palonosetron does not inhibit or induce cytochrome P450 isoenzyme 
at clinically relevant concentrations. 

Chemotherapeutic agents 
In preclinical studies, palonosetron did not inhibit the antitumour activity of the five chemotherapeutic agents 
tested (cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C). 

Metoclopramide 
In a clinical study, no significant pharmacokinetic interaction was shown between a single intravenous dose 
of palonosetron and steady state concentration of oral metoclopramide, which is a CYP2D6 inhibitor. 

CYP2D6 inducers and inhibitors.
In a population pharmacokinetic analysis, it has been shown that there was no significant effect on 
palonosetron clearance when co-administered with CYP2D6 inducers (dexamethasone and rifampicin) and 
inhibitors (including amiodarone, celecoxib, chlorpromazine, cimetidine, doxorubicin, fluoxetine, 
haloperidol, paroxetine, quinidine, ranitidine, ritonavir, sertraline or terbinafine). 

Corticosteroids 
Palonosetron has been administered safely with corticosteroids. 

Serotonergic Drugs (e.g. SSRIs and SNRIs) 
There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other 
serotonergic drugs (including SSRIs and SNRIs). 

Other medicinal products 
Palonosetron has been administered safely with analgesics, antiemetic/antinauseants, antispasmodics and 
anticholinergic medicinal products.

4.6 Fertility, pregnancy and lactation

Pregnancy
For palonosetron no clinical data on exposed pregnancies are available. Animal studies do not indicate direct 
or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal 
development. Only limited data from animal studies are available regarding the placental transfer (see 
section 5.3). 

There is no experience of palonosetron in human pregnancy. Therefore, palonosetron should not be used in 
pregnant women unless it is considered essential by the physician. 

Breast-feeding 
As there are no data concerning palonosetron excretion in breast milk, breast-feeding should be discontinued 
during therapy. 

Fertility 
There are no data concerning the effect of palonosetron on fertility.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. 
Since palonosetron may induce dizziness, somnolence or fatigue, patients should be cautioned when driving 
or operating machines.



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4.8 Undesirable effects

In clinical studies in adults at a dose of 250 micrograms (total 633 patients) the most frequently observed 
adverse reactions, at least possibly related to palonosetron, were headache (9 %) and constipation (5 %). 

In clinical studies the following adverse reactions (ARs) were observed as possibly or probably related to 
palonosetron. These were classified as common (≥1/100 to <1/10) or uncommon (≥1/1,000 to <1/100). Very 
rare (<1/10,000) adverse reactions were reported post-marketing. 
Within each frequency grouping, adverse reactions are presented below in order of decreasing seriousness.

System organ class Common ARs 
(≥1/100 to<1/10) 

Uncommon ARs 
(≥1/1,000 to <1/100) 

Very rare ARs°
(<1/10,000)

Immune system disorders Hypersensitivity, 
anaphylaxis, anaphylactic/ 
anaphylactoid reactions and 
shock

Metabolism and nutrition 
disorders 

Hyperkalaemia, metabolic 
disorders, hypocalcaemia, 
hypokalaemia, anorexia, 
hyperglycaemia, appetite 
decreased 

Psychiatric disorders Anxiety, euphoric mood 

Nervous system disorders Headache 
Dizziness 

Somnolence, insomnia, 
paraesthesia, hypersomnia, 
peripheral sensory 
neuropathy 

Eye disorders Eye irritation, amblyopia 

Ear and labyrinth disorders Motion sickness, tinnitus 

Cardiac disorders Tachycardia, bradycardia, 
extrasystoles, myocardial 
ischaemia, sinus tachycardia, 
sinus arrhythmia, 
supraventricular extrasystoles 

Vascular disorders Hypotension, hypertension, 
vein discolouration, vein 
distended 

Respiratory, thoracic and 
mediastinal disorders 

Hiccups 

Gastrointestinal disorders Constipation 
Diarrhoea 

Dyspepsia, abdominal pain, 
abdominal pain upper, dry 
mouth, flatulence 

Hepatobiliary disorders Hyperbilirubinaemia 

Skin and subcutaneous 
tissue disorders 

Dermatitis allergic, pruritic 
rash 

Musculoskeletal and 
connective tissue disorders 

Arthralgia 

Renal and urinary disorders Urinary retention, glycosuria 

General disorders and 
administration site 
conditions 

Asthenia, pyrexia, fatigue, 
feeling hot, influenza like 
illness 

Injection site reaction* 



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Investigations Elevated transaminases-, 
electrocardiogram QT 
prolonged 

° From post-marketing experience 
* Includes the following: burning, induration, discomfort and pain 

Paediatric population

In paediatric clinical trials for the prevention of nausea and vomiting induced by moderately or highly 
emetogenic chemotherapy, 402 patients received a single dose of palonosetron (3, 10 or 20 mcg/kg). The 
following common or uncommon adverse reactions were reported for palonosetron, none were reported at a 
frequency of >1%.

System organ class Common ARs 
(≥1/100 to<1/10) 

Uncommon ARs 
(≥1/1,000 to <1/100) 

Nervous system disorders Headache Dizziness, dyskinesia
Cardiac disorders Electrocardiogram QT 

prolonged conduction disorder, 
sinus tachycardia 

Respiratory, thoracic and mediastinal 
disorders 

Cough, dyspnoea, epistaxis 

Skin and subcutaneous tissue 
disorders 

Dermatitis allergic, pruritus, 
skin disorder, urticaria 

General disorders and administration 
site conditions 

Pyrexia, infusion site pain, 
infusion site reaction, pain 

Adverse reactions were evaluated in paediatric patients receiving palonosetron for up to 4 chemotherapy 
cycles.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 
continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 
to report any suspected adverse reactions via the national reporting system listed in Appendix V.

4.9 Overdose

No case of overdose has been reported. 
Doses of up to 6 mg have been used in adult clinical studies. The highest dose group showed a similar 
incidence of adverse reactions compared to the other dose groups and no dose response effects were 
observed. In the unlikely event of overdose with Palonosetron Hospira, this should be managed with 
supportive care. Dialysis studies have not been performed, however, due to the large volume of distribution, 
dialysis is unlikely to be an effective treatment for Palonosetron Hospira overdose.

Paediatric population
No case of overdose has been reported in paediatric clinical studies.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antiemetics and antinauseants, serotonin (5HT3) antagonists, ATC code: 
A04AA05 

Palonosetron is a selective high-affinity receptor antagonist of the 5HT3 receptor. 



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In two randomised, double-blind studies with a total of 1,132 patients receiving moderately emetogenic 
chemotherapy that included cisplatin ≤50 mg/m2, carboplatin, cyclophosphamide ≤1,500 mg/m2 and 
doxorubicin >25 mg/m2, palonosetron 250 micrograms and 750 micrograms were compared with 
ondansetron 32 mg (half-life 4 hours) or dolasetron 100 mg (half-life 7.3 hours) administered intravenously 
on Day 1, without dexamethasone. 

In a randomised, double-blind study with a total of 667 patients receiving highly emetogenic chemotherapy 
that included cisplatin ≥60 mg/m2, cyclophosphamide >1,500 mg/m2 and dacarbazine, palonosetron 
250 micrograms and 750 micrograms were compared with ondansetron 32 mg administered intravenously on 
Day 1. Dexamethasone was administered prophylactically before chemotherapy in 67 % of patients. 

The pivotal studies were not designed to assess efficacy of palonosetron in delayed onset nausea and 
vomiting. The antiemetic activity was observed during 0-24 hours, 24-120 hours and 0-120 hours. Results 
for the studies on moderately emetogenic chemotherapy and for the study on highly emetogenic 
chemotherapy are summarised in the following tables. 

Palonosetron was non-inferior versus the comparators in the acute phase of emesis both in moderately and 
highly emetogenic setting. 

Although comparative efficacy of palonosetron in multiple cycles has not been demonstrated in controlled 
clinical studies, 875 patients enrolled in the three phase 3 trials continued in an open label safety study and 
were treated with palonosetron 750 micrograms for up to 9 additional cycles of chemotherapy. The overall 
safety was maintained during all cycles. 

Table 1: Percentage of patients a responding by treatment group and phase in the Moderately 
Emetogenic Chemotherapy study versus ondansetron 

Palonosetron
250 micrograms

(n= 189)

Ondansetron
32 milligrams

(n= 185) Delta

% % %

Complete Response (No Emesis and No Rescue Medication) 97.5 % CI b

0 – 24 hours 81.0 68.6 12.4 [1.8 %, 22.8 %]

24 – 120 hours 74.1 55.1 19.0 [7.5 %, 30.3 %]

0 – 120 hours 69.3 50.3 19.0 [7.4 %, 30.7 %]

Complete Control (Complete Response and No More Than Mild Nausea) p-value c

0 – 24 hours 76.2 65.4 10.8 NS

24 – 120 hours 66.7 50.3 16.4 0.001

0 – 120 hours 63.0 44.9 18.1 0.001

No Nausea (Likert Scale) p-value c

0 – 24 hours 60.3 56.8 3.5 NS

24 – 120 hours 51.9 39.5 12.4 NS

0 – 120 hours 45.0 36.2 8.8 NS
a

Intent-to-treat cohort. 
b The study was designed to show non-inferiority. A lower bound greater than –15 % demonstrates non-inferiority 

between palonosetron and comparator. 
c Chi-square test. Significance level at α=0.05. 



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Table 2: Percentage of patients a responding by treatment group and phase in the Moderately 
Emetogenic Chemotherapy study versus dolasetron

Palonosetron
250 micrograms

(n= 185)

Dolasetron
100 milligrams

(n= 191) Delta

% % %

Complete Response (No Emesis and No Rescue Medication) 97.5 % CI b

0 – 24 hours 63.0 52.9 10.1 [-1.7 %, 21.9 %]

24 – 120 hours 54.0 38.7 15.3 [3.4 %, 27.1 %]

0 – 120 hours 46.0 34.0 12.0 [0.3 %, 23.7 %]

Complete Control (Complete Response and No More Than Mild Nausea) p-value c

0 – 24 hours 57.1 47.6 9.5 NS

24 – 120 hours 48.1 36.1 12.0 0.018

0 – 120 hours 41.8 30.9 10.9 0.027

No Nausea (Likert Scale) p-value c

0 – 24 hours 48.7 41.4 7.3 NS

24 – 120 hours 41.8 26.2 15.6 0.001

0 – 120 hours 33.9 22.5 11.4 0.014
a

Intent-to-treat cohort. 
b The study was designed to show non-inferiority. A lower bound greater than –15 % demonstrates non-inferiority 

between palonosetron and comparator. 
c   Chi-square test. Significance level at α=0.05. 

Table 3: Percentage of patients a responding by treatment group and phase in the Highly Emetogenic 
Chemotherapy study versus ondansetron 

Palonosetron
250 micrograms

(n= 223)

Ondansetron
32 milligrams

(n= 221) Delta

% % %

Complete Response (No Emesis and No Rescue Medication) 97.5 % CI b

0 – 24 hours 59.2 57.0 2.2 [-8.8 %, 13.1 %]

24 – 120 hours 45.3 38.9 6.4 [-4.6 %, 17.3 %]

0 – 120 hours 40.8 33.0 7.8 [-2.9 %, 18.5 %]

Complete Control (Complete Response and No More Than Mild Nausea) p-value c

0 – 24 hours 56.5 51.6 4.9 NS

24 – 120 hours 40.8 35.3 5.5 NS

0 – 120 hours 37.7 29.0 8.7 NS

No Nausea (Likert Scale) p-value c

0 – 24 hours 53.8 49.3 4.5 NS

24 – 120 hours 35.4 32.1 3.3 NS

0 – 120 hours 33.6 32.1 1.5 NS
a

Intent-to-treat cohort. 
b The study was designed to show non-inferiority. A lower bound greater than –15 % demonstrates non-inferiority 

between palonosetron and comparator. 
c Chi-square test. Significance level at α=0.05.

The effect of palonosetron on blood pressure, heart rate, and ECG parameters including QTc were 
comparable to ondansetron and dolasetron in CINV clinical studies. In non-clinical studies palonosetron 



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possesses the ability to block ion channels involved in ventricular de- and re-polarisation and to prolong 
action potential duration.

The effect of palonosetron on QTc interval was evaluated in a double blind, randomised, parallel, placebo 
and positive (moxifloxacin) controlled trial in adult men and women. The objective was to evaluate the ECG 
effects of IV administered palonosetron at single doses of 0.25, 0.75 or 2.25 mg in 221 healthy subjects. The 
study demonstrated no effect on QT/QTc interval duration as well as any other ECG interval at doses up to 
2.25 mg. No clinically significant changes were shown on heart rate, atrioventricular (AV) conduction and 
cardiac repolarisation. 

Paediatric population 

Prevention of Chemotherapy Induced Nausea and Vomiting (CINV): 

The safety and efficacy of palonosetron intravenously at single doses of 3 μg/kg and 10 μg/kg was 
investigated in the first clinical study in 72 patients in the following age groups, >28 days to 23 months (12
patients), 2 to 11 years (31 patients), and 12 to 17 years of age (29 patients), receiving highly or moderately 
emetogenic chemotherapy. No safety concerns were raised at either dose level. The primary efficacy variable 
was the proportion of patients with a complete response (CR, defined as no emetic episode and no rescue 
medication) during the first 24 hours after the start of chemotherapy administration. Efficacy after 
palonosetron 10 μg/kg compared to palonosetron 3 μg/kg was 54.1% and 37.1% respectively. 

The efficacy of palonosetron for the prevention of chemotherapy-induced nausea and vomiting in paediatric 
cancer patients was demonstrated in a second non-inferiority pivotal trial comparing a single intravenous 
infusion of palonosetron versus an intravenous ondansetron regimen. A total of 493 paediatric patients, aged 
64 days to 16.9 years, receiving moderately (69.2%) or highly emetogenic chemotherapy (30.8%) were 
treated with palonosetron 10 μg/kg (maximum 0.75 mg), palonosetron 20 μg/kg (maximum 1.5 mg) or 
ondansetron (3 x 0.15 mg/kg , maximum total dose 32 mg) 30 minutes prior to the start of emetogenic 
chemotherapy during Cycle 1. Most patients were non-naïve to chemotherapy (78.5%) across all treatment 
groups. Emetogenic chemotherapies administered included doxorubicin, cyclophosphamide (<1500 mg/m2), 
ifosfamide, cisplatin, dactinomycin, carboplatin, and daunorubicin. Adjuvant corticosteroids, including 
dexamethasone, were administered with chemotherapy in 55% of patients. The primary efficacy endpoint 
was Complete Response in the acute phase of the first cycle of chemotherapy, defined as no vomiting, no 
retching, and no rescue medication in the first 24 hours after starting chemotherapy. Efficacy was based on 
demonstrating non-inferiority of intravenous palonosetron compared to intravenous ondansetron. Non-
inferiority criteria were met if the lower bound of the 97.5% confidence interval for the difference in 
Complete Response rates of intravenous palonosetron minus intravenous ondansetron was larger than -15%. 
In the palonosetron 10 μg/kg, 20 μg/kg and ondansetron groups, the proportion of patients with CR0-24h was 
54.2%, 59.4% and 58.6%. Since the 97.5% confidence interval (stratum adjusted Mantel-Haenszel test) of 
the difference in CR0-24h between palonosetron 20 μg/kg and ondansetron was [-11.7%, 12.4%], the 20 μg/kg 
palonosetron dose demonstrated non-inferiority to ondansetron. 

While this study demonstrated that paediatric patients require a higher palonosetron dose than adults to 
prevent chemotherapy-induced nausea and vomiting, the safety profile is consistent with the established 
profile in adults (see section 4.8). Pharmacokinetic information is provided in section 5.2. 

Prevention of Post Operative Nausea and Vomiting (PONV): 

Two paediatric trials were performed. The safety and efficacy of palonosetron intravenously at single doses 
of 1 μg/kg and 3 μg/kg was compared in the first clinical study in 150 patients in the following age groups, 
>28 days to 23 months (7 patients), 2 to 11 years (96 patients), and 12 to 16 years of age (47 patients) 
undergoing elective surgery. No safety concerns were raised in either treatment group. The proportion of 
patients without emesis during 0-72 hours post-operatively was similar after palonosetron 1 μg/kg or 3 μg/kg 
(88% vs 84%). 

The second paediatric trial was a multicenter, double-blind, double-dummy, randomised, parallel group, 
active control, single-dose non-inferiority study, comparing intravenous palonosetron (1 μg/kg, max 



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0.075 mg) versus intravenous ondansetron. A total of 670 paediatric surgical patients participated, age 
30 days to 16.9 years. The primary efficacy endpoint, Complete Response (CR: no vomiting, no retching, 
and no antiemetic rescue medication) during the first 24 hours postoperatively was achieved in 78.2% of 
patients in the palonosetron group and 82.7% in the ondansetron group. Given the pre-specified non-
inferiority margin of -10%, the stratum adjusted Mantel-Haenszel statistical non-inferiority confidence 
interval for the difference in the primary endpoint, complete response (CR), was [-10.5, 1.7%], therefore 
non-inferiority was not demonstrated. No new safety concerns were raised in either treatment group. 

Please see section 4.2 for information on paediatric use.

5.2 Pharmacokinetic properties

Absorption 
Following intravenous administration, an initial decline in plasma concentrations is followed by slow 
elimination from the body with a mean terminal elimination half-life of approximately 40 hours. Mean 
maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC0-∞) are generally 
dose-proportional over the dose range of 0.3–90 μg/kg in healthy subjects and in cancer patients. 

Following intravenous administration of palonosetron 0.25 mg once every other day for 3 doses in 
11 testicular cancer patients, the mean (± SD) increase in plasma concentration from Day 1 to Day 5 was 42 
± 34 %. After intravenous administration of palonosetron 0.25 mg once daily for 3 days in 12 healthy 
subjects, the mean (± SD) increase in plasma palonosetron concentration from Day 1 to Day 3 was 110 ± 45 
%. 

Pharmacokinetic simulations indicate that the overall exposure (AUC0-∞) of 0.25 mg intravenous 
palonosetron administered once daily for 3 consecutive days was similar to a single intravenous dose of 
0.75 mg, although Cmax of the 0.75 mg single dose was higher. 

Distribution 
Palonosetron at the recommended dose is widely distributed in the body with a volume of distribution of 
approximately 6.9 to 7.9 l/kg. Approximately 62 % of palonosetron is bound to plasma proteins.

Biotransformation 
Palonosetron is eliminated by dual route, about 40 % eliminated through the kidney and with approximately 
50 % metabolised to form two primary metabolites, which have less than 1 % of the 5HT3 receptor 
antagonist activity of palonosetron. In vitro metabolism studies have shown that CYP2D6 and to a lesser 
extent, CYP3A4 and CYP1A2 isoenzymes are involved in the metabolism of palonosetron. However, 
clinical pharmacokinetic parameters are not significantly different between poor and extensive metabolisers 
of CYP2D6 substrates. Palonosetron does not inhibit or induce cytochrome P450 isoenzymes at clinically 
relevant concentrations. 

Elimination 
After a single intravenous dose of 10 micrograms/kg [14C]-palonosetron, approximately 80 % of the dose 
was recovered within 144 hours in the urine with palonosetron representing approximately 40 % of the 
administered dose, as unchanged active substance. After a single intravenous bolus administration in healthy 
subjects the total body clearance of palonosetron was 173 ± 73 ml/min and renal clearance was 53 ± 
29 ml/min. The low total body clearance and large volume of distribution resulted in a terminal elimination 
half-life in plasma of approximately 40 hours. Ten percent of patients have a mean terminal elimination half-
life greater than 100 hours.

Pharmacokinetics in special populations 

Elderly population
Age does not affect the pharmacokinetics of palonosetron. No dosage adjustment is necessary in elderly 
patients. 



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Gender 
Gender does not affect the pharmacokinetics of palonosetron. No dosage adjustment is necessary based on 
gender. 

Paediatric population 
Single-dose intravenous palonosetron pharmacokinetic data was obtained from a subset of paediatric cancer 
patients (n=280) that received 10 μg/kg or 20 μg/kg. When the dose was increased from 10 μg/kg to 20 μg/kg 
a dose-proportional increase in mean AUC was observed. Following single dose intravenous infusion of 
Palonosetron 20 μg/kg, peak plasma concentrations (CT) reported at the end of the 15 minute infusion were 
highly variable in all age groups and tended to be lower in patients < 6 years than in older paediatric patients. 
Median half-life was 29.5 hours in overall age groups and ranged from about 20 to 30 hours across age 
groups after administration of 20 μg/kg. 

The total body clearance (L/h/kg) in patients 12 to 17 years old was similar to that in healthy adults. There 
are no apparent differences in volume of distribution when expressed as L/kg. 

Table 4: Pharmacokinetic Parameters in Paediatric Cancer Patients following intravenous infusion of 
palonosetron at 20 μg/kg over 15 min and in Adult Cancer Patients receiving 3 and 10 μg/kg 
palonosetron doses via intravenous bolus.

Paediatric Cancer Patientsa Adults Cancer 
Patientsb

<2 y 2 to <6 y 6 to <12 y 12 to 
<17 y

3.0 
μg/kg

10 μg/kg

N=3 N=5 N=7 N=10 N=6 N=5

AUC0-∞, h·μg/L 69.0 
(49.5)

103.5 
(40.4)

98.7 
(47.7)

124.5 
(19.1)

35.8 
(20.9)

81.8 
(23.9)

t½, hours 24.0 28 23.3 30.5 56.4 
(5.81)

49.8 
(14.4)

N=6 N=14 N=13 N=19 N=6 N=5

Clearance c, L/h/kg 0.31 
(34.7)

0.23 
(51.3)

0.19 
(46.8)

0.16 
(27.8)

0.10 
(0.04)

0.13 
(0.05)

Volume of distribution c, d,

L/kg
6.08 

(36.5)
5.29 

(57.8)
6.26 

(40.0)
6.20 

(29.0)
7.91 

(2.53)
9.56 

(4.21)

a PK parameters expressed as Geometric Mean (CV) except for T½ which is median. 
b PK parameters expressed as Arithmetic mean (SD) 
c Clearance and Volume of distribution in paediatric patients were calculated weight-adjusted from both 10 
μg /kg and 20 μg /kg dose groups combined. In adults, different dose levels are indicated in column title. 
d Vss is reported for paediatric cancer patients, whereas Vz is reported for adult cancer patients.

Renal impairment 
Mild to moderate renal impairment does not significantly affect palonosetron pharmacokinetic parameters. 
Severe renal impairment reduces renal clearance, however total body clearance in these patients is similar to 
healthy subjects. No dosage adjustment is necessary in patients with renal insufficiency. No pharmacokinetic 
data in haemodialysis patients are available. 



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Hepatic impairment 
Hepatic impairment does not significantly affect total body clearance of palonosetron compared to the 
healthy subjects. While the terminal elimination half-life and mean systemic exposure of palonosetron is 
increased in the subjects with severe hepatic impairment, this does not warrant dose reduction.

5.3 Preclinical safety data

Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the 
maximum human exposure indicating little relevance to clinical use. 

Non-clinical studies indicate that palonosetron, only at very high concentrations, may block ion channels 
involved in ventricular de- and re-polarisation and prolong action potential duration.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal
development, parturition or postnatal development. Only limited data from animal studies are available 
regarding the placental transfer (see section 4.6). 

Palonosetron is not mutagenic. High doses of palonosetron (each dose causing at least 30 times the human 
therapeutic exposure) applied daily for two years caused an increased rate of liver tumours, endocrine 
neoplasms (in thyroid, pituitary, pancreas, adrenal medulla) and skin tumours in rats but not in mice. The 
underlying mechanisms are not fully understood, but because of the high doses employed and since 
Palonosetron Hospira is intended for single application in humans, these findings are not considered relevant 
for clinical use.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Mannitol 
Disodium edetate 
Sodium citrate 
Citric acid monohydrate 
Sodium hydroxide (for pH adjustment) 
Hydrochloric acid (for pH adjustment) 
Water for injections

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

30 months.  

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container 

Type I glass vial with a chlorobutyl rubber stopper and aluminium seal.  
Available in packs of 1 vial containing 5 ml of solution.

6.6 Special precautions for disposal 

Single use only, any unused solution should be discarded. 



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Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

8. MARKETING AUTHORISATION NUMBER(S) 

EU/1/16/1100/001

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 08 April 2016

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines
Agency http://www.ema.europa.eu



14

ANNEX II

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 
USE OF THE MEDICINAL PRODUCT



15

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers responsible for batch release

Hospira UK Limited
Horizon
Honey Lane
Hurley
SL6 6RJ
United Kingdom

Hospira Enterprises B.V.
Randstad 22-11 Almere
NL-1316 BN 
The Netherlands

Avara Liscate Pharmaceutical Services S.p.A.
Via Fosse Ardeatine, 2, 20060, Liscate (MI)
Italy

Pfizer Service Company BVBA
Hoge Wei 10
1930 Zaventem
Belgium

The printed package leaflet of the medicinal product must state the name and address of the manufacturer 

responsible for the release of the concerned batch.

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION 

 Periodic safety update reports 

The requirements for submission of periodic safety update reports for this medicinal product are set out in 

the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 

and any subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 
USE OF THE MEDICINAL PRODUCT

 Risk Management Plan (RMP)

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the agreed 

RMP presented in Module 1.8.2 of the marketing authorisation and any agreed subsequent updates of the 

RMP.

An updated RMP should be submitted:

 At the request of the European Medicines Agency;
Whenever the risk management system is modified, especially as the result of new information being 
received that may lead to a significant change to the benefit/risk profile or as the result of an important 
(pharmacovigilance or risk minimisation) milestone being reached.



16

ANNEX III

LABELLING AND PACKAGE LEAFLET



17

A. LABELLING



18

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON

1. NAME OF THE MEDICINAL PRODUCT

Palonosetron Hospira 250 micrograms solution for injection
palonosetron (as hydrochloride)

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each vial contains 250 micrograms palonosetron (as hydrochloride) in 5 ml (50 micrograms/ml)

3. LIST OF EXCIPIENTS

Also contains:  mannitol, disodium edetate, sodium citrate, citric acid monohydrate, water for
injections, sodium hydroxide, hydrochloric acid.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection
1 vial

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Intravenous use
Single use only

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



19

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/16/1100/001

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted.

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC: 
SN: 
NN: 



20

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

VIAL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Palonosetron Hospira 250 micrograms solution for injection
palonosetron
IV

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

5 ml

6. OTHER



21

B. PACKAGE LEAFLET



22

Package leaflet: Information for the patient

Palonosetron Hospira 250 micrograms solution for injection
palonosetron

Read all of this leaflet carefully before you are given 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, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet.  See section 4.

What is in this leaflet

1. What Palonosetron Hospira is and what it is used for
2. What you need to know before you are given Palonosetron Hospira
3. How Palonosetron Hospira is given
4. Possible side effects
5. How to store Palonosetron Hospira
6. Contents of the pack and other information

1. What Palonosetron Hospira is and what it is used for

Palonosetron Hospira belongs to a group of medicines known as serotonin (5HT3) antagonists.

These have the ability to block the action of the chemical, serotonin, which can cause nausea and
vomiting.

Palonosetron Hospira is used for the prevention of nausea and vomiting associated with cancer 
chemotherapy in adults, adolescents and children over one month of age.

2. What you need to know before you are given Palonosetron Hospira

You must not be given Palonosetron Hospira:
• if you are allergic to palonosetron or any of the other ingredients of this medicine (listed in 

section 6). 

Warnings and precautions
Talk to your doctor or pharmacist before you are given Palonosetron Hospira:
• if you have acute bowel obstruction or a history of repeated constipation;
• if you are using Palonosetron Hospira in addition to other medicines that may induce an 

abnormal heart rhythm such as amiodarone, nicardipine, quinidine, moxifloxacin, erythromycin, 
haloperidol, chlorpromazine, quetiapine, thioridazine, domperidone;

• if you have a personal or family history of alterations in heart rhythm (QT prolongation);
• if you have other heart problems;
• if you have an imbalance of certain minerals in your blood such as potassium and magnesium 

which has not been treated.

It is not recommended to receive Palonosetron Hospira in the days following chemotherapy unless you 
are receiving another chemotherapy cycle.

Other medicines and Palonosetron Hospira
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines, including:



23

• 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.

Pregnancy and breast-feeding
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 you are given this medicine.

If you are pregnant or think you might be, your doctor will not administer Palonosetron Hospira to you 
unless it is clearly necessary.

It is not known whether Palonosetron Hospira will cause any harmful effects when used during 
pregnancy.

It is not known if Palonosetron Hospira is found in breast milk.

Driving and using machines
Palonosetron Hospira may cause dizziness or tiredness. If affected, do not drive or use any tools or 
machines.

Important information about some of the ingredients of Palonosetron Hospira 
This medicine contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially ‘sodium- free’.

3. How Palonosetron Hospira is given

A doctor or nurse will normally inject Palonosetron Hospira about 30 minutes before the start of 
chemotherapy.

Adults 
The recommended dose of Palonosetron Hospira is 250 micrograms given as a rapid injection into a 
vein.

Children and Adolescents (aged 1 month to 17 years) 
The doctor will decide the dose, depending on bodyweight, however the maximum dose is 
1500 micrograms. Palonosetron Hospira will be given as a slow infusion into a vein.

If you have any further questions on the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Adults:

Common (may affect up to 1 in 10 people):
• headache
• dizziness
• constipation
• diarrhoea

Uncommon (may affect up to 1 in 100 people):
• high or low blood pressure
• abnormal heart rate or lack of blood flow to the heart
• change in the colour of the vein and/or veins becoming larger



24

• abnormally high or low levels of potassium in the blood
• high levels of sugar in the blood or sugar in the urine
• low levels of calcium in the blood
• high levels of the pigment bilirubin in the blood
• high levels of certain liver enzymes
• elevated moods or feelings of anxiousness
• sleepiness or trouble sleeping
• decrease or loss of appetite
• weakness, tiredness, fever or flu like symptoms
• numbness, burning, prickling or tingling sensations on the skin
• itchy skin rash
• impaired vision or eye irritation
• motion sickness
• ringing in the ear
• hiccups, flatulence, dry mouth or indigestion
• abdominal (stomach) pain
• difficulty urinating
• joint pain
• electrocardiogram abnormalities (QT prolongation)

Very rare (may affect up to 1 in 10,000 people):
Allergic reactions to Palonosetron Hospira.  The signs may include swelling of the lips, face, tongue or 
throat, having difficulty breathing or collapsing, you could also notice an itchy, lumpy rash (hives), 
burning or pain at the site of injection.

Children and Adolescents: 

Common (may affect up to 1 in 10 people): 
• headache 

Uncommon (may affect up to 1 in 100 people): 
• dizziness 
• jerky body movements 
• abnormal heart rate 
• coughing or shortness of breath 
• nosebleed 
• itchy skin rash or hives 
• fever 
• pain at the site of infusion 

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V.  By reporting side effects you can help provide more information on the safety 
of this medicine.

5. How to store Palonosetron Hospira

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the vial and carton after ‘EXP’. The
expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Single use only, any unused solution should be disposed of.



25

6. Contents of the pack and other information

What Palonosetron Hospira contains 

• The active substance is palonosetron (as hydrochloride).  Each ml of solution contains 
50 micrograms palonosetron. Each vial of 5 ml of solution contains 250 micrograms of 
palonosetron.

• The other ingredients are mannitol, disodium edetate, sodium citrate, citric acid monohydrate, 
water for injections, sodium hydroxide and hydrochloric acid (for pH adjustment).

What Palonosetron Hospira looks like and contents of the pack
Palonosetron Hospira solution for injection is a clear, colourless solution and is supplied in a pack of 
one Type I glass vial with a chlorobutyl rubber stopper and aluminium cap, which contains 5 ml of the 
solution. Each vial contains one dose.

Available in packs of 1 vial containing 5 ml of solution. 

Marketing Authorisation Holder 
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer
Hospira UK Limited, Horizon, Honey Lane, Hurley, Maidenhead, SL6 6RJ, United Kingdom

HOSPIRA Enterprises B.V., Randstad 22-11, 1316 BN Almere, The Netherlands

Avara Liscate Pharmaceutical Services S.p.A., Via Fosse Ardeatine, 2, 20060, Liscate (MI), Italy

Pfizer Service Company BVBA, Hoge Wei 10, 1930 Zaventem, Belgium

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

BE
Pfizer SA/NV
Tél/Tel: +32 2 554 62 11

LU
Pfizer SA/NV
Tél/Tel: +32 2 554 62 11

BG
Пфайзер Люксембург САРЛ, Клон България
Тел.: +359 2 970 4333

LT
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. + 370 52 51 4000

CZ
Pfizer, spol. s r.o.
Tel: +420-283-004-111

HU
Pfizer Kft.
Tel: + 36 1 488 37 00

DK
Pfizer ApS
Tlf: + 45 44 20 11 00

MT
Drugsales Ltd
Tel: + 356 21 419 070/1/2



26

DE
Pfizer Pharma PFE GmbH
Tel: + 49 (0)800 8535555

NL
Pfizer bv
Tel: +31 (0)10 406 43 01

EE
Pfizer Luxembourg SARL Eesti filiaal
Tel: +372 666 7500

NO
Pfizer AS
Tlf: +47 67 52 61 00

EL
Pfizer ΕΛΛΑΣ A.E.
Τηλ.: +30 210 6785 800

AT
Pfizer Corporation Austria Ges.m.b.H.
Tel: +43 (0)1 521 15-0

ES
Pfizer, S.L.
Tel: +34 91 490 99 00

PL
Pfizer Polska Sp. z o.o.
Tel: +48 22 335 61 00

FR
Pfizer PFE France
Tél: + 33 (0)1 58 07 34 40

PT
Laboratórios Pfizer, Lda.
Tel: + 351 21 423 55 00

HR
Pfizer Croatia d.o.o.
Tel: +385 1 3908 777

RO
Pfizer România S.R.L.
Tel: +40 (0)21 207 28 00

IE
Pfizer Healthcare Ireland
Tel: 1800 633 363 (toll free)
+44 (0) 1304 616161

SI
Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja 
farmacevtske dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

IS
Icepharma hf.
Sími: +354 540 8000

SK
Pfizer Luxembourg SARL, organizačná zložka
Tel: +421–2–3355 5500

IT
Pfizer Italia Srl
Tel: +39 06 33 18 21

FI
Pfizer PFE Finland Oy
Puh/Tel: +358 (0)9 430 040

CY
Pharmaceutical Trading Co Ltd
Τηλ: 24656165

SE
Pfizer AB
Tel: +46 (0)8 550 520 00

LV
Pfizer Luxembourg SARL filiāle Latvijā
Tel.: + 371 670 35 775

UK
Hospira UK Limited
Tel: + 44 (0) 1628 515500

This leaflet was last revised in month YYYY.

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVEUSE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET