Aloxi

1 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



2 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Aloxi 250 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 
 
Aloxi 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. 
 

Aloxi 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 
 
Aloxi 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. Aloxi should be injected over 30 seconds. 
 
The efficacy of Aloxi 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 people 
 
No dose adjustment is necessary for the elderly.  
 



3 
 

 
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 Aloxi in children aged less than 1 month have not been established. No 
data are available. There are limited data on the use of Aloxi 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. 
 
Aloxi should not be used to prevent or treat nausea and vomiting in the days following chemotherapy 
if not associated with another chemotherapy administration. 
 



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



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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. 
 
 
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 Aloxi, were headache (9 %) and constipation 
(5 %).  
 
In the clinical studies the following adverse reactions (ARs) were observed as possibly or probably 
related to Aloxi.  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. 



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° From post-marketing experience 

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* 

Investigations  Elevated transaminases-, 
electrocardiogram QT 

prolonged 

 



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* 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 Aloxi, 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 Aloxi 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. 



8 
 

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  
 

 Aloxi 
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 Aloxi 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 

 
 Aloxi 

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



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

 Aloxi 
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 Aloxi 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 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 i.v 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 3µg/kg was 54.1% 
and 37.1% respectively.  
 
The efficacy of Aloxi 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 i.v. 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 



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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 i.v at single doses of 
1µg/kg and 3µg/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 i.v. palonosetron (1 µg/kg, max 
0.075 mg) versus I.V. 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 %. 



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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 people  
Age does not affect the pharmacokinetics of palonosetron. No dosage adjustment is necessary in 
elderly patients. 
 
Gender 
Gender does not affect the pharmacokinetics of palonosetron. No dosage adjustment is necessary 
based on gender. 
 
Paediatric population 
 
Single-dose i.v. Aloxi 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 from10 µg/kg to 20 µg/kg 
a dose-proportional increase in mean AUC was observed. Following single dose intravenous infusion 
of Aloxi 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. 
 
 
 



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Table 4: Pharmacokinetic Parameters in Paediatric Cancer Patients following intravenous 
infusion of Aloxi 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. 
 
 
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). 
 



14 
 

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 Aloxi 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 
 
5 years. 
Upon opening of the vial, use immediately and discard any unused solution. 
 
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 chlorobutyl siliconised rubber stopper and aluminium cap. 
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. 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Helsinn Birex Pharmaceuticals Ltd. 
Damastown 
Mulhuddart  
Dublin 15 
Ireland 
 
 



15 
 

8. MARKETING AUTHORISATION NUMBER 
 
EU/1/04/306/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 22 March 2005 
Date of latest renewal: 23 March 2010 
 
 
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 
  

http://www.ema.europa.eu/


16 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Aloxi 500 micrograms soft capsules 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each capsule contains 500 micrograms palonosetron (as hydrochloride). 
 
Excipient(s): 
Each capsule contains 7 mg sorbitol.  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Soft capsule. 
 
Plain, light beige, opaque, round to oval, soft gelatine capsules, filled with a clear yellowish solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Aloxi is indicated in adults for the prevention of nausea and vomiting associated with moderately 
emetogenic cancer chemotherapy. 
 
4.2 Posology and method of administration 
 
Aloxi should be used only before chemotherapy administration. 
 
Posology 
 
UAdults 
 
500 micrograms palonosetron administered orally approximately one hour before the start of 
chemotherapy.  
 
UElderly population 
 
No dose adjustment is necessary for the elderly.  
 
UPaediatric population 
 
The safety and efficacy of Aloxi in children have not been established.  Currently available data are 
described in section 5.1 and section 5.2, but no recommendation on posology can be made. 
 
UHepatic impairment 
 
No dose adjustment is necessary for patients with impaired hepatic function. 
 



17 
 

URenal 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 oral use. 
Aloxi can be taken with or without food. 
 
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 QT 
corrected (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. 
  
Aloxi should not be used to prevent or treat nausea and vomiting in the days following chemotherapy 
if not associated with another chemotherapy administration. 
 
Aloxi contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take 
this medicinal product. Aloxi capsules may also contain a trace of lecithin derived from soya. 
Therefore, patients with known hypersensitivity to peanut or soya, should be monitored closely for 
signs of an allergic reaction. 
 
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. 
 
UChemotherapeutic medicinal productsU  
In preclinical studies, palonosetron did not inhibit the antitumour activity of the five chemotherapeutic 
agents tested (cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C). 
 



18 
 

 
 
UMetoclopramideU 
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.   
 
UCYP2D6 inducers and inhibitorsU 
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). 
 
UCorticosteroidsU 
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). 
 
UOther medicinal productsU 
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 so 
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. 
 
4.8 Undesirable effects 
 
In clinical studies at a dose of 500 micrograms (total 161 patients) the most frequently observed 
adverse reaction, at least possibly related to Aloxi, was headache (3.7 %).  
 



19 
 

In the clinical studies the following adverse reactions (ARs) were observed as possibly or probably 
related to Aloxi. These were classified as common (≥1/100 to <1/10) or uncommon (≥1/1,000 to 
<1/100).   
 

System Organ Class Common ARs 
 

Uncommon ARs 
 

Psychiatric disorders  Insomnia 
Nervous system disorders Headache  
Eye disorders  Eye swelling 
Cardiac disorders  Atrioventricular block first degree, 

atrioventricular block second degree 
Respiratory, thoracic and mediastinal 
disorders 

 Dyspnoea 

Gastrointestinal disorders  Constipation, nausea 
Musculoskeletal and connective tissue 
disorders 

 Myalgia 

Investigations  Blood bilirubin increased 
In post marketing very rare cases (<1/10,000) of hypersensitivity reactions occurred with palonosetron 
solution for injection for intravenous use. 
 
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 clinical trials. 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 Aloxi, 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 Aloxi overdose. 
 
 
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. 
In a multicentre, randomised, double-blind active control clinical trial of 635 patients set to receive 
moderately emetogenic cancer chemotherapy. A single-dose of 250 mcg, 500 mcg, or 750 mcg oral 
palonosetron capsules given one hour prior to moderately emetogenic chemotherapy was compared to 
a single-dose of 250 mcg intravenous Aloxi given 30 minutes prior to chemotherapy. Patients were 
randomised to either dexamethasone or placebo in addition to their assigned treatment.  The majority 



20 
 

of patients in the study were women (73 %), white (69 %), and naïve to previous chemotherapy 
(59 %). The antiemetic activity was observed during 0-24 hours, 24-120 hours and 0-120 hours.  
Efficacy was based on demonstrating non-inferiority of oral palonosetron doses compared to the 
approved intravenous formulation. Non-inferiority criteria were met if the lower bound of the two-
sided 98.3 % confidence interval for the difference in complete response rates of oral palonosetron 
dose minus approved intravenous formulation was larger than -15 %. The non-inferiority margin was 
15 %.   
 
As shown in Table 1, oral Aloxi capsules 500 micrograms demonstrated non-inferiority to the active 
comparator during the 0 to 24 hour and 0 to 120 hour time intervals; however, for the 24 to 120 hour 
time period, non-inferiority was not shown. 
 
Although comparative efficacy of palonosetron in multiple cycles has not been demonstrated in 
controlled clinical trials, 217 patients were enrolled in a multicentre, open label safety study and were 
treated with palonosetron capsules 750 micrograms for up to 4 cycles of chemotherapy in a total of 
654 chemotherapy cycles. Approximately 74 % of patients also received single dose oral or 
intravenous dexamethasone 30 minutes before chemotherapy. Complete Response was not formally 
evaluated for the repeat cycle application. However, in general the antiemetic effect for the 0-24 hour 
interval was similar throughout the consecutively repeated cycles and the overall safety was 
maintained during all cycles. 

Table 1: Proportion of patientsa responding by treatment group and phase   

 
Aloxi Oral 

500 micrograms  
(n=160) 

Aloxi Intravenous 
250 micrograms  

(n=162) 

Delta 
 

 % % %  
Complete Response (No Emesis and No Rescue Medication)                        98.3 % CIb 
0-24 hours 76.3 70.4 5.9    [-6.5 %, 18.2 %] 
24-120 hours 62.5 65.4 -2.9    [-16.3 %, 10.5 %] 
0-120 hours 58.8 59.3 -0.5   [-14.2 %, 13.2 %] 
Complete Control (Complete Response and No More Than Mild Nausea)   p-valuec  
0-24 hours 74.4 68.5 5.9 NS  
24-120 hours 56.3 62.3 -6.0 NS  
0-120 hours 52.5 56.2 -3.7 NS  
No Nausea (Likert Scale)                                                                                     p-valuec  
0-24 hours 58.8 57.4 1.4   NS  
24-120 hours 49.4 47.5 1.9   NS  
0-120 hours 45.6 42.6 3.0   NS  

a Intent-to-treat cohort 
b The study was designed to show non-inferiority. A lower bound greater that -15 % demonstrates non-
inferiority between Aloxi oral and comparator Aloxi intravenous 
c Chi-square test. Significance levels at alpha 0.0167 (adjusted for multiple comparisons). 
 
In non-clinical studies palonosetron 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 repolarization. 
 
 
 
 



21 
 

Paediatric population 
Prevention of Chemotherapy Induced Nausea and Vomiting (CINV):  
The safety and efficacy of Palonosetron i.v at single doses of 3µg/kg and 10µg/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 3µg/kg was 54.1% and 37.1% 
respectively. 
 
The efficacy of Aloxi 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 i.v. 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 i.v at single doses of 
1µg/kg and 3µg/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 i.v. palonosetron (1 µg/kg, max 
0.075 mg) versus i.v. 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. 
 



22 
 

Please see section 4.2 for information on paediatric use. 
  
5.2 Pharmacokinetic properties 
 
UAbsorption  
Following oral administration, palonosetron is well absorbed with its absolute bioavailability reaching 
97 %.  After single oral doses using buffered solution mean maximum palonosetron concentrations 
(Cmax) and area under the concentration-time curve (AUC0-∞) were dose proportional over the dose 
range of 3.0 to 80 µg/kg in healthy subjects. 
 
In 36 healthy male and female subjects given a single oral dose of palonosetron capsules 
500 micrograms, maximum plasma palonosetron concentration (Cmax) was 0.81 ± 0.17 ng/ml (mean ± 
SD) and time to maximum concentration (Tmax) was 5.1 ± 1.7 hours. In female subjects (n=18), the 
mean AUC was 35 % higher and the mean Cmax was 26 % higher than in male subjects (n=18). 
In 12 cancer patients given a single oral dose of palonosetron capsules 500 micrograms one hour prior 
to chemotherapy, Cmax was 0.93 ± 0.34 ng/ml and Tmax was 5.1 ± 5.9 hours.  The AUC was 30 % 
higher in cancer patients than in healthy subjects.   
 
A high fat meal did not affect the Cmax and AUC of oral palonosetron. Therefore, Aloxi capsules may 
be taken without regard to meals.  
 
UDistribution 
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. 
 
UBiotransformation 
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. 
 
UElimination 
Following administration of a single oral 750 micrograms dose of [14C]-palonosetron to six healthy 
subjects, 85 % to 93 % of the total radioactivity was excreted in urine, and 5 % to 8 % was eliminated 
in feces. The amount of unchanged palonosetron excreted in the urine represented approximately 
40 % of the administered dose.  In healthy subjects given palonosetron capsules 500 micrograms, the 
terminal elimination half-life (t½) of palonosetron was 37 ± 12 hours (mean ± SD), and in cancer 
patients, t½ was 48 ± 19 hours.  After a single-dose of approximately 0.75 mg intravenous 
palonosetron, the total body clearance of palonosetron in healthy subjects was 160 ± 35 ml/h/kg 
(mean ± SD) and renal clearance was 66.5 ± 18.2 ml/h/kg. 
 
UPharmacokinetics in special populations 
 
Elderly people 
Age does not affect the pharmacokinetics of palonosetron. No dose adjustment is necessary in elderly 
patients. 
 
Gender 
Gender does not affect the pharmacokinetics of palonosetron. No dose adjustment is necessary based 
on gender. 
 
 



23 
 

Paediatric patients 
 
Single-dose i.v. Aloxi 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 from10 µg/kg to 20 µg/kg 
a dose-proportional increase in mean AUC was observed. Following single dose intravenous infusion 
of Aloxi 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 2: Pharmacokinetic Parameters in Paediatric Cancer Patients following intravenous 
infusion of Aloxi 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 dose adjustment is necessary in patients with renal 
insufficiency. No pharmacokinetic data in haemodialysis patients are available. 
 
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. 



24 
 

 
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 15 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 Aloxi is intended for single application in humans, these findings are not considered relevant for 
clinical use. 
 
 

 6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
UCapsule content: 
Glycerol Monocaprylocaproate (type I)   
Polyglycerol oleate  
Glycerol 
Purified water 
Butylhydroxyanisole  
 
UCapsule shell: 
Gelatin 
Sorbitol 
Glycerol 
Titanium dioxide  
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
4 years. 
 
 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container  



25 
 

 
Polyamide/aluminium/PVC blister containing one or five soft capsules. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Helsinn Birex Pharmaceuticals Limited. 
Damastown 
Mulhuddart  
Dublin 15 
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/306/003 
EU/1/04/306/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 22 March 2005 
Date of latest renewal: 23 March 2010 
 
 
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  
  

http://www.ema.europa.eu/


26 
 

 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

B. CONDITIONS OR RETRICTIONS REGARDING SUPPLY 
AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETNG 

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

  



27 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Helsinn Birex Pharmaceuticals Ltd. 
Damastown, Mulhuddart, Dublin 15 
Ireland 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Aloxi solution for injection: Medicinal product subject to restricted medical prescription (see Annex I:  
Summary of Product Characteristics, section 4.2). 
 
 
Aloxi soft capsules: Medicinal product subject to medical prescription. 
 
 
C.     OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
• Periodic Safety Update Reports 

 
The marketing authorisation holder shall submit periodic safety update reports for this product 
in accordance with the requirements set out in the list of Union reference dates (EURD list) 
provided for under Article 107c(7) of Directive 2001/83/EC and published on the European 
medicines web-portal. 
 
 

D.      CONDITIONS OR RESTRICTIONSWITH 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. 

 
If the submission of a PSUR and the update of a RMP coincide, they can be submitted at the same 
time. 
 
  



28 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



29 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 
  



30 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Aloxi 250 micrograms solution for injection  
Palonosetron (as hydrochloride) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of solution contains 50 micrograms palonosetron (as hydrochloride). 
Each vial of 5 ml of solution contains 250 micrograms palonosetron (as hydrochloride). 
 
3. LIST OF EXCIPIENTS 
 
Also contains mannitol, disodium edetate, sodium citrate, citric acid monohydrate, water for 
injections, sodium hydroxide and hydrochloric acid. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection 
1 x 5 ml 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 
 
  



31 
 

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

 
Any unused solution should be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Helsinn Birex Pharmaceuticals Ltd. 
Damastown 
Mulhuddart  
Dublin 15 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/306/001  
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
<2D barcode carrying the unique identifier included> 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



32 
 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Aloxi 250 micrograms solution for injection 
Palonosetron  
IV use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use 
 
 
3. EXPIRY DATE 
 
EXP  
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 ml 
  



33 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Aloxi 500 micrograms soft capsules 
Palonosetron  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 500 micrograms palonosetron. (as hydrochloride). 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains sorbitol. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
1 soft capsule. 
5 soft capsules. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
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 
 
  



34 
 

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 
 
Helsinn Birex Pharmaceuticals Ltd. 
Damastown 
Mulhuddart  
Dublin 15 
Republic of Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/306/002 
EU/1/04/306/003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Aloxi 500 micrograms 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
<2D barcode carrying the unique identifier included> 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 
 
 
 
 



35 
 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Aloxi 500 micrograms soft capsules 
Palonosetron 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER  
 
Helsinn  
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 
 
 
  



36 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
  



37 
 

Package leaflet: Information for the user 
 

Aloxi 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 nurse. 
• This medicine has been prescribed for you only. Do not pass it on to others.  
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 

listed in this leaflet. See section 4. 
 
What is in this leaflet  
1. What Aloxi is and what it is used for 
2. What you need to know before you are given Aloxi 
3. How you are given Aloxi 
4. Possible side effects 
5. How to store Aloxi 
6. Contents of the pack and other information 
 
1. What Aloxi is and what it is used for 
 
Aloxi contains the active substance palonosetron. This belongs to a group of medicines called 
‘serotonin (5HT3) antagonists’.  
 
Aloxi is used in adults, adolescents and children over one month of age to help stop you feeling or 
being sick (nausea and vomiting) when having cancer treatments called chemotherapy. 
 
It works by blocking the action of a chemical called serotonin, which can cause you to feel sick or to 
vomit.  
 
 
2. What you need to know before you are given Aloxi 
 
Do not take Aloxi if: 
• you are allergic to palonosetron or any of the other ingredients of this medicine (listed in 

section 6). 
You will not be given Aloxi if any of the above apply to you. If you are not sure, talk to your doctor 
or nurse before you are given this medicine.  
 
Warnings and precautions 
Talk to your doctor or nurse before you are given Aloxi if: 
• you have a blocked bowel or have had repeated constipation in the past  
• you have had heart problems or heart problems run in your family, such as changes in your heart 

beat (‘QT prolongation’) 
• you have an imbalance of certain minerals in your blood which has not been treated - such as 

potassium and magnesium. 
 
If any of the above applies to you (or you are not sure), talk to your doctor or nurse before you are 
given Aloxi. 
 
 
 



38 
 

Other medicines and Aloxi 
Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines. In 
particular, tell them if you are taking the following medicines: 
 

Medicines for depression or anxiety 
Tell your doctor or nurse if you are taking any medicines for depression or anxiety, including: 
• medicines called SSRIs (‘selective serotonin reuptake inhibitors’) – such as fluoxetine, 

paroxetine, sertraline, fluvoxamine, citalopram, escitalopram  
• medicines called SNRIs (‘serotonin noradrenaline reuptake inhibitors’) – such as venlafaxine, 

duloxetine (can lead to the development of serotonin syndrome and should be used with caution). 
 

Medicines that can affect your heart beat 
Tell your doctor or nurse if you are taking any medicines that affect your heart beat – this is because 
they could cause a heart beat problem when taken with Aloxi. This includes: 
• medicines for heart problems such as amiodarone, nicardipine, quinidine 
• medicines for infections such as moxifloxacin, erythromycin 
• medicines for serious mental health problems such as haloperidol, chlorpromazine, quetiapine, 

thioridazine  
• a medicine for feeling or being sick (nausea and vomiting) called domperidone. 
If any of the above applies to you (or you are not sure), talk to your doctor or nurse before taking 
Aloxi – this is because these medicines could cause a heart beat problem when taken with Aloxi. 

 
Pregnancy 
If you are pregnant or think you might be pregnant, your doctor will not give you Aloxi unless it is 
clearly necessary. This is because we do not know if Aloxi may harm the baby. 
 
Ask your doctor or nurse for advice before being given this medicine if you are pregnant or think you 
might be. 
 
Breast-feeding 
It is not known if Aloxi is found in breast milk. 
 
Ask your doctor or nurse for advice before being given this medicine if you are breast-feeding. 
 
Driving and using machines 
You may feel dizzy or tired after being given this medicine. If this happens, do not drive or use any 
tools or machines. 
 
Aloxi contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium- 
free’. 
 
3. How you are given Aloxi 
 
Aloxi is normally given by a doctor or nurse. 
• You will be given the medicine about 30 minutes before the start of chemotherapy. 
 
Adults 
• The recommended dose of Aloxi is 250 micrograms. 
• It is given as an injection into a vein.  
 
Children and young people (aged 1 month to 17 years) 
• The doctor will work out the right dose based on bodyweight. 
• The maximum dose is 1500 micrograms. 



39 
 

• Aloxi will be given as a drip (a slow infusion into a vein). 
 
It is not recommended you are given Aloxi in the days following chemotherapy unless you are going 
to have another chemotherapy cycle. 
 
If you have any further questions on the use of this medicine, ask your doctor or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
The following side effects may happen with this medicine: 
 
Serious side effects 
Tell your doctor straight away if you notice any of the following serious side effects: 
• allergic reaction - the signs may include swelling of the lips, face, tongue or throat, having 

difficulty breathing or collapsing, an itchy, lumpy rash (hives). This is very rare: may affect up to 
1 in 10,000 people. 

Tell your doctor straight away if you notice any of the serious side effects listed above. 
 
Other side effects 
Tell your doctor if you notice any of the following side effects: 

 
Adults 

Common: may affect up to 1 in 10 people 
• headache, feeling dizzy,  
• constipation, diarrhoea. 
 
Uncommon: may affect up to 1 in 100 people 
• change in the colour of the vein and veins becoming larger 
• feeling happier than usual or feeling anxious 
• feeling sleepy or trouble sleeping 
• decrease or loss of appetite  
• weakness, feeling tired, 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, passing wind (flatulence), dry mouth or indigestion  
• abdominal (stomach) pain  
• difficulty passing water (urinating) 
• joint pain. 

 
Tell your doctor if you notice any of the side effects listed above. 
 
Uncommon side effects shown in tests: may affect up to 1 in 100 people 

• high or low blood pressure 
• abnormal heart rate or lack of blood flow to the heart 
• 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  



40 
 

• high levels of the pigment bilirubin in the blood 
• high levels of certain liver enzymes  
• ECG (electrocardiogram) abnormalities (‘QT prolongation’). 

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

• Burning, pain or redness at the injection site 
. 

Children and young people 

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. 

 
Tell your doctor if you notice any of the side effects listed above. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor. 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 Aloxi 
 
• 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. 
 
 
6. Contents of the pack and other information 
 
What Aloxi 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. 

 
What Aloxi looks like and contents of the pack 
Aloxi solution for injection is a clear, colourless solution and is supplied in a pack of one Type I glass 
vial with chlorobutyl siliconised 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. 



41 
 

 
 
Marketing Authorisation Holder and Manufacturer 
 
Helsinn Birex Pharmaceuticals Ltd.,  
Damastown,  
Mulhuddart,  
Dublin 15,  
Ireland. 
 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu  
 
 
  

http://www.ema.europa.eu/


42 
 

Package leaflet: Information for the patient 
 

Aloxi 500 micrograms soft capsules 
Palonosetron 

 
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, ask your doctor or pharmacist. 
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
• 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 Aloxi is and what it is used for 
2. What you need to know before you take Aloxi 
3. How to take Aloxi 
4. Possible side effects 
5. How to store Aloxi 
6.       Contents of the pack and other information 
 
 
1. What Aloxi is and what it is used for 
 
Aloxi contains the active substance palonosetron. This belongs to a group of medicines called 
‘serotonin (5HT3) antagonists’.  
 
Aloxi is used in adults to help stop you feeling or being sick (nausea and vomiting) when having 
cancer treatments called chemotherapy. 
 
It works by blocking the action of a chemical called serotonin, which can cause you to feel sick or to 
vomit. 
 
 
2. What you need to know before you take Aloxi 
 
Do not take Aloxi if: 
• you are allergic to palonosetron or any of the other ingredients of this medicine (listed in 

section 6). 
Do not take Aloxi if any of the above applies to you. If you are not sure, talk to your doctor or 
pharmacist before taking this medicine.  
 
Warnings and precautions 
Talk to your doctor or pharmacist before taking Aloxi if: 
• you have a blocked bowel  or have had repeated constipation in the past 
• you have had heart problems or heart problems run in your family, such as changes in your heart 

beat (‘QT prolongation’) 
• you have an imbalance of certain minerals in your blood which has not been treated - such as 

potassium and magnesium. 
 

 
Children 
Do not give this medicine to children  



43 
 

 
Other medicines and Aloxi 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. In particular, tell them if you are taking the following medicines: 
 

Medicines for depression or anxiety 
Tell your doctor or pharmacist if you are taking any medicines for depression or anxiety, including: 
• medicines called SSRIs (‘selective serotonin reuptake inhibitors’) – such as fluoxetine, 

paroxetine, sertraline, fluvoxamine, citalopram, escitalopram  
• medicines called SNRIs (‘serotonin noradrenaline reuptake inhibitors’) – such as venlafaxine, 

duloxetine  (can lead to the development of serotonin syndrome and should be used with caution).  
 
If any of the above applies to you (or you are not sure), talk to your doctor or pharmacist before 
taking Aloxi. 
 
Medicines that can affect your heart beat 
Tell your doctor or pharmacist if you are taking any medicines that affect your heart beat – this is 
because they could cause heart beat problems when taken with Aloxi. This includes: 
• medicines for heart problems such as amiodarone, nicardipine, quinidine 
• medicines for infections such as moxifloxacin, erythromycin 
• medicines for serious mental health problems such as haloperidol, chlorpromazine, quetiapine, 

thioridazine  
• a medicine for feeling or being sick (nausea and vomiting) called domperidone. 
 
If any of the above applies to you (or you are not sure), talk to your doctor or pharmacist before 
taking Aloxi – this is because these medicines could cause heart beat problems when taken with 
Aloxi. 

 
Pregnancy 
If you are pregnant or think you might be pregnant, your doctor will not use Aloxi unless it is clearly 
necessary. This is because we do not know if Aloxi may harm the baby.  
 
Ask your doctor or pharmacist for advice before using this medicine if you are pregnant or think you 
might be. 
 
Breast-feeding 
It is not known if Aloxi is found in breast milk.  
Ask your doctor or pharmacist for advice before using this medicine if you are breast-feeding. 
 
Driving and using machines 
You may feel dizzy or tired after taking this medicine. If this happens, do not drive or use any tools or 
machines. 
 
Aloxi contains sorbitol and may contain traces of soya 
This medicine contains 7 mg sorbitol (a type of sugar) in each capsule. If you have been told by your 
doctor that you have an intolerance to some sugars, talk to your doctor before taking this medicine. 
 
Aloxi may contain traces of lecithin which comes from soya. If you are allergic to peanut or soya, do 
not take this medicine. See your doctor straight away if you notice any signs of an allergic reaction.  
The signs may include hives, skin rash, itching, difficulty breathing or swallowing, swollen mouth, 
face, lips, tongue or throat and sometimes a drop in blood pressure. 
 
 
 



44 
 

3. How to take Aloxi 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
• The recommended dose is one capsule (500 micrograms). 
• You will normally take the capsule about 60 minutes before the start of your chemotherapy. 
• This medicine can be taken with or without food. 
 
It is not recommended to take Aloxi in the days following chemotherapy unless you are going to have 
another chemotherapy cycle. 
 
If you take more Aloxi than you should 
If you think you may have taken more than you should, tell your doctor straight away. 
 
If you forget to take Aloxi 
It is unlikely that you will forget to take this medicine. However, if you think you have forgotten to 
take your dose, tell your doctor straight away. 
 
If you stop taking Aloxi 
Do not stop taking this medicine without talking to your doctor. If you decide not to take Aloxi (or 
other similar medicines), it is likely your chemotherapy will cause you to feel sick or be sick (nausea 
and vomiting). 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them.  
The following side effects may happen with this medicine: 
 
Serious side effects 
Tell your doctor straight away if you notice any of the following serious side effects: 
• allergic reaction - the signs may include swelling of the lips, face, tongue or throat, having 

difficulty breathing or collapsing, an itchy, lumpy rash (hives). This is very rare: may affect up to 
1 in 10,000 people. 

Tell your doctor straight away if you notice any of the serious side effects listed above. 
 
Other side effects 
Tell your doctor if you notice any of the following side effects: 

Common: may affect up to 1 in 10 people 
• headache. 
 
Uncommon: may affect up to 1 in 100 people 
• trouble sleeping 
• shortness of breath 
• eye swelling 
• abnormal electrical impulses in the heart 
• constipation 
• feeling sick (nausea) 
• high levels of the pigment ‘bilirubin’ (a marker of liver problems) in the blood 
• muscle pain. 



45 
 

 
Tell your doctor if you notice any of the side effects listed above. 
 
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 Aloxi 
 
• 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 blister and carton after 

“EXP”. The expiry date refers to the last day of that month. 
• This medicine does not require any special storage conditions. 
 
 
6. Contents of the pack and other information 
 
What Aloxi contains 
• The active substance is palonosetron. Each capsule contains 500 micrograms palonosetron (as 

hydrochloride). 
• The other ingredients are glycerol monocaprylocaproate (type I), polyglycerol oleate, glycerol, 

purified water, butylhydroxyanisole, gelatin, sorbitol, titanium dioxide.  
 

What Aloxi looks like and contents of the pack 
Aloxi 500 micrograms soft capsules are plain, light beige, opaque, round to oval soft capsules, filled 
with a clear yellowish solution. They are supplied in polyamide/aluminium/PVC blisters containing 
one or five capsules. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 

Helsinn Birex Pharmaceuticals Ltd., 
Damastown, 
Mulhuddart, 
Dublin 15, 
Ireland. 
 
 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu  
 

http://www.ema.europa.eu/

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