Verzenios

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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 
 
Verzenios 50 mg film-coated tablets 
Verzenios 100 mg film-coated tablets 
Verzenios 150 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Verzenios 50 mg film-coated tablets 
 
Each film-coated tablet contains 50 mg abemaciclib. 
 
Excipients with known effect 
Each film-coated tablet contains 14 mg of lactose monohydrate. 
 
Verzenios 100 mg film-coated tablets 
 
Each film-coated tablet contains 100 mg abemaciclib. 
 
Excipients with known effect 
Each film-coated tablet contains 28 mg of lactose monohydrate. 
 
Verzenios 150 mg film-coated tablets 
 
Each film-coated tablet contains 150 mg abemaciclib. 
 
Excipients with known effect 
Each film-coated tablet contains 42 mg of lactose monohydrate. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
 
Verzenios 50 mg film-coated tablets 
 
Beige, oval tablet of 5.2 x 9.5 mm, debossed with “Lilly” on one side and “50” on the other. 
 
Verzenios 100 mg film-coated tablets 
 
White, oval tablet of 6.6 x 12.0 mm, debossed with “Lilly” on one side and “100” on the other. 
 
Verzenios 150 mg film-coated tablets 
 
Yellow, oval tablet of 7.5 x 13.7 mm, debossed with “Lilly” on one side and “150” on the other. 
 
 



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4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Verzenios is indicated for the treatment of women with hormone receptor (HR) positive, human 
epidermal growth factor receptor 2 (HER2) negative locally advanced or metastatic breast cancer in 
combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women 
who have received prior endocrine therapy. 
 
In pre- or perimenopausal women, the endocrine therapy should be combined with a luteinising 
hormone-releasing hormone (LHRH) agonist. 
 
4.2 Posology and method of administration 
 
Verzenios therapy should be initiated and supervised by physicians experienced in the use of 
anti-cancer therapies. 
 
Posology 
 
Verzenios in combination with endocrine therapy 
The recommended dose of abemaciclib is 150 mg twice daily when used in combination with 
endocrine therapy.  Please refer to the Summary of Product Characteristics of the endocrine therapy 
combination partner for the recommended posology.  
 
Verzenios should be taken continuously as long as the patient is deriving clinical benefit from therapy 
or until unacceptable toxicity occurs. 
 
If a patient vomits or misses a dose of Verzenios, the patient should be instructed to take the next dose 
at its scheduled time; an additional dose should not be taken. 
 
Dose adjustments 
Management of some adverse reactions may require dose interruption and/or dose reduction as shown 
in Tables 1-6.  
 
Table 1. Dose adjustment recommendations for adverse reactions 
 

 Verzenios dose 
combination therapy 

Recommended dose 150 mg twice daily 
First dose adjustment 100 mg twice daily 
Second dose adjustment  50 mg twice daily 

 



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Table 2. Management recommendations for haematologic toxicities 
 
Complete blood counts should be monitored prior to the start of Verzenios therapy, every two weeks 
for the first two months, monthly for the next two months, and as clinically indicated. Before 
treatment initiation, absolute neutrophil counts (ANC) ≥1500/mm3, platelets ≥100,000/mm3, and 
haemoglobin ≥8 g/dL are recommended.   
 

Toxicitya, b Management recommendations 
Grade 1 or 2 No dose adjustment required. 
Grade 3 Suspend dose until toxicity resolves to Grade 2 or less.  

Dose reduction is not required.  
Grade 3, recurrent; or Grade 4 Suspend dose until toxicity resolves to Grade 2 or less.  

Resume at next lower dose. 
Patient requires administration of 
blood cell growth factors 

Suspend abemaciclib dose for at least 48 hours after the last 
dose of blood cell growth factors was administered and until 

toxicity resolves to Grade 2 or less. 
Resume at next lower dose unless the dose was already reduced 

for the toxicity that led to the use of the growth factor. 
a NCI Common Terminology Criteria for Adverse Events (CTCAE) 
b ANC: Grade 1: ANC < LLN - 1500/mm3; Grade 2: ANC 1000 - <1500/mm3; 
 Grade 3: ANC 500 - <1000/mm3; Grade 4: ANC <500/mm3 
 LLN = lower limit of normal 
 
Table 3. Management recommendations for diarrhoea 
Treatment with antidiarrhoeal agents, such as loperamide, should be started at the first sign of loose 
stools. 
 

Toxicity a Management recommendations 
Grade 1 No dose adjustment required. 
Grade 2 If toxicity does not resolve within 24 hours to Grade 1 or less, 

suspend dose until resolution. 
Dose reduction is not required. 

Grade 2 that persists or recurs 
after resuming the same dose 
despite maximal supportive 
measures 

Suspend dose until toxicity resolves to Grade 1 or less. 
Resume at next lower dose. 

Grade 3 or 4 or requires 
hospitalisation 

a NCI CTCAE 
 



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Table 4. Management recommendations for increased aminotransferases 
 
Alanine aminotransferase (ALT) and aspartate aminostransferase (AST) should be monitored prior to 
the start of Verzenios therapy, every two weeks for the first two months, monthly for the next two 
months, and as clinically indicated. 
 

Toxicitya Management recommendations 
Grade 1 (>ULN-3.0 x ULN) 
Grade 2 (>3.0-5.0 x ULN) No dose adjustment required. 

Persistent or Recurrent Grade 2, 
or Grade 3 (>5.0-20.0 x ULN) 

Suspend dose until toxicity resolves to baseline or Grade 1. 
Resume at next lower dose. 

Elevation in AST and/or ALT >3 
x ULN WITH total bilirubin >2 
x ULN, in the absence of 
cholestasis  

Discontinue abemaciclib. 

Grade 4 (>20.0 x ULN) Discontinue abemaciclib. 
a NCI CTCAE 
ULN = upper limit of normal 
 
Table 5. Management recommendations for interstitial lung disease (ILD)/pneumonitis 
 

Toxicitya Management recommendations 
Grade 1 or 2 No dose adjustment required. 
Persistent or recurrent Grade 2 
toxicity that does not resolve 
with maximal supportive 
measures within 7 days to 
baseline or Grade 1 

Suspend dose until toxicity resolves to baseline or Grade 1. 
Resume at next lower dose. 

Grade 3 or 4  Discontinue abemaciclib. 
a NCI CTCAE 
 
Table 6. Management recommendations for non-haematologic toxicities (excluding diarrhoea, 
increased aminotransferases and interstitial lung disease (ILD)/pneumonitis) 
 

Toxicity a Management recommendations 
Grade 1 or 2 No dose adjustment required. 
Persistent or recurrent Grade 2 
toxicity that does not resolve 
with maximal supportive 
measures to baseline or Grade 1 
within 7 days 

Suspend dose until toxicity resolves to Grade 1 or less. 
Resume at next lower dose. 

 

Grade 3 or 4 
a NCI CTCAE 
 
CYP3A4 inhibitors 
Concomitant use of strong CYP3A4 inhibitors should be avoided. If strong CYP3A4 inhibitors cannot 
be avoided, the abemaciclib dose should be reduced to 100 mg twice daily. 
 
In patients who have had their dose reduced to 100 mg abemaciclib twice daily and in whom 
co-administration of a strong CYP3A4 inhibitor cannot be avoided, the abemaciclib dose should be 
further reduced to 50 mg twice daily. 
 
In patients who have had their dose reduced to 50 mg abemaciclib twice daily and in whom 
co-administration of a strong CYP3A4 inhibitor cannot be avoided, the abemaciclib dose may be 



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continued with close monitoring of signs of toxicity. Alternatively, the abemaciclib dose may be 
reduced to 50 mg once daily or discontinued. 
 
If the CYP3A4 inhibitor is discontinued, the abemaciclib dose should be increased to the dose used 
prior to the initiation of the CYP3A4 inhibitor (after 3 to 5 half-lives of the CYP3A4 inhibitor). 
 
Special populations 
 
Elderly 
No dose adjustment is required based on age (see section 5.2). 
 
Renal impairment 
No dose adjustments are necessary in patients with mild or moderate renal impairment. There are no 
data regarding abemaciclib administration in patients with severe renal impairment, end stage renal 
disease, or in patients on dialysis (see section 5.2). Abemaciclib should be administered with caution 
in patients with severe renal impairment, with close monitoring for signs of toxicity. 
 
Hepatic impairment 
No dose adjustments are necessary in patients with mild (Child Pugh A) or moderate (Child Pugh B) 
hepatic impairment. In patients with severe (Child Pugh C) hepatic impairment, a decrease in dosing 
frequency to once daily is recommended (see section 5.2). 
 
Paediatric population 
The safety and efficacy of abemaciclib in children and adolescents aged less than 18 years has not 
been established.  
No data are available.  
 
Method of administration  
 
Verzenios is for oral use. 
The dose can be taken with or without food. It should not be taken with grapefruit or grapefruit juice 
(see section 4.5). 
Patients should take the doses at approximately the same times every day. 
The tablet should be swallowed whole (patients should not chew, crush, or split tablets before 
swallowing). 
 
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 
 
Neutropenia 
 
Neutropenia was reported in patients receiving abemaciclib. Dose modification is recommended for 
patients who develop Grade 3 or 4 neutropenia (see section 4.2). Fatal events occurred in <1% of 
patients. Patients should be instructed to report any episode of fever to their healthcare provider. 
 
Infections/infestations 
 
Infections were reported in patients receiving abemaciclib plus endocrine therapy at a higher rate than 
in patients treated with placebo plus endocrine therapy. Lung infection was reported in patients 
receiving abemaciclib without concurrent neutropenia. Fatal events occurred in <1% of patients. 
Patients should be monitored for signs and symptoms of infection and treated as medically 
appropriate. 
 



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Venous thromboembolism 
 
Venous thromboembolic events were reported in 5.3% of patients treated with abemaciclib plus 
fulvestrant or aromatase inhibitors, compared to 0.8% of patients treated with placebo plus fulvestrant 
or aromatase inhibitors. Patients should be monitored for signs and symptoms of deep vein thrombosis 
and pulmonary embolism and treated as medically appropriate.  
 
Increased aminotransferases 
 
Increases in ALT and AST were reported in patients receiving abemaciclib. Based on the level of ALT 
or AST elevation, abemaciclib may require dose modification (see section 4.2).  
 
Diarrhoea 
 
Diarrhoea is the most common adverse reaction. Across clinical studies, median time to onset of the 
first diarrhoea event was approximately 6 to 8 days, and median duration of diarrhoea was 9 to 
12 days (Grade 2) and 6 to 8 days (Grade 3). Diarrhoea can be associated with dehydration. Patients 
should start treatment with antidiarrhoeal agents such as loperamide at the first sign of loose stools, 
increase oral fluids and notify their healthcare provider. Dose modification is recommended for 
patients who develop ≥ Grade 2 diarrhoea (see section 4.2).  
 
Interstitial Lung Disease (ILD)/Pneumonitis 
 
Interstitial lung disease (ILD)/pneumonitis was reported in patients receiving abemaciclib. Monitor 
patients for pulmonary symptoms indicative of ILD/pneumonitis and treat as medically appropriate. 
Based on the grade of ILD/pneumonitis, abemaciclib may require dose modification (see section 4.2). 
Permanently discontinue abemaciclib in patients with Grade 3 or 4 ILD/pneumonitis. 
 
Concomitant use of inducers of CYP3A4 
 
Concomitant use of CYP3A4 inducers should be avoided due to the risk of decreased efficacy of 
abemaciclib (see section 4.5). 
 
Visceral crisis 
 
There are no data on the efficacy and safety of abemaciclib in patients with visceral crisis. 
 
Lactose 
 
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-
galactose malabsorption should not take this medicine. 
 
Sodium 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 
“sodium-free”.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Effects of other medicinal products on the pharmacokinetics of abemaciclib  
 
Abemaciclib is primarily metabolised by CYP3A4. 
 
CYP3A4 inhibitors 
Co-administration of abemaciclib with CYP3A4 inhibitors can increase plasma concentrations of 
abemaciclib. In patients with advanced and/or metastatic cancer, co-administration of the CYP3A4 
inhibitor clarithromycin resulted in a 3.4-fold increase in the plasma exposure of abemaciclib and a 



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2.5-fold increase in the combined unbound potency adjusted plasma exposure of abemaciclib and its 
active metabolites. 
 
Use of strong CYP3A4 inhibitors together with abemaciclib should be avoided. If strong CYP3A4 
inhibitors need to be co-administered, the dose of abemaciclib should be reduced (see section 4.2), 
followed by careful monitoring of toxicity. Examples of strong CYP3A4 inhibitors include, but not 
limited to: clarithromycin, itraconazole, ketoconazole, lopinavir/ritonavir, posaconazole or 
voriconazole. Avoid grapefruit or grapefruit juice.  
 
No dose adjustment is necessary for patients treated with moderate or weak CYP3A4 inhibitors. There 
should, however, be close monitoring for signs of toxicity. 
 
CYP3A4 inducers 
Co-administration of abemaciclib with the strong CYP3A4 inducer rifampicin decreased the plasma 
concentration of abemaciclib by 95% and unbound potency adjusted plasma concentration of 
abemaciclib plus its active metabolites by 77% based on AUC0-∞. Concomitant use of strong 
CYP3A4 inducers (including, but not limited to: carbamazepine, phenytoin, rifampicin and St. John’s 
wort) should be avoided due to the risk of decreased efficacy of abemaciclib. 
 
Effects of abemaciclib on the pharmacokinetics of other medicinal products  
 
Medicinal products that are substrates of transporters 
Abemaciclib and its major active metabolites inhibit the renal transporters organic cation transporter 2 
(OCT2), multidrug and extrusion toxin protein (MATE1), and MATE2-K. In vivo interactions of 
abemaciclib with clinically relevant substrates of these transporters, such as dofetilide or creatinine, 
may occur (see section 4.8). In a clinical drug interaction study with metformin (substrate of OCT2, 
MATE1 and 2) co-administered with 400 mg abemaciclib, a small but not clinically relevant increase 
(37%) in metformin plasma exposure was observed. This was found to be due to reduced renal 
secretion with unaffected glomerular filtration. 
 
In healthy subjects, co-administration of abemaciclib and the P-glycoprotein (P-gp) substrate 
loperamide resulted in an increase in loperamide plasma exposure of 9% based on AUC0-∞ and 35% 
based on Cmax. This was not considered to be clinically relevant. However, based on the in vitro 
inhibition of P-gp and breast cancer resistance protein (BCRP) observed with abemaciclib, in vivo 
interactions of abemaciclib with narrow therapeutic index substrates of these transporters, such as 
digoxin or dabigatran etexilate, may occur. 
 
In a clinical study in patients with breast cancer, there was no clinically-relevant pharmacokinetic drug 
interaction between abemaciclib and anastrozole, fulvestrant, exemestane, letrozole or tamoxifen. 
 
It is currently unknown whether abemaciclib may reduce the effectiveness of systemically acting 
hormonal contraceptives. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential/Contraception in females 
 
Women of childbearing potential should use highly effective contraception methods (e.g. 
double-barrier contraception) during treatment and for at least 3 weeks after completing therapy (see 
section 4.5). 
 
Pregnancy 
 
There are no data from the use of abemaciclib in pregnant women. Studies in animals have shown 
reproductive toxicity (see section 5.3). Verzenios is not recommended during pregnancy and in 
women of child-bearing potential not using contraception. 
 



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Breast-feeding 
 
It is unknown whether abemaciclib is excreted in human milk. A risk to newborns/infants cannot be 
excluded. Patients receiving abemaciclib should not breast-feed. 
 
Fertility 
 
The effect of abemaciclib on fertility in humans is unknown. In animal studies, no effects on female 
reproductive organs were observed. However, cytotoxic effects to the male reproductive tract in rats 
and dogs indicate that abemaciclib may impair fertility in males (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Verzenios has minor influence on the ability to drive and use machines. Patients should be advised to 
be cautious when driving or using machines in case they experience fatigue or dizziness during 
treatment with Verzenios (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most commonly occurring adverse reactions are diarrhoea, infections, neutropenia, anaemia, 
fatigue, nausea, vomiting and decreased appetite. 
 
Tabulated list of adverse reactions 
 
In the following table, adverse reactions are listed in order of MedDRA body system organ class and 
frequency. Frequency gradings are: 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), and not known (cannot be 
estimated from the available data). Within each frequency grouping, adverse reactions are presented in 
order of decreasing seriousness. 
 
Table 7. Adverse reactions reported in phase 3 studies of abemaciclib in combination with 
endocrine therapy (N=768) 
 

System organ class 
  Frequency 
    Preferred term 

Abemaciclib plus endocrine therapya 
All Grades 

Toxicity 
(%) 

Grade 3 
Toxicity 

(%) 

Grade 4 
Toxicity  

(%) 
Infections and infestations    
  Very common    
    Infectionsb 43.6 5.2 1.0 
Blood and lymphatic system disorders    
  Very common    
    Neutropenia 45.1 22.9 2.5 
    Leukopenia 25.7 8.5 0.3 
    Anaemia 30.1 7.0 0.1 
    Thrombocytopenia 14.3 2.2 1.0 
  Common    
    Lymphopenia 7.3 3.0 0.1 
Uncommon    

Febrile neutropenia 0.9 0.7 0.1 
Metabolism and nutrition disorders    
  Very common    
    Decreased appetite 26.4 1.3 0 



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Nervous system disorders    
  Very common    
    Dysgeusia 14.3 0 0 

 Dizziness 12.9 0.5 0 
Eye disorders    
  Common    
    Lacrimation increased 6.8 0.1 0 
Vascular disorders    
  Common    
    Venous thromboembolismc 5.3 1.7 0.3 
Respiratory, thoracic and mediastinal disorders 
  Common 
    Interstitial lung disease (ILD)/pneumonitis 

 
 

3.4 

 
 

0.4 

 
 

0.1 
Gastrointestinal disorders    
  Very common    
 Diarrhoea 
 Vomiting 
 Nausea 

84.6 11.7 0 
27.7 1.2 0 
43.5 2.1 0 

Skin and subcutaneous tissue disorders    
  Very common    
    Alopecia 20.7 0 0 
    Pruritus 13.5 0 0 
    Rash 12.9 1.0 0 
  Common    
    Dry skin 9.0 0 0 
Musculoskeletal and connective tissue 
disorders    

  Common    
    Muscular weakness 8.3 0.5 0 
General disorders and administration site 
conditions    

  Very common    
    Fatigue 40.5 2.3 0 

 Pyrexia 10.7 0.1 0 
Investigations    
  Very common    
    Alanine aminotransferase increased 15.1 4.8 0.3 
    Aspartate aminotransferase increased 14.2 2.9 0 

a Abemaciclib in combination with letrozole, anastrozole, or fulvestrant. 
b Infections includes all PTs that are part of the System Organ Class Infections and infestations. 
c Venous thromboembolic events include DVT, pulmonary embolism, cerebral venous sinus thrombosis, 
 subclavian, axillary vein thrombosis,DVT inferior vena cava and pelvic venous thrombosis 
 
Description of selected adverse reactions 
 
Neutropenia 
Neutropenia was reported frequently (45.1%). and a Grade 3 or 4 decrease in neutrophil counts (based 
on laboratory findings) was reported in 28.2% of patients receiving abemaciclib in combination with 
aromatase inhibitors or fulvestrant.  The median time to onset of Grade 3 or 4 neutropenia was 29 to 
33 days, and median time to resolution was 11 to 15 days.  Febrile neutropenia was reported in 0.9% 
patients. Dose modification is recommended for patients who develop Grade 3 or 4 neutropenia (see 
section 4.2).  
 
Diarrhoea 
Diarrhoea was the most commonly reported adverse reaction (see Table 7). Incidence was greatest 
during the first month of abemaciclib treatment and was lower subsequently. The median time to onset 



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of the first diarrhoea event was approximately 6 to 8 days across studies, and the median duration of 
diarrhoea was 9 to 12 days (Grade 2) and 6 to 8 days (Grade 3) across studies. Diarrhoea returned to 
baseline or lesser grade with supportive treatment such as loperamide and/or dose adjustment (see 
section 4.2). 
 
Increased aminotransferases 
In patients receiving abemaciclib in combination with aromatase inhibitors or fulvestrant, ALT and 
AST elevations were reported frequently (15.1% and 14.2%, respectively). Grade 3 or 4 ALT or AST 
elevations (based on laboratory findings) were reported in 6.1% and 4.2% patients. The median time to 
onset of Grade 3 or 4 ALT elevation was 57 to 61 days, and median time to resolution was 14 days. 
The median time to onset of Grade 3 or 4 AST elevation was 71 to 185 days, and median time to 
resolution was 13 to 15 days. Dose modification is recommended for patients who develop Grade 3 or 
4 ALT or AST increase (see section 4.2). 
 
Creatinine 
Although not an adverse reaction, abemaciclib has been shown to increase serum creatinine in 98.3% 
of patients (based on laboratory findings), 1.9% Grade 3 or 4 (based on laboratory findings). In 
patients receiving an aromatase inhibitor or fulvestrant alone, 78.4% reported an increase in serum 
creatinine (all laboratory grades). Abemaciclib has been shown to increase serum creatinine due to 
inhibition of renal tubular secretion transporters without affecting glomerular function (as measured by 
iohexol clearance) (see section 4.5). In clinical studies, increases in serum creatinine occurred within 
the first month of abemaciclib dosing, remained elevated but stable through the treatment period, were 
reversible upon treatment discontinuation, and were not accompanied by changes in markers of renal 
function, such as blood urea nitrogen (BUN), cystatin C, or calculated glomerular filtration rate based 
on cystatin C. 
 
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 
 
In the event of an abemaciclib overdose, fatigue and diarrhoea may occur. General supportive care 
should be provided. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antineoplastic agents, protein kinases inhibitors, ATC code: L01XE50 
 
Mechanism of action 
 
Abemaciclib is a potent and selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and 
CDK6), and most active against Cyclin D1/CDK4 in enzymatic assays. Abemaciclib prevents 
retinoblastoma protein (Rb) phosphorylation, blocking cell cycle progression from the G1 to the 
S-phase of cell division, leading to suppression of tumour growth. In oestrogen receptor-positive 
breast cancer cell lines, sustained target inhibition with abemaciclib prevented rebound of Rb 
phosphorylation resulting in cell senescence and apoptosis. In vitro, Rb-negative and Rb-depleted 
cancer cell lines are generally less sensitive to abemaciclib. In breast cancer xenograft models, 
abemaciclib dosed daily without interruption at clinically relevant concentrations alone or in 
combination with anti-oestrogens resulted in reduction of tumour size. 
 

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Pharmacodynamic effects 
 
In cancer patients, abemaciclib inhibits CDK4 and CDK6 as indicated by inhibition of 
phosphorylation of Rb and topoisomerase II alpha, which results in cell cycle inhibition upstream of 
the G1 restriction point. 
 
Cardiac electrophysiology 
 
The effect of abemaciclib on the QTcF interval was evaluated in 144 patients with advanced cancer. 
No large change (that is, >20 ms) in the QTcF interval was detected at the mean observed maximal 
steady state abemaciclib concentration following a therapeutic dosing schedule. 
In an exposure-response analysis in healthy subjects at exposures comparable to a 200 mg twice-daily 
dose, abemaciclib did not prolong the QTcF interval to any clinically relevant extent. 
 
Clinical efficacy and safety 
 
Randomised Phase 3 Study MONARCH 3: Verzenios in combination with aromatase inhibitors 
 
The efficacy and safety of Verzenios in combination with an aromatase inhibitor (anastrozole or 
letrozole) was evaluated in MONARCH 3, a randomised, double-blind, placebo-controlled phase 3 
study in women with HR positive, HER2 negative locally advanced or metastatic breast cancer who 
had not received prior systemic therapy in this disease setting. Patients were randomised in a 2:1 ratio 
to receive Verzenios 150 mg twice daily plus a non-steroidal aromatase inhibitor given daily at the 
recommended dose versus placebo plus a non-steroidal aromatase inhibitor according to the same 
schedule. The primary endpoint was investigator-assessed progression-free survival (PFS) evaluated 
according to RECIST 1.1; key secondary efficacy endpoints included objective response rate (ORR), 
clinical benefit rate (CBR) and overall survival (OS). 
 
The median age of patients enrolled was 63 years (range 32-88). Approximately 39% of patients had 
received chemotherapy and 44% had received antihormonal therapy in the (neo)adjuvant setting. 
Patients with prior (neo)adjuvant endocrine therapy must have completed this therapy at least 
12 months before study randomisation. The majority of patients (96%) had metastatic disease at 
baseline. Approximately 22% of patients had bone-only disease, and 53% patients had visceral 
metastases.  
 
The study met its primary endpoint of improving PFS. Primary efficacy results are summarised in 
Table 8 and Figure 1. 
 



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Table 8. MONARCH 3: Summary of efficacy data (Investigator assessment, intent-to-treat 
population) 
 

 Verzenios plus aromatase inhibitor 
Placebo plus aromatase 

inhibitor 
Progression-free survival N=328 N=165 
Investigator assessment, number of events 
(%) 

138 (42.1) 108 (65.5) 

Median [months] (95% CI) 28.18 (23.51, NR) 14.76 (11.24, 19.20) 
Hazard ratio (95% CI) and p-value 0.540 (0.418, 0.698), p=0.000002 

Independent radiographic review, 
number of events (%) 

91 (27.7) 73 (44.2) 

Median [months] (95% CI) NR (NR, NR) 19.36 (16.37, 27.91) 
Hazard ratio (95% CI) and p-value 0.465 (0.339, 0.636); p < 0.000001 

Objective response rateb [%] (95% CI) 49.7 (44.3, 55.1) 37.0 (29.6, 44.3) 
Duration of response [months] (95% CI) 27.39 (25.74, NR) 17.46 (11.21, 22.19) 
Objective response for patients with 
measurable diseasea 

 
N=267 

 
N=132 

Objective response rateb [%] (95% CI) 61.0 (55.2, 66.9) 45.5 (37.0, 53.9) 
Complete response, (%) 3.4 0 
Partial response, (%) 57.7 45.5 

Clinical benefit ratec (measurable disease) 
[%] (95% CI) 

79.0 (74.1, 83.9) 69.7 (61.9, 77.5) 

a Measurable disease defined per RECIST version 1.1 
b Complete response + partial response 
c Complete response + partial response + stable disease for ≥ 6 months 
N=number of patients; CI=confidence interval; NR=not reached. 
 



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Figure 1. MONARCH 3: Kaplan-Meier plot of progression-free survival (Investigator 
assessment, intent-to-treat population) 

 
 
Progression-free survival (PFS) was significantly prolonged in the Verzenios plus aromatase inhibitor 
(AI) arm, (Hazard Ratio [HR] of 0.540 [95% CI, 0.418 to 0.698]); median PFS was 28.18 months in 
the Verzenios plus AI arm and was 14.76 months in the placebo plus AI arm. These results correspond 
to a clinically meaningful reduction in the risk of disease progression or death of 46% for patients 
treated with abemaciclib plus an aromatase inhibitor. 
 
Overall survival was not mature at the final PFS analysis (93 events observed across the two arms). 
The HR was 1.057 (95% CI: 0.683, 1.633), p=0.8017. 
 
A series of prespecified subgroup PFS analyses showed consistent results across patient subgroups 
including age (<65 or ≥65 years), disease site, disease setting (de novo metastatic vs recurrent 
metastatic vs locally advanced recurrent), presence of measurable disease, progesterone receptor 
status, and baseline ECOG performance status. A reduction in the risk of disease progression or death 
was observed in patients with visceral disease, (HR of 0.567 [95% CI: 0.407, 0.789]), median PFS 
21.6 months versus 14.0 months; in patients with bone-only disease (HR 0.565, [95% CI: 0.306, 
1.044]); and in patients with measurable disease (HR 0.517, [95% CI: 0.392, 0.681]). 
 
Randomised Phase 3 Study MONARCH 2: Verzenios in combination with fulvestrant 
 
The efficacy and safety of Verzenios in combination with fulvestrant was evaluated in MONARCH 2, 
a randomised, double-blind, placebo-controlled phase 3 study in women with HR positive, HER2 
negative locally advanced or metastatic breast cancer. Patients were randomised in a 2:1 ratio to 
receive Verzenios 150 mg twice daily plus fulvestrant 500 mg at intervals of one month, with an 
additional 500 mg dose given two weeks after the initial dose, versus placebo plus fulvestrant 



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according to the same schedule. The primary endpoint was investigator-assessed PFS evaluated 
according to RECIST 1.1; key secondary efficacy endpoints included objective response rate (ORR), 
clinical benefit rate (CBR) and overall survival (OS). 
 
The median age of patients enrolled was 60 years (range, 32-91 years). In each treatment arm the 
majority of patients were white, and had not received chemotherapy for metastatic disease. 17% of 
patients were pre/perimenopausal on ovarian suppression with a GnRH agonist. Approximately 56% 
patients had visceral metastases. Approximately 25% of patients had primary endocrine resistance 
(progression on endocrine therapy within the first 2 years of adjuvant endocrine therapy or within the 
first 6 months of first line endocrine therapy for metastatic breast cancer) and for the majority, 
endocrine resistance developed later. 59% of patients had most recent endocrine therapy in the 
(neo)adjuvant setting, and 38% in metastatic setting. 
 
The study met its primary endpoint of improving PFS. Primary efficacy results are summarised in 
Table 9 and Figure 2. 
 
Table 9. MONARCH 2: Summary of efficacy data (Investigator assessment, intent-to-treat 
population) 
 

 Verzenios plus fulvestrant 
Placebo plus 
fulvestrant 

Progression-free survival N=446 N=223 
Investigator assessment, number of events 
(%) 

222 (49.8) 157 (70.4) 

Median [months] (95% CI) 16.4 (14.4, 19.3) 9.3 (7.4, 12.7) 
Hazard ratio (95% CI) and p-value 0.553 (0.449, 0.681), p=0.0000001 

Independent radiographic review, 
number of events (%) 

164 (36.8) 124 (55.6) 

Median [months] (95% CI) 22.4 (18.3, NR ) 10.2 (5.8, 14.0) 
Hazard ratio (95% CI) and p-value 0.460 (0.363, 0.584);  p <.000001 

Objective response rateb [%] (95% CI) 35.2 (30.8, 39.6) 16.1 (11.3, 21.0) 
Duration of response [months] (95%CI) NR (18.05, NR) 25.6 (11.9, 25.6) 
Objective response for patients with 
measurable diseasea 

 
N=318 

 
N=164 

Objective response rateb [%] (95% CI) 48.1 (42.6, 53.6) 21.3 (15.1, 27.6) 
Complete response, (%) 3.5 0 
Partial response, (%) 44.7 21.3 

Clinical benefit ratec (measurable disease) 
[%] (95% CI) 

73.3 (68.4, 78.1) 51.8 (44.2, 59.5) 

a Measurable disease defined per RECIST version 1.1 
b Complete response + partial response 
c Complete response + partial response + stable disease for ≥ 6 months 
N=number of patients; CI=confidence interval; NR=not reached. 
 



16 

Figure 2. MONARCH 2: Kaplan-Meier plot of progression-free survival (Investigator 
assessment, intent-to-treat population) 
 

 
 
Median PFS was significantly prolonged in the Verzenios plus fulvestrant arm (HR of 0.553 [95% CI 
0.449, 0.681]); median PFS was 16.4 months versus 9.3 months in the placebo plus fulvestrant arm. 
These results correspond to a clinically meaningful reduction in the risk of disease progression or 
death of 44.7% and a 7.2 month improvement in median PFS for patients treated with Verzenios plus 
fulvestrant. Verzenios plus fulvestrant prolonged progression-free survival with neither a clinically 
meaningful or significant detriment to health-related quality of life. 
 
A series of prespecified subgroup PFS analyses showed consistent results across patient subgroups 
including age (<65 or ≥65 years), race, geographic region, disease site, endocrine therapy resistance, 
presence of measurable disease, progesterone receptor status, and menopausal status. A reduction in 
the risk of disease progression or death was observed in patients with visceral disease, (HR of 0.481 
[95% CI: 0.369, 0.627]), median PFS 14.7 months versus 6.5 months; in patients with bone-only 
disease (HR of 0.543 [95% CI: 0.355, 0.833]); patients with measurable disease (HR of 0.523 [95% 
CI: 0.412, 0.644]). In patients who were pre/perimenopausal, the hazard ratio was 0.415 (95% CI: 
0.246, 0.698); in patients who were progesterone receptor negative, the HR was 0.509 (95% CI: 0.325, 
0.797). 
 
In a sub-population with locally advanced or metastatic disease that had not received prior endocrine 
therapy, the PFS was also consistent. 
 
Overall survival (OS) analysis in the ITT population showed a statistically significant improvement in 
patients receiving Verzenios plus fulvestrant compared with those receiving placebo plus fulvestrant. 
The overall survival results are summarized in Table 10 and Figure 3. 



17 

 
Table 10. MONARCH 2: Summary of overall survival data (Intent-to-treat population) 
 

 Verzenios plus fulvestrant 
Placebo plus 
fulvestrant 

Overall survival N = 446 N = 223 
   Number of events (n, %) 211 (47.3) 127 (57.0) 

Median OS [months] (95 % CI) 46.7 (39.2, 52.2) 37.3 (34.4, 43.2) 
Hazard ratio (95 % CI) 0.757 (0.606, 0.945) 

   p-value  0.0137 
N = number of patients; CI = confidence interval; OS = overall survival 
 
Figure 3. MONARCH 2: Kaplan-Meier plot of overall survival (Intent-to-treat population) 
 

 
 
Analyses for OS by stratification factors showed OS HR of 0.675 (95 % CI: 0.511, 0.891) in patients 
with visceral disease, and 0.686 (95 % CI: 0.451, 1.043) in patients with primary endocrine resistance. 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Verzenios in all subsets of the paediatric population in breast cancer (see section 4.2 for information 
on paediatric use). 
 



18 

5.2 Pharmacokinetic properties 
 
Absorption 
 
Abemaciclib absorption is slow, with a Tmax of 8 hours and a mean absolute bioavailability of 
approximately 45 %. In the therapeutic dose range of 50-200 mg, the increase in plasma exposure 
(AUC) and Cmax is approximately dose proportional. Steady state was achieved within 5 days 
following repeated twice daily dosing, and abemaciclib accumulated with a geometric mean 
accumulation ratio of 3.7 (58% CV) and 5.8 (65% CV) based on Cmax and AUC, respectively. A 
high-fat meal increased combined AUC of abemaciclib and its active metabolites by 9% and increased 
Cmax by 26%. These changes were not considered to be clinically relevant. Therefore, abemaciclib can 
be taken with or without food. 
 
Distribution 
 
Abemaciclib is highly bound to plasma proteins in humans (mean bound fraction approximately 96% 
to 98%). The geometric mean systemic volume of distribution is approximately 750 L (69% CV), 
indicating distribution of abemaciclib into tissues. 
 
Concentrations of abemaciclib and its active metabolites in cerebrospinal fluid are comparable to 
unbound plasma concentrations.  
 
Biotransformation 
 
Hepatic metabolism is the main route of clearance for abemaciclib. Abemaciclib is metabolised to 
several metabolites primarily by cytochrome P450 (CYP) 3A4. The primary biotransformation is 
hydroxylation to a metabolite that circulates with an AUC that is 77% of parent drug. In addition, N-
desethyl and N-desethylhydroxy metabolites circulate at AUCs that are 39% and 15% of parent drug. 
These circulating metabolites are active with similar potency to abemaciclib. 
 
Elimination 
 
The geometric mean hepatic clearance (CL) of abemaciclib was 21.8 L/h (39.8% CV), and the mean 
plasma elimination half-life for abemaciclib in patients was 24.8 hours (52.1% CV). After a single oral 
dose of [14C] -abemaciclib, approximately 81% of the dose was excreted in faeces and 3.4% excreted 
in urine. The majority of the dose eliminated in faeces was metabolites.  
 
Special populations 
 
Age, gender, and body weight 
Age, gender, and body weight had no effect on the exposure of abemaciclib in a population 
pharmacokinetic analysis in patients with cancer (135 males and 859 females; age range 24-91 years; 
and body weight range 36-175 kg). 
 
Hepatic impairment 
Abemaciclib is metabolised in the liver. Mild (Child Pugh A) and moderate (Child Pugh B) hepatic 
impairment had no effect on the exposure of abemaciclib. In subjects with severe hepatic impairment 
(Child Pugh C), the AUC0-∞ of abemaciclib and potency adjusted unbound abemaciclib plus its active 
metabolites increased 2.1-fold and 2.4-fold, respectively. The half-life of abemaciclib increased from 
24 to 55 hours (see section 4.2).  
 
Renal impairment 
Renal clearance of abemaciclib and its metabolites is minor. Mild and moderate renal impairment had 
no effect on the exposure of abemaciclib. There are no data in patients with severe renal impairment, 
end stage renal disease or in patients on dialysis. 
 



19 

5.3 Preclinical safety data 
 
The primary target organ findings of potential relevance to humans included gastrointestinal and 
haematolymphopoietic organ effects in rats and dogs in studies up to 13 weeks duration. Effects in 
lung and skeletal muscle occurred only in rats at exposure levels approximately 2-fold higher than 
human exposure levels and effects in kidney occurred only in rats at exposure levels approximately 6-
fold higher than human exposure levels. Complete or partial recovery was observed for all target 
organs at the end of the 28-day recovery period. 
 
Genotoxicity 
 
Abemaciclib was not mutagenic in a bacterial reverse mutation (Ames) assay, was not clastogenic in 
an in vitro chromosomal aberration assay in human peripheral blood lymphocytes, and was not 
clastogenic in an in vivo rat bone marrow micronucleus assay. 
 
Carcinogenicity 
 
Specific animal studies to test abemaciclib for carcinogenic potential have not been performed. 
 
Developmental toxicity 
 
Abemaciclib was teratogenic and caused decreased foetal weight at maternal exposures similar to the 
recommended human dose. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
 
croscarmellose sodium  
lactose monohydrate 
microcrystalline cellulose 
colloidal hydrated silica 
sodium stearyl fumarate 
 
Film coating 
 
Verzenios 50 mg film-coated tablets 
polyvinyl alcohol (E1203) 
titanium dioxide (E171) 
macrogol (E1521) 
talc (E553b) 
iron oxide yellow (E172)  
iron oxide red (E172) 
 
Verzenios 100 mg film-coated tablets 
polyvinyl alcohol (E1203) 
titanium dioxide (E171) 
macrogol (E1521) 
talc (E553b) 
 
Verzenios 150 mg film-coated tablets 
polyvinyl alcohol (E1203) 
titanium dioxide (E171) 
macrogol (E1521) 



20 

talc (E553b) 
iron oxide yellow (E172) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
PCTFE/PE/PVC blisters sealed with an aluminium foil in a calendar blister card, in packs of 14, 28, 
42, 56, 70 or 168 film-coated tablets. 
 
Aluminium/aluminium perforated unit dose blisters of 28 x 1 film-coated tablets. 
 
Not all pack sizes may be marketed. 
 
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 
 
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528BJ Utrecht, The Netherlands. 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1307/001 
EU/1/18/1307/002 
EU/1/18/1307/003 
EU/1/18/1307/004 
EU/1/18/1307/005 
EU/1/18/1307/006 
EU/1/18/1307/007 
EU/1/18/1307/008 
EU/1/18/1307/009 
EU/1/18/1307/010 
EU/1/18/1307/011 
EU/1/18/1307/012 
EU/1/18/1307/013 
EU/1/18/1307/014 
EU/1/18/1307/015 
EU/1/18/1307/016 
EU/1/18/1307/017 
EU/1/18/1307/018 
EU/1/18/1307/019 
EU/1/18/1307/020 



21 

EU/1/18/1307/021 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation:  27 September 2018 
 
 
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/


22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
 



23 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturer(s) responsible for batch release 
 
Lilly, S.A. 
Avda. de la Industria, 30 
28108 Alcobendas, Madrid 
Spain 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 

• Periodic safety update reports (PSURs)  
 

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

• Risk management plan (RMP) 
 

The marketing authorization holder (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.  

  



24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



25 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
A. LABELLING 

  



26 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR 50 MG FILM-COATED TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Verzenios 50 mg film-coated tablets 
abemaciclib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 50 mg abemaciclib. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: lactose. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
14 film-coated tablets 
168 film-coated tablets 
28 x 1 film-coated tablets 
28 film-coated tablets 
56 film-coated tablets 
42 film-coated tablets 
70 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 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



27 

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

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528BJ Utrecht, The Netherlands. 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1307/001 (14 film-coated tablets) 
EU/1/18/1307/002 (168 film-coated tablets) 
EU/1/18/1307/003 (28 x 1 film-coated tablets) 
EU/1/18/1307/010 (28 film-coated tablets) 
EU/1/18/1307/011 (56 film-coated tablets) 
EU/1/18/1307/016 (42 film-coated tablets) 
EU/1/18/1307/017 (70 film-coated tablets) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Verzenios 50 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE  
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA  
 
PC 
SN 
NN 
  



28 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR 100 MG FILM-COATED TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Verzenios 100 mg film-coated tablets 
abemaciclib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 100 mg abemaciclib. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: lactose. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
14 film-coated tablets 
168 film-coated tablets 
28 x 1 film-coated tablets 
28 film-coated tablets 
56 film-coated tablets 
42 film-coated tablets) 
70 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 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



29 

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

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528BJ Utrecht, The Netherlands. 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1307/004 (14 film-coated tablets) 
EU/1/18/1307/005 (168 film-coated tablets) 
EU/1/18/1307/006 (28 x 1 film-coated tablets) 
EU/1/18/1307/012 (28 film-coated tablets) 
EU/1/18/1307/013 (56 film-coated tablets) 
EU/1/18/1307/018 (42 film-coated tablets) 
EU/1/18/1307/019 (70 film-coated tablets) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Verzenios 100 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE  
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA  
 
PC 
SN 
NN 



30 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR 150 MG FILM-COATED TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Verzenios 150 mg film-coated tablets 
abemaciclib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 150 mg abemaciclib. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: lactose. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
14 film-coated tablets 
168 film-coated tablets 
28 x 1 film-coated tablets 
28 film-coated tablets 
56 film-coated tablets 
42 film-coated tablets 
70 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 
 
 
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 medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528BJ Utrecht, The Netherlands. 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1307/007 (14 film-coated tablets) 
EU/1/18/1307/008 (168 film-coated tablets) 
EU/1/18/1307/009 (28 x 1 film-coated tablets) 
EU/1/18/1307/014 (28 film-coated tablets) 
EU/1/18/1307/015 (56 film-coated tablets) 
EU/1/18/1307/020 (42 film-coated tablets) 
EU/1/18/1307/021 (70 film-coated tablets) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Verzenios 150 mg 
 
 
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 BLISTERS OR STRIPS  
 
CALENDAR BLISTER CARD FOR 50 MG FILM-COATED TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Verzenios 50 mg tablets 
abemaciclib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Lilly 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Mon. 
Tue. 
Wed. 
Thu. 
Fri. 
Sat. 
Sun. 
 
Morning 
Evening 
 
Keep the blister card intact 
  



33 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER TO BE USED INSIDE THE CALENDAR BLISTER CARD FOR 50 MG FILM-
COATED TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Verzenios 50 mg 
abemaciclib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Lilly 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
  



34 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS  
 
CALENDAR BLISTER CARD FOR 100 MG FILM-COATED TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Verzenios 100 mg tablets 
abemaciclib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Lilly 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Mon. 
Tue. 
Wed. 
Thu. 
Fri. 
Sat. 
Sun.  
 
Morning 
Evening 
 
Keep the blister card intact 
 
  



35 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER TO BE USED INSIDE THE CALENDAR BLISTER CARD FOR 100 MG FILM-
COATED TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Verzenios 100 mg 
abemaciclib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Lilly 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
  



36 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS  
 
CALENDAR BLISTER CARD FOR 150 MG FILM-COATED TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Verzenios 150 mg tablets 
abemaciclib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Lilly 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Mon. 
Tue. 
Wed. 
Thu. 
Fri. 
Sat. 
Sun.  
 
Morning 
Evening 
 
Keep the blister card intact 
 
  



37 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER TO BE USED INSIDE THE CALENDAR BLISTER CARD FOR 150 MG FILM-
COATED TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Verzenios 150 mg 
abemaciclib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Lilly 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
  



38 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
PERFORATED UNIT DOSE BLISTER FOR 50 MG FILM-COATED TABLETS  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Verzenios 50 mg tablets 
abemaciclib  
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Lilly 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
  



39 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
PERFORATED UNIT DOSE BLISTER FOR 100 MG FILM-COATED TABLETS  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Verzenios 100 mg tablets 
abemaciclib  
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Lilly 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



40 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
PERFORATED UNIT DOSE BLISTER FOR 150 MG FILM-COATED TABLETS  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Verzenios 150 mg tablets 
abemaciclib  
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Lilly 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
  



41 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
B. PACKAGE LEAFLET 

  



42 

Package leaflet: Information for the patient 
 

Verzenios 50 mg film-coated tablets 
Verzenios 100 mg film-coated tablets 
Verzenios 150 mg film-coated tablets 

abemaciclib 
 

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, 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 Verzenios is and what it is used for  
2. What you need to know before you take Verzenios  
3. How to take Verzenios  
4. Possible side effects  
5. How to store Verzenios  
6. Contents of the pack and other information 
 
 
1. What Verzenios is and what it is used for 
 
Verzenios is a cancer medicine containing the active substance abemaciclib. 
 
Abemaciclib blocks the effects of proteins called cyclin-dependent kinase 4 and 6. These proteins are 
abnormally active in some cancer cells and make them grow out of control. Blocking the action of 
these proteins can slow down growth of cancer cells, shrink the tumour and delay progression of the 
cancer.  
 
Verzenios is used to treat women with certain types of breast cancer (hormone receptor-positive 
(HR+), human epidermal growth factor receptor 2-negative (HER2-)) which have spread beyond the 
original tumour and/or to other organs. It is given together with hormonal therapies, such as aromatase 
inhibitors or fulvestrant. 
 
 
2. What you need to know before you take Verzenios  
 
Do not take Verzenios: 
- if you are allergic to abemaciclib or any of the other ingredients of this medicine (listed in 

section 6). 
 
Warnings and precautions 
Verzenios may: 
- reduce the number of your white blood cells, and you may be at greater risk of getting an 

infection. Serious infections such as lung infections can be life-threatening; 
- cause blood clots in the veins; 
- cause severe or life-threatening inflammation of the lungs; 



43 

- affect the way your liver works; 
- cause diarrhoea. At the first sign of diarrhoea, start treatment with antidiarrhoeal agents, such as 

loperamide. Drink plenty of fluids. 
 
See section 4 “Possible side effects”, and talk to your doctor if you have any symptoms.  
 
What your doctor will check before and during your treatment 
You will have regular blood tests before and during treatment to check whether Verzenios affects your 
blood (white blood cells, red blood cells, platelets) or the concentration in your blood of enzymes from 
your liver.  
 
Children and adolescents 
Verzenios is not to be used in children and adolescents under 18 years of age. 
 
Other medicines and Verzenios 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
 
In particular, tell you doctor or pharmacist before taking Verzenios if you are taking the following: 
• medicines that may increase the concentration of Verzenios in the blood: 

o Clarithromycin (antibiotic used to treat bacterial infections) 
o Itraconazole, ketoconazole, posaconazole, voriconazole (used to treat fungal 

infections) 
o Lopinavir/ritonavir (used to treat HIV/AIDS) 
o Digoxin (used to treat heart disorders)  
o Dabigatran etexilate (used to reduce the risk of stroke and blood clots) 

• medicines that may reduce the effectiveness of Verzenios: 
o Carbamazepine (anti-epileptic used to treat seizures or fits) 
o Rifampicin, used to treat tuberculosis (TB) 
o Phenytoin (used to treat seizures) 
o St. John’s wort (a herbal product used to treat mild depression and anxiety) 

 
Verzenios with food and drink 
Avoid grapefruit or grapefruit juice while you are taking the medicine as they may increase the 
concentration of Verzenios in the blood. 
 
Pregnancy, breast-feeding and fertility 
Discuss contraception with your doctor if there is any possibility that you may become pregnant. If 
you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or 
pharmacist for advice before taking this medicine. 
 
Pregnancy 
You should not use Verzenios if you are pregnant. 
 
You should avoid becoming pregnant while taking Verzenios.  
 
If you are able to have children, you should use adequate contraceptive methods (e.g., double –barrier 
contraception such as condom and diaphragm) during therapy and for at least 3 weeks after 
completing therapy.  
 
You must tell your doctor if you become pregnant. 
 
Breast-feeding 
You should not breast-feed while taking Verzenios. It is not known if Verzenios passes into breast 
milk. 
 



44 

Driving and using machines 
Tiredness and dizziness are very common side effects. If you feel unusually tired or dizzy, take special 
care when driving or using machines. 
 
Verzenios contains lactose 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicine. 
 
Verzenios contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-
free’. 
 
 
3. How to take Verzenios 
 
Recommended dose 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.  
 
When given together with an aromatase inhibitor or fulvestrant to treat your breast cancer, the 
recommended dose of Verzenios is 150 mg taken by mouth twice daily. 
 
If you get certain side effects while you are taking Verzenios your doctor may lower your dose or stop 
treatment temporarily or permanently.  
 
When and how to take Verzenios 
Take Verzenios twice daily, at about the same time every day, preferably in the morning and evening, 
so there is enough medicine in your body all the time. 
 
You can take the tablets either with or without food, just avoid grapefruit and grapefruit juice (see 
section 2 “Verzenios with food and drink”). 
 
Swallow the tablet whole with a glass of water. Do not chew, crush or split the tablets before 
swallowing. 
 
How long to take Verzenios 
Take Verzenios continuously for as long as your doctor tells you to. 
 
If you take more Verzenios than you should 
If you take too many tablets, or if someone else takes your medicine, contact a doctor or hospital for 
advice. Show the Verzenios carton and this leaflet. Medical treatment may be necessary. 
 
If you miss a dose of Verzenios 
If you vomit after taking the dose or forget a dose, take your next dose at your usual time. Do not take 
a double dose to make up for the forgotten or vomited dose. 
 
If you stop taking Verzenios 
Do not stop taking Verzenios unless your doctor tells you to. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 



45 

4. Possible side effects 
 
Like all medicines, this medicine can cause side-effects, although not everybody gets them. Contact 
your doctor immediately for any of the following: 

- Symptoms such as chills or fever. These could be a sign of low white blood cell counts (which 
may affect more than 1 in 10 people) and should be treated immediately. If you have cough, 
fever and difficulty breathing or chest pain, this could be a sign of lung infection.  Serious or 
life-threatening infections are uncommon (may affect up to 1 in 100 people). 

- Painful swollen leg, chest pain, shortness of breath, rapid breathing or rapid heart rate as these 
can be signs of blood clots in the vein (which may affect up to 1 in 10 people). 

- Diarrhoea (which may affect more than 1 in 10 people).  
 
Refer to Section 2 for more information on any of the possible effects listed above. 
 
Other side effects with Verzenios may include: 
Very common side effects (may affect more than 1 in 10 people) 

• Infections 
• Reduction in white blood cells, red blood cells, and blood platelets   
• Nausea (feeling sick), vomiting  
• Decreased appetite  
• Alteration in sense of taste  
• Hair loss 
• Tiredness 
• Dizziness  
• Itching 
• Rash 
• Abnormalities in liver blood tests  

 
Common side effects (may affect up to 1 in 10 people) 

• Watering eyes  
• Muscular weakness 
• Dry skin  
• Inflammation of the lungs which causes breathlessness, cough and raised temperature 

 
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 Verzenios 
 
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. 
 
Do not use this medicine if you notice that the pack is damaged or shows signs of tampering. 
 
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. 
 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


46 

6. Contents of the pack and other information 
 
What Verzenios contains  
- The active substance is abemaciclib. Verzenios film-coated tablets come in different strengths: 

• Verzenios 50 mg film-coated tablet: each tablet contains 50 mg abemaciclib. 
• Verzenios 100 mg film-coated tablet: each tablet contains 100 mg abemaciclib.  
• Verzenios 150 mg film-coated tablet: each tablet contains 150 mg abemaciclib.  

 
- The other ingredients in this medicine are: 

• Tablet core: colloidal hydrated silica, croscarmellose sodium, lactose monohydrate, 
microcrystalline cellulose, sodium stearyl fumarate. 

• Film-coating: titanium dioxide (E171), talc (E553b), polyvinyl alcohol (E1203), 
macrogol 3350 (E1521), iron oxide yellow (E172) [50 mg and 150 mg tablets only], 
iron oxide red (E172) [50 mg tablets only]. 

 
What Verzenios looks like and contents of the pack 
 
- Verzenios 50 mg film-coated tablets are beige, oval tablets debossed with “Lilly” on one side 

and “50” on the other. 
- Verzenios 100 mg film-coated tablets are white, oval tablets debossed with “Lilly” on one side 

and “100” on the other. 
- Verzenios 150 mg film-coated tablets are yellow, oval tablets debossed with “Lilly” on one side 

and “150” on the other. 
 
Verzenios is available in calendar blister packs of 14, 28, 42, 56, 70 and 168 film-coated tablets and 
perforated unit dose blisters of 28 x 1 film-coated tablets. 
 
Not all the pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528BJ Utrecht, The Netherlands. 
 
Manufacturer 
Lilly S.A., Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

Belgique/België/Belgien 
Eli Lilly Benelux S.A./N.V. 
Tél/Tel: + 32-(0)2 548 84 84 

Lietuva 
Eli Lilly Lietuva 
Tel. +370 (5) 2649600 

България 
ТП "Ели Лили Недерланд" Б.В. - България 
тел. + 359 2 491 41 40 

Luxembourg/Luxemburg 
Eli Lilly Benelux S.A./N.V. 
Tél/Tel: + 32-(0)2 548 84 84 

Česká republika 
ELI LILLY ČR, s.r.o. 
Tel: + 420 234 664 111 

Magyarország 
Lilly Hungária Kft. 
Tel: + 36 1 328 5100 

Danmark 
Eli Lilly Danmark A/S  
Tlf: +45 45 26 60 00 

Malta 
Charles de Giorgio Ltd. 
Tel: + 356 25600 500 



47 

Deutschland 
Lilly Deutschland GmbH 
Tel. + 49-(0) 6172 273 2222 

Nederland 
Eli Lilly Nederland B.V.  
Tel: + 31-(0) 30 60 25 800 

Eesti 
Eli Lilly Nederland B.V.  
Tel: +372 6 817 280 

Norge 
Eli Lilly Norge A.S.  
Tlf: + 47 22 88 18 00 

Ελλάδα 
ΦΑΡΜΑΣΕΡΒ-ΛΙΛΛΥ Α.Ε.Β.Ε.  
Τηλ: +30 210 629 4600 

Österreich 
Eli Lilly Ges.m.b.H.  
Tel: + 43-(0) 1 711 780 

España 
Lilly S.A. 
Tel: + 34-91 663 50 00 

Polska 
Eli Lilly Polska Sp. z o.o. 
Tel: +48 22 440 33 00 

France 
Lilly France 
Tél: +33-(0) 1 55 49 34 34 

Portugal 
Lilly Portugal Produtos Farmacêuticos, Lda 
Tel: + 351-21-4126600 

Hrvatska 
Eli Lilly Hrvatska d.o.o. 
Tel: +385 1 2350 999 

România 
Eli Lilly România S.R.L. 
Tel: + 40 21 4023000 

Ireland 
Eli Lilly and Company (Ireland) Limited 
Tel: + 353-(0) 1 661 4377 

Slovenija 
Eli Lilly farmacevtska družba, d.o.o. 
Tel: +386 (0)1 580 00 10 

Ísland 
Icepharma hf. 
Sími + 354 540 8000 

Slovenská republika 
Eli Lilly Slovakia s.r.o. 
Tel: + 421 220 663 111 

Italia 
Eli Lilly Italia S.p.A. 
Tel: + 39- 055 42571 

Suomi/Finland 
Oy Eli Lilly Finland Ab  
Puh/Tel: + 358-(0) 9 85 45 250 

Κύπρος 
Phadisco Ltd  
Τηλ: +357 22 715000 

Sverige 
Eli Lilly Sweden AB 
Tel: + 46-(0) 8 7378800 

Latvija 
Eli Lilly (Suisse) S.A Pārstāvniecība Latvijā  
Tel: +371 67364000 

United Kingdom 
Eli Lilly and Company Limited 
Tel: + 44-(0) 1256 315000 

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


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