Varuby

1 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

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This medicinal product is subject to additional monitoring. This will allow quick identification of 

new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Varuby 90 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each tablet contains 90 mg of rolapitant (as hydrochloride monohydrate). 
 
Excipient(s) with known effect 
 
This medicinal product contains 230 mg of lactose (as monohydrate) per dose (two tablets). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
 
Tablets are blue, debossed with T0101 on one side and 100 on the other. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Prevention of delayed nausea and vomiting associated with highly and moderately emetogenic cancer 
chemotherapy in adults 
 
Varuby is given as part of combination therapy (see section 4.2). 
 
4.2 Posology and method of administration 
 
Posology 
 
Adults 
Varuby is given as part of a regimen that includes dexamethasone and a 5-HT3 receptor antagonist. 
 
180 mg (two tablets) should be administered within 2 hours prior to initiation of each chemotherapy 
cycle but at no less than 2-week intervals. 
 
There is no medicinal product interaction between rolapitant and dexamethasone, so no dosage 
adjustment for dexamethasone is required. 
 
The following regimens are recommended for the prevention of nausea and vomiting associated with 
emetogenic cancer therapy: 
 

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Highly emetogenic chemotherapy regimen 
 
 Day 1 Day 2  Day 3  Day 4  
Varuby  180 mg orally; 

Within 2 hours prior to chemotherapy  
None  

Dexamethasone  20 mg orally; 
30 min prior to chemotherapy  

8 mg orally 
twice 
daily 

8 mg orally 
twice 
daily 

8 mg 
orally 
twice 
daily 

5-HT3 receptor 
antagonist  

Standard dose of 5-HT3 receptor 
antagonist. See the Summary of 
Product Characteristics for the 
co-administered 5-HT3 receptor 
antagonist for appropriate dosing 
information.  

None 

 
Moderately emetogenic chemotherapy regimen 
 
 Day 1 Day 2 Day 3 Day 4 
Varuby 180 mg orally; 

Within 2 hours prior to chemotherapy  
None 

Dexamethasone  20 mg orally; 
30 min prior to chemotherapy  

None 

5-HT3 receptor 
antagonist  

Standard dose of 5-HT3 receptor 
antagonist. See the Summary of Product 
Characteristics for the co-administered 
5-HT3 receptor antagonist for 
appropriate dosing information. 

See the Summary of Product 
Characteristics for the co-administered 

5-HT3 receptor antagonist for 
appropriate dosing information. 

 
Special populations 
 
Elderly people (≥ 65 years) 
No dose adjustment is necessary for the elderly. Limited data in patients aged 75 years and older are 
available. Varuby should be used with caution in these patients (see section 5.2). 
 
Renal impairment 
No dose adjustment is necessary for patients with mild or moderate renal impairment. There are 
limited data in patients with severe renal impairment and no data in patients with end stage renal 
disease undergoing haemodialysis. Varuby should be used with caution in these patients (see 
section 5.2). 
 
Hepatic impairment 
No dose adjustment is needed in patients with mild or moderate hepatic impairment. There are no data 
in patients with severe hepatic impairment. Varuby should be used with caution in these patients (see 
sections 4.4 and 5.2). 
 
Paediatric population 
The safety and efficacy of rolapitant in children and adolescents below 18 years of age has not yet 
been established. No data are available. 
 
Method of administration 
 
The tablets should be swallowed whole, with some water and may be taken with or without food. 
 

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4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
In combination with St John’s wort (see section 4.5) 
 
4.4 Special warnings and precautions for use 
 
Patients with severe hepatic impairment 
 
There are no data in patients with severe hepatic impairment (see section 5.2). Varuby should be used 
with caution in these patients. If use cannot be avoided, patients should be monitored for adverse 
reactions to Varuby (see section 4.8). 
 
Patients with severe renal impairment 
 
There are limited data in patients with severe renal impairment (see section 5.2). Varuby should be 
used with caution in these patients. If use cannot be avoided, patients should be monitored for adverse 
reactions to Varuby (see section 4.8). 
 
Interactions 
 
Varuby is not recommended in patients who require chronic administration of strong (e.g. rifampicin, 
carbamazepine, phenobarbital, enzalutamide, phenytoin) or moderate enzyme inducers (e.g. efavirenz, 
rifabutin) (see section 4.5) 
 
The efficacy and safety of rolapitant with concurrent use of another NK1 receptor antagonist (e.g. 
aprepitant and a combination of netupitant and palonosetron hydrochloride) is not established and 
therefore not recommended (see section 4.5). 
 
Lactose 
 
Varuby contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp 
lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Effects of Varuby on the pharmacokinetics of other active substances 
 
CYP2D6 substrates 
Rolapitant is a moderate CYP2D6 inhibitor. Increased plasma concentration of CYP2D6 substrates 
may result in potential adverse reactions. A 3-fold increase in the exposure of dextromethorphan, a 
CYP2D6 substrate, was observed 7 days after a single oral dose of rolapitant and may last longer. 
 
Therefore, caution should be taken when rolapitant is combined with a medicinal product metabolised 
by CYP2D6, notably those having a narrow therapeutic margin (e.g. propafenone, tamoxifen, 
metoprolol used in heart failure, thioridazine, pimozide). 
 
UGT1A1 and UGT2B7 substrates (e.g. irinotecan and morphine, respectively) 
Rolapitant modestly inhibited UGT1A1 and UGT2B7 in vitro. Therefore, the potential interactions 
associated with the inhibition of these UGT enzymes in the intestine cannot be excluded.  
 
BCRP substrates 

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Rolapitant is an inhibitor of Breast-Cancer-Resistance Protein (BCRP). Increased plasma 
concentrations of BCRP substrates (e.g. methotrexate, irinotecan, topotecan, mitoxantrone, 
rosuvastatin, sulfasalazine, doxorubicin, bendamustine) may result in potential adverse reactions. Co-
administration of a single dose of 180 mg rolapitant with sulfasalazine, a BCRP substrate, resulted in 
an approximately 2-fold increase in Cmax and AUC of sulfasalazine. If the combination cannot be 
avoided, clinical and biological monitoring for adverse reactions related to the concomitant medicinal 
product must be made. The lowest effective dose of rosuvastatin is to be used. 
 
P-gp substrates 
Rolapitant is an inhibitor of P-glycoprotein (P-gp). A 70% increase in Cmax and 30% increase in AUC 
of digoxin, a P-gp substrate, were observed when administered with a single dose of 180 mg 
rolapitant. Therefore, clinical monitoring of adverse reactions and, if possible, biological monitoring 
are recommended when rolapitant is combined with digoxin or with other P-gp substrates (e.g. 
dabigatran or colchicine), and in particular in patients with renal impairment. 
 
OATP1B1 and 1B3 substrates 
In vitro studies suggest that rolapitant is not expected to inhibit OATP1B1 at clinically relevant 
concentrations and rolapitant is not an inhibitor of OATP1B3 at the tested concentrations up to 20 µM. 
 
OCT1 substrates 
In vitro, rolapitant is not an inhibitor of OCT1 at the tested concentrations up to 20 µM. 
 
CYP3A4 substrates 
In vivo, rolapitant is not expected to exhibit any inhibitory or inducing effect on CYP3A4. A single 
dose of 180 mg rolapitant had no significant effects on the pharmacokinetics of midazolam compared 
to oral midazolam 3 mg alone on Day 1, Day 8 and Day 11. 
 
Ondansetron 
Rolapitant had no significant effects on the pharmacokinetics of intravenous ondansetron when 
concomitantly administered with a single 180 mg dose of rolapitant on the same day. 
 
Dexamethasone 
Rolapitant had no significant effects on the pharmacokinetics of dexamethasone when oral 
dexamethasone was administered on Days 1 to 3 after a single 180 mg dose of rolapitant was co-
administered on Day 1. 
 
Other CYPs 
No clinically significant interaction is expected with the following medicinal products when 
administered with a single dose of 180 mg rolapitant on Day 1 and without rolapitant on Day 8: 
repaglinide 0.25 mg (a CYP2C8 substrate), efavirenz 600 mg (a CYP2B6 substrate), tolbutamide 
500 mg (a CYP2C9 substrate) or omeprazole 40 mg (a CYP2C19 substrate). 
 
Rolapitant had no effects on the pharmacokinetics of caffeine (a CYP1A2 substrate) when an oral dose 
of 200 mg caffeine was administered with a single dose of 180 mg rolapitant on Day 1, and without 
rolapitant on Day 8 and Day 15. 
 
Effects of other medicinal products on the pharmacokinetics of Varuby 
 
Enzyme inducers 
Concomitant administration of rifampicin, a strong enzyme inducer significantly decreased the 
systemic exposure to rolapitant and to its active metabolite. When 600 mg rifampicin was 
administered once daily for 7 days before and 7 days after administration of a single dose of 180 mg 
rolapitant, the mean AUC was reduced by 87% and its active metabolite by 89% compared to 
administration of rolapitant alone. Varuby in patients who require chronic administration of strong 

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inducers (e.g. rifampicin, carbamazepine, enzalutamide, phenytoin) is not recommended (see 
section 4.4). 
 
The effect of moderate inducers (e.g. efavirenz, rifabutin) is not established; therefore, the use of 
rolapitant in patients already given a moderate inducer is not recommended (see section 4.4). 
 
Due to its strong inducing effect, St John’s wort is contraindicated with rolapitant (see section 4.3). 
 
CYP3A4 inhibitors 
No clinically significant effect was seen on the pharmacokinetics of rolapitant when ketoconazole, a 
strong CYP3A4 inhibitor was administered with rolapitant. Concurrent administration of 400 mg 
ketoconazole once daily for 21 days following a single 90 mg dose of rolapitant, did not significantly 
affect the Cmax of rolapitant while the AUC increased by 21%. This is not expected to be clinically 
relevant. 
 
Other interactions 
 
The efficacy and safety of rolapitant with concurrent use of another NK1 receptor antagonist (e.g. 
aprepitant and a combination of netupitant and palonosetron hydrochloride) is not established and 
therefore not recommended (see section 4.4). 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no available data on rolapitant use in pregnant women. Studies in animals have shown no 
teratogenic or embryo-foetal effects. In the pre- and postnatal developmental study, at a dose 
equivalent to half of the recommended human dose, there was a decrease in memory in female pups in 
a maze test and a decrease in pup body weight (see section 5.3). Varuby should not be used during 
pregnancy unless clearly necessary. 
 
Breast-feeding 
 
There are no data on the presence of rolapitant in human milk. Rolapitant administered orally to 
lactating female rats was present in milk. Breast-feeding is not recommended during treatment with 
Varuby. 
 
Fertility 
 
Rolapitant did not affect the fertility or general reproductive performance of male rats. Decreases in 
the number of corpora lutea and implantation sites were observed in the female rat fertility and early 
embryonic development study (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Varuby has minor influence on the ability to drive and use machines. Dizziness and fatigue may occur 
following administration of rolapitant (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of safety profile 
 
Over 4,375 patients have been treated with Varuby or a comparator across Phase 1, 2, and 3 clinical 
studies. A total of 2,798 subjects received oral rolapitant at any dose, including 1,567 subjects in the 
CINV (chemotherapy-induced nausea and vomiting) studies. 

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The most common adverse reactions were fatigue (1.9%) and headache (1.5%). The safety profile in 
the multiple-cycle extensions of highly and moderately emetogenic chemotherapy studies for up to 
6 cycles of chemotherapy is similar to the profile observed in Cycle 1. 
 
Tabulated list of adverse reactions 
 
The following adverse reactions were observed in a pooled analysis of the Highly Emetogenic 
Chemotherapy (HEC) and Moderately Emetogenic Chemotherapy (MEC) studies. 
 
Frequencies are defined as: Very common (≥1/10); common (≥1/100 to < 1/10); uncommon (≥1/1,000 
to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known: frequency cannot be 
estimated from the available data. 
 

Adverse reactions per system organ class 
System organ class Common Uncommon  Rare 
Infections and 
infestations 

 Oral fungal infection 
 

Candidiasis 
Oral candidiasis 

Blood and lymphatic 
system disorders 

 Neutropenia International Normalised 
Ratio increased 
Leukopenia 
Neutrophil count decreased 
Thrombocytopenia 

Immune system 
disorders 

  Hypersensitivity 
 

Metabolism and nutrition 
disorders 

 Decreased appetite Dehydration 
Hypomagnesaemia 

Psychiatric disorders  Insomnia 
 

Anxiety 
Bruxism 

Nervous system 
disorders 

Headache Dizziness 
Disturbance in 
attention 
Dysgeusia 
Somnolence 

Balance disorder 
Movement disorder 
Syncope 

Ear and labyrinth 
disorders 

  Hypoacusis 
Tinnitus 

Eye disorders   Vision blurred 
Cardiac disorders   Heart rate increased 
Gastrointestinal 
disorders 

Constipation Diarrhoea 
Dyspepsia 
Nausea 
Abdominal distension 
Abdominal pain 
Stomatitis 

Abdominal discomfort 
Change of bowel habit 
Dry mouth 
Gastrooesophageal reflux 
disease 
Retching 

Vascular disorders   Hypertension 
Respiratory, thoracic and 
mediastinal disorders 

 Hiccups Dyspnoea 

Skin and subcutaneous 
tissue disorders 

  Alopecia 
Angioedema 
Dermatitis acneiform 
Dry skin 

Musculoskeletal and 
connective tissue 
disorders 

 Myalgia 
 

Arthralgia 
Back pain 
Muscular weakness 
Rhabdomyolysis 

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Adverse reactions per system organ class 
System organ class Common Uncommon  Rare 
General disorders and 
administration site 
conditions 

Fatigue Asthenia Gait disturbance 

 
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 
 
Rolapitant doses up to 720 mg have been used in clinical studies without any safety concerns. In case 
of overdose, the medicinal product should be discontinued and general supportive treatment and 
monitoring should be provided. Because of the antiemetic activity of rolapitant, emesis induced by a 
medicinal product may not be effective. Dialysis studies have not been performed. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antiemetics and antinauseants, other antiemetics, ATC code: A04AD14 
 
Mechanism of action 
 
Rolapitant is a selective antagonist of human substance P/neurokinin 1 (NK1) receptors. 
 
Clinical efficacy and safety 
 
Cisplatin-Based Highly Emetogenic Chemotherapy (HEC) 
 
Study 1 and Study 2 (HEC) 
 
In two multicentre, randomised, double-blind, parallel group, controlled clinical studies (Study 1 and 
Study 2), the rolapitant regimen (180 mg rolapitant, 10 mcg/kg intravenous granisetron and 20 mg oral 
dexamethasone) was compared with control therapy (placebo, 10 mcg/kg intravenous granisetron and 
20 mg oral dexamethasone) on Day 1 in patients receiving a chemotherapy regimen that included 
cisplatin ≥60 mg/m2. On Day 2 to 4, patients received 8 mg twice daily of oral dexamethasone. Study 
medicinal products were administered prior to chemotherapy on Day 1 at the following intervals: 
rolapitant (1 to 2 hours prior); granisetron and dexamethasone (30 minutes prior). 
 
A total of 1087 patients were randomised to either the rolapitant regimen (N=544) or control therapy 
(N=543) across Study 1 and Study 2; 1070 patients were included in the evaluation of efficacy; 37% 
were women and 63% were men. Of the 1070 patients, 26% were greater than 65 years of age and 3% 
were greater than 75 years of age. 
 
The primary endpoint in both studies was complete response (defined as no emetic episodes and no 
rescue medicinal product) in the delayed phase (>24 to 120 hours) of chemotherapy-induced nausea 
and vomiting. The following additional pre-specified endpoints were also evaluated: complete 
response in the acute phase (0 to 24 hours) and overall phase (0 to 120 hours); no emesis in each 

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CINV phase, no significant nausea in each CINV phase, and time to first emesis or use of rescue 
medicinal product. 
 
The results were evaluated for each individual study and for the two studies combined. Individual 
results from Studies 1 and 2 as well as a summary of the key results from the combined analysis are 
shown in Table 1 below. 
 

Table 1: Proportion of patients receiving cisplatin chemotherapy responding by treatment group and 
phase (Studies 1 and 2 – HEC Individual Results) 
 
 
Efficacy 
Endpointsa 

HEC Study 1 HEC Study 2 Study 1 and 2 Combined 
Rolapitant 

(N=264) 
Rate (%) 

Control 
(N=262) 

Rate 
(%) 

 

P-Valueb 

Rolapitant 
(N=271) 
Rate (%) 

Control 
(N=273) 

Rate 
(%) 

 

P-Valueb 

Rolapitant 
(N=535) 
Rate (%) 

Control 
(N=535) 

Rate 
(%) 

 

P-Valuec 

Complete Response 

Delayed  72.7 58.4 <0.001 70.1 61.9 0.043 71.4 60.2 <0.001 
Acute 83.7 73.7 0.005 83.4 79.5 N.S. 83.6 76.6 0.004 
Overall  70.1 56.5 0.001 67.5 60.4 N.S. 68.8 58.5 <0.001 

No Emesis 

Acute 86.4 76.0 0.002 85.6 81.7 N.S. 86.0 78.9 0.002 
Delayed  78.0 61.8 <0.001 73.1 65.2 0.046* 75.5 63.6 <0.001 
Overall  75.4 59.2 <0.001 70.8 64.1 N.S. 73.1 61.7 <0.001 

No Significant Nausea 

Acute 86.4 79.4 0.035 90.0 85.7 N.S. 88.2 82.6 0.009 

Delayed 73.5 64.9 0.034 74.5 68.9 N.S. 74.0 66.9 0.011 

Overall 71.6 63.0 0.037 72.7 67.8 N.S. 72.1 65.4 0.017 
a Primary endpoint was complete response in the delayed phase. Delayed phase: >24 to 120 hours post-
cisplatin treatment; Acute phase: 0 to 24 hours post-cisplatin treatment; Overall phase: 0 to 120 hours post-
cisplatin treatment 
b Unadjusted P-values are obtained from Cochran-Mantel Haenszel test, stratified for sex. 
c Unadjusted P-values are obtained from Cochran-Mantel-Haenszel test, stratified by study and sex. 
N.S.=Not significant (p>0.05) 
*Not significant after applying pre-specified multiplicity adjustment. 

 
The estimated time to first emesis in the combined analysis is depicted by the Kaplan-Meier plot in  
Figure 1. 
 

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Figure 1: Kaplan-Meier Plot of Proportions of Patients without Emesis or Use of Rescue Medication 
(Study 1 and Study 2 Combined – HEC) 
 

 
 
Moderately Emetogenic Chemotherapy and Combinations of Anthracycline and Cyclophosphamide 
Chemotherapy 
 
Study 3 (MEC) 
 
In Study 3, a multicentre, randomised, double-blind, parallel group, controlled clinical study in 
moderately emetogenic chemotherapy, the rolapitant regimen (180 mg rolapitant, 2 mg oral 
granisetron and 20 mg oral dexamethasone) was compared with control therapy (placebo, 2 mg oral 
granisetron and 20 mg oral dexamethasone) on Day 1 in patients receiving a moderately emetogenic 
chemotherapy regimen that included 53% of patients receiving a combination of anthracycline and 
cyclophosphamide (AC). On Day 2 to 3, patients received 2 mg once daily of oral granisetron. Study 
medicinal products were administered prior to chemotherapy on Day 1 at the following intervals: 
rolapitant (1 to 2 hours prior); granisetron and dexamethasone (30 minutes prior). At the time the 
study was designed, AC containing chemotherapy regimens were considered to be moderately 
emetogenic. Recent guidance has updated these regimens to highly emetogenic. The percentage of 
patients who received carboplatin in Cycle 1 was 30%. 
 
A total of 1369 patients were randomised to either the rolapitant regimen (N=684) or control therapy 
(N=685). A total of 1332 patients were included in the evaluation of efficacy, 80% were women and 
20% were men. Of these 1332 patients, 28% were greater than 65 years of age and 6% were greater 
than 75 years of age. Of these 1332 patients, 629 received non-AC chemotherapy. 
 
The primary endpoint was complete response (defined as no emetic episodes and no rescue medicinal 
product) in the delayed phase (>24 to 120 hours) of chemotherapy-induced nausea and vomiting. The 
following additional pre-specified endpoints were also evaluated: complete response in the acute phase 
(0 to 24 hours) and overall phase (0 to 120 hours); no emesis in each CINV phase, no significant 
nausea in each CINV phase and time to first emesis or use of rescue medicinal product. 
 
A summary of the study results from the MEC Study (Study 3) is shown in Table 2 below. A summary 
of the results from the non-AC and AC subsets are provided in Table 3. 
 

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0.5

0.6

0.7

0.8

0.9

1.0

Time (Hours) to First Emesis or Use of Rescue Medication

0 24 48 72 96 120

    
      

                  

          

p=<0.001 for the between-group comparison

Control Rolapitant

p<0.001 for the between-group comparison 
 

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Table 2:  Proportion of Patients Receiving Moderately Emetogenic Chemotherapy 
Responding by Treatment Group and Phase 

 
 
Efficacy Endpointsa 

Study 3 – MEC 
Rolapitant 
(N=666) 
Rate (%) 

Control 
(N=666) 
Rate (%) 

 
P-Valueb 

Complete Response    
Delayed  71.3 61.6 <0.001 
Acute 83.5 80.3 N.S. 
Overall 68.6 57.8 <0.001* 
No Emesis    
Acute 87.8 84.5 N.S. 
Delayed  80.5 69.8 <0.001* 
Overall  78.7 65.3 <0.001* 
No Significant Nausea (maximum VAS 
<25 on 0-100 scale) 

   

Acute 82.1 84.7 N.S. 

Delayed 72.7 69.4 N.S. 

Overall 70.6 66.5 N.S. 

a Primary endpoint was complete response in the delayed phase. Acute phase: 0 to 24 hours after 
AC or non-AC regimen; Delayed phase: >24 to 120 hours after AC or non-AC regimen; Overall 
phase: 0 to 120 hours after AC or non-AC regimen 
b Unadjusted P-values are obtained from Cochran-Mantel-Haenszel test, stratified by sex. 
N.S.=Not significant (p>0.05) 
* N.S. after pre-specified multiplicity adjustment. 

 

 
Table 3:   Proportion of Patients Receiving AC or non-AC Chemotherapy Achieving 
Complete Response  
Complete Response Rolapitant Control P-Valuea 
Non-AC N=322 N=307  
  Delayed 76.1 63.8 <0.001 
  Acute 90.7 84.4 0.016 
  Overall 74.8 61.2 <0.001 
AC N=344 N=359  
  Delayed 66.9 59.6 0.047 
  Acute 76.7 76.9 N.S. 
  Overall 62.8 54.9 0.033 
a Unadjusted P-values are obtained from Cochran-Mantel-Haenszel test. 
N.S.=Not significant (p>0.05) 

 
The estimated time to first emesis or use of rescue medicinal product in patients receiving a MEC 
regimen is depicted by the Kaplan-Meier plot in Figure 2. 
 
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Figure 2: Kaplan-Meier Plot of Proportions of Patients without Emesis or Use of Rescue Medication 
(Study 3--MEC) 
 

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0.5

0.6

0.7

0.8

0.9

1.0

Time (Hours) to First Emesis or Use of Rescue Medication

0 24 48 72 96 120

    
      

                 

          

p=<0.001 for the between-group comparison

Control Rolapitant

 
 
The impact of nausea and vomiting on patients’ daily lives was assessed using the Functional Living 
Index-Emesis (FLIE). The proportion of patients with no impact on daily life was higher in the Varuby 
group than in the control group (MEC: 73.2% vs. 67.4%; p=0.027). 
 
Multiple-Cycle Extension: In each study, patients had the option of continuing into a multiple-cycle 
extension for up to 5 additional cycles of chemotherapy receiving the same treatment as assigned in 
cycle 1. At Day 6 to 8 following initiation of chemotherapy, patients were asked to recall whether they 
had any episode of vomiting or retching or nausea that interfered with normal daily life. Antiemetic 
activity of rolapitant was maintained throughout repeat cycles for those patients continuing in each of 
the multiple cycles. 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
rolapitant in all subsets of the paediatric population in prevention of acute and delayed nausea and 
vomiting associated with initial and repeat courses of highly emetogenic cisplatin-based cancer 
therapy and moderately emetogenic cancer therapy (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Rolapitant displays linear PK with exposures increased in a dose-proportional manner. Rolapitant is 
slowly eliminated with a mean terminal half-life of approximately 7 days. Rolapitant is eliminated 
mainly through the hepatobiliary route, with minor contributions from renal elimination. Rolapitant is 
metabolised by CYP3A4 to form a major active metabolite, M19. In vitro studies suggest that 
rolapitant is not an inhibitor of CYP2E1. 
 
Absorption 
 
Following a single dose administration of 180 mg rolapitant under fasting conditions to healthy 
subjects, rolapitant was measurable in plasma between 30 minutes and the peak plasma concentration 
(Cmax) for rolapitant which was reached in about 4 hours and mean Cmax was 968 ng/mL (%CV:28%). 

p<0.001 for the between-group comparison 
 
 

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Following multiple oral doses 9 to 45 mg once daily of rolapitant; accumulation of rolapitant was 
approximately 5-fold. 
 
The systemic exposures (Cmax and AUC) to rolapitant increased in a dose-proportional manner when 
the dose of rolapitant increased from 4.5 mg to 180 mg. With an increase in dose by 4 times from the 
recommended clinical dose of 180 mg, the Cmax and AUC of rolapitant increased by 3.1 fold and 
3.7 fold, respectively. 
 
The absolute bioavailability of rolapitant is approximately 100%, indicating minimal first pass effect. 
 
Concomitant administration of a high fat meal did not significantly affect the pharmacokinetics of 
rolapitant after administration of 180 mg rolapitant. 
 
Distribution 
 
Rolapitant was highly protein bound to human plasma (99.8%). The apparent volume of distribution 
(Vd/F) was 460 L in healthy subjects, indicating an extensive tissue distribution of rolapitant. In a 
population pharmacokinetic analysis of rolapitant, the Vd/F was 387 L in cancer patients. 
 
Biotransformation 
 
Rolapitant is metabolised by CYP3A4 to form a major active metabolite, M19 (C4-pyrrolidine-
hydroxylated rolapitant). In a mass balance study, the metabolite M19 was the major circulating 
metabolite. The formation of M19 was significantly delayed with the median Tmax of 120 hours (range: 
24-168 hours) and the mean half-life of M19 was 158 hours. The exposure ratio of M19 to rolapitant 
was approximately 50% in plasma. 
 
Elimination 
 
Following single oral doses (4.5 to 180 mg) of rolapitant, the mean terminal half-life (t1/2) of rolapitant 
ranged from 169 to 183 hours (approximately 7 days) and was independent of dose. In a population 
pharmacokinetic analysis the apparent total clearance (CL/F) of rolapitant was 0.96 L/hour in cancer 
patients. 
 
Rolapitant is eliminated primarily through the hepatobiliary route. Following administration of a 
single oral 180-mg dose of [14C]-rolapitant, on average 14.2% (range 9% to 20%) and 73% (range 
52% to 89%) of the dose was recovered in the urine and feces, respectively over 6 weeks. In pooled 
samples collected over 2 weeks, 8.3% of the dose was recovered in the urine primarily as metabolites 
and 37.8% of the dose was recovered in the feces primarily as unchanged rolapitant. Unchanged 
rolapitant or M19 were not found in pooled urine sample. Drug metabolising enzymes (and drug 
transporters) other than CYP3A4 involved in rolapitant hepatobiliary elimination remain to be 
elucidated. 
 
Pharmacokinetics in special populations 
 
Age, Sex and Race/Ethnicity 
Population pharmacokinetic analyses indicated that age, sex and race had no significant impact on the 
pharmacokinetics of Varuby. There are limited data in patients aged 75 years and older. 
 
Hepatic Impairment 
Following administration of a single dose of 180 mg rolapitant to patients with mild hepatic 
impairment (Child-Pugh Class A), the pharmacokinetics of rolapitant were comparable with those of 
healthy subjects. In patients with moderate hepatic impairment (Child-Pugh Class B), the mean Cmax 
was 25% lower while mean AUC of rolapitant was similar compared to those of healthy subjects. The 
median Tmax for M19 was delayed to 204 hours in patients with mild or moderate hepatic impairment 

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14 
 

compared to 168 hours in healthy subjects. The pharmacokinetics of Varuby was not studied in 
patients with severe hepatic impairment (Child-Pugh Class C). 
 
Renal Impairment 
In population pharmacokinetic analyses, creatinine clearance (CLcr) at baseline did not show a 
significant effect on rolapitant pharmacokinetics in cancer patients with mild (CLcr: 60 to 90 mL/min) 
or moderate (CLcr: 30 to 60 mL/min) renal impairment compared to cancer patients with normal 
kidney function. Information is insufficient for the effect of severe renal impairment. The 
pharmacokinetics of Varuby was not studied in patients with end-stage renal disease requiring 
haemodialysis. 
 
Relationship between concentration and effect 
 
NK1 Receptor Occupancy 
A human Positron Emission Tomography (PET) study with rolapitant demonstrated that rolapitant 
crosses the blood brain barrier and occupies brain NK1 receptors. A dose-dependent increase in mean 
NK1 receptor occupancy was observed in the dose range from 4.5 mg to 180 mg of rolapitant. At 
rolapitant plasma concentrations of >15 ng/mL and 348 ng/mL, the NK1 receptor occupancies in the 
cortical regions were approximately >50% and 90% respectively. At the 180 mg dose of rolapitant, the 
mean NK1 receptor occupancy in the cortical regions was greater than 90% for at least 120 hours. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, genotoxicity, teratogenic potential, and carcinogenic potential. 
 
The mechanism of the significant difference of half-lives observed between the rat and monkey (6-8 h) 
and human (7 days) is not elucidated. 
 
In rodents, rolapitant was tested in repeated dose oral toxicity studies up to 26 weeks in duration, and 
the liver, thyroid, kidneys, epididymis and uterus were identified as target organs. In a three-month rat 
study, clonic convulsions were observed in a single animal at 125 mg/kg/day (approximately 6 times 
the recommended human dose on a body surface area basis). In the one-month monkey study, 
convulsions were observed at 60 mg/kg/day (approximately 5.8 times the recommended human dose 
on a body surface area basis). The relevance of convulsions for humans is unknown. 
 
In a fertility and early embryonic development study in female rats, rolapitant hydrochloride at an oral 
dose equivalent to 9 mg/kg per day free base (approximately 0.5 times the recommended human dose 
on a body surface area basis) caused a transient decrease in maternal body weight gain and increases 
in the incidence of pre- and post-implantation loss. At a dose equivalent to 4.5 mg/kg per day free base 
(approximately 0.2 times the recommended human dose on a body surface area basis), there were 
decreases in the number of corpora lutea and implantation sites. 
 
In a pre- and post-natal development rat study, maternal toxicity was evident based on 
mortality/moribund condition, decreased body weight and food consumption, total litter loss, 
prolonged parturition, decreased length of gestation, and increased number of unaccounted for 
implantation sites at a dose equivalent to 22.5 mg/kg per day free base (approximately 1.2 times the 
recommended human dose on a body surface area basis). Effects on offspring at this dose included 
decreased postnatal survival, and decreased body weights and body weight gain, and may be related to 
the maternal toxicity observed. At a maternal dose equivalent to 9 mg/kg per day rolapitant free base 
(approximately 0.5 times the recommended human dose on a body surface area basis), there was a 
decrease in memory in female pups in a maze test and a decrease in pup body weight. 
 
Based on the environmental risk assessment, rolapitant is considered as very persistent, 
bioaccumulative and not readily biodegradable. 

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6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet content 
 
Lactose monohydrate 
Pregelatinised starch 
Microcrystalline cellulose (E460) 
Povidone (K-30) 
Croscarmellose sodium 
Colloidal silicon dioxide 
Magnesium stearate 
 
Tablet coating 
 
Polyvinyl alcohol 
Titanium dioxide (E171) 
Macrogol 
Talc 
Indigo carmine (E132) 
Polysorbate 80 
 
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 
 
Polyvinyl chloride/polychlorotrifluoroethylene/aluminium foil twinned blister. 
Pack size of two tablets. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
TESARO Bio Netherlands B.V. 
Joop Geesinkweg 901 
1114 AB Amsterdam-Duivendrecht 
Netherlands 
 
 

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8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1180/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 20 April 2017 
 
 
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. 
 
 

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


17 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURERS 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 

 

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A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Manufacturing Packaging Farmaca (MPF) B.V. 
Appelhof 13  
NL-8465 RX Oudehaske 
Netherlands 
 
Manufacturing Packaging Farmaca (MPF) B.V. 
Neptunus 12  
NL-8448 CN Heerenveen 
Netherlands 
 
TESARO Bio Netherlands B.V. 
Joop Geesinkweg 901 
1114 AB Amsterdam-Duivendrecht 
Netherlands 
 
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. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 
 
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; 
 

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• 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. 

 
 

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20 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

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A. LABELLING 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
Wallet card, each containing 2 film-coated tablets – WITH BLUE BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Varuby 90 mg film-coated tablets 
Rolapitant 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 90 mg of rolapitant. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains lactose. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
2 film-coated tablets 
 
 
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 
 
Single dose = 2 tablets 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 

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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 
 
TESARO Bio Netherlands B.V. 
Joop Geesinkweg 901 
1114 AB Amsterdam-Duivendrecht 
Netherlands  
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1180/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
VARUBY 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Varuby 90 mg tablets 
Rolapitant 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
TESARO Bio Netherlands B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 

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B. PACKAGE LEAFLET 

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Package leaflet: Information for the patient 
 

Varuby 90 mg film-coated tablets 
Rolapitant 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
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 or nurse. 
- 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, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Varuby is and what it is used for 
2. What you need to know before you take Varuby 
3. How to take Varuby 
4. Possible side effects 
5. How to store Varuby 
6. Contents of the pack and other information 
 
 
1. What Varuby is and what it is used for 
 
What Varuby is 
Varuby contains the active substance rolapitant. 
  
What Varuby is used for 
Varuby is used to help prevent adults with cancer feeling sick (nauseous) or being sick (vomiting) 
while having cancer treatment chemotherapy. 
 
How Varuby works 
Chemotherapy can cause the body to release “substance P.” 
Substance P attaches to nerve cells in the brain’s vomiting centre and makes you feel sick or be sick. 
Rolapitant, the active substance in Varuby, blocks substance P from attaching to these nerve cells and 
this helps prevent nausea and vomiting. 
 
 
2. What you need to know before you take Varuby 
 
Do not take Varuby: 
- if you are allergic to rolapitant or any of the other ingredients of this medicine (listed in 

section 6). 
- if you take an herbal medicine called St John’s wort (Hypericum performatum), used to treat 

depression and difficulty sleeping (see section 2 under ‘Other medicines and Varuby’). 
 
If you are not sure, talk to your doctor, pharmacist or nurse before taking this medicine. 
 
Warnings and precautions 
Talk to your doctor, pharmacist or nurse before taking this medicine if: 

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- you have severe liver or kidney problems 
- you need to take certain medicines which may reduce the effectiveness of Varuby, such as: 

- rifampicin, to treat tuberculosis and other infections 
- carbamazepine, to treat epilepsy and nerve pain 
- phenobarbital, to treat epilepsy 
- enzalutamide, to treat prostate cancer 
- phenytoin, to treat epilepsy 
- efavirenz, to treat human immunodeficiency virus (HIV) 
- rifabutin, to treat tuberculosis and other infections 
- other medicines that contain an NK1 antagonist, such as aprepitant and a combination of 

netupitant and palonosetron hydrochloride (for the prevention of nausea and vomiting 
associated with cancer chemotherapy) (see section 2 under ‘Other medicines and Varuby’) 

 
Children and adolescents 
Varuby should not be taken by children and adolescents under 18 years because it has not been studied 
in this group. 
 
Other medicines and Varuby 
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 
medicines. Varuby may affect how some other medicines work. These include: 
- propafenone (used to treat irregular or abnormal heart beat) 
- tamoxifen (used to treat breast cancer) 
- metoprolol (used to treat high blood pressure and heart conditions) 
- thioridazine (used to treat psychiatric conditions like schizophrenia) 
- pimozide (used to treat psychiatric conditions like schizophrenia) 
- morphine (used to treat moderate to severe pain) 
- methotrexate (used to treat cancer, psoriasis, and rheumatoid arthritis) 
- irinotecan (used to treat cancer) 
- topotecan (used to treat cancer) 
- mitoxantrone (used to treat cancer) 
- sulfasalazine (used to treat bowel disease and rheumatoid arthritis) 
- doxorubicin (used in cancer chemotherapy) 
- bendamustine (used in the treatment of leukaemia) 
- digoxin (used to treat heart conditions) 
- dabigatran (used to prevent blood clots) 
- colchicine (used to treat gout) 
- medicines called ‘statins,’ such as atorvastatin, fluvastatin, rosuvastatin and simvastatin, that are 

used in the treatment of high levels of fats (such as cholesterol) in the blood 
- bosentan (used to treat high blood pressure in the pulmonary artery) 
- fexofenadine (used to treat allergy symptoms) 
 
Pregnancy and breast-feeding 
There is no information on the effects of this medicine if taken during pregnancy. If you are pregnant, 
think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking 
this medicine. 
 
It is not known whether Varuby is present in milk; therefore, breast-feeding is not recommended 
during treatment with this medicine. It is important that you tell your doctor if you are breast-feeding 
or are planning to breast-feed before taking this medicine. 
 
Driving and using machines 
Varuby has minor influence on your ability to drive and use machines. You may feel dizzy or tired 
after taking this medicine. If this happens, do not drive or use any tools or machines. 
 

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https://en.wikipedia.org/wiki/Prostate_cancer
https://en.wikipedia.org/wiki/HIV


28 
 

Varuby contains lactose 
Each dose (two tablets) contains 230 mg of lactose. If you have been told by your doctor that you have 
an intolerance to some sugars, contact your doctor before taking this medicinal product. 
 
 
3. How to take Varuby 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor, pharmacist or 
nurse if you are not sure. 
 
How much to take 
- The recommended dose is 180 mg (two 90 mg tablets). Swallow the tablets whole, with some 

water. 
- Take the tablets within 2 hours before you start your chemotherapy cycle. 
- You can take Varuby with or without food. 
 
Taking Varuby before chemotherapy prevents sickness and feelings of sickness. Do not take this 
medicine in the days after you have chemotherapy - unless you are about to have another 
chemotherapy cycle. Do not take Varuby more than once every two weeks. 
 
If you take more Varuby than you should 
The usual dose is two tablets. If you think you may have taken more than you should, tell your doctor 
straight away. 
 
If you forget to take Varuby 
If you have forgotten to take your dose, tell your doctor straight away. 
 
If you stop taking Varuby 
Varuby helps prevent feeling sick and being sick when you have chemotherapy. If you do not want to 
take this medicine, discuss this with your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Tell your doctor, pharmacist or nurse if you notice any of the following side effects: 
 
Serious side effects: 
Rare: may affect up to 1 in 1,000 people 
If you have symptoms of an allergic reaction, such as sudden shortness of breath,  swelling of the lips 
or tongue or change in taste, swelling of skin or tissue or sudden rash or fever, or faster heartbeats, tell 
your doctor or nurse immediately. They will provide appropriate treatment. 
 
Other side effects: 
 
Common: may affect up to 1 in 10 people 
- headache 
- constipation 
- feeling tired 
 
Uncommon: may affect up to 1 in 100 people 
- sore or painful muscles 

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- feeling dizzy, difficulty concentrating, lack of energy, feeling sleepy (somnolence) or trouble 
sleeping (insomnia) 

- stomach problems including stomach discomfort, bloating, nausea, pain, indigestion, and 
diarrhoea 

- low levels of white blood cells which fight infections (shown in blood tests) 
- infection in the mouth 
- mouth sores 
- decreased appetite 
- hiccups 
- weakness 
 
Rare: may affect up to 1 in 1,000 people 
- thrush in the mouth or skin 
- a reduction in number of platelets (shown in blood tests) 
- increased risk of bleeding 
- decrease in white blood cells that fight infections (shown in blood tests) 
- dehydration 
- low levels of magnesium in the blood (shown in blood tests) 
- feelings of worry or fear, restlessness 
- teeth grinding 
- losing your balance 
- difficulty in moving 
- passing out or the feeling of nearly passing out 
- partial loss of hearing 
- ringing in the ears 
- blurry vision 
- heart rate increased 
- stomach discomfort 
- change in bowel habit 
- dry mouth 
- acid reflux or heartburn 
- gagging or sensation of throwing up 
- high blood pressure 
- hair loss 
- skin rash, similar to acne 
- dry skin 
- pain in joint 
- back pain 
- muscle weakness 
- muscle weakness, tenderness or pain and particularly, if at the same time, you feel unwell, have a 

high temperature or have dark urine. They may be caused by an abnormal muscle breakdown (a 
condition called rhabdomyolysis). 

- problems walking 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Varuby 
 
Keep this medicine out of the sight and reach of children. 
 

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30 
 

Do not use this medicine after the expiry date which is stated on the carton and blister after ‘EXP’. 
The expiry date refers to the last day of that month. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Varuby contains 
The active substance is rolapitant. Each tablet contains 90 mg of rolapitant. 
 
The other ingredients are: 
- Tablet core: lactose monohydrate (see section 2 under ‘Varuby contains lactose’), pregelatinised 

starch, microcrystalline cellulose (E460), povidone (K-30), croscarmellose sodium, colloidal 
silicon dioxide and magnesium stearate. 

 
- Film-coat: polyvinyl alcohol, titanium dioxide (E171), macrogol, talc, indigo carmine (E132), and 

polysorbate 80. 
 
What Varuby looks like and contents of the pack 
The tablets are blue, debossed with T0101 on one side and 100 on the other side. 
 
Pack size of two tablets in a polyvinyl chloride/polychlorotrifluoroethylene/aluminium foil twinned 
blister. 
 
Marketing Authorisation Holder 
TESARO Bio Netherlands B.V. 
Joop Geesinkweg 901 
1114 AB Amsterdam-Duivendrecht 
Netherlands 
 
Manufacturers 
Manufacturing Packaging Farmaca (MPF) B.V. 
Appelhof 13 
8465 RX Oudehaske 
Netherlands 
 
Manufacturing Packaging Farmaca (MPF) B.V. 
Neptunus 12 
8448 CN Heerenveen 
Netherlands 
 
TESARO Bio Netherlands B.V. 
Joop Geesinkweg 901 
1114 AB Amsterdam-Duivendrecht 
Netherlands 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
TESARO Bio Netherlands B.V. 

 +32 240 12501 

Lietuva 
TESARO Bio Netherlands B.V. 

 +44 330 3328100 
 

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31 
 

България 
TESARO Bio Netherlands B.V. 

 +44 330 3328100 
 

Luxembourg/Luxemburg 
TESARO Bio Netherlands B.V. 
       +352 278 62096 

Česká republika 
TESARO Bio Netherlands B.V. 
     +44 330 3328100 

Magyarország 
TESARO Bio Netherlands B.V. 

 +44 330 3328100 
 

Danmark 
TESARO Bio Netherlands B.V. 

 +45 787 74077 

Malta 
TESARO Bio Netherlands B.V. 

 +44 330 3328100 
 
Deutschland 
TESARO Bio GERMANY GmbH 

 +49 308 8789661 

 
Nederland 
TESARO Bio Netherlands B.V. 

 +31 207 091042 
 
Eesti 
TESARO Bio Netherlands B.V. 

 +44 330 3328100  

 
Norge 
TESARO Bio Netherlands B.V. 

 +47 219 39680 
 
Ελλάδα 
TESARO Bio Netherlands B.V. 

 +44 330 3328100 

 
Österreich 
TESARO Bio Netherlands B.V. 

 +43 192 86528 
 
España 
TESARO Bio Spain S.L.U 

 +34 911 147439 
 

 
Polska 
TESARO Bio Netherlands B.V. 

 +44 330 3328100 
 

France 
TESARO Bio France SAS 

 +33 176 728915 

Portugal 
TESARO BIO SPAIN S.L.U.,  
SUCURSAL EM PORTUGAL 

 +351 211 143976 
 

Hrvatska 
TESARO Bio Netherlands B.V. 

 +44 330 3328100 
 
Ireland 
TESARO Bio Netherlands B.V. 

 +44 330 3328100 

România 
TESARO Bio Netherlands B.V. 

 +44 330 3328100 
 
Slovenija 
TESARO Bio Netherlands B.V. 

 +44 330 3328100 
 

Ísland 
TESARO Bio Netherlands B.V. 

 +44 330 3328100 

Slovenská republika 
TESARO Bio Netherlands B.V. 
     +44 330 3328100 
 

Italia 
TESARO Bio Italy S.r.l. 

 +39 068 7501295 
 

Suomi/Finland 
TESARO Bio Netherlands B.V. 
     +358 974 790114 
 

Κύπρος 
TESARO Bio Netherlands B.V. 

 +44 330 3328100 

Sverige 
TESARO Bio Sweden AB 

 +46 850 619678 
 

Latvija 
TESARO Bio Netherlands B.V. 

 +44 330 3328100 

United Kingdom 
TESARO Bio Netherlands B.V. 

 +44 330 3328100 

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32 
 

 
This leaflet was last revised in <{MM/YYYY}>. 
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 

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	SUMMARY OF PRODUCT CHARACTERISTICS
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