Alecensa

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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 
 
Alecensa 150 mg hard capsules 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each hard capsule contains alectinib hydrochloride equivalent to 150 mg alectinib. 
 
Excipients with known effect  
Each hard capsule contains 33.7 mg lactose (as monohydrate) and 6 mg sodium (as sodium 
laurilsulfate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Hard capsule. 
 
White hard capsule of 19.2 mm length, with “ALE” printed in black ink on the cap and “150 mg” 
printed in black ink on the body.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Alecensa as monotherapy is indicated for the first-line treatment of adult patients with anaplastic 
lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). 
 
Alecensa as monotherapy is indicated for the treatment of adult patients with ALK-positive advanced 
NSCLC previously treated with crizotinib. 
 
4.2 Posology and method of administration 
 
Treatment with Alecensa should be initiated and supervised by a physician experienced in the use of 
anticancer medicinal products. 
 
A validated ALK assay is necessary for the selection of ALK-positive NSCLC patients. ALK-positive 
NSCLC status should be established prior to initiation of Alecensa therapy.  
 
Posology 
The recommended dose of Alecensa is 600 mg (four 150 mg capsules) taken twice daily with food 
(total daily dose of 1200 mg).  
 
Patients with underlying severe hepatic impairment (Child-Pugh C) should receive a starting dose of 
450 mg taken twice daily with food (total daily dose of 900 mg). 
 
Duration of treatment 
Treatment with Alecensa should be continued until disease progression or unacceptable toxicity. 
 



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Delayed or missed doses 
If a planned dose of Alecensa is missed, patients can make up that dose unless the next dose is due 
within 6 hours. Patients should not take two doses at the same time to make up for a missed dose. If 
vomiting occurs after taking a dose of Alecensa, patients should take the next dose at the scheduled 
time. 
 
Dose adjustments 
Management of adverse events may require dose reduction, temporary interruption, or discontinuation 
of treatment with Alecensa. The dose of Alecensa should be reduced in steps of 150 mg twice daily 
based on tolerability. Alecensa treatment should be permanently discontinued if patients are unable to 
tolerate the 300 mg twice daily dose.  
 
Dose modification advice is provided in Tables 1 and 2 below. 
 
Table 1 Dose reduction schedule 
 

Dose reduction schedule Dose level 
Dose 600 mg twice daily 
First dose reduction 450 mg twice daily 
Second dose reduction 300 mg twice daily 
 
Table 2 Dose modification advice for specified Adverse Drug Reactions (see sections 4.4 and 4.8) 
 
CTCAE grade Alecensa treatment 

ILD/pneumonitis of any severity grade  Immediately interrupt and permanently 
discontinue Alecensa if no other potential causes 
of ILD/pneumonitis have been identified. 

ALT or AST elevation of Grade ≥ 3 (> 5 times 
ULN) with total bilirubin ≤ 2 times ULN 

Temporarily withhold until recovery to baseline or 
≤ Grade 1 (≤ 3 times ULN), then resume at 
reduced dose (see Table 1). 

ALT or AST elevation of Grade ≥ 2 (> 3 times 
ULN) with total bilirubin elevation > 2 times 
ULN in the absence of cholestasis or haemolysis  

Permanently discontinue Alecensa.  

Bradycardiaa Grade 2 or Grade 3 (symptomatic, 
may be severe and medically significant, 
medical intervention indicated)  

 

Temporarily withhold until recovery to ≤ Grade 1 
(asymptomatic) bradycardia or to a heart rate of 
≥ 60 bpm. Evaluate concomitant medicinal 
products known to cause bradycardia, as well as 
anti-hypertensive medicinal products. 

If a contributing concomitant medicinal product is 
identified and discontinued, or its dose is adjusted, 
resume at previous dose upon recovery to 
≤ Grade 1 (asymptomatic) bradycardia or to a heart 
rate of ≥ 60 bpm.  

If no contributing concomitant medicinal product 
is identified, or if contributing concomitant 
medicinal products are not discontinued or dose 



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CTCAE grade Alecensa treatment 

modified, resume at reduced dose (see Table 1) 
upon recovery to ≤ Grade 1 (asymptomatic) 
bradycardia or to a heart rate of ≥ 60 bpm. 

Bradycardiaa Grade 4 (life-threatening 
consequences, urgent intervention indicated) 

Permanently discontinue if no contributing 
concomitant medicinal product is identified. 

If a contributing concomitant medicinal product is 
identified and discontinued, or its dose is adjusted, 
resume at reduced dose (see Table 1) upon 
recovery to ≤ Grade 1 (asymptomatic) bradycardia 
or to a heart rate of ≥ 60 bpm, with frequent 
monitoring as clinically indicated.  

Permanently discontinue in case of recurrence. 

CPK elevation > 5 times ULN Temporarily withhold until recovery to baseline or 
to ≤ 2.5 times ULN, then resume at the same dose. 

CPK elevation > 10 times ULN or second 
occurrence of CPK elevation of > 5 times ULN 

Temporarily withhold until recovery to baseline or 
to ≤ 2.5 times ULN, then resume at reduced dose 
as per Table 1.  

ALT = alanine aminotransferase; AST = aspartate aminotransferase; CPK = creatine phosphokinase; CTCAE = 
NCI Common Terminology Criteria for Adverse Events; ILD = interstitial lung disease; ULN = upper limit of 
normal 
a Heart rate less than 60 beats per minute (bpm). 
 
Special populations 
 
Hepatic impairment 
No starting dose adjustment is required in patients with underlying mild (Child-Pugh A) or moderate 
(Child-Pugh B) hepatic impairment. Patients with underlying severe hepatic impairment (Child-Pugh 
C) should receive a starting dose of 450 mg taken twice daily (total dose of 900 mg) (see section 5.2). 
For all patients with hepatic impairment, appropriate monitoring (e.g. markers of liver function) is 
advised, see section 4.4. 
 
Renal impairment 
No dose adjustment is required in patients with mild or moderate renal impairment. Alecensa has not 
been studied in patients with severe renal impairment. However, since alectinib elimination via the 
kidney is negligible, no dose adjustment is required in patients with severe renal impairment (see 
section 5.2).  
 
Elderly (≥ 65 years) 
The limited data on the safety and efficacy of Alecensa in patients aged 65 years and older do not 
suggest that a dose adjustment is required in elderly patients (see section 5.2). There are no available 
data on patients over 80 years of age. 
 
Paediatric population 
The safety and efficacy of Alecensa in children and adolescents below 18 years of age have not been 
established. No data are available. 
 



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Extreme body weight (>130 kg) 
Although PK simulations for Alecensa do not indicate a low exposure in patients with extreme body 
weight (i.e. >130 kg), alectinib is widely distributed and clinical studies for alectinib enrolled patients 
within a range of body weights of 36.9−123 kg. There are no available data on patients with body 
weight above 130 kg. 
 
Method of administration  
Alecensa is for oral use. The hard capsules should be swallowed whole, and must not be opened or 
dissolved. They must be taken with food (see section 5.2). 
 
4.3 Contraindications 
 
Hypersensitivity to alectinib or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Interstitial lung disease (ILD)/pneumonitis 
Cases of ILD/pneumonitis have been reported in clinical trials with Alecensa (see section 4.8). 
Patients should be monitored for pulmonary symptoms indicative of pneumonitis. Alecensa should be 
immediately interrupted in patients diagnosed with ILD/pneumonitis and should be permanently 
discontinued if no other potential causes of ILD/pneumonitis have been identified (see section 4.2).  
 
Hepatotoxicity 
Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 
5 times the ULN as well as bilirubin elevations of more than 3 times the ULN occurred in patients in 
pivotal clinical trials with Alecensa (see section 4.8). The majority of these events occurred during the 
first 3 months of treatment. In the pivotal Alecensa clinical trials it was reported that three patients 
with Grade 3-4 AST/ALT elevations had drug induced liver injury. Concurrent elevations in ALT or 
AST greater than or equal 3 times the ULN and total bilirubin greater than or equal 2 times the ULN, 
with normal alkaline phosphatase, occurred in one patient treated in Alecensa clinical trials. 
 
Liver function, including ALT, AST, and total bilirubin should be monitored at baseline and then 
every 2 weeks during the first 3 months of treatment. Thereafter, monitoring should be performed 
periodically, since events may occur later than 3 months, with more frequent testing in patients who 
develop aminotransferase and bilirubin elevations. Based on the severity of the adverse drug reaction, 
Alecensa should be withheld and resumed at a reduced dose, or permanently discontinued as described 
in Table 2 (see section 4.2).  
 
Severe myalgia and creatine phosphokinase (CPK) elevation 
Myalgia or musculoskeletal pain was reported in patients in pivotal trials with Alecensa, including 
Grade 3 events (see section 4.8).  
 
Elevations of CPK occurred in pivotal trials with Alecensa, including Grade 3 events (see section 4.8). 
Median time to Grade 3 CPK elevation was 14 days across clinical trials (NP28761, NP28673, 
BO28984).   
 
Patients should be advised to report any unexplained muscle pain, tenderness, or weakness. CPK 
levels should be assessed every two weeks for the first month of treatment and as clinically indicated 
in patients reporting symptoms. Based on the severity of the CPK elevation, Alecensa should be 
withheld, then resumed or dose reduced (see section 4.2). 
 
Bradycardia 
Symptomatic bradycardia can occur with Alecensa (see section 4.8). Heart rate and blood pressure 
should be monitored as clinically indicated. Dose modification is not required in case of asymptomatic 
bradycardia (see section 4.2). If patients experience symptomatic bradycardia or life-threatening 
events, concomitant medicinal products known to cause bradycardia, as well as anti-hypertensive 



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medicinal products should be evaluated and Alecensa treatment should be adjusted as described in 
Table 2 (see sections 4.2 and 4.5, ‘P-gp substrates’ and ‘BCRP substrates’). 
 
Gastrointestinal perforation 
Cases of gastrointestinal perforations have been reported in patients at increased risk (e.g., history of 
diverticulitis, metastases to the gastrointestinal tract, concomitant use of medicinal product with a 
recognized risk of gastrointestinal perforation) treated with alectinib. Discontinuation of alectinib in 
patients who develop gastrointestinal perforation should be considered. Patients should be informed of 
the signs and symptoms of gastrointestinal perforations and advised to consult rapidly in case of 
occurrence. 
 
Photosensitivity 
Photosensitivity to sunlight has been reported with Alecensa administration (see section 4.8). Patients 
should be advised to avoid prolonged sun exposure while taking Alecensa, and for at least 7 days after 
discontinuation of treatment. Patients should also be advised to use a broad-spectrum Ultraviolet A 
(UVA)/ Ultraviolet B (UVB) sun screen and lip balm (SPF ≥50) to help protect against potential 
sunburn.   
 
Women of child-bearing potential 
Alecensa may cause foetal harm when administered to a pregnant woman. Female patients of 
child-bearing potential receiving Alecensa, must use highly effective contraceptive methods during 
treatment and for at least 3 months following the last dose of Alecensa (see sections 4.6 and 5.3).  
 
Lactose intolerance 
This medicinal product contains lactose. Patients with rare hereditary problems of galactose 
intolerance, a congenital lactase deficiency or glucose-galactose malabsorption should not take this 
medicinal product. 
 
Sodium content 
This medicinal product contains 48 mg sodium per daily dose (1200 mg), equivalent to 2.4% of the 
WHO recommended maximum daily intake of 2 g sodium for an adult. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Effects of other medicinal products on alectinib 
Based on in vitro data, CYP3A4 is the primary enzyme mediating the metabolism of both alectinib 
and its major active metabolite M4, and CYP3A contributes to 40% − 50% of total hepatic metabolism. 
M4 has shown similar in vitro potency and activity against ALK. 
 
CYP3A inducers 
Co-administration of multiple oral doses of 600 mg rifampicin once daily, a strong CYP3A inducer, 
with a single oral dose of 600 mg alectinib reduced alectinib Cmax, and AUCinf by 51% and 73% 
respectively and increased M4 Cmax and AUCinf 2.20 and 1.79-fold respectively. The effect on the 
combined exposure of alectinib and M4 was minor, reducing Cmax and AUCinf by 4% and 18%, 
respectively. Based on the effects on the combined exposure of alectinib and M4, no dose adjustments 
are required when Alecensa is co-administered with CYP3A inducers. Appropriate monitoring is 
recommended for patients taking concomitant strong CYP3A inducers (including, but not limited to, 
carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin and St. John’s Wort (Hypericum 
perforatum)). 
 
CYP3A inhibitors  
Co-administration of multiple oral doses of 400 mg posaconazole twice daily, a strong CYP3A 
inhibitor, with a single oral dose of 300 mg alectinib increased alectinib exposure Cmax and AUCinf by 
1.18 and 1.75-fold respectively, and reduced M4 Cmax and AUCinf by 71% and 25% respectively.The 
effect on the combined exposure of alectinib and M4 was minor, reducing Cmax by 7% and increasing 
AUCinf 1.36-fold. Based on the effects on the combined exposure of alectinib and M4, no dose 
adjustments are required when Alecensa is co-administered with CYP3A inhibitors. Appropriate 



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monitoring is recommended for patients taking concomitant strong CYP3A inhibitors (including, but 
not limited to, ritonavir, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, 
posaconazole nefazodone, grapefruit or Seville oranges). 
 
Medicinal products that increase gastric pH  
Multiple doses of esomeprazole, a proton pump inhibitor, 40 mg once daily, demonstrated no 
clinically relevant effect on the combined exposure of alectinib and M4. Therefore, no dose 
adjustments are required when Alecensa is co-administered with proton pump inhibitors or other 
medicinal products which raise gastric pH (e.g. H2 receptor antagonists or antacids). 
 
Effect of transporters on alectinib disposition 
M4 is a substrate of P-gp. As alectinib inhibits P-gp, it is not expected that co-medication with P-gp 
inhibitors has a relevant effect on M4 exposure. 
 
Effects of alectinib on other medicinal products 
 
P-gp substrates 
In vitro, alectinib and its major active metabolite M4 are inhibitors of the efflux transporter  
P-glycoprotein (P-gp). Therefore, alectinib and M4 may have the potential to increase plasma 
concentrations of co-administered substrates of P-gp. When Alecensa is co-administered with P-gp 
substrates (e.g., digoxin, dabigatran etexilate, topotecan, sirolimus, everolimus, nilotinib and 
lapatinib), appropriate monitoring is recommended.  
 
BCRP substrates 
In vitro, alectinib and M4 are inhibitors of the efflux transporter Breast Cancer Resistance Protein 
(BCRP). Therefore, alectinib and M4 may have the potential to increase plasma concentrations of 
co-administered substrates of BCRP. When Alecensa is co-administered with BCRP substrates (e.g., 
methotrexate, mitoxantrone, topotecan and lapatinib), appropriate monitoring is recommended.  
 
CYP substrates 
In vitro, alectinib and M4 show weak time-dependent inhibition of CYP3A4, and alectinib exhibits a 
weak induction potential of CYP3A4 and CYP2B6 at clinical concentrations.   
 
Multiple doses of 600 mg alectinib had no influence on the exposure of midazolam (2 mg), a sensitive 
CYP3A substrate. Therefore, no dose adjustment is required for co-administered CYP3A substrates.  
 
A risk for induction of CYP2B6 and PXR regulated enzymes apart from CYP3A4 cannot be 
completely excluded. The effectiveness of concomitant administration of oral contraceptives may be 
reduced. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential/contraception  
Women of childbearing potential must be advised to avoid pregnancy while on Alecensa. Female 
patients of child-bearing potential receiving Alecensa must use highly effective contraceptive methods 
during treatment and for at least 3 months following the last dose of Alecensa. 
 
Pregnancy 
There are no or limited amount of data from the use of Alecensa in pregnant women. Based on its 
mechanism of action, Alecensa may cause foetal harm when administered to a pregnant woman. 
Studies in animals have shown reproductive toxicity (see section 5.3).  
 
Female patients, who become pregnant while taking Alecensa or during the 3 months following the 
last dose of Alecensa must contact their doctor and should be advised of the potential harm to the 
foetus. 
 



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Breast-feeding 
It is unknown whether alectinib and its metabolites are excreted in human milk. A risk to the 
newborn/infant cannot be excluded. Mothers should be advised against breast-feeding while receiving 
Alecensa. 
 
Fertility 
No fertility studies in animals have been performed to evaluate the effect of Alecensa. No adverse 
effects on male and female reproductive organs were observed in general toxicology studies (see 
section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Alecensa has minor influence on the ability to drive and use machines. Caution should be exercised 
when driving or operating machines as patients may experience symptomatic bradycardia (e.g., 
syncope, dizziness, hypotension) or vision disorders while taking Alecensa (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The data described below reflect exposure to Alecensa in 405 patients with ALK-positive advanced 
NSCLC who participated in one randomised Phase III clinical trial (BO28984) and in two single-arm 
phase II clinical trials (NP28761, NP28673). These patients were treated with the recommended dose 
of 600 mg twice daily. In  the phase II clinical trials (NP28761, NP28673; N=253), the median 
duration of exposure to Alecensa was 11 months. In BO28984 (ALEX; N=152) the median duration of 
exposure to Alecensa was 17.9 months, whereas the median duration of exposure to crizotinib was 
10.7 months.  
 
The most common adverse drug reactions (ADRs) (≥ 20%) were constipation (35%), oedema (30%, 
including oedema peripheral, oedema, generalised oedema, eyelid oedema, periorbital oedema, face 
oedema and localised oedema), and myalgia (28%, including myalgia and musculoskeletal pain).  
 
Tabulated list of adverse drug reactions 
Table 3 lists the ADRs occurring in patients who received Alecensa across two phase II clinical trials 
(NP28761, NP28673) and one phase III clinical trial (BO28984; ALEX),  and during post-marketing.  
 
The ADRs listed in Table 3 are presented by system organ class and frequency categories, defined 
using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon 
(≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000). Within each system organ 
class, undesirable effects are presented in order of decreasing frequency. 
 
Table 3 ADRs reported in Alecensa clinical trials (NP28761, NP28673, BO28984; N=405) and 
during post-marketing 
 
System organ class 
    ADRs (MedDRA) 

Alecensa 
N=405 

 All grades  
(%) 

Frequency category 
(all grades) 

Grades 3-4  
(%) 

Blood and lymphatic system disorders 
    Anaemia1) 17 Very common 3.0 
Nervous system disorders 
    Dysgeusia 2)  5.2 Common 0.2  
Eye disorders 
    Vision disorders3) 8.6 Common 0 
Cardiac disorders 
    Bradycardia4) 8.9 Common 0 



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System organ class 
    ADRs (MedDRA) 

Alecensa 
N=405 

 All grades  
(%) 

Frequency category 
(all grades) 

Grades 3-4  
(%) 

Respiratory, thoracic and mediastinal disorders 
    Interstitial lung disease / 
pneumonitis 

0.7 Uncommon 0.2 

Gastrointestinal disorders 
    Constipation  35 Very common 0 
    Nausea  19 Very common 0.5 
    Diarrhoea  16 Very common 0.7 
    Vomiting  11 Very common 0.2 
    Stomatitis 5) 3.0 Common 0 
Hepatobiliary disorders 
    Increased bilirubin6)  18 Very common 3.2 
    Increased AST  15 Very common 3.7 
    Increased ALT  14 Very common 3.7 
    Increased alkaline 
phosphatase** 

6.2 Common 0.2 

    Drug-induced liver injury7) 0.7 Uncommon 0.7 
Skin and subcutaneous tissue disorders 
    Rash8)  18 Very common 0.5 
    Photosensitivity 9.1 Common 0.2 
Musculoskeletal and connective tissues disorders 
    Myalgia9) 28 Very common 0.7 
    Increased blood creatine 
phosphokinase 

10 Very common 3.2 

Renal and urinary disorders 
    Blood creatinine increased 7.2 Common 0.7* 
    Acute kidney injury 1.0 Common 1.0* 
General disorders and administration site conditions 
    Oedema10)  30 Very common 0.7 
Investigations 
    Weight increased 12 Very common 0.7 
* Includes one Grade 5 event 
** Increased alkaline phosphatase was reported in the post-marketing period and in pivotal phase II and phase III 
clinical trials.  
1) includes cases of anaemia and haemoglobin decreased  
2) includes cases of dysgeusia and hypogeusia 
3) includes cases of blurred vision, visual impairment, vitreous floaters, reduced visual acuity, asthenopia, and 
diplopia 
4) includes cases of bradycardia and sinus bradycardia 
5) includes cases of stomatitis and mouth ulceration 
6) includes cases of blood bilirubin increased, hyperbilirubinaemia and bilirubin conjugated increased  
7) includes two patients with reported MedDRA term of drug-induced liver injury as well as one patient with 
reported Grade 4 increased AST and ALT who had documented drug-induced liver injury by liver biopsy 
8) includes cases of rash, rash maculopapular, dermatitis acneiform, erythema, rash generalised, rash papular, 
rash pruritic, rash macular and exfoliative rash 
9) includes cases of myalgia and musculoskeletal pain 
10) includes cases of oedema peripheral, oedema, generalised oedema, eyelid oedema, periorbital oedema, face 
oedema and localised oedema 
 



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Description of selected adverse drug reactions 
 
The safety profile of Alecensa was generally consistent across the pivotal phase III clinical trial 
BO28984 (ALEX) and phase II trials (NP28761, NP28673). 
 
Interstitial lung disease (ILD) / pneumonitis  
Severe ILD/pneumonitis occurred in patients treated with Alecensa. Across clinical trials (NP28761, 
NP28673, BO28984), 1 out of 405 patients treated with Alecensa (0.2%) had a Grade 3 ILD. This 
event led to withdrawal from Alecensa treatment. In the phase III clinical trial BO28984, Grade 3 or 4 
ILD/pneumonitis was not observed in patients receiving Alecensa versus 2.0% of patients receiving 
crizotinib. There were no fatal cases of ILD in any of the clinical trials. Patients should be monitored 
for pulmonary symptoms indicative of pneumonitis (see sections 4.2 and 4.4). 
 
Hepatotoxicity 
Across clinical trials (NP28761, NP28673, BO28984) two patients with Grade 3-4 AST/ALT 
elevations had documented drug induced liver injury by liver biopsy. In addition, one patient 
experienced a Grade 4 adverse event of drug-induced liver injury. Two of these cases led to 
withdrawal from Alecensa treatment. Adverse reactions of increased AST and ALT levels (15% and 
14% respectively) were reported in patients treated with Alecensa across clinical trials (NP28761, 
NP28673, BO28984). The majority of these events were of Grade 1 and 2 intensity, and events of 
Grade ≥ 3 were reported in 3.7% and 3.7% of the patients, respectively. The events generally occurred 
during the first 3 months of treatment, were usually transient and resolved upon temporary interruption 
of Alecensa treatment (reported for 1.5% and 3.0% of the patients, respectively) or dose reduction 
(2.2% and 1.2%, respectively). In 1.2% and 1.5% of the patients, AST and ALT elevations, 
respectively, led to withdrawal from Alecensa treatment. Grade 3 or 4 ALT or AST elevations were 
each observed in 5% of patients receiving Alecensa versus 15% and 11% of patients receiving 
crizotinib in the phase III clinical trial BO28984.  
 
Adverse reactions of bilirubin elevations were reported in 18% of the patients treated with Alecensa 
across clinical trials (NP28761, NP28673, BO28984). The majority of the events were of Grade 1 and 
2 intensity; Grade 3 events were reported in 3.2% of the patients. The events generally occurred during 
the first 3 months of treatment, were usually transient and the majority resolved upon dose 
modification. In 5.2% of patients, bilirubin elevations led to dose modifications and in 1.5% of 
patients, bilirubin elevations led to withdrawal from Alecensa treatment. In the phase III clinical trial 
BO28984, Grade 3 or 4 bilirubin elevations occurred in 3.3% of patients receiving Alecensa versus no 
patient receiving crizotinib.  
 
Concurrent elevations in ALT or AST greater than or equal to three times the ULN and total bilirubin 
greater than or equal to two times the ULN, with normal alkaline phosphatase, occurred in one patient 
(0.2%) treated in Alecensa clinical trials. 
 
Patients should be monitored for liver function including ALT, AST, and total bilirubin as outlined in 
section 4.4 and managed as recommended in section 4.2. 
 
Bradycardia  
Cases of bradycardia (8.9%) of Grade 1 or 2 have been reported in patients treated with Alecensa 
across clinical trials (NP28761, NP28673, BO28984). No patients had events of Grade ≥ 3 severity. 
There were 66 of 365 patients (18%) treated with Alecensa who had post-dose heart rate values below 
50 beats per minutes (bpm). In the phase III clinical trial BO28984 15% of patients treated with 
Alecensa had post-dose heart rate values below 50 bpm versus 20% of patients treated with crizotinib. 
Patients who develop symptomatic bradycardia should be managed as recommended in sections 4.2 
and 4.4. No case of bradycardia led to withdrawal from Alecensa treatment. 
 



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Severe myalgia and CPK elevations  
Cases of myalgia (28%) including myalgia events (22%) and musculoskeletal pain (7.4%) have been 
reported in patients treated with Alecensa across clinical trials (NP28761, NP28673, BO28984). The 
majority of events were Grades 1 or 2 and three patients (0.7%) had a Grade 3 event. Dose 
modifications of Alecensa treatment due to these adverse events were only required for two patients 
(0.5%); Alecensa treatment was not withdrawn due to these events of myalgia. Elevations of CPK 
occurred in 43% of 362 patients with CPK laboratory data available across clinical trials (NP28761, 
NP28673, BO28984) with Alecensa. The incidence of Grade 3 elevations of CPK was 3.7%. Median 
time to Grade 3 CPK elevation was 14 days across trials (NP28761, NP28673, BO28984). Dose 
modifications for elevation of CPK occurred in 3.2% of patients; withdrawal from Alecensa treatment 
did not occur due to CPK elevations. Severe myalgia has not been reported in the clinical trial 
BO28984. Grade 3 elevation of CPK was reported for 2.6% of patients receiving Alecensa and 1.3% 
of patients receiving crizotinib;  and median time to Grade 3 CPK elevation was 27.5 days and 369 
days, respectively, in the pivotal phase III clinical trial BO28984 (ALEX).   
 
Gastrointestinal effects  
Constipation (35%), nausea (19%), diarrhoea (16%) and vomiting (11%) were the most commonly 
reported gastrointestinal (GI) reactions. Most of these events were of mild or moderate severity; 
Grade 3 events were reported for diarrhea (0.7%), nausea (0.5%), and vomiting (0.2%). These events 
did not lead to withdrawal from Alecensa treatment. Median time to onset for constipation, nausea, 
diarrhea, and/or vomiting events across clinical trials (NP28761, NP28673, BO28984) was 21 days. 
The events declined in frequency after the first month of treatment. In the phase III clinical trial 
BO28984, one patient (0.2%) experienced a Grade 4 event of nausea in the Alecensa arm and the 
incidence of Grade 3 and 4 events for nausea, vomiting, and diarrhoea was 3.3%, 3.3%, and 2.0%, 
respectively, in the crizotinib arm.  
 
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 
 
Patients who experience overdose should be closely supervised and general supportive care instituted. 
There is no specific antidote for overdose with Alecensa. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: anti-neoplastic agents, protein kinase inhibitor; ATC code: L01XE36. 
 
Mechanism of action 
 
Alectinib is a highly selective and potent ALK and RET tyrosine kinase inhibitor. In preclinical 
studies, inhibition of ALK tyrosine kinase activity led to blockage of downstream signalling pathways 
including STAT 3 and PI3K/AKT and induction of tumour cell death (apoptosis). 
 
Alectinib demonstrated in vitro and in vivo activity against mutant forms of the ALK enzyme, 
including mutations responsible for resistance to crizotinib. The major metabolite of alectinib (M4) 
has shown similar in vitro potency and activity.  
 
Based on preclinical data, alectinib is not a substrate of p-glycoprotein or BCRP, which are both efflux 
transporters in the blood brain barrier, and is therefore able to distribute into and be retained within the 
central nervous system.  

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


12 

 
Clinical efficacy and safety  
 
ALK positive non-small cell lung cancer 
 
Treatment-naïve patients 
 
The safety and efficacy of Alecensa were studied in a global randomised Phase III open label clinical 
trial (BO28984, ALEX) in ALK-positive NSCLC patients who were treatment naïve. Central testing 
for ALK protein expression positivity of tissue samples from all patients by Ventana anti-ALK (D5F3) 
immunohistochemistry (IHC) was required before randomisation into the study. 
 
A total of 303 patients were included in the Phase III trial, 151 patients randomised to the crizotinib 
arm and 152 patients randomised to the Alecensa arm receiving Alecensa orally, at the recommended 
dose of 600 mg twice daily.  
 
ECOG PS (0/1 vs. 2), race (Asian vs. non-Asian), and CNS metastases at baseline (yes vs. no) were 
stratification factors for randomisation. The primary endpoint of the trial was to demonstrate 
superiority of Alecensa versus crizotinib based on Progression Free survival (PFS) as per investigator 
assessment using RECIST 1.1. Baseline demographic and disease characteristics for Alecensa were 
median age 58 years (54 years for crizotinib), 55% female (58% for crizotinib), 55% non-Asian (54% 
for crizotinib), 61% with no smoking history (65% for crizotinib), 93% ECOG PS of 0 or 1 (93% for 
crizotinib), 97% Stage IV disease (96% for crizotinib), 90% adenocarcinoma histology (94% for 
crizotinib), 40% CNS metastases at baseline (38% for crizotinib) and 17% having received prior CNS 
radiation (14% for crizotinib).  
 
The trial met its primary endpoint at the primary analysis, demonstrating a statistically significant 
improvement in PFS by investigator. Efficacy data are summarised in Table 4 and the Kaplan-Meier 
curve for investigator assessed PFS is shown in Figure 1. 
 



13 

Table 4 Summary of efficacy results from study BO28984 (ALEX) 
 

 Crizotinib N=151 
Alecensa 
N=152 

Median duration of follow-up (months) 17.6 (range 0.3 – 27.0) 
18.6 

(range 0.5 – 29.0) 

Primary efficacy parameter 
 

  

PFS (INV)  
Number of patients with event n (%) 
Median (months) 
[95% CI] 

 
102 (68%) 

11.1  
[9.1; 13.1] 

 
62 (41%) 

NE 
[17.7; NE] 

 
HR 
[95% CI] 
Stratified log-rank p-value 
 

 
0.47 

[0.34, 0.65] 
p <0.0001 

Secondary efficacy parameters 
 

  

PFS (IRC)* 
Number of patients with event n (%) 
Median (months) 
[95% CI] 

 
92 (61%) 

10.4 
[7.7; 14.6] 

 
63 (41%) 

25.7 
[19.9; NE] 

 
HR 
[95% CI] 
Stratified log-rank p-value 

 

 
0.50 

[0.36; 0.70] 
p < 0.0001 

Time to CNS progression (IRC)*, ** 
Number of patients with event n (%) 

 
68 (45%) 

 
18 (12%) 

 
Cause-specific HR  
[95% CI] 
Stratified log-rank p-value 
 

 
0.16 

[0.10; 0.28] 
p < 0.0001 

 
12-month cumulative incidence of CNS 
progression (IRC)  
[95% CI] 
 

 
41.4% 

[33.2; 49.4] 

 
9.4% 

[5.4; 14.7] 

ORR (INV)*, *** 
Responders n (%) 
[95% CI] 
 

 
114 (75.5%) 
[67.8; 82.1] 

 
126 (82.9%) 
[76.0; 88.5] 

Overall survival* 
Number of patients with event n (%) 
Median (months) 
[95% CI] 

 
40 (27%) 

NE 
[NE; NE] 

 
35 (23%) 

NE 
[NE; NE] 

 
HR 
[95% CI] 

 
0.76 

[0.48; 1.20] 
 

Duration of response (INV) 
Median (months) 
[95 % CI] 
 

N=114 
11.1 

[7.9; 13.0] 

N=126 
NE 

[NE; NE] 



14 

 Crizotinib N=151 
Alecensa 
N=152 

CNS-ORR in patients with measurable CNS 
metastases at baseline 

CNS responders n (%) 
[95% CI] 
 
CNS-CR n (%) 
 
CNS-DOR, median (months) 
[95% CI] 

 

N=22 
 

11 (50.0%) 
 [28.2; 71.8] 

 
1 (5%) 

 
5.5 

[2.1, 17.3] 

N=21 
 

17 (81.0%) 
[58.1; 94.6] 

 
8 (38%) 

 
17.3 

[14.8, NE] 

CNS-ORR in patients with measurable and 
non-measurable CNS metastases at baseline 
(IRC) 

CNS responders n (%) 
[95% CI] 

 
CNS-CR n (%)  
 
CNS-DOR, median (months) 
[95% CI] 
 

N=58 
 
 

15 (25.9%) 
[15.3; 39.0] 

 
5 (9%) 

 
3.7 

[3.2, 6.8] 

N=64 
 
 

38 (59.4%) 
[46.4; 71.5] 

 
29 (45%) 

 
NE 

[17.3, NE] 

* Key secondary endpoints part of the hierarchical testing 
** Competing risk analysis of CNS progression, systemic progression and death as competing events 
*** 2 patients in the crizotinib arm and 6 patients in the alectinib arm had CR 
CI = confidence interval; CNS = central nervous system; CR = complete response; DOR = duration of response; 
HR = hazard ratio; IRC = Independent Review Committee; INV = investigator; NE = not estimable; 
ORR = objective response rate; PFS = progression free survival 
 
The PFS benefit was consistent for patients with CNS metastases at baseline (HR = 0.40, 95% CI: 
0.25-0.64, median PFS for Alecensa = NE, 95% CI: 9.2-NE, median PFS for crizotinib = 7.4 months, 
95%CI: 6.6-9.6) and without CNS metastases at baseline (HR = 0.51, 95% CI: 0.33-0.80, median PFS 
for Alecensa = NE, 95% CI: NE, NE, median PFS for crizotinib = 14.8 months, 95% CI:10.8-20.3), 
indicating benefit of Alecensa over crizotinib in both subgroups.  



15 

Figure 1: Kaplan Meier Plot of INV Assessed PFS in BO28984 (ALEX) 
 

 

 
Crizotinib pre-treated patients 
 
The safety and efficacy of Alecensa in ALK-positive NSCLC patients pre-treated with crizotinib were 
studied in two Phase I/II clinical trials (NP28673 and NP28761).  
 
NP28673 
Study NP28673 was a Phase I/II single arm, multicentre study conducted in patients with 
ALK-positive advanced NSCLC who have previously progressed on crizotinib treatment. In addition 
to crizotinib, patients may have received previous treatment with chemotherapy. A total of 
138 patients were included in the phase II part of the study and received Alecensa orally, at the 
recommended dose of 600 mg twice daily.  
 
The primary endpoint was to evaluate the efficacy of Alecensa by Objective Response Rate (ORR) as 
per central Independent Review Committee (IRC) assessment using Response Evaluation Criteria in 
Solid Tumors (RECIST) version 1.1 in the overall population (with and without prior exposure of 
cytotoxic chemotherapy treatments). The co-primary endpoint was to evaluate the ORR as per central 
IRC assessment using RECIST 1.1 in patients with prior exposure of cytotoxic chemotherapy 
treatments. A lower confidence limit for the estimated ORR above the pre-specified threshold of 35% 
would achieve a statistically significant result. 
 
Patient demographics were consistent with that of a NSCLC ALK positive population. The 
demographic characteristics of the overall study population were 67% Caucasian, 26% Asian, 56% 
females, and the median age was 52 years. The majority of patients had no history of smoking (70%). 
The ECOG (Eastern Cooperative Oncology Group) performance status at baseline was 0 or 1 in 90.6% 
of patients and 2 in 9.4% of patients. At the time of entry in the study, 99% of patients had stage IV 
disease, 61% had brain metastases and in 96% of patients tumours were classified as adenocarcinoma. 
Among patients included in the study, 20% of the patients had previously progressed on crizotinib 
treatment only, and 80% had previously progressed on crizotinib and at least one chemotherapy 
treatment.   
 



16 

Study NP28761 
Study NP28761 was a Phase I/II single arm multicentre study conducted in patients with ALK positive 
advanced NSCLC who have previously progressed on crizotinib treatment. In addition to crizotinib, 
patients may have received previous treatment with chemotherapy. A total of 87 patients were 
included in the phase II part of the study and received Alecensa orally, at the recommended dose of 
600 mg twice daily.  
 
The primary endpoint was to evaluate the efficacy of Alecensa by ORR as per central IRC assessment 
using RECIST version 1.1. A lower confidence limit for the estimated ORR above the pre-specified 
threshold of 35% would achieve a statistically significant result. 
 
Patient demographics were consistent with that of a NSCLC ALK positive population. The 
demographic characteristics of the overall study population were 84% Caucasian, 8% Asian, 55% 
females. The median age was 54 years. The majority of patients had no history of smoking (62%). The 
ECOG performance status at baseline was 0 or 1 in 89.7% of patients and 2 in 10.3% of patients. At 
the time of entry in the study, 99% of patients had stage IV disease, 60% had brain metastases and in 
94% of patients tumours were classified as adenocarcinoma. Among the patients included in the study, 
26% of the patients had previously progressed on crizotinib treatment only, and 74% had previously 
progressed on crizotinib and at least one chemotherapy treatment.  
 
The main efficacy results from studies NP28673 and NP28761 are summarised in Table 5. A summary 
of pooled analysis of CNS endpoints is presented in Table 6. 
 



17 

Table 5 Efficacy results from studies NP28673 and NP28761  
 
  

NP28673 
Alecensa 600 mg  

twice daily 

 
NP28761 

Alecensa 600 mg  
twice daily 

 

Median duration of follow-up (months) 21  (range 1 – 30) 
17  

(range 1 – 29) 
Primary efficacy parameters 
 

  

ORR (IRC) in RE population 
Responders N (%) 
[95% CI] 
 

N=122 a 
62 (50.8%) 

[41.6%, 60.0%] 
 

N = 67 b 
35 (52.2%) 

[39.7%, 64.6%] 

ORR (IRC) in patients pre-treated with 
chemotherapy 

Responders N (%) 
[95% CI] 
 

N = 96 
 

43 (44.8%) 
[34.6%, 55.3%] 

 
 
 

Secondary efficacy parameters 
 

  

DOR (IRC)  
Number of patients with events N (%) 
Median (months) 
[95% CI] 
 

N = 62 
36 (58.1%) 

15.2 
[11.2, 24.9] 

N = 35 
20 (57.1%) 

14.9 
[6.9, NE] 

PFS (IRC) 
Number of patients with events N (%) 
Median duration (months) 
[95% CI]  
 

N = 138 
98 (71.0%) 

8.9 
[5.6, 12.8] 

N = 87 
58 (66.7%) 

8.2 
[6.3, 12.6] 

CI = confidence interval; DOR = duration of response; IRC = independent review committee; NE = not 
estimable; ORR = objective response rate; PFS= progression free survival; RE =  response evaluable 
a 16 patients did not have measurable disease at baseline according to the IRC and were not included in the IRC 
response evaluable population. 
b 20 patients did not have measurable disease at baseline according to the IRC and were not included in the IRC 
response evaluable population 
 
ORR results for studies NP28673 and NP28761 were consistent across subgroups of baseline patient 
characteristics such as age, gender, race, ECOG performance status, Central Nervous System (CNS) 
metastasis and prior chemotherapy use, especially when considering the small number of patients in 
some subgroups.  
 



18 

Table 6 Summary of the pooled analysis of CNS endpoints from studies NP28673 and NP28761 
 
CNS Parameters (NP28673 and NP28761) Alecensa 600 mg twice daily 
Patients with measurable CNS lesions at baseline  
CNS ORR (IRC) 

Responders (%) 
[95% CI] 
Complete response 
Partial response 
 

CNS DOR (IRC)  
Number of patients with events (%) 
Median (months) 
[95%CI]  

N = 50 
 

32 (64.0%) 
 [49.2%, 77.1%] 

11 (22.0%) 
21 (42.0%) 

 
N=32 

18 (56.3%) 
11.1 

[7.6, NE] 
CI = confidence interval; DOR = duration of response; IRC = independent review committee; ORR = objective 
response rate; NE = not estimable 
 
Paediatric population 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Alecensa in all subsets of the paediatric population in lung carcinoma (small cell and non-small cell 
carcinoma) (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetic parameters for alectinib and its major active metabolite (M4) have been 
characterised in ALK-positive NSCLC patients and healthy subjects. Based on population 
pharmacokinetic analysis, the geometric mean (coefficient of variation %) steady-state Cmax, Cmin and 
AUC0-12hr for alectinib were approximately 665 ng/mL (44.3%), 572 ng/mL (47.8%) and 7430 
ng*h/mL (45.7%), respectively. The geometric mean steady-state Cmax, Cmin and AUC0-12hr for M4 
were approximately 246 ng/mL (45.4%), 222 ng/mL (46.6%) and 2810 ng*h/mL (45.9%), 
respectively. 
 
Absorption 
Following oral administration of 600 mg twice daily under fed conditions in ALK-positive NSCLC 
patients, alectinib was absorbed reaching Tmax after approximately 4 to 6 hours.  
 
Alectinib steady-state is reached within 7 days with continuous 600 mg twice daily dosing. The 
accumulation ratio for the twice-daily 600 mg regimen was approximately 6-fold. Population PK 
analysis supports dose proportionality for alectinib across the dose range of 300 to 900 mg under fed 
conditions. 
 
The absolute bioavailability of alectinib capsules was 36.9% (90% CI: 33.9%, 40.3%) under fed 
conditions in healthy subjects. 
 
Following a single oral administration of 600 mg with a high-fat, high-calorie meal, alectinib and M4 
exposure was increased by around 3-fold relative to fasted conditions (see section 4.2).  
 
Distribution 
Alectinib and its major metabolite M4 are highly bound to human plasma proteins (>99%), 
independent of active substance concentration. The mean in vitro human blood-to-plasma 
concentration ratios of alectinib and M4 are 2.64 and 2.50, respectively, at clinically relevant 
concentrations.   
The geometric mean volume of distribution at steady state (Vss) of alectinib following IV 
administration was 475 L, indicating extensive distribution into tissues. 
 



19 

Based on in vitro data, alectinib is not a substrate of P-gp. Alectinib and M4 are not substrates of 
BCRP or organic anion-transporting polypeptide (OATP) 1B1/B3. 
 
Biotransformation 
In vitro metabolism studies showed that CYP3A4 is the main CYP isozyme mediating alectinib and its 
major metabolite M4 metabolism, and is estimated to contribute 40-50% of alectinib metabolism. 
Results from the human mass balance study demonstrated that alectinib and M4 were the main 
circulating moieties in plasma with 76% of the total radioactivity in plasma. The geometric mean 
Metabolite/Parent ratio at steady state is 0.399.  
Metabolite M1b was detected as a minor metabolite from in vitro and in human plasma in healthy 
subjects. Formation of metabolite M1b and its minor isomer M1a is likely to be catalyzed by a 
combination of CYP isozymes (including isozymes other than CYP3A) and aldehyde dehydrogenase 
(ALDH) enzymes. 
 
In vitro studies indicate that neither alectinib nor its major active metabolite (M4) inhibits CYP1A2, 
CYP2B6, CYP2C9, CYP2C19, or CYP2D6 at clinically relevant concentrations.  Alectinib did not 
inhibit OATP1B1/OATP1B3, OAT1, OAT3 or OCT2 at clinically relevant concentrations in vitro. 
 
Elimination 
Following administration of a single dose of 14C-labeled alectinib administered orally to healthy 
subjects the majority of radioactivity was excreted in faeces (mean recovery 97.8%) with minimal 
excretion in urine (mean recovery 0.46%). In faeces, 84% and 5.8% of the dose was excreted as 
unchanged alectinib or M4, respectively.    
Based on a population PK analysis, the apparent clearance (CL/F) of alectinib was 81.9 L/hour. The 
geometric mean of the individual elimination half-life estimates for alectinib was 32.5 hours. The 
corresponding values for M4 were 217 L/hour and 30.7 hours, respectively.  
 
Pharmacokinetics in special populations 
 
Renal impairment 
Negligible amounts of alectinib and the active metabolite M4 are excreted unchanged in urine (< 0.2% 
of the dose). Based on a population pharmacokinetic analysis alectinib and M4 exposures were similar 
in patients with mild and moderate renal impairment and normal renal function. The pharmacokinetics 
of alectinib has not been studied in patients with severe renal impairment. 
 
Hepatic impairment 
As elimination of alectinib is predominantly through metabolism in the liver, hepatic impairment may 
increase the plasma concentration of alectinib and/or its major metabolite M4. Based on a population 
pharmacokinetic analysis, alectinib and M4 exposures were similar in patients with mild hepatic 
impairment and normal hepatic function.  
 
Following administration of a single oral dose of 300 mg alectinib in subjects with severe (Child-Pugh 
C) hepatic impairment, alectinib Cmax was the same  and AUCinf was 2.2-fold higher compared with the 
same parameters in matched healthy subjects. M4 Cmax and AUCinf was 39% and 34% lower 
respectively, resulting in a combined exposure of alectinib and M4 (AUCinf) 1.8-fold higher in patients 
with severe hepatic impairment compared with matched healthy subjects.  
 
The hepatic impairment study also included a group with moderate (Child-Pugh B) hepatic 
impairment, and a modestly higher alectinib exposure was observed in this  group compared with 
matched healthy subjects. The subjects in the Child Pugh B group however did in general not suffer 
from abnormal bilirubin, albumin or prothrombin time, indicating that they may not be fully 
representative of moderately hepatically impaired subjects with decreased metabolic capacity. 
 



20 

Effects of age, body weight, race and gender 
Age, body weight, race and gender had no clinically meaningful effect on the systemic exposure of 
alectinib and M4. The range of body weights for patients enrolled in clinical studies is 36.9-123 kg. 
There are no available data on patients with extreme body weight (>130 kg) (see section 4.2). 
 
5.3 Preclinical safety data 
 
Carcinogenicity 
Carcinogenicity studies have not been performed to establish the carcinogenic potential of Alecensa. 
 
Mutagenicity 
Alectinib was not mutagenic in vitro in the bacterial reverse mutation (Ames) assay but induced a 
slight increase in numerical aberrations in the in vitro cytogenetic assay using Chinese Hamster Lung 
(CHL) cells with metabolic activation, and micronuclei in a rat bone marrow micronucleus test. The 
mechanism of micronucleus induction was abnormal chromosome segregation (aneugenicity), and not 
a clastogenic effect on chromosomes. 
 
Impairment of fertility 
No fertility studies in animals have been performed to evaluate the effect of Alecensa. No adverse 
effects on male and female reproductive organs were observed in general toxicology studies. These 
studies were conducted in rats and monkeys at exposures equal to or greater than 2.6- and 0.5-fold, 
respectively, of the human exposure, measured by AUC, at the recommended dose of 600 mg twice 
daily. 
 
Teratogenicity 
Alectinib caused embryo-foetal toxicity in pregnant rats and rabbits. In pregnant rats, alectinib caused 
total embryo-foetal loss (miscarriage) at exposures 4.5-fold of the human AUC exposure and small 
foetuses with retarded ossification and minor abnormalities of the organs at exposures 2.7-fold of the 
human AUC exposure. In pregnant rabbits, alectinib caused embryo-foetal loss, small fetuses and 
increased incidence of skeletal variations at exposures 2.9-fold of the human AUC exposure at the 
recommended dose. 
 
Other 
Alectinib absorbs UV light between 200 and 400 nm and demonstrated a phototoxic potential in an in 
vitro photosafety test in cultured murine fibroblasts after UVA irradiation. 
 
Target organs in both rat and monkey at clinically relevant exposures in the repeat-dose toxicology 
studies included, but were not limited to the erythroid system, gastrointestinal tract, and hepatobiliary 
system.  
 
Abnormal erythrocyte morphology was observed at exposures equal or greater than 10-60% the 
human exposure by AUC at the recommended dose. Proliferative zone extension in GI mucosa in both 
species was observed at exposures equal to or greater than 20-120% of the human AUC exposure at 
the recommended dose. Increased hepatic alkaline phosphatase (ALP) and direct bilirubin as well as 
vacuolation/degeneration/necrosis of bile duct epithelium and enlargement/focal necrosis of 
hepatocytes was observed in rats and/or monkeys at exposures equal to or greater than 20-30% of the 
human exposure by AUC at the recommended dose.  
 
A mild hypotensive effect has been observed in monkeys at around clinically relevant exposures. 
 
 



21 

6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Capsule content 
Lactose monohydrate 
Hydroxypropylcellulose 
Sodium laurilsulfate 
Magnesium stearate 
Carmellose calcium 
 
Capsule shell 
Hypromellose 
Carrageenan 
Potassium chloride 
Titanium dioxide (E171) 
Maize starch 
Carnauba wax 
 
Printing ink 
Red iron oxide (E172) 
Yellow iron oxide (E172) 
Indigo carmine aluminum lake (E132) 
Carnauba wax 
White shellac 
Glyceryl monooleate 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
Blisters: 
Store in the original package in order to protect from moisture. 
 
Bottles: 
Store in the original package and keep the bottle tightly closed in order to protect from moisture. 
 
6.5 Nature and contents of container  
 
Aluminium/aluminium (PA/Alu/PVC/Alu) blisters containing 8 hard capsules.  
Pack size: 224 (4 packs of 56) hard capsules. 
 
HDPE bottle with a child-resistant closure and an integrated desiccant.  
Pack size: 240 hard capsules.  
 
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.  



22 

 
 
7. MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1  
79639 Grenzach-Wyhlen  
Germany  
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1169/001 
EU/1/16/1169/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 16 February 2017 
Date of latest renewal: 1 December 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.

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


23 

 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 
 



24 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
Roche Pharma AG 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
GERMANY 
 
 
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  
 
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 agreeed 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.  

 



25 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



26 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



27 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON FOR BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Alecensa 150 mg hard capsules  
alectinib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each hard capsule contains alectinib hydrochloride equivalent to 150 mg alectinib.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose and sodium. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Hard capsule 
 
224 (4 packs of 56) hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use 
Read the package leaflet before 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 
 
Store in the original package in order to protect from moisture 
 
 



28 

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 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1  
79639 Grenzach-Wyhlen  
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1169/001  
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
alecensa 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



29 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
INTERMEDIATE CARTON FOR BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Alecensa 150 mg hard capsules  
alectinib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each hard capsule contains alectinib hydrochloride equivalent to 150 mg alectinib.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose and sodium. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Hard capsule 
 
56 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use 
Read the package leaflet before 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 
 
Store in the original package in order to protect from moisture 
 
 



30 

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 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1  
79639 Grenzach-Wyhlen  
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1169/001  
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
alecensa 
 



31 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Alecensa 150 mg hard capsules  
alectinib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



32 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON FOR BOTTLE  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Alecensa 150 mg hard capsules  
alectinib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each hard capsule contains alectinib hydrochloride equivalent to 150 mg alectinib.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose and sodium. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Hard capsule 
 
240 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use 
Read the package leaflet before 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 
 
Store in the original package and keep the bottle tightly closed in order to protect from moisture 
 
 



33 

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 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1  
79639 Grenzach-Wyhlen  
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1169/002 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
alecensa 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



34 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING  
 
BOTTLE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Alecensa 150 mg hard capsules  
alectinib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each hard capsule contains alectinib hydrochloride equivalent to 150 mg alectinib.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose and sodium. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Hard capsule 
 
240 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use 
Read the package leaflet before 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 
 
Store in the original package and keep the bottle tightly closed in order to protect from moisture 
 
 



35 

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 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1  
79639 Grenzach-Wyhlen  
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1169/002 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 



36 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



37 

Package leaflet: Information for the patient 
 

Alecensa 150 mg hard capsules  
alectinib 

 
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 Alecensa is and what it is used for 
2. What you need to know before you take Alecensa  
3. How to take Alecensa  
4. Possible side effects 
5. How to store Alecensa  
6. Contents of the pack and other information 
 
 
1. What Alecensa is and what it is used for 
 
What Alecensa is 
Alecensa is a cancer medicine that contains the active substance alectinib. 
 
What Alecensa is used for 
Alecensa is used to treat adults with a type of lung cancer called ‘non-small cell lung cancer’ 
(‘NSCLC’). It is used if your lung cancer: 
● is ‘ALK-positive’ - this means your cancer cells have a fault in a gene that makes an enzyme called 

ALK (‘anaplastic lymphoma kinase’), see ‘How Alecensa works’, below 
● and is advanced. 
 
Alecensa can be prescribed to you as first treatment of your lung cancer, or if you have been 
previously treated with a medicine containing ‘crizotinib’. 
 
How Alecensa works 
Alecensa blocks the action of an enzyme called ‘ALK tyrosine kinase’. Abnormal forms of this 
enzyme (due to fault in the gene that makes it) help encourage cancer cell growth. Alecensa may slow 
down or stop the growth of your cancer. It may also help to shrink your cancer. 
 
If you have any questions about how Alecensa works or why this medicine has been prescribed for 
you, ask your doctor, pharmacist or nurse. 
 
 



38 

2. What you need to know before you take Alecensa  
 

Do not take Alecensa: 
● if you are allergic to alectinib or any of the other ingredients of this medicine (listed in section 6). 
If you are not sure, talk to your doctor, pharmacist or nurse before taking Alecensa. 
 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before taking Alecensa: 
● if you have ever had stomach or intestine problems as holes (perforation), or if you have conditions 

causing inflammation inside the abdomen (diverticulitis), or if you have spread of cancer inside the 
abdomen (metastasis). It is possible that Alecensa may increase the risk of developing holes in the 
wall of your gut. 

●  if you have an inherited problem called ‘galactose intolerance’, ‘congenital lactase deficiency’ or 
‘glucose-galactose malabsorption’. 

If you are not sure, talk to your doctor, pharmacist or nurse before taking Alecensa. 
 
Talk to your doctor right away after having taken Alecensa:  
●  if you are experiencing severe stomach or abdominal pain, fever, chills, sickness, vomiting, or     
abdominal rigidity or bloating, as these could be symptoms of a hole in the wall of your gut. 
Alecensa can cause side effects that you need to tell your doctor about straight away. These include: 
● liver injury (hepatotoxicity). Your doctor will take blood tests before you start treatment, then 

every 2 weeks for the first 3 months of your treatment and then less often. This is to check you do 
not have any liver problems while taking Alecensa. Tell your doctor straight away if you get any of 
the following signs: yellowing of your skin or the whites of your eyes, pain on the right side of 
your stomach area, dark urine, itchy skin, feeling less hungry than usual, nausea or vomiting, 
feeling tired, bleeding or bruising more easily than normal. 

● slow heart beat (bradycardia).  
● lung inflammation (pneumonitis). Alecensa may cause severe or life-threatening swelling 

(inflammation) of the lungs during treatment. The signs may be similar to those from your lung 
cancer. Tell your doctor straight away if you have any new or worsening signs including difficulty 
in breathing, shortness of breath, or cough with or without mucous, or fever.  

● severe muscle pain, tenderness, and weakness (myalgia). Your doctor will do blood tests at least 
every 2 weeks for the first month and as needed during treatment with Alecensa. Tell your doctor 
straight away if you get new or worsening signs of muscle problems, including unexplained muscle 
pain or muscle pain that does not go away, tenderness, or weakness. 

 
Look out for these while you are taking Alecensa. See ‘Side effects’ in section 4 for more information. 
Sensitivity to sunlight 
Do not expose yourself to the sun for any long period of time while you are taking Alecensa and for 
7 days after you stop. You need to apply sunscreen and lip balm with a Sun Protection Factor of 50 or 
higher to help prevent sunburn. 
 
Children and adolescents 
Alecensa has not been studied in children or adolescents. Do not give this medicine to children or 
adolescents under the age of 18 years. 
 
Tests and checks 
When you take Alecensa your doctor will do blood tests before you start treatment, then every 2 weeks 
for the first 3 months of your treatment and then less often. This is to check you do not have any liver 
or muscle problems while taking Alecensa. 
 
Other medicines and Alecensa 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
This includes medicines obtained without a prescription, and herbal medicines. This is because 
Alecensa can affect the way some other medicines work. Also some other medicines can affect the 
way Alecensa works. 



39 

 
In particular tell your doctor or pharmacist if you are taking any of the following medicines: 
● digoxin, a medicine used to treat heart problems 
● dabigatran etexilate, a medicine used to treat blood clots 
● methotrexate, a medicine used to treat certain types of cancer or to treat autoimmune diseases (e.g. 

rheumatoid arthritis) 
● nilotinib, a medicine used to treat certain types of cancer 
● lapatinib, a medicine used to treat certain types of breast cancer 
● mitoxantrone, a medicine used to treat certain types of cancer or autoimmune diseases (e.g. 

multiple sclerosis) 
● everolimus, a medicine used to treat certain types of cancer or used to prevent the body’s immune 

system from rejecting a transplanted kidney, heart or liver 
● sirolimus, a medicine used to prevent the body’s immune system from rejecting a transplanted 

kidney, heart or liver 
● topotecan, a medicine used to treat certain types of cancer 
● medicines used to treat AIDS/HIV (e.g. ritonavir, saquinavir)  
● medicines used to treat infections. These include medicines that treat fungal infections (antifungals 

such as ketoconazole, itraconazole, voriconazole, posaconazole) and medicines that treat certain 
types of bacterial infection (antibiotics such as telithromycin) 

● St. John’s Wort, a herbal medicine used to treat depression  
● medicines used to stop seizures or fits (anti-epileptics such as phenytoin, carbamazepine, or 

phenobarbital)  
● medicines used to treat tuberculosis (e.g. rifampicin, rifabutin) 
● nefazodone, a medicine used to treat depression 
 
Oral contraceptives 
If you take Alecensa whilst using oral contraceptives, the oral contraceptives may be less effective. 
 
Alecensa with food and drink 
You should use caution when drinking grapefruit juice or eating grapefruit or Seville oranges while on 
treatment with Alecensa as they may change the amount of Alecensa in your body.  
 
Contraception, pregnancy, and breast-feeding - information for women  
Contraception – information for women 

● You should not become pregnant while taking this medicine. If you are able to become pregnant, 
you must use highly effective contraception while on treatment and for at least 3 months after 
stopping treatment. Talk to your doctor about the right methods of contraception for you and 
your partner. If you take Alecensa whilst using oral contraceptives, the oral contraceptives may 
be less effective. 

 
Pregnancy  

● Do not take Alecensa if you are pregnant. This is because it may harm your baby.  
● If you become pregnant when taking the medicine or during the 3 months after taking your last 

dose, tell your doctor straight away.  
 
Breast-feeding  

● Do not breast-feed while taking this medicine. This is because it is not known if Alecensa can 
pass over into breast milk and could therefore harm your baby. 

 
Driving and using machines 
Take special care when driving and using machines as you may develop problems with vision or 
slowing of the heartbeat or low blood pressure that can lead to fainting or dizziness while you are 
taking Alecensa. 
 
Alecensa contains lactose 
Alecensa contains lactose (a type of sugar). If you have been told by your doctor that you cannot 
tolerate or digest some sugars, talk to your doctor before taking this medicine. 



40 

 
Alecensa contains sodium 
This medicine contains 48 mg sodium (main component of cooking/table salt) per recommended daily 
dose (1200 mg). This is equivalent to 2.4% of the recommended maximum daily dietary intake of 
sodium for an adult. 
 
 
3. How to take Alecensa 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor, 
pharmacist or nurse if you are not sure.  
 
How much to take 
● The recommended dose is 4 capsules (600 mg) twice a day. 
● This means you take a total of 8 capsules (1200 mg) each day. 
 
If you have severe liver problems before starting your treatment with Alecensa: 
● The recommended dose is 3 capsules (450 mg) twice a day.  
● This means you take a total of 6 capsules (900 mg) each day. 
 
Sometimes your doctor may lower your dose, stop your treatment for a short time or stop your 

treatment completely if you feel unwell. 
 
How to take  
● Alecensa is taken by mouth. Swallow each capsule whole. Do not open or dissolve the capsules. 
● You must take Alecensa with food. 
 
If you vomit after taking Alecensa 
If you vomit after taking a dose of Alecensa, do not take an extra dose, just take your next dose at the 
usual time. 
 
If you take more Alecensa than you should 
If you take more Alecensa than you should, talk to a doctor or go to hospital straight away. Take the 
medicine pack and this leaflet with you. 
 
If you forget to take Alecensa 
● If it is more than 6 hours until your next dose, take the missed dose as soon as you remember. 
● If it is less than 6 hours until your next dose, skip the missed dose. Then take your next dose at the 

usual time. 
● Do not take a double dose to make up for a missed dose. 
 
If you stop taking Alecensa 
Do not stop taking this medicine without talking to your doctor first. It is important to take Alecensa 
twice a day for as long as your doctor prescribes it for you. 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 



41 

4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. The 
following side effects may happen with this medicine. 
 
Some side effects could be serious. 
Tell your doctor straight away if you notice any of the following side effects. Your doctor may 
lower your dose, stop your treatment for a short time or stop your treatment completely: 

● Yellowing of your skin or the whites of your eyes, pain on the right side of your stomach area, 
dark urine, itchy skin, feeling less hungry than usual, nausea or vomiting, feeling tired, bleeding 
or bruising more easily than normal (potential signs of liver problems)  

● New or worsening signs of muscle problems, including unexplained muscle pain or muscle pain 
that does not go away, tenderness, or weakness (potential signs of muscle problems). 

● Fainting, dizziness and low blood pressure (potential signs of slow heart beat) 
● New or worsening signs including difficulty in breathing, shortness of breath, or cough with or 

without mucous, or fever - the signs may be similar to those from your lung cancer (potential 
signs of lung inflammation – pneumonitis). Alecensa can cause severe or life-threatening 
inflammation of the lungs during treatment. 

 
Other side effects  
Tell your doctor, pharmacist or nurse if you notice any of the following side effects: 
 
Very common (may affect more than 1 in 10 people):  

● abnormal results of blood tests to check for liver problems (high levels of alanine 
aminotransferase, aspartate aminotransferase and bilirubin) 

● abnormal results of blood tests to check for muscle damage (high level of creatine 
phosphokinase)  

● you may feel tired, weak or short of breath due to a reduction in the number of red blood cells, 
known as anaemia 

● vomiting – if you vomit after taking a dose of Alecensa, do not take an extra dose, just take your 
next dose at the usual time 

● constipation 
● diarrhoea 
● nausea 
● rash 
● swelling caused by fluid build-up in the body (oedema) 
● weight gain. 
 

Common (may affect up to 1 in 10 people): 
● abnormal results of blood tests to check kidney function (high level of creatinine) 
● blurred vision, loss of sight, black dots or white spots in your vision, and seeing double 

(problems with your eyes)  
● abnormal results of blood tests to check for liver disease or bone disorders (high level of 

alkaline phosphatase) 
● inflammation of the mucous membrane of the mouth 
● sensitivity to sunlight – do not expose yourself to the sun for any long period of time while you 

are taking Alecensa and for 7 days after you stop. You need to apply sunscreen and lip balm 
with a Sun Protection Factor of 50 or higher to help prevent sunburn. 

● alteration in sense of taste 
● rapid loss of kidney function (kidney problems). 
 

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. 
 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


42 

 
5. How to store Alecensa 
 
● Keep this medicine out of the sight and reach of children. 
● Do not take this medicine after the expiry date which is stated on the carton and either the blister 

or the bottle after EXP. The expiry date refers to the last day of that month. 
● If Alecensa is packed in blisters, store in the original package in order to protect from moisture. 
● If Alecensa is packed in bottles, store in the original package and keep the bottle tightly closed to 

protect from moisture. 
● 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 Alecensa contains 
● The active substance is alectinib. Each hard capsule contains alectinib hydrochloride equivalent to 

150 mg alectinib.  
● The other ingredients are: 

● Capsule content: lactose monohydrate (see section 2 ‘Alecensa contains lactose’), 
hydroxypropylcellulose, sodium laurilsulfate (see section 2 ‘Alecensa contains sodium’), 
magnesium stearate and carmellose calcium 

● Capsule shell: hypromellose, carrageenan, potassium chloride, titanium dioxide (E171), maize 
starch and carnauba wax 

● Printing ink: red iron oxide (E172), yellow iron oxide (E172), indigo carmine aluminium 
lake (E132), carnauba wax, white shellac and glyceryl monooleate. 

 

What Alecensa looks like and contents of the pack 
Alecensa hard capsule are white, with ‘ALE’ printed in black ink on the cap and ‘150 mg’ printed in 
black ink on the body. 
 
The capsules are provided in blisters and are available in cartons containing 224 hard capsules 
(4 packs of 56). The capsules are also available in plastic bottles containing 240 hard capsules. 
 
Not all pack sizes may be marketed.  
 
Marketing Authorisation Holder  
Roche Registration GmbH 
Emil-Barell-Strasse 1  
79639 Grenzach-Wyhlen  
Germany  
 
Manufacturer 
Roche Pharma AG 
Emil-Barell-Strasse 1 
D-79639 Grenzach-Wyhlen 
Germany 
 



43 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
N.V. Roche S.A. 
Tél/Tel: +32 (0) 2 525 82 11 
 

Lietuva 
UAB “Roche Lietuva” 
Tel: +370 5 2546799 
 

България 
Рош България ЕООД 
Тел: +359 2 818 44 44 
 

Luxembourg/Luxemburg 
(Voir/siehe Belgique/Belgien) 
 

Česká republika 
Roche s. r. o. 
Tel: +420 - 2 20382111 

Magyarország 
Roche (Magyarország) Kft. 
Tel: +36 - 23 446 800 
 

Danmark 
Roche a/s 
Tlf: +45 - 36 39 99 99 
 

Malta 
(See Ireland)  

Deutschland 
Roche Pharma AG 
Tel: +49 (0) 7624 140 
 

Nederland 
Roche Nederland B.V. 
Tel: +31 (0) 348 438050 
 

Eesti 
Roche Eesti OÜ 
Tel: + 372 - 6 177 380 
 

Norge 
Roche Norge AS 
Tlf: +47 - 22 78 90 00 
 

Ελλάδα 
Roche (Hellas) A.E.  
Τηλ: +30 210 61 66 100 
 

Österreich 
Roche Austria GmbH 
Tel: +43 (0) 1 27739 
 

España 
Roche Farma S.A. 
Tel: +34 - 91 324 81 00 
 

Polska 
Roche Polska Sp.z o.o. 
Tel: +48 - 22 345 18 88 
 

France 
Roche 
Tél: +33 (0) 1 47 61 40 00 
 

Portugal 
Roche Farmacêutica Química, Lda 
Tel: +351 - 21 425 70 00 
 

Hrvatska 
Roche d.o.o. 
Tel: +385 1 4722 333 
 

România 
Roche România S.R.L. 
Tel: +40 21 206 47 01 
 

Ireland 
Roche Products (Ireland) Ltd. 
Tel: +353 (0) 1 469 0700 
 

Slovenija 
Roche farmacevtska družba d.o.o. 
Tel: +386 - 1 360 26 00 
 

Ísland  
Roche a/s 
c/o Icepharma hf 
Sími: +354 540 8000 
 

Slovenská republika  
Roche Slovensko, s.r.o. 
Tel: +421 - 2 52638201 
 

Italia 
Roche S.p.A. 
Tel: +39 - 039 2471 
 

Suomi/Finland 
Roche Oy  
Puh/Tel: +358 (0) 10 554 500 
 



44 

Kύπρος  
Γ.Α.Σταμάτης & Σια Λτδ. 
Τηλ: +357 - 22 76 62 76 
 

Sverige 
Roche AB 
Tel: +46 (0) 8 726 1200 
 

Latvija 
Roche Latvija SIA 
Tel: +371 - 6 7039831 

United Kingdom 
Roche Products Ltd. 
Tel: +44 (0) 1707 366000 
 

 
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.  

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


45 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 
 

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS 
OF THE MARKETING AUTHORISATION(S) 

 
 
 
 
 

 



46 

Scientific conclusions 

Taking into account the PRAC Assessment Report on the PSUR(s) for alectinib, the scientific 
conclusions of CHMP are as follows:  

Following the evaluation of the cumulative review and detailed analysis of GI perforation, ulceration, 
haemorrhage or obstruction cases, there were 17 AEs identified for alectinib in 14 patients from 
clinical trials and further 73 cases from post-marketing were identified within the company safety 
database. In all of them some risk factor was present, mostly some concomitant disease (such as 
diverticulitis, appendicitis, gastritis, gastroenteritis, metastases to intestine or ileus of intestine) or 
concomitantly used medications (such as bevacizumab, opioids, dexamethasone or other/unspecified 
corticosteroids).  

The results from toxicology studies, in monkeys treated with alectinib, a dilatation of the large 
intestine was seen, and a decreased stool, no-faeces, and retention of GI contents were seen in both 
rats and monkeys at 60 mg/kg/day and were accompanied by very slight erosions/ulcers in the 
stomach, duodenum, caecum and colon. 

The risk of GI perforation is currently not present in the SmPC for alectinib.  The SmPC for crizotinib 
which also belongs to the ALK inhibitor class includes the GI perforation in sections 4.4 and 4.8.  

The retrieved cases of GI perforation do not provide a clear causal association with alectinib treatment. 
However, considering the results from toxicology studies in monkeys and rats, the seriousness of the 
events of GI perforation which might lead to death and the importance of early recognition and prompt 
medical intervention, it is considered that the product information of alectinib should include the 
warning on possible risk of gastrointestinal perforation in patients who are at higher risk of 
development of such condition and recommended actions in the section 4.4 of SmPC and in the 
corresponding part of the Package leaflet. 

The CHMP agrees with the scientific conclusions made by the PRAC. 

 

Grounds for the variation to the terms of the marketing authorisation(s) 

On the basis of the scientific conclusions for alectinib the CHMP is of the opinion that the benefit-
risk balance of the medicinal product(s) containing alectinib is unchanged subject to the proposed 
changes to the product information 

The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 

 

 
 

 


	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
	SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF THE MARKETING AUTHORISATION(S)