Tasigna

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 

Tasigna 50 mg hard capsules 

Tasigna 200 mg hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Tasigna 50 mg hard capsules 

 

One hard capsule contains 50 mg nilotinib (as hydrochloride monohydrate). 

 

Excipient with known effect 

One hard capsule contains 39.03 mg lactose monohydrate. 

 

Tasigna 200 mg hard capsules 

 

One hard capsule contains 200 mg nilotinib (as hydrochloride monohydrate). 

 

Excipient with known effect 

One hard capsule contains 156.11 mg lactose monohydrate. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Hard capsule. 

 

Tasigna 50 mg hard capsules 

 

White to yellowish powder in hard gelatin capsule with red opaque cap and light yellow opaque body, 

size 4 with black radial imprint “NVR/ABL” on cap. 

 

Tasigna 200 mg hard capsules 

 

White to yellowish powder in light yellow opaque hard gelatin capsules, size 0 with red axial imprint 

“NVR/TKI”. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Tasigna is indicated for the treatment of: 

- adult and paediatric patients with newly diagnosed Philadelphia chromosome positive chronic 
myelogenous leukaemia (CML) in the chronic phase, 

- adult patients with chronic phase and accelerated phase Philadelphia chromosome positive CML 
with resistance or intolerance to prior therapy including imatinib. Efficacy data in patients with 

CML in blast crisis are not available, 

- paediatric patients with chronic phase Philadelphia chromosome positive CML with resistance 
or intolerance to prior therapy including imatinib. 

 

  



3 

4.2 Posology and method of administration 

 

Therapy should be initiated by a physician experienced in the diagnosis and the treatment of patients 

with CML. 

 

Posology 

Treatment should be continued as long as clinical benefit is observed or until unacceptable toxicity 

occurs. 

 

If a dose is missed the patient should not take an additional dose, but take the usual prescribed next 

dose. 

 

Posology for Philadelphia chromosome positive CML adult patients 

The recommended dose is: 

- 300 mg twice daily in newly diagnosed patients with CML in the chronic phase, 
- 400 mg twice daily in patients with chronic or accelerated phase CML with resistance or 

intolerance to prior therapy. 

 

For a dose of 300 mg twice daily, 150 mg hard capsules are available. 

 

Posology for Philadelphia chromosome positive CML paediatric patients 

Dosing in paediatric patients is individualised and is based on body surface area (mg/m2). The 

recommended dose of nilotinib is 230 mg/m2 twice daily, rounded to the nearest 50 mg dose (to a 

maximum single dose of 400 mg) (see Table 1). Different strengths of Tasigna hard capsules can be 

combined to attain the desired dose. 

 

There is no experience with treatment of paediatric patients below 2 years of age. There are no data in 

newly diagnosed paediatric patients below 10 years of age and limited data in imatinib-resistant or 

intolerant paediatric patients below 6 years of age. 

 

Table 1 Paediatric dosing scheme of nilotinib 230 mg/m2 twice daily 

 

Body Surface Area 

(BSA) 

Dose in mg 

(twice daily) 

Up to 0.32 m2 50 mg 

0.33 – 0.54 m2 100 mg 

0.55 – 0.76 m2 150 mg 

0.77 – 0.97 m2 200 mg 

0.98 – 1.19 m2 250 mg 

1.20 – 1.41 m2 300 mg 

1.42 – 1.63 m2 350 mg 

≥1.64 m2 400 mg 

 

Adult Philadelphia chromosome positive CML patients in chronic phase who have been treated with 

nilotinib as first-line therapy and who achieved a sustained deep molecular response (MR4.5) 

Discontinuation of treatment may be considered in eligible adult Philadelphia chromosome positive 

(Ph+) CML patients in chronic phase who have been treated with nilotinib at 300 mg twice daily for a 

minimum of 3 years if a deep molecular response is sustained for a minimum of one year immediately 

prior to discontinuation of therapy. Discontinuation of nilotinib therapy should be initiated by a 

physician experienced in the treatment of patients with CML (see sections 4.4 and 5.1). 

 

Eligible patients who discontinue nilotinib therapy must have their BCR-ABL transcript levels and 

complete blood count with differential monitored monthly for one year, then every 6 weeks for the 

second year, and every 12 weeks thereafter. Monitoring of BCR-ABL transcript levels must be 

performed with a quantitative diagnostic test validated to measure molecular response levels on the 

International Scale (IS) with a sensitivity of at least MR4.5 (BCR-ABL/ABL ≤0.0032% IS). 



4 

 

For patients who lose MR4 (MR4=BCR-ABL/ABL ≤0.01%IS) but not MMR 

(MMR=BCR-ABL/ABL ≤0.1%IS) during the treatment-free phase, BCR-ABL transcript levels should 

be monitored every 2 weeks until BCR-ABL levels return to a range between MR4 and MR4.5. 

Patients who maintain BCR-ABL levels between MMR and MR4 for a minimum of 4 consecutive 

measurements can return to the original monitoring schedule. 

 

Patients who lose MMR must re-initiate treatment within 4 weeks of when loss of remission is known 

to have occurred. Nilotinib therapy should be re-initiated at 300 mg twice daily or at a reduced dose 

level of 400 mg once daily if the patient had a dose reduction prior to discontinuation of therapy. 

Patients who re-initiate nilotinib therapy should have their BCR-ABL transcript levels monitored 

monthly until MMR is re-established and every 12 weeks thereafter (see section 4.4). 

 

Adult Philadelphia chromosome positive CML patients in chronic phase who have achieved a 

sustained deep molecular response (MR 4.5) on nilotinib following prior imatinib therapy 

Discontinuation of treatment may be considered in eligible adult Philadelphia chromosome positive 

(Ph+) CML patients in chronic phase who have been treated with nilotinib for a minimum of 3 years if 

a deep molecular response is sustained for a minimum of one year immediately prior to 

discontinuation of therapy. Discontinuation of nilotinib therapy should be initiated by a physician 

experienced in the treatment of patients with CML (see sections 4.4 and 5.1). 

 

Eligible patients who discontinue nilotinib therapy must have their BCR-ABL transcript levels and 

complete blood count with differential monitored monthly for one year, then every 6 weeks for the 

second year, and every 12 weeks thereafter. Monitoring of BCR-ABL transcript levels must be 

performed with a quantitative diagnostic test validated to measure molecular response levels on the 

International Scale (IS) with a sensitivity of at least MR4.5 (BCR-ABL/ABL ≤0.0032% IS). 

 

Patients with confirmed loss of MR4 (MR4= BCR-ABL/ABL ≤0.01%IS) during the treatment-free 

phase (two consecutive measures separated by at least 4 weeks showing loss of MR4) or loss of major 

molecular response (MMR=BCR-ABL/ABL ≤0.1%IS) must re-initiate treatment within 4 weeks of 

when loss of remission is known to have occurred. Nilotinib therapy should be re-initiated at either 

300 mg or 400 mg twice daily. Patients who re-initiate nilotinib therapy should have their BCR-ABL 

transcript levels monitored monthly until previous major molecular response or MR4 level is 

re-established and every 12 weeks thereafter (see section 4.4). 

 

Dose adjustments or modifications 

Tasigna may need to be temporarily withheld and/or dose reduced for haematological toxicities 

(neutropenia, thrombocytopenia) that are not related to the underlying leukaemia (see Table 2). 

 



5 

Table 2 Dose adjustments for neutropenia and thrombocytopenia 

 

Adult patients with newly 

diagnosed chronic phase 

CML at 300 mg twice 

daily 

and 

imatinib-resistant or 

intolerant CML in 

chronic phase at 400 mg 

twice daily 

ANC* <1.0 x 109/l and/or 

platelet counts <50 x 109/l 

1. Treatment with nilotinib must be 
interrupted and blood count monitored. 

2. Treatment must be resumed within 
2 weeks at prior dose if ANC 

>1.0 x 109/l and/or platelets >50 x 109/l. 

3. If blood counts remain low, a dose 
reduction to 400 mg once daily may be 

required. 

Adult patients with 

imatinib-resistant or 

intolerant CML in 

accelerated phase at 

400 mg twice daily 

ANC* <0.5 x 109/l and/or 

platelet counts <10 x 109/l 

1. Treatment with nilotinib must be 
interrupted and blood count monitored. 

2. Treatment must be resumed within 
2 weeks at prior dose if ANC >1.0 x 

109/l and/or platelets >20 x 109/l. 

3. If blood counts remain low, a dose 
reduction to 400 mg once daily may be 

required. 

Paediatric patients with 

newly diagnosed CML in 

chronic phase at 

230 mg/m2 twice daily 

and 

imatinib-resistant or 

intolerant CML in 

chronic phase at 

230 mg/m2 twice daily 

ANC* <1.0 x 109/l and/or 

platelet counts <50 x 109/l 

1. Treatment with nilotinib must be 
interrupted and blood count monitored. 

2. Treatment must be resumed within 
2 weeks at prior dose if ANC 

>1.5 x 109/l and/or platelets >75 x 109/l. 

3. If blood counts remain low, a dose 
reduction to 230 mg/m2 once daily may 

be required. 

4. If event occurs after dose reduction, 
consider discontinuing treatment. 

*ANC = absolute neutrophil count 

 

If clinically significant moderate or severe non-haematological toxicity develops, dosing should be 

interrupted, and patients should be monitored and treated accordingly. If the prior dose was 300 mg 

twice daily in adult newly diagnosed patients with CML in the chronic phase, or 400 mg twice daily in 

adult patients with imatinib-resistant or intolerant CML in chronic or accelerated phase, or 230 mg/m2 

twice daily in paediatric patients, dosing may be resumed at 400 mg once daily in adult patients and at 

230 mg/m2 once daily in paediatric patients once the toxicity has resolved. If the prior dose was 

400 mg once daily in adult patients or 230 mg/m2 once daily in paediatric patients, treatment should be 

discontinued. If clinically appropriate, re-escalation of the dose to the starting dose of 300 mg twice 

daily in adult newly diagnosed patients with CML in the chronic phase or to 400 mg twice daily in 

adult patients with imatinib-resistant or intolerant CML in chronic or accelerated phase or to 

230 mg/m2 twice daily in paediatric patients should be considered. 

 

Elevated serum lipase: For Grade 3-4 serum lipase elevations, doses in adult patients should be 

reduced to 400 mg once daily or interrupted. In paediatric patients, treatment must be interrupted until 

the event returns to Grade 1. Thereafter, if the prior dose was 230 mg/m2 twice daily, treatment can 

be resumed at 230 mg/m2 once daily. If the prior dose was 230 mg/m2 once daily, treatment should be 

discontinued. Serum lipase levels should be tested monthly or as clinically indicated (see section 4.4). 

 

Elevated bilirubin and hepatic transaminases: For Grade 3-4 bilirubin and hepatic transaminase 

elevations in adult patients, doses should be reduced to 400 mg once daily or interrupted. For 

Grade 2 bilirubin elevations or Grade 3 hepatic transaminase elevations in paediatric patients, 

treatment must be interrupted until the levels return to Grade 1. Thereafter, if the prior dose was 

230 mg/m2 twice daily, treatment can be resumed at 230 mg/m2 once daily. If the prior dose was 

230 mg/m2 once daily, and recovery to Grade 1 takes longer than 28 days, treatment should be 

discontinued. Bilirubin and hepatic transaminases levels should be tested monthly or as clinically 

indicated. 



6 

 

Special populations 

Elderly 

Approximately 12% of subjects in the Phase III study in patients with newly diagnosed CML in 

chronic phase and approximately 30% of subjects in the Phase II study in patients with 

imatinib-resistant or intolerant CML in chronic phase and accelerated phase were 65 years of age or 

over. No major differences were observed for safety and efficacy in patients ≥65 years of age as 

compared to adults aged 18 to 65 years. 

 

Renal impairment 

Clinical studies have not been performed in patients with impaired renal function. 

Since nilotinib and its metabolites are not renally excreted, a decrease in total body clearance is not 

anticipated in patients with renal impairment. 

 

Hepatic impairment 

Hepatic impairment has a modest effect on the pharmacokinetics of nilotinib. Dose adjustment is not 

considered necessary in patients with hepatic impairment. However, patients with hepatic impairment 

should be treated with caution (see section 4.4). 

 

Cardiac disorders 

In clinical studies, patients with uncontrolled or significant cardiac disease (e.g., recent myocardial 

infarction, congestive heart failure, unstable angina or clinically significant bradycardia) were 

excluded. Caution should be exercised in patients with relevant cardiac disorders (see section 4.4). 

 

Increases in total serum cholesterol levels have been reported with nilotinib therapy (see section 4.4). 

Lipid profiles should be determined prior to initiating nilotinib therapy, assessed at month 3 and 6 

after initiating therapy and at least yearly during chronic therapy. 

 

Increases in blood glucose levels have been reported with nilotinib therapy (see section 4.4). Blood 

glucose levels should be assessed prior to initiating nilotinib therapy and monitored during treatment. 

 

Paediatric population 

The safety and efficacy of Tasigna in paediatric patients with Philadelphia chromosome positive CML 

in chronic phase from 2 to less than 18 years of age have been established (see sections 4.8, 5.1 and 

5.2). There is no experience in paediatric patients below 2 years of age or in paediatric patients with 

Philadelphia chromosome positive CML in accelerated phase or blast crisis. There are no data in 

newly diagnosed paediatric patients below 10 years of age and limited data in imatinib-resistant or 

intolerant paediatric patients below 6 years of age. 

 

Method of administration 

 

Tasigna should be taken twice daily approximately 12 hours apart and must not be taken with food. 

The hard capsules should be swallowed whole with water. No food should be consumed for 2 hours 

before the dose is taken and no food should be consumed for at least one hour after the dose is taken. 

 

For patients who are unable to swallow hard capsules, the content of each hard capsule may be 

dispersed in one teaspoon of apple sauce (puréed apple) and should be taken immediately. Not more 

than one teaspoon of apple sauce and no food other than apple sauce must be used (see sections 4.4 

and 5.2). 

 

4.3 Contraindications 
 

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

 



7 

4.4 Special warnings and precautions for use 
 

Myelosuppression 

 

Treatment with nilotinib is associated with (National Cancer Institute Common Toxicity Criteria 

grade 3-4) thrombocytopenia, neutropenia and anaemia. Occurrence is more frequent in patients with 

imatinib-resistant or intolerant CML, in particular in patients with accelerated-phase CML. Complete 

blood counts should be performed every two weeks for the first 2 months and then monthly thereafter, 

or as clinically indicated. Myelosuppression was generally reversible and usually managed by 

withholding Tasigna temporarily or dose reduction (see section 4.2). 

 

QT prolongation 

 

Nilotinib has been shown to prolong cardiac ventricular repolarisation as measured by the QT interval 

on the surface ECG in a concentration-dependent manner in adult and paediatric patients. 

 

In the Phase III study in patients with newly diagnosed CML in chronic phase receiving 300 mg 

nilotinib twice daily, the change from baseline in mean time-averaged QTcF interval at steady state 

was 6 msec. No patient had a QTcF >480 msec. No episodes of torsade de pointes were observed. 

 

In the Phase II study in imatinib-resistant and intolerant CML patients in chronic and accelerated 

phase receiving 400 mg nilotinib twice daily, the change from baseline in mean time-averaged QTcF 

interval at steady state was 5 and 8 msec, respectively. QTcF of >500 msec was observed in <1% of 

these patients. No episodes of torsade de pointes were observed in clinical studies. 

 

In a healthy volunteer study with exposures that were comparable to the exposures observed in 

patients, the time-averaged mean placebo-subtracted QTcF change from baseline was 7 msec 

(CI ± 4 msec). No subject had a QTcF >450 msec. Additionally, no clinically relevant arrhythmias 

were observed during the conduct of the trial. In particular, no episodes of torsade de pointes (transient 

or sustained) were observed. 

 

Significant prolongation of the QT interval may occur when nilotinib is inappropriately taken with 

strong CYP3A4 inhibitors and/or medicinal products with a known potential to prolong the QT 

interval, and/or food (see section 4.5). The presence of hypokalaemia and hypomagnesaemia may 

further enhance this effect. Prolongation of the QT interval may expose patients to the risk of fatal 

outcome. 

 

Tasigna should be used with caution in patients who have or who are at significant risk of developing 

prolongation of QTc, such as those: 

- with congenital long QT prolongation 
- with uncontrolled or significant cardiac disease including recent myocardial infarction, 

congestive heart failure, unstable angina or clinically significant bradycardia. 

- taking anti-arrhythmic medicinal products or other substances that lead to QT prolongation. 
 

Close monitoring for an effect on the QTc interval is advisable and a baseline ECG is recommended 

prior to initiating nilotinib therapy and as clinically indicated. Hypokalaemia or hypomagnesaemia 

must be corrected prior to Tasigna administration and should be monitored periodically during 

therapy. 

 

Sudden death 

 

Uncommon cases (0.1 to 1%) of sudden deaths have been reported in patients with imatinib-resistant 

or intolerant CML in chronic phase or accelerated phase with a past medical history of cardiac disease 

or significant cardiac risk factors. Co-morbidities in addition to the underlying malignancy were also 

frequently present as were concomitant medicinal products. Ventricular repolarisation abnormalities 

may have been contributory factors. No cases of sudden death were reported in the Phase III study in 

newly diagnosed patients with CML in chronic phase. 



8 

 

Fluid retention and oedema 

 

Severe forms of drug-related fluid retention such as pleural effusion, pulmonary oedema, and 

pericardial effusion were uncommonly (0.1 to 1%) observed in a Phase III study of newly diagnosed 

CML patients. Similar events were observed in post-marketing reports. Unexpected, rapid weight gain 

should be carefully investigated. If signs of severe fluid retention appear during treatment with 

nilotinib, the aetiology should be evaluated and patients treated accordingly (see section 4.2 for 

instructions on managing non-haematological toxicities). 

 

Cardiovascular events 

 

Cardiovascular events were reported in a randomised Phase III study in newly diagnosed CML 

patients and observed in post-marketing reports. In this clinical study with a median on-therapy time 

of 60.5 months, Grade 3-4 cardiovascular events included peripheral arterial occlusive disease (1.4% 

and 1.1% at 300 mg and 400 mg nilotinib twice daily, respectively), ischaemic heart disease (2.2% and 

6.1% at 300 mg and 400 mg nilotinib twice daily, respectively) and ischaemic cerebrovascular events 

(1.1% and 2.2% at 300 mg and 400 mg nilotinib twice daily, respectively). Patients should be advised 

to seek immediate medical attention if they experience acute signs or symptoms of cardiovascular 

events. The cardiovascular status of patients should be evaluated and cardiovascular risk factors 

monitored and actively managed during nilotinib therapy according to standard guidelines. 

Appropriate therapy should be prescribed to manage cardiovascular risk factors (see section 4.2 for 

instructions on managing non-haematological toxicities). 

 

Hepatitis B reactivation 

 

Reactivation of hepatitis B in patients who are chronic carriers of this virus has occurred after these 

patients received BCR-ABL tyrosine kinase inhibitors. Some cases resulted in acute hepatic failure or 

fulminant hepatitis leading to liver transplantation or a fatal outcome. 

 

Patients should be tested for HBV infection before initiating treatment with nilotinib. Experts in liver 

disease and in the treatment of hepatitis B should be consulted before treatment is initiated in patients 

with positive hepatitis B serology (including those with active disease) and for patients who test 

positive for HBV infection during treatment. Carriers of HBV who require treatment with nilotinib 

should be closely monitored for signs and symptoms of active HBV infection throughout therapy and 

for several months following termination of therapy (see section 4.8). 
 

Special monitoring of adult Ph+ CML patients in chronic phase who have achieved a sustained deep 

molecular response 

 

Eligibility for discontinuation of treatment 

Eligible patients who are confirmed to express the typical BCR-ABL transcripts, e13a2/b2a2 or 

e14a2/b3a2, can be considered for treatment discontinuation. Patients must have typical BCR-ABL 

transcripts to allow quantitation of BCR-ABL, evaluation of the depth of molecular response, and 

determination of a possible loss of molecular remission after discontinuation of treatment with 

nilotinib. 

 

Monitoring of patients who have discontinued therapy 

Frequent monitoring of BCR-ABL transcript levels in patients eligible for treatment discontinuation 

must be performed with a quantitative diagnostic test validated to measure molecular response levels 

with a sensitivity of at least MR4.5 (BCR-ABL/ABL ≤0.0032% IS). BCR-ABL transcript levels must 

be assessed prior to and during treatment discontinuation (see sections 4.2 and 5.1). 

 

  



9 

Loss of major molecular response (MMR=BCR-ABL/ABL ≤0.1%IS) in CML patients who received 

nilotinib as first- or second-line therapy, or confirmed loss of MR4 (two consecutive measures 
separated by at least 4 weeks showing loss of MR4 (MR4=BCR-ABL/ABL ≤0.01%IS)) in CML 

patients who received nilotinib as second-line therapy will trigger treatment re-initiation within 
4 weeks of when loss of remission is known to have occurred. Molecular relapse can occur during the 

treatment-free phase, and long-term outcome data are not yet available. It is therefore crucial to 

perform frequent monitoring of BCR-ABL transcript levels and complete blood count with differential 

in order to detect possible loss of remission (see section 4.2). For patients who fail to achieve MMR 

after three months of treatment re-initiation, BCR-ABL kinase domain mutation testing should be 

performed. 

 

Laboratory tests and monitoring 

 

Blood lipids 

In a Phase III study in newly diagnosed CML patients, 1.1% of the patients treated with 400 mg 

nilotinib twice daily showed a Grade 3-4 elevation in total cholesterol; no Grade 3-4 elevations were 

however observed in the 300 mg twice daily dose group (see section 4.8). It is recommended that the 

lipid profiles be determined before initiating treatment with nilotinib, assessed at month 3 and 6 after 

initiating therapy and at least yearly during chronic therapy (see section 4.2). If a HMG-CoA reductase 

inhibitor (a lipid-lowering agent) is required, please refer to section 4.5 before initiating treatment 

since certain HMG-CoA reductase inhibitors are also metabolised by the CYP3A4 pathway. 

 

Blood glucose 

In a Phase III study in newly diagnosed CML patients, 6.9% and 7.2% of the patients treated with 

400 mg nilotinib and 300 mg nilotinib twice daily, respectively, showed a Grade 3-4 elevation in 

blood glucose. It is recommended that the glucose levels be assessed before initiating treatment with 

Tasigna and monitored during treatment, as clinically indicated (see section 4.2). If test results warrant 

therapy, physicians should follow their local standards of practice and treatment guidelines. 

 

Interactions with other medicinal products 

 

The administration of Tasigna with agents that are strong CYP3A4 inhibitors (including, but not 

limited to, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir) should 

be avoided. Should treatment with any of these agents be required, it is recommended that nilotinib 

therapy be interrupted if possible (see section 4.5). If transient interruption of treatment is not possible, 

close monitoring of the individual for prolongation of the QT interval is indicated (see sections 4.2, 

4.5 and 5.2). 

 

Concomitant use of nilotinib with medicinal products that are potent inducers of CYP3A4 (e.g., 

phenytoin, rifampicin, carbamazepine, phenobarbital and St. John’s Wort) is likely to reduce exposure 

to nilotinib to a clinically relevant extent. Therefore, in patients receiving nilotinib, co-administration 

of alternative therapeutic agents with less potential for CYP3A4 induction should be selected (see 

section 4.5). 

 

Food effect 

 

The bioavailability of nilotinib is increased by food. Tasigna must not be taken in conjunction with 

food (see sections 4.2 and 4.5) and should be taken 2 hours after a meal. No food should be consumed 

for at least one hour after the dose is taken. Grapefruit juice and other foods that are known to inhibit 

CYP3A4 should be avoided. For patients who are unable to swallow hard capsules, the content of each 

hard capsule may be dispersed in one teaspoon of apple sauce and should be taken immediately. Not 

more than one teaspoon of apple sauce and no food other than apple sauce must be used (see 

section 5.2). 

 

  



10 

Hepatic impairment 

 

Hepatic impairment has a modest effect on the pharmacokinetics of nilotinib. Single dose 

administration of 200 mg of nilotinib resulted in increases in AUC of 35%, 35% and 19% in subjects 

with mild, moderate and severe hepatic impairment, respectively, compared to a control group of 

subjects with normal hepatic function. The predicted steady-state Cmax of nilotinib showed an increase 

of 29%, 18% and 22%, respectively. Clinical studies have excluded patients with alanine transaminase 

(ALT) and/or aspartate transaminase (AST) >2.5 (or >5, if related to disease) times the upper limit of 

the normal range and/or total bilirubin >1.5 times the upper limit of the normal range. Metabolism of 

nilotinib is mainly hepatic. Patients with hepatic impairment might therefore have increased exposure 

to nilotinib and should be treated with caution (see section 4.2). 

 

Serum lipase 

 

Elevation in serum lipase has been observed. Caution is recommended in patients with previous 

history of pancreatitis. In case lipase elevations are accompanied by abdominal symptoms, nilotinib 

therapy should be interrupted and appropriate diagnostic measures considered to exclude pancreatitis. 

 

Total gastrectomy 

 

The bioavailability of nilotinib might be reduced in patients with total gastrectomy (see section 5.2). 

More frequent follow-up of these patients should be considered. 

 

Tumour lysis syndrome 

 

Due to possible occurrence of tumour lysis syndrome (TLS) correction of clinically significant 

dehydration and treatment of high uric acid levels are recommended prior to initiating nilotinib 

therapy (see section 4.8). 

 

Lactose 

 

Tasigna hard capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, 

the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. 

 

Paediatric population 

 

Laboratory abnormalities of mild to moderate transient elevations of aminotransferases and total 

bilirubin have been observed in children at a higher frequency than in adults, indicating a higher risk 

of hepatotoxicity in the paediatric population (see section 4.8). Liver function (bilirubin and hepatic 

transaminases levels) should be monitored monthly or as clinically indicated. Elevations of bilirubin 

and hepatic transaminases should be managed by withholding nilotinib temporarily, dose reduction 

and/or discontinuation of nilotinib (see section 4.2). The long-term effects of prolonged treatment with 

nilotinib in paediatric patients are unknown. In a study in the CML paediatric population, growth 

retardation has been documented in patients treated with nilotinib (see section 4.8). Close monitoring 

of growth in paediatric patients under nilotinib treatment is recommended. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Tasigna may be given in combination with haematopoietic growth factors such as erythropoietin or 

granulocyte colony-stimulating factor (G-CSF) if clinically indicated. It may be given with 

hydroxyurea or anagrelide if clinically indicated. 

 

Nilotinib is mainly metabolised in the liver with CYP3A4 expected to be the main contributor to the 

oxidative metabolism. Nilotinib is also a substrate for the multi-drug efflux pump, P-glycoprotein 

(P-gp). Therefore, absorption and subsequent elimination of systemically absorbed nilotinib may be 

influenced by substances that affect CYP3A4 and/or P-gp. 

 



11 

Substances that may increase nilotinib serum concentrations 

 
Concomitant administration of nilotinib with imatinib (a substrate and moderator of P-gp and 

CYP3A4), had a slight inhibitory effect on CYP3A4 and/or P-gp. The AUC of imatinib was increased 

by 18% to 39%, and the AUC of nilotinib was increased by 18% to 40%. These changes are unlikely 

to be clinically important. 

 

The exposure to nilotinib in healthy subjects was increased 3-fold when co-administered with the 

strong CYP3A4 inhibitor ketoconazole. Concomitant treatment with strong CYP3A4 inhibitors, 

including ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, and telithromycin, 

should therefore be avoided (see section 4.4). Increased exposure to nilotinib might also be expected 

with moderate CYP3A4 inhibitors. Alternative concomitant medicinal products with no or minimal 

CYP3A4 inhibition should be considered. 

 

Substances that may decrease nilotinib serum concentrations 

 
Rifampicin, a potent CYP3A4 inducer, decreases nilotinib Cmax by 64% and reduces nilotinib AUC by 

80%. Rifampicin and nilotinib should not be used concomitantly. 

 

The concomitant administration of other medicinal products that induce CYP3A4 (e.g. phenytoin, 

carbamazepine, phenobarbital and St. John’s Wort) is likewise likely to reduce exposure to nilotinib to 

a clinically relevant extent. In patients for whom CYP3A4 inducers are indicated, alternative agents 

with less enzyme induction potential should be selected. 

 

Nilotinib has pH dependent solubility, with lower solubility at higher pH. In healthy subjects receiving 

esomeprazole at 40 mg once daily for 5 days, gastric pH was markedly increased, but nilotinib 

absorption was only decreased modestly (27% decrease in Cmax and 34% decrease in AUC0-∞). 

Nilotinib may be used concurrently with esomeprazole or other proton pump inhibitors as needed. 

 

In a healthy subjects study, no significant change in nilotinib pharmacokinetics was observed when a 

single 400 mg dose of nilotinib was administered 10 hours after and 2 hours before famotidine. 

Therefore, when the concurrent use of a H2 blocker is necessary, it may be administered 

approximately 10 hours before and approximately 2 hours after the dose of Tasigna. 

 

In the same study as above, administration of an antacid (aluminium hydroxide/magnesium 

hydroxide/simethicone) 2 hours before or after a single 400 mg dose of nilotinib also did not alter 

nilotinib pharmacokinetics. Therefore, if necessary, an antacid may be administered approximately 

2 hours before or approximately 2 hours after the dose of Tasigna. 

 

Substances that may have their systemic concentration altered by nilotinib 

 

In vitro, nilotinib is a relatively strong inhibitor of CYP3A4, CYP2C8, CYP2C9, CYP2D6 and 

UGT1A1, with Ki value being lowest for CYP2C9 (Ki=0.13 microM). 

 

A single-dose drug-drug interaction study in healthy volunteers with 25 mg warfarin, a sensitive 

CYP2C9 substrate, and 800 mg nilotinib did not result in any changes in warfarin pharmacokinetic 

parameters or warfarin pharmacodynamics measured as prothrombin time (PT) and international 

normalised ratio (INR). There are no steady-state data. This study suggests that a clinically meaningful 

drug-drug interaction between nilotinib and warfarin is less likely up to a dose of 25 mg of warfarin. 

Due to lack of steady-state data, control of warfarin pharmacodynamic markers (INR or PT) following 

initiation of nilotinib therapy (at least during the first 2 weeks) is recommended. 

 

  



12 

In CML patients, nilotinib administered at 400 mg twice daily for 12 days increased the systemic 

exposure (AUC and Cmax) of oral midazolam (a substrate of CYP3A4) 2.6-fold and 2.0-fold, 

respectively. Nilotinib is a moderate CYP3A4 inhibitor. As a result, the systemic exposure of other 

medicinal products primarily metabolised by CYP3A4 (e.g. certain HMG-CoA reductase inhibitors) 

may be increased when co-administered with nilotinib. Appropriate monitoring and dose adjustment 

may be necessary for medicinal products that are CYP3A4 substrates and have a narrow therapeutic 

index (including but not limited to alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, 

sirolimus and tacrolimus) when co-administered with nilotinib. 

 

Anti-arrhythmic medicinal products and other substances that may prolong the QT interval 

 

Nilotinib should be used with caution in patients who have or may develop prolongation of the QT 

interval, including those patients taking anti-arrhythmic medicinal products such as amiodarone, 

disopyramide, procainamide, quinidine and sotalol or other medicinal products that may lead to QT 

prolongation such as chloroquine, halofantrine, clarithromycin, haloperidol, methadone and 

moxifloxacin (see section 4.4). 

 

Food interactions 

 

The absorption and bioavailability of nilotinib are increased if it is taken with food, resulting in a 

higher serum concentration (see sections 4.2, 4.4 and 5.2). Grapefruit juice and other foods that are 

known to inhibit CYP3A4 should be avoided. 

 

Paediatric population 

 

Interaction studies have only been performed in adults. 

 

4.6 Fertility, pregnancy and lactation 
 

Women of childbearing potential/Contraception 

 

Women of childbearing potential have to use highly effective contraception during treatment with 

nilotinib and for up to two weeks after ending treatment. 

 

Pregnancy 

 

There are no or limited amount of data from the use of nilotinib in pregnant women. Studies in 

animals have shown reproductive toxicity (see section 5.3). Tasigna should not be used during 

pregnancy unless the clinical condition of the woman requires treatment with nilotinib. If it is used 

during pregnancy, the patient must be informed of the potential risk to the foetus. 

 

If a woman who is being treated with nilotinib is considering pregnancy, treatment discontinuation 

may be considered based on the eligibility criteria for discontinuing treatment as described in 

sections 4.2 and 4.4. There is a limited amount of data on pregnancies in patients while attempting 

treatment-free remission (TFR). If pregnancy is planned during the TFR phase, the patient must be 

informed of a potential need to re-initiate nilotinib treatment during pregnancy (see sections 4.2 and 

4.4). 

 

Breast-feeding 

 

It is unknown whether nilotinib is excreted in human milk. Available toxicological data in animals 

have shown excretion of nilotinib in milk (see section 5.3). Since a risk to the newborns/infants cannot 

be excluded, women should not breast-feed during Tasigna treatment and for 2 weeks after the last 

dose. 

 



13 

Fertility 

 

Animal studies did not show an effect on fertility in male and female rats (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

Tasigna has no or negligible influence on the ability to drive and use machines. However, it is 

recommended that patients experiencing dizziness, fatigue, visual impairment or other undesirable 

effects with a potential impact on the ability to drive or use machines safely should refrain from these 

activities as long as the undesirable effects persist (see section 4.8). 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

The data described below reflect exposure to nilotinib in a total of 737 adult patients from a 

randomised Phase III study in patients with newly diagnosed Ph+ CML in chronic phase treated at the 

recommended dose of 300 mg twice daily (n=279) and from an open-label multicentre Phase II study 

in adult patients with imatinib-resistant or intolerant CML in chronic phase (n=321) and accelerated 

phase (n=137) treated at the recommended dose of 400 mg twice daily. Safety information from two 

Tasigna treatment discontinuation studies is also provided. 

 

In adult patients with newly diagnosed CML in chronic phase 

The median duration of exposure was 60.5 months (range 0.1-70.8 months). 

 

The most frequent (≥10%) non-haematological adverse reactions were rash, pruritus, headache, 

nausea, fatigue, alopecia, myalgia and upper abdominal pain. Most of these adverse reactions were 

mild to moderate in severity. Constipation, dry skin, asthenia, muscle spasms, diarrhoea, arthralgia, 

abdominal pain, vomiting and peripheral oedema were observed less commonly (<10% and ≥5%) 

were of mild to moderate severity, manageable and generally did not require dose reduction. 

 

Treatment-emergent haematological toxicities include myelosuppression: thrombocytopenia (18%), 

neutropenia (15%) and anaemia (8%). Biochemical adverse drug reactions include alanine 

aminotransferase increased (24%), hyperbilirubinaemia (16%), aspartate aminotransferase increased 

(12%), lipase increased (11%), blood bilirubin increased (10%), hyperglycaemia (4%), 

hypercholesterolaemia (3%) and hypertriglyceridaemia (<1%). Pleural and pericardial effusions, 

regardless of causality, occurred in 2% and <1% of patients, respectively, receiving nilotinib 300 mg 

twice daily. Gastrointestinal haemorrhage, regardless of causality, was reported in 3% of these 

patients. 

 

The change from baseline in mean time-averaged QTcF interval at steady state was 6 msec. No patient 

had an absolute QTcF >500 msec while on the study medicinal product. QTcF increase from baseline 

exceeding 60 msec was observed in <1% of patients while on the study medicinal product. No sudden 

deaths or episodes of torsade de pointes (transient or sustained) were observed. No decrease from 

baseline in mean left ventricular ejection fraction (LVEF) was observed at any time during treatment. 

No patient had a LVEF of <45% during treatment nor an absolute reduction in LVEF of more than 

15%. 

 

Discontinuation due to adverse drug reactions was observed in 10% of patients. 

 

In adult patients with imatinib-resistant or intolerant CML in chronic phase and accelerated phase 

The data described below reflect exposure to nilotinib in 458 adult patients in an open-label 

multicentre Phase II study in patients with imatinib-resistant or intolerant CML in chronic phase 

(n=321) and accelerated phase (n=137) treated at the recommended dose of 400 mg twice daily. 

 

  



14 

The most frequent (≥10%) non-haematological drug-related adverse events were rash, pruritus, 

nausea, fatigue, headache, vomiting, myalgia, constipation and diarrhoea. Most of these adverse events 

were mild to moderate in severity. Alopecia, muscle spasms, decreased appetite, arthralgia, abdominal 

pain, bone pain, peripheral oedema, asthenia, upper abdominal pain, dry skin, erythema and pain in 

extremity were observed less commonly (<10% and ≥5%) and have been of mild to moderate severity 

(Grade 1 or 2). Discontinuation due to adverse drug reactions was observed in 16% of chronic phase 

and 10% of accelerated phase patients. 

 

Treatment-emergent haematological toxicities include myelosuppression: thrombocytopenia (31%), 

neutropenia (17%) and anaemia (14%). Pleural and pericardial effusions as well as complications of 

fluid retention occurred in <1% of patients receiving Tasigna. Cardiac failure was observed in <1% of 

patients. Gastrointestinal and CNS haemorrhage were reported in 1% and <1% of patients, 

respectively. 

 

QTcF exceeding 500 msec was observed in <1% of patients. No episodes of torsade de pointes 

(transient or sustained) were observed. 

 

Tabulated list of adverse reactions 

 

The adverse reactions are ranked under heading of frequency 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 

<1/1,000), 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. 

 

Most frequently reported adverse reactions in Tasigna clinical studies 

Non-haematological adverse reactions (excluding laboratory abnormalities) that are reported in at least 

5% of the adult patients in Tasigna clinical studies that serve as the basis for the approved indications 

are shown in Table 3. 

 



15 

Table 3 Non-haematological adverse reactions (≥5% of all patients)* 
 

 Newly diagnosed CML-CP 

300 mg twice daily 

 

n=279 

Imatinib-resistant or intolerant 

CML-CP and CML-AP 

400 mg twice daily 

n=458 

 60-month analysis 24-month analysis 

 

System organ 

class/ 

Adverse 

reaction 

 

Frequency 

 

All 

grades 

 

 

Grade 

3-4 

 

Frequency 

 

All 

grades 

 

Grade 

3-4 

CML-

CP 

n=321 

Grade 

3-4 

CML-

AP 

n=137 

Grade 

3-4 

  % %  % % % % 

Metabolism and nutrition disorders 

Decreased 

appetite ** 

Common 4 0 Common 8 <1 <1 0 

Nervous system disorders 

Headache Very 

common 

16 2 Very 

common 

15 1 2 <1 

Gastrointestinal disorders 

Nausea Very 

common 

14 <1 Very 

common 

20 <1 <1 <1 

Constipation Common 10 0 Very 

common 

12 <1 <1 0 

Diarrhoea Common 9 <1 Very 

common 

11 2 2 <1 

Vomiting Common 6 0 Very 

common 

10 <1 <1 0 

Upper 

abdominal pain 

Very 

common 

10 1 Common 5 <1 <1 0 

Abdominal 

pain 

Common 6 0 Common 6 <1 <1 <1 

Dyspepsia Common 5 0 Common 3 0 0 0 

Skin and subcutaneous tissue disorders 

Rash Very 

common 

33 <1 Very 

common 

28 1 2 0 

Pruritus Very 

common 

18 <1 Very 

common 

24 <1 <1 0 

Alopecia Very 

common 

10 0 Common 9 0 0 0 

Dry skin Common 10 0 Common 5 0 0 0 

Erythema Common 3 0 Common 5 <1 <1 0 

Musculoskeletal and connective tissue disorders 

Myalgia Very 

common 

10 <1 Very 

common 

10 <1 <1 <1 

Muscle spasms Common 9 0 Common 8 <1 <1 0 

Arthralgia Common 8 <1 Common 7 <1 1 0 

Bone pain Common 4 0 Common 6 <1 <1 0 

Pain in 

extremity 

Common 5 <1 Common 5 <1 <1 <1 



16 

General disorders and administration site conditions 

Fatigue Very 

common 

12 0 Very 

common 

17 1 1 <1 

Asthenia Common 9 <1 Common 6 0 0 0 

Oedema 

peripheral 

Common 5 <1 Common 6 0 0 0 

* Percentages are rounded to integer for presentation in this table. However, percentages with one 

decimal precision are used to identify terms with a frequency of at least 5% and to classify terms 

according to frequency categories. 

**Also includes preferred term anorexia 

 

Adverse reactions that were reported in adult patients in the Tasigna clinical studies which serve as a 

basis for the approved indications at a frequency of less than 5% are shown in Table 4. For laboratory 

abnormalities, very common adverse reactions not included in Table 3 are also reported. These 

adverse reactions are included based on clinical relevance. 

 

Table 4 Adverse reactions in adult patients in Tasigna clinical studies (<5% of all patients) 

 

Infections and infestations 

Common: Folliculitis, upper respiratory tract infection (including pharyngitis, 

nasopharyngitis, rhinitis) 

Uncommon: Pneumonia, urinary tract infection, gastroenteritis, bronchitis, herpes virus 

infection, candidiasis (including oral candidiasis) 

Not known: Sepsis, subcutaneous abscess, anal abscess, furuncle, tinea pedis, hepatitis B 

reactivation 

Neoplasms benign, malignant and unspecified (including cysts and polyps) 

Common: Skin papilloma 

Not known: Oral papilloma, paraproteinaemia 

Blood and lymphatic system disorders 

Common: Leukopenia, eosinophilia, febrile neutropenia, pancytopenia, lymphopenia 

Uncommon: Thrombocythaemia, leukocytosis 

Immune system disorders 

Not known: Hypersensitivity 

Endocrine disorders 

Uncommon: Hyperthyroidism, hypothyroidism 

Not known: Hyperparathyroidism secondary, thyroiditis 

Metabolism and nutrition disorders 

Very common: Hypophosphataemia (including blood phosphorus decreased) 

Common: Electrolyte imbalance (including hypomagnesaemia, hyperkalaemia, 

hypokalaemia, hyponatraemia, hypocalcaemia, hypercalcaemia, 

hyperphosphataemia), diabetes mellitus, hyperglycaemia, 

hypercholesterolaemia, hyperlipidaemia, hypertriglyceridaemia 

Uncommon: Dehydration, increased appetite, gout, dyslipidaemia 

Not known: Hyperuricaemia, hypoglycaemia 

Psychiatric disorders 

Common: Depression, insomnia, anxiety 

Not known: Disorientation, confusional state, amnesia, dysphoria 

Nervous system disorders 

Common: Dizziness, peripheral neuropathy, hypoaesthesia, paraesthesia 

Uncommon: Intracranial haemorrhage, ischaemic stroke, transient ischaemic attack, 

cerebral infarction, migraine, loss of consciousness (including syncope), 

tremor, disturbance in attention, hyperaesthesia 

Not known: Cerebrovascular accident, brain oedema, optic neuritis, lethargy, dysaesthesia, 

restless legs syndrome 



17 

Eye disorders 

Common: Eye haemorrhage, periorbital oedema, eye pruritus, conjunctivitis, dry eye 

(including xerophthalmia) 

Uncommon: Visual impairment, vision blurred, conjunctival haemorrhage, visual acuity 

reduced, eyelid oedema, photopsia, hyperaemia (scleral, conjunctival, ocular), 

eye irritation 

Not known: Papilloedema, chorioretinopathy, diplopia, photophobia, eye swelling, 

blepharitis, eye pain, conjunctivitis allergic, ocular surface disease 

Ear and labyrinth disorders 

Common: Vertigo 

Not known: Hearing impaired, ear pain, tinnitus 

Cardiac disorders 

Common: Angina pectoris, arrhythmia (including atroventricular block, cardiac flutter, 

extrasystoles, tachycardia, atrial fibrillation, bradycardia), palpitations, 

electrocardiogram QT prolonged 

Uncommon: Cardiac failure, myocardial infarction, coronary artery disease, cardiac 

murmur, pericardial effusion, cyanosis 

Not known: Ventricular dysfunction, pericarditis, ejection fraction decreased 

Vascular disorders 

Common: Hypertension, flushing, peripheral artery stenosis 

Uncommon: Hypertensive crisis, peripheral arterial occlusive disease, intermittent 

claudication, arterial stenosis limb, haematoma, arteriosclerosis 

Not known: Shock haemorrhagic, hypotension, thrombosis 

Respiratory, thoracic and mediastinal disorders 

Common: Dyspnoea, dyspnoea exertional, epistaxis, cough, dysphonia 

Uncommon: Pulmonary oedema, pleural effusion, interstitial lung disease, pleuritic pain, 

pleurisy, pharyngolaryngeal pain, throat irritation 

Not known: Pulmonary hypertension, wheezing, oropharyngeal pain 

Gastrointestinal disorders 

Common: Pancreatitis, abdominal discomfort, abdominal distension, dysgeusia, 

flatulence 

Uncommon: Gastrointestinal haemorrhage, melaena, mouth ulceration, gastroesophageal 

reflux, stomatitis, oesophageal pain, dry mouth, gastritis, sensitivity of teeth 

Not known: Gastrointestinal ulcer perforation, retroperitoneal haemorrhage, 

haematemesis, gastric ulcer, oesophagitis ulcerative, subileus, enterocolitis, 

haemorrhoids, hiatus hernia, rectal haemorrhage, gingivitis 

Hepatobiliary disorders 

Very common: Hyperbilirubinaemia (including blood bilirubin increased) 

Common: Hepatic function abnormal 

Uncommon: Hepatotoxicity, toxic hepatitis, jaundice 

Not known: Cholestasis, hepatomegaly 

Skin and subcutaneous tissue disorders 

Common: Night sweats, eczema, urticaria, hyperhidrosis, contusion, acne, dermatitis 

(including allergic, exfoliative and acneiform) 

Uncommon: Exfoliative rash, drug eruption, skin pain, ecchymosis, swelling face 

Not known: Erythema multiforme, erythema nodosum, skin ulcer, palmar-plantar 

erythrodysaesthesia syndrome, petechiae, photosensitivity, blister, dermal 

cysts, sebaceous hyperplasia, skin atrophy, skin discolouration, skin 

exfoliation, skin hyperpigmentation, skin hypertrophy, hyperkeratosis, 

psoriasis 

Musculoskeletal and connective tissue disorders 

Common: Musculoskeletal chest pain, musculoskeletal pain, back pain, flank pain, neck 

pain, muscular weakness 

Uncommon: Musculoskeletal stiffness, joint swelling 

Not known: Arthritis 



18 

Renal and urinary disorders 

Common: Pollakiuria 

Uncommon: Dysuria, micturition urgency, nocturia 

Not known: Renal failure, haematuria, urinary incontinence, chromaturia 

Reproductive system and breast disorders 

Uncommon: Breast pain, gynaecomastia, erectile dysfunction 

Not known: Breast induration, menorrhagia, nipple swelling 

General disorders and administration site conditions 

Common: Chest pain (including non-cardiac chest pain), pain, pyrexia, chest discomfort, 

malaise 

Uncommon: Face oedema, gravitational oedema, influenza-like illness, chills, feeling body 

temperature change (including feeling hot, feeling cold) 

Not known: Localised oedema 

Investigations 

Very common: Alanine aminotransferase increased, aspartate aminotransferase increased, 

lipase increased, lipoprotein cholesterol (including low density and high 

density) increased, total cholesterol increased, blood triglycerides increased 

Common: Haemoglobin decreased, blood amylase increased, blood alkaline phosphatase 

increased, gamma-glutamyltransferase increased, blood creatinine 

phosphokinase increased, weight decreased, weight increased, blood insulin 

increased, globulins decreased 

Uncommon: Blood lactate dehydrogenase increased, blood glucose decreased, blood urea 

increased 

Not known: Troponin increased, blood bilirubin unconjugated increased, blood insulin 

decreased, insulin C-peptide decreased, blood parathyroid hormone increased 

 

Clinically relevant or severe abnormalities of routine haematological or biochemistry laboratory 

values in adult patients are presented in Table 5. 

 



19 

Table 5 Grade 3-4 laboratory abnormalities* 

 

 Newly diagnosed 

CML-CP 

300 mg twice 

daily 

Imatinib-resistant or intolerant 

CML-CP and CML-AP 

400 mg twice daily 

  

n=279 

(%) 

CML-CP 

n=321 

(%) 

CML-AP 

n=137 

(%) 

Haematological parameters    

Myelosuppression    

- Neutropenia 12 31 42 

- Thrombocytopenia 10 30 42 

- Anaemia 4 11 27 

Biochemistry parameters    

- Elevated creatinine 0 1 <1 

- Elevated lipase 9 18 18 

- Elevated SGOT (AST) 1 3 2 

- Elevated SGPT (ALT) 4 4 4 

- Hypophosphataemia 8 17 15 

- Elevated bilirubin (total) 4 7 9 

- Elevated glucose 7 12 6 

- Elevated cholesterol 

(total) 
0 ** ** 

- Elevated triglycerides 0 ** ** 

*Percentages with one decimal precision are used and rounded to integer for presentation in this table 

**Parameters not collected 

 

Treatment discontinuation in adult Ph+ CML patients in chronic phase who have achieved a sustained 

deep molecular response 

 

After discontinuation of nilotinib therapy within the framework of attempting TFR, patients may 

experience musculoskeletal symptoms more frequently than before treatment discontinuation, e.g., 

myalgia, pain in extremity, arthralgia, bone pain, spinal pain or musculoskeletal pain. 

 

In a Phase II clinical study with newly diagnosed adult patients with Ph+ CML in chronic phase 

(N=190), musculoskeletal symptoms were reported within a year of Tasigna discontinuation in 24.7% 

versus 16.3% within the previous year on nilotinib treatment. 

 

In a Phase II clinical study with adult patients with Ph+ CML in chronic phase on nilotinib treatment 

and previously treated with imatinib (N=126), musculoskeletal symptoms were reported within a year 

of discontinuation in 42.1% versus 14.3% within the previous year on nilotinib treatment. 

 

Description of selected adverse reactions 

 

Sudden death 

Uncommon cases (0.1 to 1%) of sudden deaths have been reported in Tasigna clinical trials and/or 

compassionate use programs in patients with imatinib-resistant or intolerant CML in chronic phase or 

accelerated phase with a past medical history of cardiac disease or significant cardiac risk factors (see 

section 4.4). 

 

Hepatitis B reactivation 

Hepatitis B reactivation has been reported in association with BCR-ABL TKIs. Some cases resulted in 

acute hepatic failure or fulminant hepatitis leading to liver transplantation or a fatal outcome (see 

section 4.4). 



20 

 

Post-marketing experience 

 

The following adverse reactions have been derived from post-marketing experience with Tasigna via 
spontaneous case reports, literature cases, expanded access programmes, and clinical studies other 

than the global registration trials. Since these reactions are reported voluntarily from a population of 

uncertain size, it is not always possible to reliably estimate their frequency or establish a causal 

relationship to nilotinib exposure. 

 

Frequency very common: Growth retardation has been documented in paediatric patients treated with 

nilotinib. 

 

Frequency rare: Cases of tumour lysis syndrome have been reported in patients treated with nilotinib. 

 

Paediatric population 

 

The safety of nilotinib in paediatric patients (from 2 to <18 years of age) with Philadelphia 

chromosome positive CML in chronic phase (n=69) has been investigated in two studies (see 

section 5.1). In paediatric patients, the frequency, type and severity of adverse reactions observed have 

been generally consistent with those observed in adults, with the exception of the laboratory 

abnormalities hyperbilirubinaemia (Grade 3/4: 13.0%) and transaminase elevation (AST Grade 3/4: 

1.4%, ALT Grade 3/4: 8.7%) which were reported at a higher frequency than in adult patients. 

Bilirubin and hepatic transaminase levels should be monitored during treatment (see sections 4.2 and 

4.4). 

 

Growth retardation in paediatric population 

In an interim analysis in a study in the CML paediatric population, with a median exposure of 

33 months in each cohort (newly diagnosed and resistant or intolerant Ph+ CML-CP), growth 

retardation (crossing two main percentile lines from baseline) has been documented in 12.1%. Close 

monitoring of growth in paediatric patients under nilotinib treatment is recommended (see 

section 4.4). 

 

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 
 

Isolated reports of intentional overdose with nilotinib were reported, where an unspecified number of 

Tasigna hard capsules were ingested in combination with alcohol and other medicinal products. Events 

included neutropenia, vomiting and drowsiness. No ECG changes or hepatotoxicity were reported. 

Outcomes were reported as recovered. 

 

In the event of overdose, the patient should be observed and appropriate supportive treatment given. 

 

 



21 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antineoplastic agents, protein kinase inhibitors, ATC code: L01XE08 

 

Mechanism of action 

 

Nilotinib is a potent inhibitor of the ABL tyrosine kinase activity of the BCR-ABL oncoprotein both in 

cell lines and in primary Philadelphia-chromosome positive leukaemia cells. The substance binds with 

high affinity to the ATP-binding site in such a manner that it is a potent inhibitor of wild-type 

BCR-ABL and maintains activity against 32/33 imatinib-resistant mutant forms of BCR-ABL. As a 

consequence of this biochemical activity, nilotinib selectively inhibits the proliferation and induces 

apoptosis in cell lines and in primary Philadelphia-chromosome positive leukaemia cells from CML 

patients. In murine models of CML, as a single agent nilotinib reduces tumour burden and prolongs 

survival following oral administration. 

 

Pharmacodynamic effects 

 

Nilotinib has little or no effect against the majority of other protein kinases examined, including Src, 

except for the PDGF, KIT and Ephrin receptor kinases, which it inhibits at concentrations within the 

range achieved following oral administration at therapeutic doses recommended for the treatment of 

CML (see Table 6). 

 

Table 6 Kinase profile of nilotinib (phosphorylation IC50 nM) 

 

BCR-ABL PDGFR KIT 

20 69 210 

 

Clinical efficacy 

 

Clinical studies in newly diagnosed CML in chronic phase 

An open-label, multicentre, randomised Phase III study was conducted to determine the efficacy of 

nilotinib versus imatinib in 846 adult patients with cytogenetically confirmed newly diagnosed 

Philadelphia chromosome positive CML in the chronic phase. Patients were within six months of 

diagnosis and were previously untreated, with the exception of hydroxyurea and/or anagrelide. 

Patients were randomised 1:1:1 to receive either nilotinib 300 mg twice daily (n=282), nilotinib 

400 mg twice daily (n=281) or imatinib 400 mg once daily (n=283). Randomisation was stratified by 

Sokal risk score at the time of diagnosis. 

 

Baseline characteristics were well balanced between the three treatment arms. Median age was 

47 years in both nilotinib arms and 46 years in the imatinib arm, with 12.8%, 10.0% and 12.4% of 

patients were ≥65 years of age in the nilotinib 300 mg twice daily, nilotinib 400 mg twice daily and 

imatinib 400 mg once daily treatment arms, respectively. There were slightly more male than female 

patients (56.0%, 62.3% and 55.8%, in the nilotinib 300 mg twice daily, 400 mg twice daily and 

imatinib 400 mg once daily arm, respectively). More than 60% of all patients were Caucasian and 25% 

of all patients were Asian. 

 

The primary data analysis time point was when all 846 patients completed 12 months of treatment (or 

discontinued earlier). Subsequent analyses reflect when patients completed 24, 36, 48, 60 and 

72 months of treatment (or discontinued earlier). The median time on treatment was approximately 

70 months in the nilotinib treatment groups and 64 months in the imatinib group. The median actual 

dose intensity was 593 mg/day for nilotinib 300 mg twice daily, 772 mg/day for nilotinib 400 mg 

twice daily and 400 mg/day for imatinib 400 mg once daily. This study is ongoing. 

  



22 

 

The primary efficacy endpoint was major molecular response (MMR) at 12 months. MMR was 

defined as ≤0.1% BCR-ABL/ABL% by international scale (IS) measured by RQ-PCR, which 

corresponds to a ≥3 log reduction of BCR-ABL transcript from standardised baseline. The MMR rate 

at 12 months was statistically significantly higher for nilotinib 300 mg twice daily compared to 

imatinib 400 mg once daily (44.3% versus 22.3%, p<0.0001). The rate of MMR at 12 months, was 

also statistically significantly higher for nilotinib 400 mg twice daily compared to imatinib 400 mg 

once daily (42.7% versus 22.3%, p<0.0001). 

 

The rates of MMR at 3, 6, 9 and 12 months were 8.9%, 33.0%, 43.3% and 44.3% for nilotinib 300 mg 

twice daily, 5.0%, 29.5%, 38.1% and 42.7% for nilotinib 400 mg twice daily and 0.7%, 12.0%, 18.0% 

and 22.3% for imatinib 400 mg once daily. 

 

The MMR rate at 12, 24, 36, 48, 60 and 72 months is presented in Table 7. 

 

Table 7 MMR rate 

 

 Nilotinib 

300 mg twice daily 

n=282 

(%) 

Nilotinib 

400 mg twice daily 

n=281 

(%) 

Imatinib 

400 mg once daily 

n=283 

(%) 

MMRat 12 months    

Response (95% CI) 44.31 (38.4; 50.3) 42.71 (36.8; 48.7) 22.3 (17.6; 27.6) 

MMR at 24 months    

Response (95% CI) 61.71 (55.8; 67.4) 59.11 (53.1; 64.9) 37.5 (31.8; 43.4) 

MMR at 36 months2    

Response (95% CI) 58.51 (52.5; 64.3) 57.31 (51.3; 63.2) 38.5 (32.8; 44.5) 

MMR at 48 months3    

Response (95% CI) 59.91 (54.0; 65.7) 55.2 (49.1; 61.1) 43.8 (38.0; 49.8) 

MMR at 60 months4    

Response (95% CI) 62.8 (56.8; 68.4) 61.2 (55.2; 66.9) 49.1 (43.2; 55.1) 

MMR at 72 months5    

Response (95% CI) 52.5 (46.5; 58.4) 57.7 (51.6; 63.5) 41.7 (35.9; 47.7) 
1 Cochran-Mantel-Haenszel (CMH) test p-value for response rate (vs. imatinib 400 mg) <0.0001 
2 Only patients who were in MMR at a specific time point are included as responders for that time 

point. A total of 199 (35.2%) of all patients were not evaluable for MMR at 36 months (87 in the 

nilotinib 300 mg twice daily group and 112 in the imatinib group) due to missing/unevaluable PCR 

assessments (n=17), atypical transcripts at baseline (n=7), or discontinuation prior to the 36-month 

time point (n=175). 
3 Only patients who were in MMR at a specific time point are included as responders for that time 

point. A total of 305 (36.1%) of all patients were not evaluable for MMR at 48 months (98 in the 

nilotinib 300 mg BID group, 88 in the nilotinib 400 mg BID group and 119 in the imatinib group) due 

to missing/unevaluable PCR assessments (n=18), atypical transcripts at baseline (n=8), or 

discontinuation prior to the 48-month time point (n=279). 
4 Only patients who were in MMR at a specific time point are included as responders for that time 

point. A total of 322 (38.1%) of all patients were not evaluable for MMR at 60 months (99 in the 

nilotinib 300 mg twice daily group, 93 in the nilotinib 400 mg twice daily group and 130 in the 

imatinib group) due to missing/unevaluable PCR assessments (n=9), atypical transcripts at baseline 

(n=8) or discontinuation prior to the 60-month time point (n=305). 
5 Only patients who were in MMR at a specific time point are included as responders for that time 

point. A total of 395 (46.7%) of all patients were not evaluable for MMR at 72 months (130 in the 

nilotinib 300 mg twice daily group, 110 in the nilotinib 400 mg twice daily group and 155 in the 

imatinib group) due to missing/unevaluable PCR assessments (n=25), atypical transcripts at baseline 

(n=8) or discontinuation prior to the 72-month time point (n=362). 

 

MMR rates by different time points (including patients who achieved MMR at or before those time 

points as responders) are presented in the cumulative incidence of MMR (see Figure 1). 



23 

 

Figure 1 Cumulative incidence of MMR 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

For all Sokal risk groups, the MMR rates at all time points remained consistently higher in the two 

nilotinib groups than in the imatinib group. 

 

In a retrospective analysis, 91% (234/258) of patients on nilotinib 300 mg twice daily achieved 

BCR-ABL levels ≤10% at 3 months of treatment compared to 67% (176/264) of patients on imatinib 

400 mg once daily. Patients with BCR-ABL levels ≤10% at 3 months of treatment show a greater 

overall survival at 72 months compared to those who did not achieve this molecular response level 

(94.5% vs. 77.1% respectively [p=0.0005]). 

 

Based on the Kaplan-Meier analysis of time to first MMR the probability of achieving MMR at 

different time points was higher for both nilotinib at 300 mg and 400 mg twice daily compared to 

imatinib 400 mg once daily (HR=2.17 and stratified log-rank p<0.0001 between nilotinib 300 mg 

twice daily and imatinib 400 mg once daily, HR=1.88 and stratified log-rank p<0.0001 between 

nilotinib 400 mg twice daily and imatinib 400 mg once daily). 

 

The proportion of patients who had a molecular response of ≤0.01% and ≤0.0032% by IS at different 

time points are presented in Table 8 and the proportion of patients who had a molecular response of 

≤0.01% and ≤0.0032% by IS by different time points are presented in Figures 2 and 3. Molecular 

responses of ≤0.01% and ≤0.0032% by IS correspond to a ≥4 log reduction and ≥4.5 log reduction, 

respectively, of BCR-ABL transcripts from a standardised baseline. 

 

0 6 12 18 24 30 36 42 48 54 60 

0 

20 

40 

60 

80 

100 

Months since randomisation 

 C
u

m
u

la
ti

v
e

 i
n

c
id

e
n

c
e
 o

f 
M

M
R

, 
%

 

 

10 

30 

50 

70 

90 

66 72 

  

 

 

By 1 year 
 

By 2 years
 

By 3 years
 

By 4 years
 

By 5 years
 

55%; P < .0001 

71%; P < .0001 
73%; P < .0001 

76%; P < .0001 77%; P < .0001 

60% 
56% 

53% 

44% 

27% 

61%;  
P < .0001 

 

70%; P < .0001 
73%; P < .0001 

77%; P < .0001 

51%;  
P < .0001 

Nilotinib 300 mg twice daily (n = 282) 

Nilotinib 400 mg twice daily (n = 281) 
 Imatinib 400 mg once daily (n = 283) 

By 6 years
 

79%; P < .0001 

61% 

77%; P < .0001 



24 

Table 8 Proportions of patients who had molecular response of ≤0.01% (4 log reduction) and 

≤0.0032% (4.5 log reduction) 

 

 
Nilotinib 

300 mg twice daily 

n=282 

(%) 

Nilotinib 

400 mg twice daily 

n=281 

(%) 

Imatinib 

400 mg once daily 

n=283 

(%) 

 ≤0.01% ≤0.0032% ≤0.01% ≤ 0.0032% ≤0.01% ≤0.0032% 

At 12 months 11.7 4.3 8.5 4.6 3.9 0.4 

At 24 months 24.5 12.4 22.1 7.8 10.2 2.8 

At 36 months 29.4 13.8 23.8 12.1 14.1 8.1 

At 48 months 33.0 16.3 29.9 17.1 19.8 10.2 

At 60 months 47.9 32.3 43.4 29.5 31.1 19.8 

At 72 months 44.3 31.2 45.2 28.8 27.2 18.0 

 

 

Figure 2 Cumulative incidence of molecular response of ≤0.01% (4-log reduction) 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

0 6 12 18 24 30 36 42 48 54 60 

0 

20 

40 

60 

80 

100 

 C
u

m
u

la
ti

v
e

 i
n

c
id

e
n

c
e
 o

f 
M

R
4
 

(B
C

R
-A

B
L

 ≤
0
.0

1
%

 o
n

 t
h

e
 i

n
te

rn
a
ti

o
n

a
l 

s
c
a
le

),
 %

 

10 

30 

50 

70 

90 

66 72 

 

  

39%; P < .0001 

50%; P < .0001 

56%; P < .0001 

66%; P < .0001 

42% 

32% 

26% 

18% 

6% 

33%; 
P < .0001 

44%;  
P < .0001 

50%; P < .0001 

63%; 
P < .0001 

43% 

67%; P < .0001 

65%; P < .0001 

20%; P < .0001 
 
 

15%; P = .0004 

Months since randomisation  

Nilotinib 300 mg twice daily (n = 282) 

Nilotinib 400 mg twice daily (n = 281) 

Imatinib 400 mg once daily (n = 283) 

By 1 year
 

By 2 years
 

By 3 years
 

By 4 years
 

By 5 years
 

By 6 years
 



25 

Figure 3 Cumulative incidence of molecular response of ≤0.0032% (4.5 log reduction) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Based on Kaplan-Meier estimates of the duration of first MMR, the proportions of patients who were 

maintaining response for 72 months among patients who achieved MMR were 92.5% (95% CI: 

88.6-96.4%) in the nilotinib 300 mg twice daily group, 92.2% (95% CI: 88.5-95.9%) in the nilotinib 

400 mg twice daily group and 88.0% (95% CI: 83.0-93.1%) in the imatinib 400 mg once daily group. 

 

Complete cytogenetic response (CCyR) was defined as 0% Ph+ metaphases in the bone marrow based 

on a minimum of 20 metaphases evaluated. Best CCyR rate by 12 months (including patients who 

achieved CCyR at or before the 12 month time point as responders) was statistically higher for both 

nilotinib 300 mg and 400 mg twice daily compared to imatinib 400 mg once daily, see Table 9. 

 

CCyR rate by 24 months (includes patients who achieved CCyR at or before the 24 month time point 

as responders) was statistically higher for both the nilotinib 300 mg twice daily and 400 mg twice 

daily groups compared to the imatinib 400 mg once daily group. 

 

0 6 12 18 24 30 36 42 48 54 60 

0 

20 

40 

60 

80 

100 

10 

30 

50 

70 

90 

66 72 

 

  

25%; P < .0001 

32%; P < .0001 

40%; P < .0001 

54%; P < .0001 

31% 

23% 

15% 
9% 

1% 19%; 
P = .0006 

28%;  
P = .0003 

37%; 
P = .0002 

52%; 
P < .0001 

33% 

56%; P < .0001 

55%; P < .0001 

11%; P < .0001 
7%; P < .0001  C

u
m

u
la

ti
v
e

 i
n

c
id

e
n

c
e
 o

f 
M

R
4
.5
 

(B
C

R
-A

B
L

 ≤
0
.0

0
3
2
%

 o
n

 t
h

e
 n

te
rn

a
ti

o
n

a
l 

s
c

a
le

),
 %

 
Nilotinib 300 mg twice daily (n = 282) 

Nilotinib 400 mg twice daily (n = 281) 

Imatinib 400 mg once daily (n = 283) 

Months since randomisation 

By 1 year
 

By 2 years
 

By 3 years
 

By 4 years
 

By 5 years
 

By 6 years
 



26 

Table 9 Best CCyR rate 

 

 Nilotinib 

300 mg twice 

daily 

n=282 

(%) 

Nilotinib 

400 mg twice 

daily 

n=281 

(%) 

Imatinib 

400 mg once daily 

n=283 

(%) 

By 12 months    

Response (95% CI) 80.1 (75.0; 84.6) 77.9 (72.6; 82.6) 65.0 (59.2; 70.6) 

No response 19.9 22.1 35.0 

CMH test p-value for response rate 

(versus imatinib 400 mg once 

daily) 

<0.0001 0.0005  

By 24 months    

Response (95% CI) 86.9 (82.4; 90.6) 84.7 (79.9; 88.7) 77.0 (71.7; 81.8) 

No response 13.1 15.3 23.0 

CMH test p-value for response rate 

(versus imatinib 400 mg once 

daily) 

0.0018 0.0160  

 

Based on Kaplan-Meier estimates, the proportions of patients who were maintaining response for 

72 months among patients who achieved CCyR were 99.1% (95% CI: 97.9-100%) in the nilotinib 

300 mg twice daily group, 98.7% (95% CI: 97.1-100%) in the nilotinib 400 mg twice daily group and 

97.0% (95% CI: 94.7-99.4%) in the imatinib 400 mg once daily group. 

 

Progression to accelerated phase (AP) or blast crisis (BC) on treatment is defined as the time from the 

date of randomisation to the first documented disease progression to accelerated phase or blast crisis 

or CML-related death. Progression to accelerated phase or blast crisis on treatment was observed in a 

total of 17 patients: 2 patients on nilotinib 300 mg twice daily, 3 patients on nilotinib 400 mg twice 

daily and 12 patients on imatinib 400 mg once daily. The estimated rates of patients free from 

progression to accelerated phase or blast crisis at 72 months were 99.3%, 98.7% and 95.2%, 

respectively (HR=0.1599 and stratified log-rank p=0.0059 between nilotinib 300 mg twice daily and 

imatinib once daily, HR=0.2457 and stratified log-rank p=0.0185 between nilotinib 400 mg twice 

daily and imatinib once daily). No new events of progression to AP/BC were reported on-treatment 

since the 2-year analysis. 

 

Including clonal evolution as a criterion for progression, a total of 25 patients progressed to 

accelerated phase or blast crisis on treatment by the cut-off date (3 in the nilotinib 300 mg twice daily 

group, 5 in the nilotinib 400 mg twice daily group and 17 in the imatinib 400 mg once daily group). 

The estimated rates of patients free from progression to accelerated phase or blast crisis including 

clonal evolution at 72 months were 98.7%, 97.9% and 93.2%, respectively (HR=0.1626 and stratified 

log-rank p=0.0009 between nilotinib 300 mg twice daily and imatinib once daily, HR=0.2848 and 

stratified log-rank p=0.0085 between nilotinib 400 mg twice daily and imatinib once daily). 

 

A total of 55 patients died during treatment or during the follow-up after discontinuation of treatment 

(21 in the nilotinib 300 mg twice daily group, 11 in the nilotinib 400 mg twice daily group and 23 in 

the imatinib 400 mg once daily group). Twenty-six (26) of these 55 deaths were related to CML (6 in 

the nilotinib 300 mg twice daily group, 4 in the nilotinib 400 mg twice daily group and 16 in the 

imatinib 400 mg once daily group). The estimated rates of patients alive at 72 months were 91.6%, 

95.8% and 91.4%, respectively (HR=0.8934 and stratified log-rank p=0.7085 between nilotinib 

300 mg twice daily and imatinib, HR=0.4632 and stratified log-rank p=0.0314 between nilotinib 

400 mg twice daily and imatinib). Considering only CML-related deaths as events, the estimated rates 

of overall survival at 72 months were 97.7%, 98.5% and 93.9%, respectively (HR=0.3694 and 

stratified log-rank p=0.0302 between nilotinib 300 mg twice daily and imatinib, HR=0.2433 and 

stratified log-rank p=0.0061 between nilotinib 400 mg twice daily and imatinib). 

 



27 

Clinical studies in imatinib-resistant or intolerant CML in chronic phase and accelerated phase 

An open-label, uncontrolled, multicentre Phase II study was conducted to determine the efficacy of 

nilotinib in adult patients with imatinib resistant or intolerant CML with separate treatment arms for 

chronic and accelerated phase disease. Efficacy was based on 321 CP patients and 137 AP patients 

enrolled. Median duration of treatment was 561 days for CP patients and 264 days for AP patients (see 

Table 10). Tasigna was administered on a continuous basis (twice daily 2 hours after a meal and with 

no food for at least one hour after administration) unless there was evidence of inadequate response or 

disease progression. The dose was 400 mg twice daily and dose escalation to 600 mg twice daily was 

allowed. 

 

Table 10 Duration of exposure with nilotinib 

 

 Chronic phase 

n=321 

Accelerated phase 

n=137 

Median duration of therapy in days 

(25th-75th percentiles) 

561 

(196-852) 

264 

(115-595) 

 

Resistance to imatinib included failure to achieve a complete haematological response (by 3 months), 

cytogenetic response (by 6 months) or major cytogenetic response (by 12 months) or progression of 

disease after a previous cytogenetic or haematological response. Imatinib intolerance included patients 

who discontinued imatinib because of toxicity and were not in major cytogenetic response at time of 

study entry. 

 

Overall, 73% of patients were imatinib-resistant, while 27% were imatinib-intolerant. The majority of 

patients had a long history of CML that included extensive prior treatment with other antineoplastic 

agents, including imatinib, hydroxyurea, interferon, and some had even failed organ transplant 

(Table 11). The median highest prior imatinib dose had been 600 mg/day. The highest prior imatinib 

dose was 600 mg/day in 74% of all patients, with 40% of patients receiving imatinib doses 

800 mg/day. 

 

Table 11 CML disease history characteristics 

 

 Chronic phase 

(n=321) 

Accelerated phase 

(n=137)* 

Median time since diagnosis in months 

(range) 

58 

(5–275) 

71 

(2–298) 

Imatinib 

Resistant 

Intolerant without MCyR 

 

226 (70%) 

95 (30%) 

 

109 (80%) 

27 (20%) 

Median time of imatinib treatment in 

days 

(25th-75th percentiles) 

975 

(519-1,488) 

857 

(424-1,497) 

Prior hydroxyurea 83% 91% 

Prior interferon 58% 50% 

Prior bone marrow transplant 7% 8% 

* Missing information on imatinib-resistant/intolerant status for one patient. 

 

The primary endpoint in the CP patients was major cytogenetic response (MCyR), defined as 

elimination (CCyR, complete cytogenetic response) or significant reduction to <35% Ph+ metaphases 

(partial cytogenetic response) of Ph+ haematopoietic cells. Complete haematological response (CHR) 

in CP patients was evaluated as a secondary endpoint. The primary endpoint in the AP patients was 

overall confirmed haematological response (HR), defined as either a complete haematological 

response, no evidence of leukaemia or return to chronic phase. 

 

  



28 

Chronic phase 

The MCyR rate in 321 CP patients was 51%. Most responders achieved their MCyR rapidly within 

3 months (median 2.8 months) of starting nilotinib treatment and these were sustained. The median 

time to achieve CCyR was just past 3 months (median 3.4 months). Of the patients who achieved 

MCyR, 77% (95% CI: 70% - 84%) were maintaining response at 24 months. Median duration of 

MCyR has not been reached. Of the patients who achieved CCyR, 85% (95% CI: 78% - 93%) were 

maintaining response at 24 months. Median duration of CCyR has not been reached. Patients with a 

CHR at baseline achieved a MCyR faster (1.9 versus 2.8 months). Of CP patients without a baseline 

CHR, 70% achieved a CHR, median time to CHR was 1 month and median duration of CHR was 

32.8 months. The estimated 24-month overall survival rate in CML-CP patients was 87%. 

 

Accelerated phase 

The overall confirmed HR rate in 137 AP patients was 50%. Most responders achieved a HR early 

with nilotinib treatment (median 1.0 months) and these have been durable (median duration of 

confirmed HR was 24.2 months). Of the patients who achieved HR, 53% (95% CI: 39% - 67%) were 

maintaining response at 24 months. MCyR rate was 30% with a median time to response of 

2.8 months. Of the patients who achieved MCyR, 63% (95% CI: 45% - 80%) were maintaining 

response at 24 months. Median duration of MCyR was 32.7 months. The estimated 24-month overall 

survival rate in CML-AP patients was 70%. 

 

The rates of response for the two treatment arms are reported in Table 12. 

 

Table 12 Response in CML 

 

(Best response rate) Chronic phase 

 

Accelerated phase 

 

 Intoleran

t 

(n=95) 

Resistant 

(n=226) 

Total 

(n=321) 

Intoleran

t 

(n=27) 

Resistant 

(n=109) 

Total* 

(n=137) 

Haematological 

Response (%) 

Overall (95%CI) 

Complete 

NEL 

Return to CP 

- 

87 

(74-94) 

- 

- 

- 

65 

(56-72) 

- 

- 

- 

701 

(63-76) 

- 

 

48 

(29-68) 

37 

7 

4 

51 

(42-61) 

28 

10 

13 

50 

(42-59) 

30 

9 

11 

Cytogenetic 

Response (%) 

Major (95%CI) 

Complete 

Partial 

57 

(46-67) 

41 

16 

 

49 

(42-56) 

35 

14 

 

51 (46-57) 

37 

15 

 

33 

(17-54) 

22 

11 

29 

(21-39) 

19 

10 

30 

(22-38) 

20 

10 

 

NEL = no evidence of leukaemia/marrow response 
1 114 CP patients had a CHR at baseline and were therefore not assessable for complete 

haematological response 

* Missing information on imatinib-resistant/intolerant status for one patient. 

 

Efficacy data in patients with CML-BC are not yet available. Separate treatment arms were also 

included in the Phase II study to investigate Tasigna in a group of CP and AP patients who had been 

extensively pre-treated with multiple therapies including a tyrosine kinase inhibitor agent in addition 

to imatinib. Of these patients 30/36 (83%) were treatment resistant not intolerant. In 22 CP patients 

evaluated for efficacy nilotinib induced a 32% MCyR rate and a 50% CHR rate. In 11 AP patients, 

evaluated for efficacy, treatment induced a 36% overall HR rate. 

 

  



29 

After imatinib failure, 24 different BCR-ABL mutations were noted in 42% of chronic phase and 54% 

of accelerated phase CML patients who were evaluated for mutations. Tasigna demonstrated efficacy 

in patients harboring a variety of BCR-ABL mutations associated with imatinib resistance, except 

T315I. 

 

Treatment discontinuation in adult Ph+ CML patients in chronic phase who have been treated with 

nilotinib as first-line therapy and who have achieved a sustained deep molecular response 

In an open-label, single-arm study, 215 adult patients with Ph+ CML in chronic phase treated with 

nilotinib in first-line for ≥2 years who achieved MR4.5 as measured with the MolecularMD MRDx 

BCR-ABL test were enrolled to continue nilotinib treatment for additional 52 weeks (nilotinib 

consolidation phase). 190 of 215 patients (88.4%) entered the TFR phase after achieving a sustained 

deep molecular response during the consolidation phase, defined by the following criteria: 

- the 4 last quarterly assessments (taken every 12 weeks) were at least MR4.0 (BCR-ABL/ABL 
≤0.01% IS), and maintained for one year 

- the last assessment being MR4.5 (BCR-ABL/ABL ≤0.0032% IS) 
- no more than two assessments falling between MR4.0 and MR4.5 

(0.0032% IS < BCR-ABL/ABL ≤0.01% IS). 

 

The primary endpoint was the percentage of patients in MMR at 48 weeks after starting the TFR phase 

(considering any patient who required re-initiation of treatment as non-responder). Of the 190 patients 

who entered the TFR phase, 98 patients (51.6% [95% CI: 44.2, 58.9]) were in MMR at 48 weeks. 

 

Eighty-eight patients (46.3%) discontinued the TFR phase due to loss of MMR, and 1 (0.5%), 

1 (0.5%), and 3 patients (1.6%) due to death from unknown cause, physician decision and subject 

decision, respectively. Among these 88 patients, 86 patients restarted nilotinib treatment and 2 patients 

permanently discontinued the study. Eighty-five of these 86 patients (98.8%) regained MMR, (one 

patient discontinued study permanently due to subject decision) and 76 patients (88.4%) regained 

MR4.5 by the time of the cut-off date. 

 

The Kaplan-Meier (KM) estimated median time on nilotinib treatment to regain MMR and MR4.5 was 

7.9 weeks (95% CI: 5.1, 8.0) and 13.1 weeks (95% CI: 12.3, 15.7), respectively. The KM estimated 

MMR and MR4.5 rates at 24 weeks of re-initiation were 98.8 % (95% CI: 94.2, 99.9) and 90.9 % 

(95% CI: 83.2, 96.0), respectively. 

 

The KM estimate of median treatment-free survival (TFS) has not yet been reached (Figure 4); 99 of 

190 patients (52.1%) did not have a TFS event. 

 



30 

Figure 4 Kaplan-Meier estimate of treatment-free survival after start of TFR (full analysis 

set) 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
 

Pat   Evt   Cen 
190   91     99 

Censored observations 

T
re

a
tm

e
n

t-
fr

e
e

 S
u

rv
iv

a
l 

(%
) 

100 

90 

80 

70 

60 

50 

40 

30 

20 

10 

0 

Time since TFR (weeks) 

 

96 84 72 60 48 0 

0:9
1 

1:9
1 

12:9
1 

38:9
1 

90:8
9 

190:
0 

At risk : Events 
 

36 

108:8
1 

24 

120:7
0 

12 

165:2
5 



31 

Treatment discontinuation in adult CML patients in chronic phase who have achieved a sustained 

deep molecular response on nilotinib treatment following prior imatinib therapy 

In an open-label, single-arm study, 163 adult patients with Ph+ CML in chronic phase taking tyrosine 

kinase inhibitors (TKIs) for ≥3 years (imatinib as initial TKI therapy for more than 4 weeks without 

documented MR4.5 on imatinib at the time of switch to nilotinib, then switched to nilotinib for at least 

two years), and who achieved MR4.5 on nilotinib treatment as measured with the MolecularMD 

MRDx BCR-ABL test were enrolled to continue nilotinib treatment for additional 52 weeks (nilotinib 

consolidation phase). 126 of 163 patients (77.3%) entered the TFR phase after achieving a sustained 

deep molecular response during the consolidation phase, defined by the following criterion: 

- The 4 last quarterly assessments (taken every 12 weeks) showed no confirmed loss of MR4.5 
(BCR-ABL/ABL ≤0.0032% IS) during one year. 

 

The primary endpoint was the proportion of patients without confirmed loss of MR4.0 or loss of MMR 

within 48 weeks following treatment discontinuation. Of the 126 patients who entered the TFR phase, 

73 patients (57.9%, [95% CI: 48.8, 66.7]) had no loss of MMR, no confirmed loss of MR4.0, and no 

re-initiation of nilotinib within 48 weeks. 

 

Among the 53 patients who discontinued the TFR phase due to confirmed loss of MR4.0 or loss of 

MMR, 51 patients restarted nilotinib and 2 patients discontinued the study. Forty-eight of these 

51 patients (94.1%) regained MR4.0 and 47 patients (92.2%) regained MR4.5 by the time of the 

cut-off date. 

 

The Kaplan-Meier (KM) estimated median time on nilotinib to regain MR4.0 and MR4.5 was 

12.0 weeks (95% CI: 8.3, 12.7) and 13.1 weeks (95% CI: 12.4, 16.1), respectively. The KM estimated 

MR4.0 and MR4.5 rates at 48 weeks of re-initiation were 100.0% (95% CI: not estimated) and 94.8% 

(95% CI: 85.1, 99.0), respectively. 

 

The median TFS has not yet been reached (Figure 5); 74 of 126 patients (58.7%) did not have a TFS 

event. 

 

Figure 5 Kaplan-Meier estimate of treatment-free survival after start of TFR (full analysis 

set) 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
 

 

  

10 

20 

30 

40 

50 

60 

0 

Censored observations 

Pat 
126 

 

Evt 
52 
 

Cen 
74 

 

T
re

a
tm

e
n

t-
fr

e
e

 S
u

rv
iv

a
l 

(%
) 

70 

80 

90 

100 

0 12 24 36 48 60 72 84 96 

126:0 107:19 76:49 74:51 61:52 36:52 14:52 1:52 0:52 

Time since TFR (weeks) 
At risk : Events 



32 

Paediatric population 

 

The safety and efficacy of nilotinib in paediatric patients with Ph+ CML in chronic phase have been 

investigated in two studies. A total of 69 paediatric patients (from 2 to <18 years of age) with either 

newly diagnosed Ph+ CML in chronic phase (n=25) or imatinib/dasatinib resistant or 

imatinib-intolerant Ph+ CML in chronic phase (n=44) received nilotinib treatment at a dose of 

230 mg/m2 twice daily, rounded to the nearest 50 mg dose (to a maximum single dose of 400 mg). 

 

In the pooled CML patient population, the median actual dose intensity was 435.5 mg/m2/day (range: 

149 to 517 mg/m2/day), and the median relative dose intensity was 94.7% (range: 32 to 112%). Forty 

patients (58.0%) had relative dose intensity superior to 90%. The median time on treatment with 

nilotinib was 13.80 months (range: 0.7-30.9 months). 

 

In the resistant or intolerant CML patients, the major molecular response (MMR; BCR-ABL/ABL 

≤0.1% IS) rate was 40.9% (95% CI: 26.3, 56.8) at 12 cycles, with 18 patients being in MMR. In the 

newly diagnosed CML patients, the MMR rate was 60.0% (95% CI: 38.7, 78.9) at 12 cycles, with 

15 patients achieving MMR. In resistant or intolerant CML patients, the cumulative MMR rate was 

47.7% by cycle 12. In newly diagnosed CML patients, the cumulative MMR rate was 64.0% by 

cycle 12. 

 

Among the 21 resistant or intolerant CML patients who were in MMR at any time on treatment, the 

median time to first MMR was 2.76 months (95% CI: 0.03, 5.55). For the 17 newly diagnosed CML 

patients who achieved MMR, the median time to first MMR was 5.55 months (95% CI: 5.52, 5.75). 

 

Among resistant or intolerant CML patients, the percentage of patients who achieved BCR-ABL/ABL 

≤0.01% IS (MR4.0) by the cut-off date was 11.4%, while 4.5% of the patients achieved 

BCR-ABL/ABL ≤0.0032% IS (MR4.5). Among newly diagnosed patients, the percentage of patients 

who achieved MR4.0 was 32%, while 28.0% achieved MR4.5. 

 

None of the 21 resistant or intolerant CML patients who were in MMR on treatment had confirmed 

loss of MMR. Among the 17 newly diagnosed CML patients who achieved MMR, one patient had 

confirmed loss of MMR (the patient lost CHR due to an increase in basophil count, however did not 

progress to AP/BC). 

 

One resistant or intolerant CML patient progressed to AP/BC after about 10 months on treatment. 

 

No deaths were reported on treatment or after treatment discontinuation in both studies. 

 

5.2 Pharmacokinetic properties 
 

Absorption 

 

Peak concentrations of nilotinib are reached 3 hours after oral administration. Nilotinib absorption 

following oral administration was approximately 30%. The absolute bioavailability of nilotinib has not 

been determined. As compared to an oral drink solution (pH of 1.2 to 1.3), relative bioavailability of 

nilotinib capsule is approximately 50%. In healthy volunteers, Cmax and area under the serum 

concentration-time curve (AUC) of nilotinib are increased by 112% and 82%, respectively, compared 

to fasting conditions when Tasigna is given with food. Administration of Tasigna 30 minutes or 

2 hours after food increased bioavailability of nilotinib by 29% or 15%, respectively (see sections 4.2, 

4.4 and 4.5). 

 

Nilotinib absorption (relative bioavailability) might be reduced by approximately 48% and 22% in 

patients with total gastrectomy and partial gastrectomy, respectively. 

 

  



33 

Distribution 

 

The blood-to-plasma ratio of nilotinib is 0.71. Plasma protein binding is approximately 98% on the 

basis of in vitro experiments. 

 

Biotransformation 

 

Main metabolic pathways identified in healthy subjects are oxidation and hydroxylation. Nilotinib is 

the main circulating component in the serum. None of the metabolites contribute significantly to the 

pharmacological activity of nilotinib. Nilotinib is primarily metabolised by CYP3A4, with possible 

minor contribution from CYP2C8. 

 

Elimination 

 

After a single dose of radiolabelled nilotinib in healthy subjects, more than 90% of the dose was 

eliminated within 7 days, mainly in faeces (94% of the dose). Unchanged nilotinib accounted for 69% 

of the dose. 

 

The apparent elimination half-life estimated from the multiple-dose pharmacokinetics with daily 

dosing was approximately 17 hours. Inter-patient variability in nilotinib pharmacokinetics was 

moderate to high. 

 

Linearity/non-linearity 
 

Steady-state nilotinib exposure was dose-dependent, with less than dose-proportional increases in 

systemic exposure at dose levels higher than 400 mg given as once-daily dosing. Daily systemic 

exposure to nilotinib with 400 mg twice-daily dosing at steady state was 35% higher than with 800 mg 

once-daily dosing. Systemic exposure (AUC) of nilotinib at steady state at a dose level of 400 mg 

twice daily was approximately 13.4% higher than at a dose level of 300 mg twice daily. The average 

nilotinib trough and peak concentrations over 12 months were approximately 15.7% and 14.8% higher 

following 400 mg twice-daily dosing compared to 300 mg twice daily. There was no relevant increase 

in exposure to nilotinib when the dose was increased from 400 mg twice daily to 600 mg twice daily. 

 

Steady-state conditions were essentially achieved by day 8. An increase in serum exposure to nilotinib 

between the first dose and steady state was approximately 2-fold for daily dosing and 3.8-fold for 

twice-daily dosing. 

 

Bioavailability/bioequivalence studies 

 

Single-dose administration of 400 mg nilotinib, using 2 hard capsules of 200 mg whereby the content 

of each hard capsule was dispersed in one teaspoon of apple sauce, was shown to be bioequivalent 

with a single-dose administration of 2 intact hard capsules of 200 mg. 

 

Paediatric population 

 

Following administration of nilotinib in paediatric patients at 230 mg/m2 twice daily, rounded to the 

nearest 50 mg dose (to a maximum single dose of 400 mg), steady-state exposure and clearance of 

nilotinib were found to be similar (within 2-fold) to adult patients treated with 400 mg twice daily. The 

pharmacokinetic exposure of nilotinib following a single or multiple doses appeared to be comparable 

between paediatric patients from 2 years to <10 years and from ≥10 years to <18 years. 

 

  



34 

5.3 Preclinical safety data 
 

Nilotinib has been evaluated in safety pharmacology, repeated-dose toxicity, genotoxicity, 

reproductive toxicity, phototoxicity and carcinogenicity (rats and mice) studies. 

 

Safety pharmacology studies 

 

Nilotinib did not have effects on CNS or respiratory functions. In vitro cardiac safety studies 

demonstrated a preclinical signal for QT prolongation, based upon block of hERG currents and 

prolongation of the action potential duration in isolated rabbit hearts by nilotinib. No effects were seen 

in ECG measurements in dogs or monkeys treated for up to 39 weeks or in a special telemetry study in 

dogs. 

 

Repeated-dose toxicity studies 

 

Repeated-dose toxicity studies in dogs of up to 4 weeks’ duration and in cynomolgus monkeys of up 

to 9 months’ duration revealed the liver as the primary target organ of toxicity of nilotinib. Alterations 

included increased alanine aminotransferase and alkaline phosphatase activity and histopathology 

findings (mainly sinusoidal cell or Kupffer cell hyperplasia/hypertrophy, bile duct hyperplasia and 

periportal fibrosis). In general the changes in clinical chemistry were fully reversible after a four-week 

recovery period and the histological alterations showed partial reversibility. Exposures at the lowest 

dose levels at which the liver effects were seen were lower than the exposure in humans at a dose of 

800 mg/day. Only minor liver alterations were seen in mice or rats treated for up to 26 weeks. Mainly 

reversible increases in cholesterol levels were seen in rats, dogs and monkeys. 

 

Genotoxicity studies 

 

Genotoxicity studies in bacterial in vitro systems and in mammalian in vitro and in vivo systems with 

and without metabolic activation did not reveal any evidence for a mutagenic potential of nilotinib. 

 

Carcinogenicity studies 

 

In the 2-year rat carcinogenicity study, the major target organ for non-neoplastic lesions was the uterus 

(dilatation, vascular ectasia, endothelial cell hyperplasia, inflammation and/or epithelial hyperplasia). 

There was no evidence of carcinogenicity upon administration of nilotinib at 5, 15 and 40 mg/kg/day. 

Exposures (in terms of AUC) at the highest dose level represented approximately 2x to 3x human 

daily steady-state exposure (based on AUC) to nilotinib at the dose of 800 mg/day. 

 

In the 26-week Tg.rasH2 mouse carcinogenicity study, in which nilotinib was administered at 30, 100 

and 300 mg/kg/day, skin papillomas/carcinomas were detected at 300 mg/kg, representing 

approximately 30 to 40 times (based on AUC) the human exposure at the maximum approved dose of 

800 mg/day (administered as 400 mg twice daily). The No-Observed-Effect-Level for the skin 

neoplastic lesions was 100 mg/kg/day, representing approximately 10 to 20 times the human exposure 

at the maximum approved dose of 800 mg/day (administered as 400 mg twice daily). The major target 

organs for non-neoplastic lesions were the skin (epidermal hyperplasia), the growing teeth 

(degeneration/atrophy of the enamel organ of upper incisors and inflammation of the 

gingiva/odontogenic epithelium of incisors) and the thymus (increased incidence and/or severity of 

decreased lymphocytes). 

 

  



35 

Reproductive toxicity and fertility studies 

 

Nilotinib did not induce teratogenicity, but did show embryo- and foetotoxicity at doses that also 

showed maternal toxicity. Increased post-implantation loss was observed in both the fertility study, 

which involved treatment of both males and females, and the embryotoxicity study, which involved 

treatment of females. Embryo-lethality and foetal effects (mainly decreased foetal weights, premature 

fusion of the facial bones (fused maxilla/zygomatic) visceral and skeletal variations) in rats and 

increased resorption of foetuses and skeletal variations in rabbits were present in the embryotoxicity 

studies. In a pre- and postnatal development study in rats, maternal exposure to nilotinib caused 

reduced pup body weight with associated changes in physical development parameters as well as 

reduced mating and fertility indices in the offspring. Exposure to nilotinib in females at 

No-Observed-Adverse-Effect-Levels was generally less or equal to that in humans at 800 mg/day. 

 

No effects on sperm count/motility or on fertility were noted in male and female rats up to the highest 

tested dose, approximately 5 times the recommended dosage for humans. 

 

Juvenile animal studies 

 

In a juvenile development study, nilotinib was administered via oral gavage to juvenile rats from the 

first week post partum through young adult (day 70 post partum) at doses of 2, 6 and 20 mg/kg/day. 

Besides standard study parameters, evaluations of developmental landmarks, CNS effects, mating and 

fertility were performed. Based on a reduction in body weight in both genders and a delayed preputial 

separation in males (which may be associated with the reduction in weight), the 

No-Observed-Effect-Level in juvenile rats was considered to be 6 mg/kg/day. The juvenile animals 

did not exert increased sensitivity to nilotinib relative to adults. In addition, the toxicity profile in 

juvenile rats was comparable to that observed in adult rats. 

 

Phototoxicity studies 

 

Nilotinib was shown to absorb light in the UV-B and UV-A range, is distributed into the skin and 

showed a phototoxic potential in vitro, but no effects have been observed in vivo. Therefore the risk 

that nilotinib causes photosensitisation in patients is considered very low. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Tasigna 50 mg hard capsules 

 

Capsule content 

Lactose monohydrate 

Crospovidone Type A 

Poloxamer 188 

Colloidal anhydrous silica 

Magnesium stearate 

 

Capsule shell 

Gelatin 

Titanium dioxide (E171) 

Red iron oxide (E172) 

Yellow iron oxide (E172) 

 



36 

Printing ink 

Shellac 

Black iron oxide (E172) 

Propylene glycol 

Ammonium hydroxide 

 

Tasigna 200 mg hard capsules 

 

Capsule content 

Lactose monohydrate 

Crospovidone Type A 

Poloxamer 188 

Colloidal anhydrous silica 

Magnesium stearate 

 

Capsule shell 

Gelatin 

Titanium dioxide (E171) 

Yellow iron oxide (E172) 

 

Printing ink 

Shellac (E904) 

Dehydrated alcohol 

Isopropyl alcohol 

Butyl alcohol 

Propylene glycol 

Strong ammonia solution 

Potassium hydroxide 

Red iron oxide (E172) 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 
 

3 years. 

 

6.4 Special precautions for storage 
 

Do not store above 30°C. 

 

Store in the original package in order to protect from moisture. 

 

6.5 Nature and contents of container 

 

Tasigna is available in the following pack sizes: 

 

Tasigna 50 mg hard capsules 

 

PVC/PVDC/Alu blisters 

 Pack containing 120 (3 packs of 40) hard capsules. 
 



37 

Tasigna 200 mg hard capsules 

 

PVC/PVDC/Alu blisters 

 Unit packs containing 28 hard capsules in a wallet. 

 Unit packs containing 28 hard capsules (7 daily blisters, each containing 4 hard capsules) or 
40 hard capsules (5 blisters, each containing 8 hard capsules). 

 Multipacks containing 112 (4 wallets of 28) hard capsules. 

 Multipacks containing 112 (4 packs of 28) hard capsules, 120 (3 packs of 40) hard capsules or 
392 (14 packs of 28) hard capsules. 

PA/Alu/PVC/Alu blisters 

 Unit packs containing 28 hard capsules in a wallet. 

 Multipacks containing 112 (4 packs of 28) 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. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

Tasigna 50 mg hard capsules 

 

EU/1/07/422/015 

 

Tasigna 200 mg hard capsules 

 

EU/1/07/422/001-004 

EU/1/07/422/007-008 

EU/1/07/422/011-012 

EU/1/07/422/014 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 19 November 2007 

Date of latest renewal: 19 November 2012 

 

 

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 

 



38 

1. NAME OF THE MEDICINAL PRODUCT 
 

Tasigna 150 mg hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

One hard capsule contains 150 mg nilotinib (as hydrochloride monohydrate). 

 

Excipient with known effect 

 

One hard capsule contains 117.08 mg lactose monohydrate. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Hard capsule. 

 

White to yellowish powder in red opaque hard gelatin capsules, size 1 with black axial imprint 

“NVR/BCR”. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Tasigna is indicated for the treatment of: 

- adult and paediatric patients with newly diagnosed Philadelphia chromosome positive chronic 
myelogenous leukaemia (CML) in the chronic phase, 

- paediatric patients with Philadelphia chromosome positive CML in chronic phase with 
resistance or intolerance to prior therapy including imatinib. 

 

4.2 Posology and method of administration 

 

Therapy should be initiated by a physician experienced in the diagnosis and the treatment of patients 

with CML. 

 

Posology 

 

Treatment should be continued as long as clinical benefit is observed or until unacceptable toxicity 

occurs. 

 

If a dose is missed the patient should not take an additional dose, but take the usual prescribed next 

dose. 

 

Posology for Philadelphia chromosome positive CML adult patients 

The recommended dose is 300 mg twice daily. 

 

For a dose of 400 mg once daily (see dose adjustments below), 200 mg hard capsules are available. 

 

Posology for Philadelphia chromosome positive CML paediatric patients 

Dosing in paediatric patients is individualised and is based on body surface area (mg/m2). The 

recommended dose of nilotinib is 230 mg/m2 twice daily, rounded to the nearest 50 mg dose (to a 

maximum single dose of 400 mg) (see Table 1). Different strengths of Tasigna hard capsules can be 

combined to attain the desired dose. 



39 

 

There is no experience with treatment of paediatric patients below 2 years of age. There are no data in 

newly diagnosed paediatric patients below 10 years of age and limited data in imatinib-resistant or 

intolerant paediatric patients below 6 years of age. 

 

Table 1 Paediatric dosing scheme of nilotinib 230 mg/m2 twice daily 

 

Body Surface Area 

(BSA) 

Dose in mg 

(twice daily) 

Up to 0.32 m2 50 mg 

0.33 – 0.54 m2 100 mg 

0.55 – 0.76 m2 150 mg 

0.77 – 0.97 m2 200 mg 

0.98 – 1.19 m2 250 mg 

1.20 – 1.41 m2 300 mg 

1.42 – 1.63 m2 350 mg 

≥1.64 m2 400 mg 

 

Adult Philadelphia chromosome positive CML patients in chronic phase who have been treated with 

nilotinib as first-line therapy and who achieved a sustained deep molecular response (MR4.5) 

Discontinuation of treatment may be considered in eligible adult Philadelphia chromosome positive 

(Ph+) CML patients in chronic phase who have been treated with nilotinib at 300 mg twice daily for a 

minimum of 3 years if a deep molecular response is sustained for a minimum of one year immediately 

prior to discontinuation of therapy. Discontinuation of nilotinib therapy should be initiated by a 

physician experienced in the treatment of patients with CML (see sections 4.4 and 5.1). 

 

Eligible patients who discontinue nilotinib therapy must have their BCR-ABL transcript levels and 

complete blood count with differential monitored monthly for one year, then every 6 weeks for the 

second year, and every 12 weeks thereafter. Monitoring of BCR-ABL transcript levels must be 

performed with a quantitative diagnostic test validated to measure molecular response levels on the 

International Scale (IS) with a sensitivity of at least MR4.5 (BCR-ABL/ABL ≤0.0032% IS). 

 

For patients who lose MR4 (MR4=BCR-ABL/ABL ≤0.01%IS) but not MMR 

(MMR=BCR-ABL/ABL ≤0.1%IS) during the treatment-free phase, BCR-ABL transcript levels should 

be monitored every 2 weeks until BCR-ABL levels return to a range between MR4 and MR4.5. 

Patients who maintain BCR-ABL levels between MMR and MR4 for a minimum of 4 consecutive 

measurements can return to the original monitoring schedule. 

 

Patients who lose MMR must re-initiate treatment within 4 weeks of when loss of remission is known 

to have occurred. Nilotinib therapy should be re-initiated at 300 mg twice daily or at a reduced dose 

level of 400 mg once daily if the patient had a dose reduction prior to discontinuation of therapy. 

Patients who re-initiate nilotinib therapy should have their BCR-ABL transcript levels monitored 

monthly until MMR is re-established and every 12 weeks thereafter (see section 4.4). 

 

Dose adjustments or modifications 

Tasigna may need to be temporarily withheld and/or dose reduced for haematological toxicities 

(neutropenia, thrombocytopenia) that are not related to the underlying leukaemia (see Table 2). 

 



40 

Table 2 Dose adjustments for neutropenia and thrombocytopenia 

 

Adult patients with 

newly diagnosed 

chronic phase CML at 

300 mg twice daily 

ANC* <1.0 x 109/l and/or 

platelet counts <50 x 109/l 

1. Treatment with nilotinib must be 
interrupted and blood count 

monitored. 

2. Treatment must be resumed within 
2 weeks at prior dose if ANC 

>1.0 x 109/l and/or platelets 

>50 x 109/l. 

3. If blood counts remain low, a dose 
reduction to 400 mg once daily may 

be required. 

Paediatric patients with 

newly diagnosed 

chronic phase CML at 

230 mg/m2 twice daily 

and 

imatinib-resistant or 

intolerant CML in 

chronic phase at 

230 mg/m2 twice daily 

ANC* <1.0 x 109/l and/or 

platelet counts <50 x 109/l 

1. Treatment with nilotininb must be 
interrupted and blood count 

monitored. 

2. Treatment must be resumed within 
2 weeks at prior dose if ANC 

>1.5 x 109/l and/or platelets 

>75 x 109/l. 

3. If blood counts remain low, a dose 
reduction to 230 mg/m2 once daily 

may be required. 

4. If event occurs after dose reduction, 
consider discontinuing treatment. 

*ANC = absolute neutrophil count 

 

If clinically significant moderate or severe non-haematological toxicity develops, dosing should be 

interrupted, and patients should be monitored and treated accordingly. If the prior dose was 300 mg 

twice daily in adult patients or 230 mg/m2 twice daily in paediatric patients, dosing may be resumed at 

400 mg once daily in adult patients and at 230 mg/m2 once daily in paediatric patients once the 

toxicity has resolved. If the prior dose was 400 mg once daily in adult patients or 230 mg/m2 once 

daily in paediatric patients, treatment should be discontinued. If clinically appropriate, re-escalation of 

the dose to 300 mg twice daily in adult patients or to 230 mg/m2 twice daily in paediatric patients 

should be considered. 

 

Elevated serum lipase: For Grade 3-4 serum lipase elevations, doses in adult patients should be 

reduced to 400 mg once daily or interrupted. In paediatric patients, treatment must be interrupted until 

the event returns to Grade 1. Thereafter, if the prior dose was 230 mg/m2 twice daily, treatment can 

be resumed at 230 mg/m2 once daily. If the prior dose was 230 mg/m2 once daily, treatment should be 

discontinued. Serum lipase levels should be tested monthly or as clinically indicated (see section 4.4). 

 

Elevated bilirubin and hepatic transaminases: For Grade 3-4 bilirubin and hepatic transaminase 

elevations in adult patients, doses should be reduced to 400 mg once daily or interrupted. For 

Grade 2 bilirubin elevations or Grade 3 hepatic transaminase elevations in paediatric patients, 

treatment must be interrupted until the levels return to Grade 1. Thereafter, if the prior dose was 

230 mg/m2 twice daily, treatment can be resumed at 230 mg/m2 once daily. If the prior dose was 

230 mg/m2 once daily, and recovery to Grade 1 takes longer than 28 days, treatment should be 

discontinued. Bilirubin and hepatic transaminases levels should be tested monthly or as clinically 

indicated. 

 

Special populations 

Elderly 

Approximately 12% of subjects in the clinical study were 65 years of age or over. No major 

differences were observed for safety and efficacy in patients ≥65 years of age as compared to adults 

aged 18 to 65 years. 

 



41 

Renal impairment 

Clinical studies have not been performed in patients with impaired renal function. 

Since nilotinib and its metabolites are not renally excreted, a decrease in total body clearance is not 

anticipated in patients with renal impairment. 

 

Hepatic impairment 

Hepatic impairment has a modest effect on the pharmacokinetics of nilotinib. Dose adjustment is not 

considered necessary in patients with hepatic impairment. However, patients with hepatic impairment 

should be treated with caution (see section 4.4). 

 

Cardiac disorders 

In clinical studies, patients with uncontrolled or significant cardiac disease (e.g., recent myocardial 

infarction, congestive heart failure, unstable angina or clinically significant bradycardia) were 

excluded. Caution should be exercised in patients with relevant cardiac disorders (see section 4.4). 

 

Increases in total serum cholesterol levels have been reported with nilotinib therapy (see section 4.4). 

Lipid profiles should be determined prior to initiating nilotinib therapy, assessed at month 3 and 6 

after initiating therapy and at least yearly during chronic therapy. 

 

Increases in blood glucose levels have been reported with nilotinib therapy (see section 4.4). Blood 

glucose levels should be assessed prior to initiating nilotinib therapy and monitored during treatment. 

 

Paediatric population 

The safety and efficacy of Tasigna in paediatric patients with Philadelphia chromosome positive CML 

in chronic phase from 2 to less than 18 years of age have been established (see sections 4.8, 5.1 and 

5.2). There is no experience in paediatric patients below 2 years of age or in paediatric patients with 

Philadelphia chromosome positive CML in accelerated phase or blast crisis. There are no data in 

newly diagnosed paediatric patients below 10 years of age and limited data in imatinib-resistant or 

intolerant paediatric patients below 6 years of age. 

 

Method of administration 

 

Tasigna should be taken twice daily approximately 12 hours apart and must not be taken with food. 

The hard capsules should be swallowed whole with water. No food should be consumed for 2 hours 

before the dose is taken and for at least one hour after. 

 

For patients who are unable to swallow hard capsules, the content of each hard capsule may be 

dispersed in one teaspoon of apple sauce (puréed apple) and should be taken immediately. Not more 

than one teaspoon of apple sauce and no food other than apple sauce must be used (see sections 4.4 

and 5.2). 

 

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 
 

Myelosuppression 

 

Treatment with nilotinib is associated with (National Cancer Institute Common Toxicity Criteria 

grade 3-4) thrombocytopenia, neutropenia and anaemia. Complete blood counts should be performed 

every two weeks for the first 2 months and then monthly thereafter, or as clinically indicated. 

Myelosuppression was generally reversible and usually managed by withholding Tasigna temporarily 

or dose reduction (see section 4.2). 

 



42 

QT prolongation 

 

Nilotinib has been shown to prolong cardiac ventricular repolarisation as measured by the QT interval 

on the surface ECG in a concentration-dependent manner in adult and paediatric patients. 

 

In the Phase III study in patients with newly diagnosed CML in chronic phase receiving 300 mg 

nilotinib twice daily, the change from baseline in mean time-averaged QTcF interval at steady state 

was 6 msec. No patient had a QTcF >480 msec. No episodes of torsade de pointes were observed. 

 

In a healthy volunteer study with exposures that were comparable to the exposures observed in 

patients, the time-averaged mean placebo-subtracted QTcF change from baseline was 7 msec 

(CI ± 4 msec). No subject had a QTcF >450 msec. Additionally, no clinically relevant arrhythmias 

were observed during the conduct of the trial. In particular, no episodes of torsade de pointes (transient 

or sustained) were observed. 

 

Significant prolongation of the QT interval may occur when nilotinib is inappropriately taken with 

strong CYP3A4 inhibitors and/or medicinal products with a known potential to prolong the QT 

interval, and/or food (see section 4.5). The presence of hypokalaemia and hypomagnesaemia may 

further enhance this effect. Prolongation of the QT interval may expose patients to the risk of fatal 

outcome. 

 

Tasigna should be used with caution in patients who have or who are at significant risk of developing 

prolongation of QTc, such as those: 

- with congenital long QT prolongation 
- with uncontrolled or significant cardiac disease including recent myocardial infarction, 

congestive heart failure, unstable angina or clinically significant bradycardia. 

- taking anti-arrhythmic medicinal products or other substances that lead to QT prolongation. 
 

Close monitoring for an effect on the QTc interval is advisable and a baseline ECG is recommended 

prior to initiating nilotinib therapy and as clinically indicated. Hypokalaemia or hypomagnesaemia 

must be corrected prior to Tasigna administration and should be monitored periodically during 

therapy. 

 

Sudden death 

 

Uncommon cases (0.1 to 1%) of sudden deaths have been reported in patients with imatinib-resistant 

or intolerant CML in chronic phase or accelerated phase with a past medical history of cardiac disease 

or significant cardiac risk factors. Co-morbidities in addition to the underlying malignancy were also 

frequently present as were concomitant medicinal products. Ventricular repolarisation abnormalities 

may have been contributory factors. No cases of sudden death were reported in the Phase III study in 

newly diagnosed patients with CML in chronic phase. 

 

Fluid retention and oedema 

 

Severe forms of drug-related fluid retention such as pleural effusion, pulmonary oedema, and 

pericardial effusion were uncommonly (0.1 to 1%) observed in a Phase III study of newly diagnosed 

CML patients. Similar events were observed in post-marketing reports. Unexpected, rapid weight gain 

should be carefully investigated. If signs of severe fluid retention appear during treatment with 

nilotinib, the aetiology should be evaluated and patients treated accordingly (see section 4.2 for 

instructions on managing non-haematological toxicities). 

 

  



43 

Cardiovascular events 

 

Cardiovascular events were reported in a randomised Phase III study in newly diagnosed CML 

patients and observed in post-marketing reports. In this clinical study with a median on-therapy time 

of 60.5 months, Grade 3-4 cardiovascular events included peripheral arterial occlusive disease (1.4% 

and 1.1% at 300 mg and 400 mg nilotinib twice daily, respectively), ischaemic heart disease (2.2% and 

6.1% at 300 mg and 400 mg nilotinib twice daily, respectively) and ischaemic cerebrovascular events 

(1.1% and 2.2% at 300 mg and 400 mg nilotinib twice daily, respectively). Patients should be advised 

to seek immediate medical attention if they experience acute signs or symptoms of cardiovascular 

events. The cardiovascular status of patients should be evaluated and cardiovascular risk factors 

monitored and actively managed during nilotinib therapy according to standard guidelines. 

Appropriate therapy should be prescribed to manage cardiovascular risk factors (see section 4.2 for 

instructions on managing non-haematological toxicities). 

 

Hepatitis B reactivation 

 

Reactivation of hepatitis B in patients who are chronic carriers of this virus has occurred after these 

patients received BCR-ABL tyrosine kinase inhibitors. Some cases resulted in acute hepatic failure or 

fulminant hepatitis leading to liver transplantation or a fatal outcome. 

 

Patients should be tested for HBV infection before initiating treatment with nilotinib. Experts in liver 

disease and in the treatment of hepatitis B should be consulted before treatment is initiated in patients 

with positive hepatitis B serology (including those with active disease) and for patients who test 

positive for HBV infection during treatment. Carriers of HBV who require treatment with nilotinib 

should be closely monitored for signs and symptoms of active HBV infection throughout therapy and 

for several months following termination of therapy (see section 4.8). 
 

Special monitoring of adult Ph+ CML patients in chronic phase who have achieved a sustained deep 

molecular response 

 

Eligibility for discontinuation of treatment 

Eligible patients who are confirmed to express the typical BCR-ABL transcripts, e13a2/b2a2 or 

e14a2/b3a2, can be considered for treatment discontinuation. Patients must have typical BCR-ABL 

transcripts to allow quantitation of BCR-ABL, evaluation of the depth of molecular response, and 

determination of a possible loss of molecular remission after discontinuation of treatment with 

nilotinib. 

 

Monitoring of patients who have discontinued therapy 

Frequent monitoring of BCR-ABL transcript levels in patients eligible for treatment discontinuation 

must be performed with a quantitative diagnostic test validated to measure molecular response levels 

with a sensitivity of at least MR4.5 (BCR-ABL/ABL ≤0.0032% IS). BCR-ABL transcript levels must 

be assessed prior to and during treatment discontinuation (see sections 4.2 and 5.1). 

 

Loss of major molecular response (MMR=BCR-ABL/ABL ≤0.1%IS) will trigger treatment 

re-initiation within 4 weeks of when loss of remission is known to have occurred. Molecular relapse 

can occur during the treatment-free phase, and long-term outcome data are not yet available. It is 

therefore crucial to perform frequent monitoring of BCR-ABL transcript levels and complete blood 

count with differential in order to detect possible loss of remission (see section 4.2). For patients who 

fail to achieve MMR after three months of treatment re-initiation, BCR-ABL kinase domain mutation 

testing should be performed. 

 

  



44 

Laboratory tests and monitoring 

 

Blood lipids 

In a Phase III study in newly diagnosed CML patients, 1.1% of the patients treated with 400 mg 

nilotinib twice daily showed a Grade 3-4 elevation in total cholesterol; no Grade 3-4 elevations were 

however observed in the 300 mg twice daily dose group (see section 4.8). It is recommended that the 

lipid profiles be determined before initiating treatment with nilotinib, assessed at month 3 and 6 after 

initiating therapy and at least yearly during chronic therapy (see section 4.2). If a HMG-CoA reductase 

inhibitor (a lipid-lowering agent) is required, please refer to section 4.5 before initiating treatment 

since certain HMG-CoA reductase inhibitors are also metabolised by the CYP3A4 pathway. 

 

Blood glucose 

In a Phase III study in newly diagnosed CML patients, 6.9% and 7.2% of the patients treated with 

400 mg nilotinib and 300 mg nilotinib twice daily, respectively, showed a Grade 3-4 elevation in 

blood glucose. It is recommended that the glucose levels be assessed before initiating treatment with 

Tasigna and monitored during treatment, as clinically indicated (see section 4.2). If test results warrant 

therapy, physicians should follow their local standards of practice and treatment guidelines. 

 

Interactions with other medicinal products 

 

The administration of Tasigna with agents that are strong CYP3A4 inhibitors (including, but not 

limited to, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir) should 

be avoided. Should treatment with any of these agents be required, it is recommended that nilotinib 

therapy be interrupted if possible (see section 4.5). If transient interruption of treatment is not possible, 

close monitoring of the individual for prolongation of the QT interval is indicated (see sections 4.2, 

4.5 and 5.2). 

 

Concomitant use of nilotinib with medicinal products that are potent inducers of CYP3A4 (e.g., 

phenytoin, rifampicin, carbamazepine, phenobarbital and St. John’s Wort) is likely to reduce exposure 

to nilotinib to a clinically relevant extent. Therefore, in patients receiving nilotinib, co-administration 

of alternative therapeutic agents with less potential for CYP3A4 induction should be selected (see 

section 4.5). 

 

Food effect 

 

The bioavailability of nilotinib is increased by food. Tasigna must not be taken in conjunction with 

food (see sections 4.2 and 4.5) and should be taken 2 hours after a meal. No food should be consumed 

for at least one hour after the dose is taken. Grapefruit juice and other foods that are known to inhibit 

CYP3A4 should be avoided. For patients who are unable to swallow hard capsules, the content of each 

hard capsule may be dispersed in one teaspoon of apple sauce and should be taken immediately. Not 

more than one teaspoon of apple sauce and no food other than apple sauce must be used (see 

section 5.2). 

 

Hepatic impairment 

 

Hepatic impairment has a modest effect on the pharmacokinetics of nilotinib. Single dose 

administration of 200 mg of nilotinib resulted in increases in AUC of 35%, 35% and 19% in subjects 

with mild, moderate and severe hepatic impairment, respectively, compared to a control group of 

subjects with normal hepatic function. The predicted steady-state Cmax of nilotinib showed an increase 

of 29%, 18% and 22%, respectively. Clinical studies have excluded patients with alanine transaminase 

(ALT) and/or aspartate transaminase (AST) >2.5 (or >5, if related to disease) times the upper limit of 

the normal range and/or total bilirubin >1.5 times the upper limit of the normal range. Metabolism of 

nilotinib is mainly hepatic. Patients with hepatic impairment might therefore have increased exposure 

to nilotinib and should be treated with caution (see section 4.2). 

 



45 

Serum lipase 

 

Elevation in serum lipase has been observed. Caution is recommended in patients with previous 

history of pancreatitis. In case lipase elevations are accompanied by abdominal symptoms, nilotinib 

therapy should be interrupted and appropriate diagnostic measures considered to exclude pancreatitis. 

 

Total gastrectomy 

 

The bioavailability of nilotinib might be reduced in patients with total gastrectomy (see section 5.2). 

More frequent follow-up of these patients should be considered. 

 

Tumour lysis syndrome 

 

Due to possible occurrence of tumour lysis syndrome (TLS) correction of clinically significant 

dehydration and treatment of high uric acid levels are recommended prior to initiating nilotinib 

therapy (see section 4.8). 

 

Lactose 

 

Tasigna hard capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, 

the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. 

 

Paediatric population 

 

Laboratory abnormalities of mild to moderate transient elevations of aminotransferases and total 

bilirubin have been observed in children at a higher frequency than in adults, indicating a higher risk 

of hepatotoxicity in the paediatric population (see section 4.8). Liver function (bilirubin and hepatic 

transaminases levels) should be monitored monthly or as clinically indicated. Elevations of bilirubin 

and hepatic transaminases should be managed by withholding nilotinib temporarily, dose reduction 

and/or discontinuation of nilotinib (see section 4.2). The long-term effects of prolonged treatment with 

nilotinib in paediatric patients are unknown. In a study in the CML paediatric population, growth 

retardation has been documented in patients treated with nilotinib (see section 4.8). Close monitoring 

of growth in paediatric patients under nilotinib treatment is recommended. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Tasigna may be given in combination with haematopoietic growth factors such as erythropoietin or 

granulocyte colony-stimulating factor (G-CSF) if clinically indicated. It may be given with 

hydroxyurea or anagrelide if clinically indicated. 

 

Nilotinib is mainly metabolised in the liver with CYP3A4 expected to be the main contributor to the 

oxidative metabolism. Nilotinib is also a substrate for the multi-drug efflux pump, P-glycoprotein 

(P-gp). Therefore, absorption and subsequent elimination of systemically absorbed nilotinib may be 

influenced by substances that affect CYP3A4 and/or P-gp. 

 

Substances that may increase nilotinib serum concentrations 

 

Concomitant administration of nilotinib with imatinib (a substrate and moderator of P-gp and 

CYP3A4), had a slight inhibitory effect on CYP3A4 and/or P-gp. The AUC of imatinib was increased 

by 18% to 39%, and the AUC of nilotinib was increased by 18% to 40%. These changes are unlikely 

to be clinically important. 

 

  



46 

The exposure to nilotinib in healthy subjects was increased 3-fold when co-administered with the 

strong CYP3A4 inhibitor ketoconazole. Concomitant treatment with strong CYP3A4 inhibitors, 

including ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, and telithromycin, 

should therefore be avoided (see section 4.4). Increased exposure to nilotinib might also be expected 

with moderate CYP3A4 inhibitors. Alternative concomitant medicinal products with no or minimal 

CYP3A4 inhibition should be considered. 

 

Substances that may decrease nilotinib serum concentrations 

 

Rifampicin, a potent CYP3A4 inducer, decreases nilotinib Cmax by 64% and reduces nilotinib AUC by 

80%. Rifampicin and nilotinib should not be used concomitantly. 

 

The concomitant administration of other medicinal products that induce CYP3A4 (e.g., phenytoin, 

carbamazepine, phenobarbital and St. John’s Wort) is likewise likely to reduce exposure to nilotinib to 

a clinically relevant extent. In patients for whom CYP3A4 inducers are indicated, alternative agents 

with less enzyme induction potential should be selected. 

 

Nilotinib has pH dependent solubility, with lower solubility at higher pH. In healthy subjects receiving 

esomeprazole at 40 mg once daily for 5 days, gastric pH was markedly increased, but nilotinib 

absorption was only decreased modestly (27% decrease in Cmax and 34% decrease in AUC0-∞). 

Nilotinib may be used concurrently with esomeprazole or other proton pump inhibitors as needed. 

 

In a healthy subjects study, no significant change in nilotinib pharmacokinetics was observed when a 

single 400 mg dose of nilotinib was administered 10 hours after and 2 hours before famotidine. 

Therefore, when the concurrent use of a H2 blocker is necessary, it may be administered 

approximately 10 hours before and approximately 2 hours after the dose of Tasigna. 

 

In the same study as above, administration of an antacid (aluminium hydroxide/magnesium 

hydroxide/simethicone) 2 hours before or after a single 400 mg dose of nilotinib also did not alter 

nilotinib pharmacokinetics. Therefore, if necessary, an antacid may be administered approximately 

2 hours before or approximately 2 hours after the dose of Tasigna. 

 

Substances that may have their systemic concentration altered by nilotinib 

 

In vitro, nilotinib is a relatively strong inhibitor of CYP3A4, CYP2C8, CYP2C9, CYP2D6 and 

UGT1A1, with Ki value being lowest for CYP2C9 (Ki=0.13 microM). 

 

A single-dose drug-drug interaction study in healthy volunteers with 25 mg warfarin, a sensitive 

CYP2C9 substrate, and 800 mg nilotinib did not result in any changes in warfarin pharmacokinetic 

parameters or warfarin pharmacodynamics measured as prothrombin time (PT) and international 

normalised ratio (INR). There are no steady-state data. This study suggests that a clinically meaningful 

drug-drug interaction between nilotinib and warfarin is less likely up to a dose of 25 mg of warfarin. 

Due to lack of steady-state data, control of warfarin pharmacodynamic markers (INR or PT) following 

initiation of nilotinib therapy (at least during the first 2 weeks) is recommended. 

 

In CML patients, nilotinib administered at 400 mg twice daily for 12 days increased the systemic 

exposure (AUC and Cmax) of oral midazolam (a substrate of CYP3A4) 2.6-fold and 2.0-fold, 

respectively. Nilotinib is a moderate CYP3A4 inhibitor. As a result, the systemic exposure of other 

medicinal products primarily metabolised by CYP3A4 (e.g., certain HMG-CoA reductase inhibitors) 

may be increased when co-administered with nilotinib. Appropriate monitoring and dose adjustment 

may be necessary for medicinal products that are CYP3A4 substrates and have a narrow therapeutic 

index (including but not limited to alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, 

sirolimus and tacrolimus) when co-administered with nilotinib. 

 

  



47 

Anti-arrhythmic medicinal products and other substances that may prolong the QT interval 

 

Nilotinib should be used with caution in patients who have or may develop prolongation of the QT 

interval, including those patients taking anti-arrhythmic medicinal products such as amiodarone, 

disopyramide, procainamide, quinidine and sotalol or other medicinal products that may lead to QT 

prolongation such as chloroquine, halofantrine, clarithromycin, haloperidol, methadone and 

moxifloxacin (see section 4.4). 

 

Food interactions 

 

The absorption and bioavailability of nilotinib are increased if it is taken with food, resulting in a 

higher serum concentration (see sections 4.2, 4.4 and 5.2). Grapefruit juice and other foods that are 

known to inhibit CYP3A4 should be avoided. 

 

Paediatric population 

 

Interaction studies have only been performed in adults. 

 

4.6 Fertility, pregnancy and lactation 
 

Women of childbearing potential/Contraception 

 

Women of childbearing potential have to use highly effective contraception during treatment with 

nilotinib and for up to two weeks after ending treatment. 

 

Pregnancy 

 

There are no or limited amount of data from the use of nilotinib in pregnant women. Studies in 

animals have shown reproductive toxicity (see section 5.3). Tasigna should not be used during 

pregnancy unless the clinical condition of the woman requires treatment with nilotinib. If it is used 

during pregnancy, the patient must be informed of the potential risk to the foetus. 

 

If a woman who is being treated with nilotinib is considering pregnancy, treatment discontinuation 

may be considered based on the eligibility criteria for discontinuing treatment as described in 

sections 4.2 and 4.4. There is a limited amount of data on pregnancies in patients while attempting 

treatment-free remission (TFR). If pregnancy is planned during the TFR phase, the patient must be 

informed of a potential need to re-initiate nilotinib treatment during pregnancy (see sections 4.2 and 

4.4). 

 

Breast-feeding 

 

It is unknown whether nilotinib is excreted in human milk. Available toxicological data in animals 

have shown excretion of nilotinib in milk (see section 5.3). Since a risk to the newborns/infants cannot 

be excluded, women should not breast-feed during Tasigna treatment and for 2 weeks after the last 

dose. 

 

Fertility 

 

Animal studies did not show an effect on fertility in male and female rats (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

Tasigna has no or negligible influence on the ability to drive and use machines. However, it is 

recommended that patients experiencing dizziness, fatigue, visual impairment or other undesirable 

effects with a potential impact on the ability to drive or use machines safely should refrain from these 

activities as long as the undesirable effects persist (see section 4.8). 

 



48 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

The data described below reflect exposure to nilotinib in 279 adult patients from a randomised 

Phase III study in patients with newly diagnosed Ph+ CML in chronic phase treated with 300 mg of 

nilotinib twice daily. Safety information from a Tasigna treatment discontinuation study in CML 

patients who have been treated with nilotinib as first-line therapy is also provided. 

 

The median duration of exposure was 60.5 months (range 0.1-70.8 months). 

 

The most frequent (≥10%) non-haematological adverse reactions were rash, pruritus, headache, 

nausea, fatigue, alopecia, myalgia and upper abdominal pain. Most of these adverse reactions were 

mild to moderate in severity. Constipation, dry skin, asthenia, muscle spasms, diarrhoea, arthralgia, 

abdominal pain, vomiting and peripheral oedema were observed less commonly (<10% and ≥5%), 

were of mild to moderate severity, manageable and generally did not require dose reduction. 

 

Treatment-emergent haematological toxicities include myelosuppression: thrombocytopenia (18%), 

neutropenia (15%) and anaemia (8%). Biochemical adverse drug reactions include alanine 

aminotransferase increased (24%), hyperbilirubinaemia (16%), aspartate aminotransferase increased 

(12%), lipase increased (11%), blood bilirubin increased (10%), hyperglycaemia (4%), 

hypercholesterolaemia (3%) and hypertriglyceridaemia (<1%). Pleural and pericardial effusions, 

regardless of causality, occurred in 2% and <1% of patients, respectively, receiving nilotinib 300 mg 

twice daily. Gastrointestinal haemorrhage, regardless of causality, was reported in 3% of these 

patients. 

 

The change from baseline in mean time-averaged QTcF interval at steady state was 6 msec. No patient 

had an absolute QTcF >500 msec while on the study medicinal product. QTcF increase from baseline 

exceeding 60 msec was observed in <1% of patients while on the study medicinal product. No sudden 

deaths or episodes of torsade de pointes (transient or sustained) were observed. No decrease from 

baseline in mean left ventricular ejection fraction (LVEF) was observed at any time during treatment. 

No patient had a LVEF of <45% during treatment nor an absolute reduction in LVEF of more than 

15%. 

 

Discontinuation due to adverse drug reactions was observed in 10% of patients. 

 

Tabulated list of adverse reactions 

 

The adverse reactions are ranked under heading of frequency 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 

<1/1,000), 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. 

 

Most frequently reported adverse reactions in Tasigna clinical studies 

Non-haematological adverse reactions (excluding laboratory abnormalities) that are reported in at least 

5% of the adult patients treated with 300 mg of nilotinib twice daily in the randomised Phase III study 

are shown in Table 3. 

 



49 

Table 3 Non-haematological adverse reactions (≥5% of all patients)* 

 

System organ class Frequency Adverse reaction All 

grades 

Grade 

3-4 

   % % 

Nervous system disorders Very common Headache 16 2 

Gastrointestinal disorders Very common Nausea 14 <1 

Very common Abdominal pain 

upper 

10 1 

Common Constipation 10 0 

Common Diarrhoea 9 <1 

Common Abdominal pain 6 0 

Common Vomiting 6 0 

Common Dyspepsia 5 0 

Skin and subcutaneous tissue 

disorders 

Very common Rash 33 <1 

Very common Pruritus 18 <1 

Very common Alopecia 10 0 

Common Dry skin 10 0 

Musculoskeletal and 

connective tissue disorders 

Very common Myalgia 10 <1 

Common Muscle spasms 9 0 

Common Arthralgia 8 <1 

Common Pain in extremity 5 <1 

General disorders and 

administration site conditions 

Very common Fatigue 12 0 

Common Asthenia 9 <1 

Common Oedema peripheral 5 <1 

*Percentages are rounded to integer for presentation in this table. However, percentages with one 

decimal precision are used to identify terms with a frequency of at least 5% and to classify terms 

according to frequency categories. 

 

Adverse reactions that were reported in adult patients in the Tasigna Phase III study at a frequency of 

less than 5% are shown in Table 4. For laboratory abnormalities, very common events (1/10) not 

included in Table 3 are also reported. These adverse reactions are included based on clinical relevance 

and ranked in order of decreasing seriousness within each category using the following convention: 

very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), not known 

(cannot be estimated from the available data). 

 

Table 4 Adverse reactions in adult patients in the Tasigna Phase III study (<5% of all 

patients) 

 

Infections and infestations 

Common: Folliculitis, upper respiratory tract infection (including pharyngitis, 

nasopharyngitis, rhinitis) 

Not known: Herpes virus infection, oral candidiasis, subcutaneous abscess, anal abscess, 

tinea pedis, hepatitis B reactivation 

Neoplasms benign, malignant and unspecified (including cysts and polyps) 

Common: Skin papilloma 

Not known: Oral papilloma, paraproteinaemia 

Blood and lymphatic system disorders 

Common: Leukopenia, eosinophilia, lymphopenia 

Uncommon: Pancytopenia 

Not known: Febrile neutropenia 

Immune system disorders 

Not known: Hypersensitivity 

Endocrine disorders 

Not known: Hyperparathyroidism secondary 



50 

Metabolism and nutrition disorders 

Very common: Hypophosphataemia (including blood phosphorus decreased) 

Common: Diabetes mellitus, hypercholesterolaemia, hyperlipidaemia, 

hypertriglyceridaemia, hyperglycaemia, decreased appetite, hypocalcaemia, 

hypokalaemia 

Uncommon: Hyperkalaemia, dyslipidaemia, gout 

Not known: Hyperuricaemia, hypoglycaemia, appetite disorder 

Psychiatric disorders 

Common: Insomnia, depression, anxiety 

Not known: Amnesia, dysphoria 

Nervous system disorders 

Common: Dizziness, hypoaesthesia, peripheral neuropathy 

Uncommon: Ischaemic stroke, cerebral infarction, migraine, paraestheisa 

Not known: Cerebrovascular accident, basilar artery stenosis, syncope, tremor, lethargy, 

dysaesthesia, restless legs syndrome, hyperaesthesia 

Eye disorders 

Common: Eye pruritus, conjunctivitis, dry eye (including xerophthalmia) 

Uncommon: Eyelid oedema, photopsia, conjunctival haemorrhage, hyperaemia (scleral, 

conjunctival, ocular) 

Not known: Periorbital oedema, blepharitis, eye pain, chorioretinopathy, conjunctivitis 

allergic, ocular surface disease, vision blurred 

Ear and labyrinth disorders 

Common: Vertigo 

Cardiac disorders 

(reported in 300 mg twice daily and/or 400 mg twice daily treatment arm of phase III study) 

Common: Angina pectoris, arrhythmia (including atroventricular block, tachycardia, 

atrial fibrillation, ventricular extrasystoles, bradycardia), electrocardiogram 

QT prolonged, palpitations, myocardial infarction 

Uncommon: Cardiac failure, cyanosis 

Not known: Ejection fraction decrease, pericardial effusion, pericarditis, diastolic 

dysfunction, left bundle branch block 

Vascular disorders 

Common: Hypertension, flushing 

Uncommon: Intermittent claudication, peripheral arterial occulsive disease, arteriosclerosis 

Not known: Haematoma, peripheral artery stenosis 

Respiratory, thoracic and mediastinal disorders 

Common: Dyspnoea, cough 

Uncommon: Pleural effusion 

Not known: Dyspnoea exertional, pleurisy, epistaxis, oropharyngeal pain 

Gastrointestinal disorders 

Common: Abdominal distension, abdomnial discomfort, dysgeusia, flatulence 

Uncommon: Pancreatitis, gastritis, sensitivity of teeth 

Not known: Oesophageal ulcer, gastric ulcer, oesophageal pain, stomatitis, dry mouth, 

enterocolitis, haemorrhoids, hiatus hernia, rectal haemorrhage, gingivitis 

Hepatobiliary disorders 

Very common: Hyperbilirubinaemia (including blood bilirubin increased) 

Common: Hepatic function abnormal 

Uncommon: Jaundice 

Not known: Toxic hepatitis 



51 

Skin and subcutaneous tissue disorders 

Common: Erythema, hyperhidrosis, contusion, acne, dermatitis (including allergic, 

exfoliative and acneiform), night sweats, eczema 

Uncommon: Drug eruption, skin pain 

Not known: Erythema multiforme, urticaria, blister, dermal cyst, sebaceous hyperplasia, 

swelling face, skin atrophy, skin hypertrophy, skin exfoliation, skin 

hyperpigmentation, skin discolouration, hyperkeratosis, psoriasis 

Musculoskeletal and connective tissue disorders 

Common: Bone pain, back pain, muscular weakness 

Uncommon: Musculoskeletal pain, flank pain 

Renal and urinary disorders 

Not known: Dysuria, polliakiuria, chromaturia 

Reproductive system and breast disorders 

Uncommon: Erectile dysfunction 

Not known: Gynaecomastia, breast induration, menorrhagia, nipple swelling 

General disorders and administration site conditions 

Common: Pyrexia, chest pain (including non-cardiac chest pain), chest discomfort 

Uncommon: Pain, chills, feeling body temperature change (including feeling hot, feeling 

cold), malaise 

Not known: Face oedema, localised oedema 

Investigations 

Very common: Alanine aminotransferase increased, aspartate aminotransferase increased, 

lipase increased, lipoprotein cholesterol (including low density and high 

density) increased, total cholesterol increased, blood triglycerides increased 

Common: Haemoglobin decreased, blood amylase increased, blood alkaline phosphatase 

increased, gamma-glutamyltransferase increased, weight increased, blood 

insulin increased, globulins decreased 

Not known: Blood parathyroid hormone increased, blood insulin decreased, insulin 

C-peptide decreased, weight decreased 

 

Clinically relevant or severe abnormalities of routine haematological or biochemistry laboratory 

values in adult patients are presented in Table 5. 

 

Table 5 Grade 3-4 laboratory abnormalities* 

 

 n=279 

(%) 

Haematological parameters  

Myelosuppression  

- Neutropenia 12 

- Thrombocytopenia 10 

- Anaemia 4 

Biochemistry parameters  

- Elevated creatinine 0 

- Elevated lipase 9 

- Elevated SGOT (AST) 1 

- Elevated SGPT (ALT) 4 

- Hypophosphataemia 8 

- Elevated bilirubin (total) 4 

- Elevated glucose 7 

- Elevated cholesterol (total) 0 

- Elevated triglycerides 0 

*Percentages with one decimal precision are used and rounded to integer for presentation in this table. 



52 

 

Treatment discontinuation in adult Ph+ CML patients in chronic phase who have achieved a sustained 

deep molecular response 

 

After discontinuation of nilotinib therapy within the framework of attempting TFR, patients may 

experience musculoskeletal symptoms more frequently than before treatment discontinuation, e.g., 

myalgia, pain in extremity, arthralgia, bone pain, spinal pain or musculoskeletal pain. 

 

In a Phase II clinical study with newly diagnosed adult patients with Ph+ CML in chronic phase 

(N=190), musculoskeletal symptoms were reported within a year of Tasigna discontinuation in 24.7% 

versus 16.3% within the previous year on nilotinib treatment. 

 

Description of selected adverse reactions 

 

Hepatitis B reactivation 

Hepatitis B reactivation has been reported in association with BCR-ABL TKIs. Some cases resulted in 

acute hepatic failure or fulminant hepatitis leading to liver transplantation or a fatal outcome (see 

section 4.4). 

 

Post-marketing experience 

 

The following adverse reactions have been derived from post-marketing experience with Tasigna via 

spontaneous case reports, literature cases, expanded access programmes, and clinical studies other 

than the global registration trials. Since these reactions are reported voluntarily from a population of 

uncertain size, it is not always possible to reliably estimate their frequency or establish a causal 

relationship to nilotinib exposure. 

 

Frequency very common: Growth retardation has been documented in paediatric patients treated with 

nilotinib. 

 

Frequency rare: Cases of tumour lysis syndrome have been reported in patients treated with nilotinib. 

 

Paediatric population 

 

The safety of nilotinib in paediatric patients (from 2 to <18 years of age) with Philadelphia 

chromosome positive CML in chronic phase (n=69) has been investigated in two studies (see 

section 5.1). In paediatric patients, the frequency, type and severity of adverse reactions observed have 

been generally consistent with those observed in adults, with the exception of the laboratory 

abnormalities hyperbilirubinaemia (Grade 3/4: 13.0%) and transaminase elevation (AST Grade 3/4: 

1.4%, ALT Grade 3/4: 8.7%) which were reported at a higher frequency than in adult patients. 

Bilirubin and hepatic transaminase levels should be monitored during treatment (see sections 4.2 and 

4.4). 

 

Growth retardation in paediatric population 

In an interim analysis in a study in the CML paediatric population, with a median exposure of 

33 months in each cohort (newly diagnosed and resistant or intolerant Ph+ CML-CP), growth 

retardation (crossing two main percentile lines from baseline) has been documented in 12.1%. Close 

monitoring of growth in paediatric patients under nilotinib treatment is recommended (see 

section 4.4). 

 

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. 

 



53 

4.9 Overdose 
 

Isolated reports of intentional overdose with nilotinib were reported, where an unspecified number of 

Tasigna hard capsules were ingested in combination with alcohol and other medicinal products. Events 

included neutropenia, vomiting and drowsiness. No ECG changes or hepatotoxicity were reported. 

Outcomes were reported as recovered. 

 

In the event of overdose, the patient should be observed and appropriate supportive treatment given. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antineoplastic agents, protein kinase inhibitors, ATC code: L01XE08 

 

Mechanism of action 

 

Nilotinib is a potent inhibitor of the ABL tyrosine kinase activity of the BCR-ABL oncoprotein both in 

cell lines and in primary Philadelphia-chromosome positive leukaemia cells. The substance binds with 

high affinity to the ATP-binding site in such a manner that it is a potent inhibitor of wild-type 

BCR-ABL and maintains activity against 32/33 imatinib-resistant mutant forms of BCR-ABL. As a 

consequence of this biochemical activity, nilotinib selectively inhibits the proliferation and induces 

apoptosis in cell lines and in primary Philadelphia-chromosome positive leukaemia cells from CML 

patients. In murine models of CML, as a single agent nilotinib reduces tumour burden and prolongs 

survival following oral administration. 

 

Pharmacodynamic effects 

 

Nilotinib has little or no effect against the majority of other protein kinases examined, including Src, 

except for the PDGF, KIT and Ephrin receptor kinases, which it inhibits at concentrations within the 

range achieved following oral administration at therapeutic doses recommended for the treatment of 

CML (see Table 6). 

 

Table 6 Kinase profile of nilotinib (phosphorylation IC50 nM) 

 

BCR-ABL PDGFR KIT 

20 69 210 

 

Clinical efficacy 

 

Clinical studies in newly diagnosed CML in chronic phase 

An open-label, multicentre, randomised Phase III study was conducted to determine the efficacy of 

nilotinib versus imatinib in 846 adult patients with cytogenetically confirmed newly diagnosed 

Philadelphia chromosome positive CML in the chronic phase. Patients were within six months of 

diagnosis and were previously untreated, with the exception of hydroxyurea and/or anagrelide. 

Patients were randomised 1:1:1 to receive either nilotinib 300 mg twice daily (n=282), nilotinib 

400 mg twice daily (n=281) or imatinib 400 mg once daily (n=283). Randomisation was stratified by 

Sokal risk score at the time of diagnosis. 

 

Baseline characteristics were well balanced between the three treatment arms. Median age was 

47 years in both nilotinib arms and 46 years in the imatinib arm, with 12.8%, 10.0% and 12.4% of 

patients were ≥65 years of age in the nilotinib 300 mg twice daily, nilotinib 400 mg twice daily and 

imatinib 400 mg once daily treatment arms, respectively. There were slightly more male than female 

patients (56.0%, 62.3% and 55.8%, in the nilotinib 300 mg twice daily, 400 mg twice daily and 

imatinib 400 mg once daily arm, respectively). More than 60% of all patients were Caucasian and 25% 

of all patients were Asian. 



54 

 

The primary data analysis time point was when all 846 patients completed 12 months of treatment (or 

discontinued earlier). Subsequent analyses reflect when patients completed 24, 36, 48, 60 and 

72 months of treatment (or discontinued earlier). The median time on treatment was approximately 

70 months in the nilotinib treatment groups and 64 months in the imatinib group. The median actual 

dose intensity was 593 mg/day for nilotinib 300 mg twice daily, 772 mg/day for nilotinib 400 mg 

twice daily and 400 mg/day for imatinib 400 mg once daily. This study is ongoing. 

 

The primary efficacy endpoint was major molecular response (MMR) at 12 months. MMR was 

defined as ≤0.1% BCR-ABL/ABL% by international scale (IS) measured by RQvPCR, which 

corresponds to a ≥3 log reduction of BCR-ABL transcript from standardised baseline. The MMR rate 

at 12 months was statistically significantly higher for nilotinib 300 mg twice daily compared to 

imatinib 400 mg once daily (44.3% versus 22.3%, p<0.0001). The rate of MMR at 12 months, was 

also statistically significantly higher for nilotinib 400 mg twice daily compared to imatinib 400 mg 

once daily (42.7% versus 22.3%, p<0.0001). 

 

The rates of MMR at 3, 6, 9 and 12 months were 8.9%, 33.0%, 43.3% and 44.3% for nilotinib 300 mg 

twice daily, 5.0%, 29.5%, 38.1% and 42.7% for nilotinib 400 mg twice daily and 0.7%, 12.0%, 18.0% 

and 22.3% for imatinib 400 mg once daily. 

 

The MMR rate at 12, 24, 36, 48, 60 and 72 months is presented in Table 7. 

 



55 

Table 7 MMR rate 

 

 Nilotinib 

300 mg twice daily 

n=282 

(%) 

Nilotinib 

400 mg twice daily 

n=281 

(%) 

Imatinib 

400 mg once daily 

n=283 

(%) 

MMR at 12 months    

Response (95% CI) 44.31 (38.4; 50.3) 42.71 (36.8; 48.7) 22.3 (17.6; 27.6) 

MMR at 24 months    

Response (95% CI) 61.71 (55.8; 67.4) 59.11 (53.1; 64.9) 37.5 (31.8; 43.4) 

MMR at 36 months2    

Response (95% CI) 58.51 (52.5; 64.3) 57.31 (51.3; 63.2) 38.5 (32.8; 44.5) 

MMR at 48 months3    

Response (95% CI) 59.91 (54.0; 65.7) 55.2 (49.1; 61.1) 43.8 (38.0; 49.8) 

MMR at 60 months4    

Response (95% CI) 62.8 (56.8; 68.4) 61.2 (55.2; 66.9) 49.1 (43.2; 55.1) 

MMR at 72 months5    

Response (95% CI) 52.5 (46.5; 58.4) 57.7 (51.6; 63.5) 41.7 (35.9; 47.7) 
1 Cochran-Mantel-Haenszel (CMH) test p-value for response rate (vs. imatinib 400 mg) <0.0001 
2 Only patients who were in MMR at a specific time point are included as responders for that time 

point. A total of 199 (35.2%) of all patients were not evaluable for MMR at 36 months (87 in the 

nilotinib 300 mg twice daily group and 112 in the imatinib group) due to missing/unevaluable PCR 

assessments (n=17), atypical transcripts at baseline (n=7), or discontinuation prior to the 36-month 

time point (n=175). 
3 Only patients who were in MMR at a specific time point are included as responders for that time 

point. A total of 305 (36.1%) of all patients were not evaluable for MMR at 48 months (98 in the 

nilotinib 300 mg twice daily group, 88 in the nilotinib 400 mg twice daily group and 119 in the 

imatinib group) due to missing/unevaluable PCR assessments (n=18), atypical transcripts at baseline 

(n=8), or discontinuation prior to the 48-month time point (n=279). 
4 Only patients who were in MMR at a specific time point are included as responders for that time 

point. A total of 322 (38.1%) of all patients were not evaluable for MMR at 60 months (99 in the 

nilotinib 300 mg twice daily group, 93 in the nilotinib 400 mg twice daily group and 130 in the 

imatinib group) due to missing/unevaluable PCR assessments (n=9), atypical transcripts at baseline 

(n=8) or discontinuation prior to the 60-month time point (n=305). 
5 Only patients who were in MMR at a specific time point are included as responders for that time 

point. A total of 395 (46.7%) of all patients were not evaluable for MMR at 72 months (130 in the 

nilotinib 300 mg twice daily group, 110 in the nilotinib 400 mg twice daily group and 155 in the 

imatinib group) due to missing/unevaluable PCR assessments (n=25), atypical transcripts at baseline 

(n=8) or discontinuation prior to the 72-month time point (n=362). 

 

MMR rates by different time points (including patients who achieved MMR at or before those time 

points as responders) are presented in the cumulative incidence of MMR (see Figure 1). 

 



56 

Figure 1 Cumulative incidence of MMR 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

For all Sokal risk groups, the MMR rates at all time points remained consistently higher in the two 

nilotinib groups than in the imatinib group. 

 

In a retrospective analysis, 91% (234/258) of patients on nilotinib 300 mg twice daily achieved 

BCR-ABL levels ≤10% at 3 months of treatment compared to 67% (176/264) of patients on imatinib 

400 mg once daily. Patients with BCR-ABL levels ≤10% at 3 months of treatment show a greater 

overall survival at 72 months compared to those who did not achieve this molecular response level 

(94.5% vs. 77.1% respectively [p=0.0005]). 

 

Based on the Kaplan-Meier analysis of time to first MMR the probability of achieving MMR at 

different time points was higher for both nilotinib at 300 mg and 400 mg twice daily compared to 

imatinib 400 mg once daily (HR=2.17 and stratified log-rank p<0.0001 between nilotinib 300 mg 

twice daily and imatinib 400 mg once daily, HR=1.88 and stratified log-rank p<0.0001 between 

nilotinib 400 mg twice daily and imatinib 400 mg once daily). 

 

The proportion of patients who had a molecular response of ≤0.01% and ≤0.0032% by IS at different 

time points are presented in Table 8 and the proportion of patients who had a molecular response of 

≤0.01% and ≤0.0032% by IS by different time points are presented in Figures 2 and 3. Molecular 

responses of ≤0.01% and ≤0.0032% by IS correspond to a ≥4 log reduction and ≥4.5 log reduction, 

respectively, of BCR-ABL transcripts from a standardised baseline. 

 

0 6 12 18 24 30 36 42 48 54 60 

0 

20 

40 

60 

80 

100 

Months since randomisation 

 C
u

m
u

la
ti

v
e

 i
n

c
id

e
n

c
e
 o

f 
M

M
R

, 
%

 

 

10 

30 

50 

70 

90 

66 72 

  

 

 

By 1 year 
 

By 2 years
 

By 3 years
 

By 4 years
 

By 5 years
 

55%; P < .0001 

71%; P < .0001 
73%; P < .0001 

76%; P < .0001 77%; P < .0001 

60% 
56% 

53% 

44% 

27% 

61%;  
P < .0001 

 

70%; P < .0001 
73%; P < .0001 

77%; P < .0001 

51%;  
P < .0001 

Nilotinib 300 mg twice daily (n = 282) 

Nilotinib 400 mg twice daily (n = 281) 
 Imatinib 400 mg once daily (n = 283) 

By 6 years
 

79%; P < .0001 

61% 

77%; P < .0001 



57 

Table 8 Proportions of patients who had molecular response of ≤0.01% (4 log reduction) and 

≤0.0032% (4.5 log reduction) 

 

 
Nilotinib 

300 mg twice daily 

n=282 

(%) 

Nilotinib 

400 mg twice daily 

n=281 

(%) 

Imatinib 

400 mg once daily 

n=283 

(%) 

 ≤0.01% ≤0.0032% ≤0.01% ≤ 0.0032% ≤0.01% ≤0.0032% 

At 12 months 11.7 4.3 8.5 4.6 3.9 0.4 

At 24 months 24.5 12.4 22.1 7.8 10.2 2.8 

At 36 months 29.4 13.8 23.8 12.1 14.1 8.1 

At 48 months 33.0 16.3 29.9 17.1 19.8 10.2 

At 60 months 47.9 32.3 43.4 29.5 31.1 19.8 

At 72 months 44.3 31.2 45.2 28.8 27.2 18.0 

 

Figure 2 Cumulative incidence of molecular response of ≤0.01% (4-log reduction) 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

0 6 12 18 24 30 36 42 48 54 60 

0 

20 

40 

60 

80 

100 

 C
u

m
u

la
ti

v
e

 i
n

c
id

e
n

c
e
 o

f 
M

R
4
 

(B
C

R
-A

B
L

 ≤
0
.0

1
%

 o
n

 t
h

e
 i

n
te

rn
a
ti

o
n

a
l 

s
c
a
le

),
 %

 

10 

30 

50 

70 

90 

66 72 

 

  

39%; P < .0001 

50%; P < .0001 

56%; P < .0001 

66%; P < .0001 

42% 

32% 

26% 

18% 

6% 

33%; 
P < .0001 

44%;  
P < .0001 

50%; P < .0001 

63%; 
P < .0001 

43% 

67%; P < .0001 

65%; P < .0001 

20%; P < .0001 
 
 

15%; P = .0004 

Months since randomisation  

Nilotinib 300 mg twice daily (n = 282) 

Nilotinib 400 mg twice daily (n = 281) 

Imatinib 400 mg once daily (n = 283) 

By 1 year
 

By 2 years
 

By 3 years
 

By 4 years
 

By 5 years
 

By 6 years
 



58 

Figure 3 Cumulative incidence of molecular response of ≤0.0032% (4.5 log reduction) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Based on Kaplan-Meier estimates of the duration of first MMR, the proportions of patients who were 

maintaining response for 72 months among patients who achieved MMR were 92.5% (95% CI: 

88.6-96.4%) in the nilotinib 300 mg twice daily group, 92.2% (95% CI: 88.5-95.9%) in the nilotinib 

400 mg twice daily group and 88.0% (95% CI: 83.0-93.1%) in the imatinib 400 mg once daily group. 

 

Complete cytogenetic response (CCyR) was defined as 0% Ph+ metaphases in the bone marrow based 

on a minimum of 20 metaphases evaluated. Best CCyR rate by 12 months (including patients who 

achieved CCyR at or before the 12 month time point as responders) was statistically higher for both 

nilotinib 300 mg and 400 mg twice daily compared to imatinib 400 mg once daily, see Table 9. 

 

CCyR rate by 24 months (includes patients who achieved CCyR at or before the 24 month time point 

as responders) was statistically higher for both the nilotinib 300 mg twice daily and 400 mg twice 

daily groups compared to the imatinib 400 mg once daily group. 

 

0 6 12 18 24 30 36 42 48 54 60 

0 

20 

40 

60 

80 

100 

10 

30 

50 

70 

90 

66 72 

 

  

25%; P < .0001 

32%; P < .0001 

40%; P < .0001 

54%; P < .0001 

31% 

23% 

15% 
9% 

1% 19%; 
P = .0006 

28%;  
P = .0003 

37%; 
P = .0002 

52%; 
P < .0001 

33% 

56%; P < .0001 

55%; P < .0001 

11%; P < .0001 
7%; P < .0001  C

u
m

u
la

ti
v
e

 i
n

c
id

e
n

c
e
 o

f 
M

R
4
.5
 

(B
C

R
-A

B
L

 ≤
0
.0

0
3
2
%

 o
n

 t
h

e
 i

n
te

rn
a
ti

o
n

a
l 

s
c

a
le

),
 %

 Nilotinib 300 mg twice daily (n = 282) 
Nilotinib 400 mg twice daily (n = 281) 

Imatinib 400 mg once daily (n = 283) 

Months since randomisation 

By 1 year
 

By 2 years
 

By 3 years
 

By 4 years
 

By 5 years
 

By 6 years
 



59 

Table 9 Best CCyR rate 

 

 Nilotinib 

300 mg twice daily 

n=282 

(%) 

Nilotinib 

400 mg twice daily 

n=281 

(%) 

Imatinib 

400 mg once daily 

n=283 

(%) 

By 12 months    

Response (95% CI) 80.1 (75.0; 84.6) 77.9 (72.6; 82.6) 65.0 (59.2; 70.6) 

No response 19.9 22.1 35.0 

CMH test p-value for response 

rate (versus imatinib 400 mg 

once daily) 

<0.0001 0.0005  

By 24 months    

Response (95% CI) 86.9 (82.4; 90.6) 84.7 (79.9; 88.7) 77.0 (71.7; 81.8) 

No response 13.1 15.3 23.0 

CMH test p-value for response 

rate (versus imatinib 400 mg 

once daily) 

0.0018 0.0160  

 

Based on Kaplan-Meier estimates, the proportions of patients who were maintaining response for 

72 months among patients who achieved CCyR were 99.1% (95% CI: 97.9-100%) in the nilotinib 

300 mg twice daily group, 98.7% (95% CI: 97.1-100%) in the nilotinib 400 mg twice daily group and 

97.0% (95% CI: 94.7-99.4%) in the imatinib 400 mg once daily group. 

 

Progression to accelerated phase (AP) or blast crisis (BC) on treatment is defined as the time from the 

date of randomisation to the first documented disease progression to accelerated phase or blast crisis 

or CML-related death. Progression to accelerated phase or blast crisis on treatment was observed in a 

total of 17 patients: 2 patients on nilotinib 300 mg twice daily, 3 patients on nilotinib 400 mg twice 

daily and 12 patients on imatinib 400 mg once daily. The estimated rates of patients free from 

progression to accelerated phase or blast crisis at 72 months were 99.3%, 98.7% and 95.2%, 

respectively (HR=0.1599 and stratified log-rank p=0.0059 between nilotinib 300 mg twice daily and 

imatinib once daily, HR=0.2457 and stratified log-rank p=0.0185 between nilotinib 400 mg twice 

daily and imatinib once daily). No new events of progressions to AP/BC were reported on-treatment 

since the 2-year analysis. 

 

Including clonal evolution as a criterion for progression, a total of 25 patients progressed to 

accelerated phase or blast crisis on treatment by the cut-off date (3 in the nilotinib 300 mg twice daily 

group, 5 in the nilotinib 400 mg twice daily group and 17 in the imatinib 400 mg once daily group). 

The estimated rates of patients free from progression to accelerated phase or blast crisis including 

clonal evolution at 72 months were 98.7%, 97.9% and 93.2%, respectively (HR=0.1626 and stratified 

log-rank p=0.0009 between nilotinib 300 mg twice daily and imatinib once daily, HR=0.2848 and 

stratified log-rank p=0.0085 between nilotinib 400 mg twice daily and imatinib once daily). 

 

A total of 55 patients died during treatment or during the follow-up after discontinuation of treatment. 

(21 in the nilotinib 300 mg twice daily group, 11 in the nilotinib 400 mg twice daily group and 23 in 

the imatinib 400 mg once daily group). Twenty-six (26) of these 55 deaths were related to CML (6 in 

the nilotinib 300 mg twice daily group, 4 in the nilotinib 400 mg twice daily group and 16 in the 

imatinib 400 mg once daily group). The estimated rates of patients alive at 72 months were 91.6%, 

95.8% and 91.4%, respectively (HR=0.8934 and stratified log-rank p=0.7085 between nilotinib 

300 mg twice daily and imatinib, HR=0.4632 and stratified log-rank p=0.0314 between nilotinib 

400 mg twice daily and imatinib). Considering only CML-related deaths as events, the estimated rates 

of overall survival at 72 months were 97.7%, 98.5% and 93.9%, respectively (HR=0.3694 and 

stratified log-rank p=0.0302 between nilotinib 300 mg twice daily and imatinib, HR=0.2433 and 

stratified log-rank p=0.0061 between nilotinib 400 mg twice daily and imatinib). 

 



60 

Treatment discontinuation in adult Ph+ CML patients in chronic phase who have been treated with 

nilotinib as first-line therapy and who have achieved a sustained deep molecular response 

In an open-label, single-arm study, 215 adult patients with Ph+ CML in chronic phase treated with 

nilotinib in first-line for ≥2 years who achieved MR4.5 as measured with the MolecularMD MRDx 

BCR-ABL test were enrolled to continue nilotinib treatment for additional 52 weeks (nilotinib 

consolidation phase). 190 of 215 patients (88.4%) entered the TFR phase after achieving a sustained 

deep molecular response during the consolidation phase, defined by the following criteria: 

- the 4 last quarterly assessments (taken every 12 weeks) were at least MR4.0 (BCR-ABL/ABL 
≤0.01% IS), and maintained for one year 

- the last assessment being MR4.5 (BCR-ABL/ABL ≤0.0032% IS) 
- no more than two assessments falling between MR4.0 and MR4.5 

(0.0032% IS < BCR-ABL/ABL ≤0.01% IS). 

 

The primary endpoint was the percentage of patients in MMR at 48 weeks after starting the TFR phase 

(considering any patient who required re-initiation of treatment as non-responder). Of the 190 patients 

who entered the TFR phase, 98 patients (51.6% [95% CI: 44.2, 58.9]) were in MMR at 48 weeks. 

 

Eighty-eight patients (46.3%) discontinued the TFR phase due to loss of MMR, and 1 (0.5%), 

1 (0.5%), and 3 patients (1.6%) due to death from unknown cause, physician decision and subject 

decision, respectively. Among these 88 patients, 86 patients restarted nilotinib treatment and 2 patients 

permanently discontinued the study. Eighty-five of these 86 patients (98.8%) regained MMR, (one 

patient discontinued study permanently due to subject decision) and 76 patients (88.4%) regained 

MR4.5 by the time of the cut-off date. 

 

The Kaplan-Meier (KM) estimated median time on nilotinib treatment to regain MMR and MR4.5 was 

7.9 weeks (95% CI: 5.1, 8.0) and 13.1 weeks (95% CI: 12.3, 15.7), respectively. The KM estimated 

MMR and MR4.5 rates at 24 weeks of re-initiation were 98.8% (95% CI: 94.2, 99.9) and 90.9% (95% 

CI: 83.2, 96.0), respectively. 

 

The KM estimate of median treatment-free survival (TFS) has not yet been reached (Figure 4); 99 of 

190 patients (52.1%) did not have a TFS event. 

 

Figure 4 Kaplan-Meier estimate of treatment-free survival after start of TFR (full analysis 

set) 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
 

 

 Pat   Evt   Cen 
190   91     99 

Censored observations 

T
re

a
tm

e
n

t-
fr

e
e

 S
u

rv
iv

a
l 

(%
) 

100 

90 

80 

70 

60 

50 

40 

30 

20 

10 

0 

Time since TFR (weeks) 

 

96 84 72 60 48 0 

0:9
1 

1:9
1 

12:9
1 

38:9
1 

90:8
9 

190:
0 

At risk : Events 

36 

108:8
1 

24 

120:7
0 

12 

165:2
5 



61 

Paediatric population 

 

The safety and efficacy of nilotinib in paediatric patients with Ph+ CML in chronic phase have been 

investigated in two studies. A total of 69 paediatric patients (from 2 to <18 years of age) with either 

newly diagnosed Ph+ CML in chronic phase (n=25) or imatinib/dasatinib resistant or 

imatinib-intolerant Ph+ CML in chronic phase (n=44) received nilotinib treatment at a dose of 

230 mg/m2 twice daily, rounded to the nearest 50 mg dose (to a maximum single dose of 400 mg). 

 

In the pooled CML patient population, the median actual dose intensity was 435.5 mg/m2/day (range: 

149 to 517 mg/m2/day), and the median relative dose intensity was 94.7% (range: 32 to 112%). Forty 

patients (58.0%) had relative dose intensity superior to 90%. The median time on treatment with 

nilotinib was 13.80 months (range: 0.7-30.9 months). 

 

In the resistant or intolerant CML patients, the major molecular response (MMR; BCR-ABL/ABL 

≤0.1% IS) rate was 40.9% (95% CI: 26.3, 56.8) at 12 cycles, with 18 patients being in MMR. In the 

newly diagnosed CML patients, the MMR rate was 60.0% (95% CI: 38.7, 78.9) at 12 cycles, with 

15 patients achieving MMR. In resistant or intolerant CML patients, the cumulative MMR rate was 

47.7% by cycle 12. In newly diagnosed CML patients, the cumulative MMR rate was 64.0% by 

cycle 12. 

 

Among the 21 resistant or intolerant CML patients who were in MMR at any time on treatment, the 

median time to first MMR was 2.76 months (95% CI: 0.03, 5.55). For the 17 newly diagnosed CML 

patients who achieved MMR, the median time to first MMR was 5.55 months (95% CI: 5.52, 5.75). 

 

Among resistant or intolerant CML patients, the percentage of patients who achieved BCR-ABL/ABL 

≤0.01% IS (MR4.0) by the cut-off date was 11.4%, while 4.5% of the patients achieved 

BCR-ABL/ABL ≤0.0032% IS (MR4.5). Among newly diagnosed patients, the percentage of patients 

who achieved MR4.0 was 32%, while 28.0% achieved MR4.5. 

 

None of the 21 resistant or intolerant CML patients who were in MMR on treatment, had confirmed 

loss of MMR. Among the 17 newly diagnosed CML patients who achieved MMR, one patient had 

confirmed loss of MMR (the patient lost CHR due to an increase in basophil count, however, did not 

progress to AP/BC). 

 

One resistant or intolerant CML patient progressed to AP/BC after about 10 months on treatment. 

 

No deaths were reported on treatment or after treatment discontinuation in both studies. 

 

5.2 Pharmacokinetic properties 
 

Absorption 

 

Peak concentrations of nilotinib are reached 3 hours after oral administration. Nilotinib absorption 

following oral administration was approximately 30%. The absolute bioavailability of nilotinib has not 

been determined. As compared to an oral drink solution (pH of 1.2 to 1.3), relative bioavailability of 

nilotinib capsule is approximately 50%. In healthy volunteers, Cmax and area under the serum 

concentration-time curve (AUC) of nilotinib are increased by 112% and 82%, respectively, compared 

to fasting conditions when Tasigna is given with food. Administration of Tasigna 30 minutes or 

2 hours after food increased bioavailability of nilotinib by 29% or 15%, respectively (see sections 4.2, 

4.4 and 4.5). 

 

Nilotinib absorption (relative bioavailability) might be reduced by approximately 48% and 22% in 

patients with total gastrectomy and partial gastrectomy, respectively. 

 

  



62 

Distribution 

 

The blood-to-plasma ratio of nilotinib is 0.71. Plasma protein binding is approximately 98% on the 

basis of in vitro experiments. 

 

Biotransformation 

 

Main metabolic pathways identified in healthy subjects are oxidation and hydroxylation. Nilotinib is 

the main circulating component in the serum. None of the metabolites contribute significantly to the 

pharmacological activity of nilotinib. Nilotinib is primarily metabolised by CYP3A4, with possible 

minor contribution from CYP2C8. 

 

Elimination 

 

After a single dose of radiolabelled nilotinib in healthy subjects, more than 90% of the dose was 

eliminated within 7 days, mainly in faeces (94% of the dose). Unchanged nilotinib accounted for 69% 

of the dose. 

 

The apparent elimination half-life estimated from the multiple-dose pharmacokinetics with daily 

dosing was approximately 17 hours. Inter-patient variability in nilotinib pharmacokinetics was 

moderate to high. 

 

Linearity/non-linearity 
 

Steady-state nilotinib exposure was dose-dependent, with less than dose-proportional increases in 

systemic exposure at dose levels higher than 400 mg given as once-daily dosing. Daily systemic 

exposure to nilotinib with 400 mg twice-daily dosing at steady state was 35% higher than with 800 mg 

once-daily dosing. Systemic exposure (AUC) of nilotinib at steady state at a dose level of 400 mg 

twice daily was approximately 13.4% higher than at a dose level of 300 mg twice daily. The average 

nilotinib trough and peak concentrations over 12 months were approximately 15.7% and 14.8% higher 

following 400 mg twice daily dosing compared to 300 mg twice daily. There was no relevant increase 

in exposure to nilotinib when the dose was increased from 400 mg twice daily to 600 mg twice daily. 

 

Steady-state conditions were essentially achieved by day 8. An increase in serum exposure to nilotinib 

between the first dose and steady state was approximately 2-fold for daily dosing and 3.8-fold for 

twice-daily dosing. 

 

Bioavailability/bioequivalence studies 

 

Single-dose administration of 400 mg nilotinib, using 2 hard capsules of 200 mg whereby the content 

of each hard capsule was dispersed in one teaspoon of apple sauce, was shown to be bioequivalent 

with a single-dose administration of 2 intact hard capsules of 200 mg. 

 

Paediatric population 

 

Following administration of nilotinib in paediatric patients at 230 mg/m2 twice daily, rounded to the 

nearest 50 mg dose (to a maximum single dose of 400 mg), steady-state exposure and clearance of 

nilotinib were found to be similar (within 2-fold) to adult patients treated with 400 mg twice daily. The 

pharmacokinetic exposure of nilotinib following a single or multiple doses appeared to be comparable 

between paediatric patients from 2 years to <10 years and from ≥10 years to <18 years. 

 

5.3 Preclinical safety data 
 

Nilotinib has been evaluated in safety pharmacology, repeated dose toxicity, genotoxicity, 

reproductive toxicity, phototoxicity and carcinogenicity (rats and mice) studies. 

 



63 

Safety pharmacology studies 

 

Nilotinib did not have effects on CNS or respiratory functions. In vitro cardiac safety studies 

demonstrated a preclinical signal for QT prolongation, based upon block of hERG currents and 

prolongation of the action potential duration in isolated rabbit hearts by nilotinib. No effects were seen 

in ECG measurements in dogs or monkeys treated for up to 39 weeks or in a special telemetry study in 

dogs. 

 

Repeated-dose toxicity studies 

 

Repeated-dose toxicity studies in dogs of up to 4 weeks’ duration and in cynomolgus monkeys of up 

to 9 months’ duration revealed the liver as the primary target organ of toxicity of nilotinib. Alterations 

included increased alanine aminotransferase and alkaline phosphatase activity and histopathology 

findings (mainly sinusoidal cell or Kupffer cell hyperplasia/hypertrophy, bile duct hyperplasia and 

periportal fibrosis). In general the changes in clinical chemistry were fully reversible after a four-week 

recovery period and the histological alterations showed partial reversibility. Exposures at the lowest 

dose levels at which the liver effects were seen were lower than the exposure in humans at a dose of 

800 mg/day. Only minor liver alterations were seen in mice or rats treated for up to 26 weeks. Mainly 

reversible increases in cholesterol levels were seen in rats, dogs and monkeys. 

 

Genotoxicity studies 

 

Genotoxicity studies in bacterial in vitro systems and in mammalian in vitro and in vivo systems with 

and without metabolic activation did not reveal any evidence for a mutagenic potential of nilotinib. 

 

Carcinogenicity studies 

 

In the 2-year rat carcinogenicity study, the major target organ for non-neoplastic lesions was the uterus 

(dilatation, vascular ectasia, endothelial cell hyperplasia, inflammation and/or epithelial hyperplasia). 

There was no evidence of carcinogenicity upon administration of nilotinib at 5, 15 and 40 mg/kg/day. 

Exposures (in terms of AUC) at the highest dose level represented approximately 2x to 3x human 

daily steady-state exposure (based on AUC) to nilotinib at the dose of 800 mg/day. 

 

In the 26-week Tg.rasH2 mouse carcinogenicity study, in which nilotinib was administered at 30, 100 

and 300 mg/kg/day, skin papillomas/carcinomas were detected at 300 mg/kg, representing 

approximately 30 to 40 times (based on AUC) the human exposure at the maximum approved dose of 

800 mg/day (administered as 400 mg twice daily). The No-Observed-Effect-Level for the skin 

neoplastic lesions was 100 mg/kg/day, representing approximately 10 to 20 times the human exposure 

at the maximum approved dose of 800 mg/day (administered as 400 mg twice daily). The major target 

organs for non-neoplastic lesions were the skin (epidermal hyperplasia), the growing teeth 

(degeneration/atrophy of the enamel organ of upper incisors and inflammation of the 

gingiva/odontogenic epithelium of incisors) and the thymus (increased incidence and/or severity of 

decreased lymphocytes). 

 

Reproductive toxicity and fertility studies 

 

Nilotinib did not induce teratogenicity, but did show embryo- and foetotoxicity at doses that also 

showed maternal toxicity. Increased post-implantation loss was observed in both the fertility study, 

which involved treatment of both males and females, and the embryotoxicity study, which involved 

treatment of females. Embryo-lethality and foetal effects (mainly decreased foetal weights, premature 

fusion of the facial bones (fused maxilla/zygomatic) visceral and skeletal variations) in rats and 

increased resorption of foetuses and skeletal variations in rabbits were present in the embryotoxicity 

studies. In a pre- and postnatal development study in rats, maternal exposure to nilotinib caused 

reduced pup body weight with associated changes in physical development parameters as well as 

reduced mating and fertility indices in the offspring. Exposure to nilotinib in females at 

No-Observed-Adverse-Effect-Levels was generally less or equal to that in humans at 800 mg/day. 

 



64 

No effects on sperm count/motility or on fertility were noted in male and female rats up to the highest 

tested dose, approximately 5 times the recommended dosage for humans. 

 

Juvenile animal studies 

 

In a juvenile development study, nilotinib was administered via oral gavage to juvenile rats from the 

first week post partum through young adult (day 70 post partum) at doses of 2, 6 and 20 mg/kg/day. 

Besides standard study parameters, evaluations of developmental landmarks, CNS effects, mating and 

fertility were performed. Based on a reduction in body weight in both genders and a delayed preputial 

separation in males (which may be associated with the reduction in weight), the 

No-Observed-Effect-Level in juvenile rats was considered to be 6 mg/kg/day. The juvenile animals 

did not exert increased sensitivity to nilotinib relative to adults. In addition, the toxicity profile in 

juvenile rats was comparable to that observed in adult rats. 

 

Phototoxicity studies 

 

Nilotinib was shown to absorb light in the UV-B and UV-A range, is distributed into the skin and 

showed a phototoxic potential in vitro, but no effects have been observed in vivo. Therefore the risk 

that nilotinib causes photosensitisation in patients is considered very low. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Capsule content 

 

Lactose monohydrate 

Crospovidone Type A 

Poloxamer 188 

Colloidal anhydrous silica 

Magnesium stearate 

 

Capsule shell 

 

Gelatin 

Titanium dioxide (E171) 

Red iron oxide (E172) 

Yellow iron oxide (E172) 

 

Printing ink 

 

Shellac 

Black iron oxide (E172) 

n-Butyl alcohol 

Propylene glycol 

Dehydrated ethanol 

Isopropylalcohol 

Ammonium hydroxide 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 
 

3 years. 



65 

 

6.4 Special precautions for storage 
 

Do not store above 30°C. 

 

Store in the original package in order to protect from moisture. 

 

6.5 Nature and contents of container 

 

PVC/PVDC/Alu blisters. 

 

Tasigna is available in the following pack sizes: 

 Unit packs containing 28 hard capsules (7 daily blisters, each containing 4 hard capsules) or 
40 hard capsules (5 blisters, each containing 8 hard capsules). 

 Multipacks containing 112 (4 packs of 28) hard capsules, 120 (3 packs of 40) hard capsules or 
392 (14 packs of 28) 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. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/422/005-006 

EU/1/07/422/009-010 

EU/1/07/422/013 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 19 November 2007 

Date of latest renewal: 19 November 2012 

 

 

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 

 

  



66 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 



67 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturer responsible for batch release 

 

50 mg hard capsules 

Novartis Farmacéutica SA 

Ronda de Santa Maria, 158 

08210 Barberà del Vallès (Barcelona) 

Spain 

 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

150 mg hard capsules and 200 mg hard capsules 

Lek d.d., PE PROIZVODNJA LENDAVA 

Trimlini 2D 

Lendava, 9220 

Slovenia 

 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

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

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to 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. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

- Risk Management Plan (RMP) 
 

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

the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 

subsequent updates of the RMP. 

 



68 

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. 

 

- Obligation to conduct post-authorisation measures 
 

The MAH shall complete, within the stated timeframe, the below measures: 

 

Description Due date 

Post authorisation efficacy study (PAES): In order to investigate the efficacy of 

nilotinib in paediatric patients with Ph+ CML-CP resistant or intolerant to either 

imatinib or dasatinib and in newly diagnosed patients, the MAH should submit 

the final results of the phase II CAMN107A2203 study. 

Final CSR: 

April 2021 

 

  



69 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



70 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
  



71 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasigna 50 mg hard capsules 

nilotinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One hard capsule contains 50 mg nilotinib (as hydrochloride monohydrate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose – see the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Hard capsule 

 

120 (3 packs of 40) hard capsules. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 



72 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/422/015 120 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Tasigna 50 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



73 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasigna 50 mg hard capsules 

nilotinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One hard capsule contains 50 mg nilotinib (as hydrochloride monohydrate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose – see the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Hard capsule 

 

40 hard capsules. Not to be sold separately. 

 

 

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 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 



74 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/422/015 120 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Tasigna 50 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

  



75 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasigna 50 mg hard capsules 

nilotinib 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



76 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasigna 150 mg hard capsules 

nilotinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One hard capsule contains 150 mg nilotinib (as hydrochloride monohydrate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose – see the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Hard capsule 

 

28 hard capsules 

40 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 



77 

 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/422/005 28 hard capsules 

EU/1/07/422/009 40 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Tasigna 150 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



78 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasigna 150 mg hard capsules 

nilotinib 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



79 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF MULTIPACK (INCLUDING BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasigna 150 mg hard capsules 

nilotinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One hard capsule contains 150 mg nilotinib (as hydrochloride monohydrate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose – see the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Hard capsule 

 

Multipack: 112 (4 packs of 28) hard capsules. 

Multipack: 120 (3 packs of 40) hard capsules. 

Multipack: 392 (14 packs of 28) hard capsules. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



80 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/422/006 112 hard capsules 

EU/1/07/422/010 120 hard capsules 

EU/1/07/422/013 392 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Tasigna 150 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



81 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasigna 150 mg hard capsules 

nilotinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One hard capsule contains 150 mg nilotinib (as hydrochloride monohydrate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose – see the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Hard capsule 

 

28 hard capsules. Component of a multipack. Not to be sold separately. 

40 hard capsules. Component of a multipack. Not to be sold separately. 

 

 

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 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 



82 

 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/422/006 112 hard capsules 

EU/1/07/422/010 120 hard capsules 

EU/1/07/422/013 392 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Tasigna 150 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

  



83 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK (WALLET) 

CARTON OF UNIT PACK (CARTON) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasigna 200 mg hard capsules 

nilotinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One hard capsule contains 200 mg nilotinib (as hydrochloride monohydrate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose – see the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Hard capsule 

 

28 hard capsules 

40 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



84 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/422/001 PVC/PVDC/Alu [in wallet] 28 hard capsules 

EU/1/07/422/002 PA/Alu/PVC/Alu [in wallet] 28 hard capsules 

EU/1/07/422/007 PVC/PVDC/Alu [in carton] 28 hard capsules 

EU/1/07/422/011 PVC/PVDC/Alu [in carton] 40 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Tasigna 200 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



85 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasigna 200 mg hard capsules 

nilotinib 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



86 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF MULTIPACK (WALLET) (INCLUDING BLUE BOX) 

CARTON OF MULTIPACK (CARTON) (INCLUDING BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasigna 200 mg hard capsules 

nilotinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One hard capsule contains 200 mg nilotinib (as hydrochloride monohydrate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose – see the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Hard capsule 

 

Multipack: 112 (4 wallets of 28) hard capsules. 

Multipack: 112 (4 packs of 28) hard capsules. 

Multipack: 120 (3 packs of 40) hard capsules. 

Multipack: 392 (14 packs of 28) hard capsules. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



87 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/422/003 PVC/PVDC/Alu [in wallet] 112 hard capsules 

EU/1/07/422/004 PA/Alu/PVC/Alu [in wallet] 112 hard capsules 

EU/1/07/422/008 PVC/PVDC/Alu [in carton] 112 hard capsules 

EU/1/07/422/012 PVC/PVDC/Alu [in carton] 120 hard capsules 

EU/1/07/422/014 PVC/PVDC/Alu [in carton] 392 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Tasigna 200 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 



88 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE WALLET OF MULTIPACK (WITHOUT BLUE BOX) 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasigna 200 mg hard capsules 

nilotinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One hard capsule contains 200 mg nilotinib (as hydrochloride monohydrate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose – see the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Hard capsule 

 

28 hard capsules. Component of a multipack comprising 4 wallets. Not to be sold separately. 

28 hard capsules. Component of a multipack comprising 4 cartons. Not to be sold separately. 

40 hard capsules. Component of a multipack comprising 3 cartons. Not to be sold separately. 

28 hard capsules. Component of a multipack comprising 14 cartons. Not to be sold separately. 

 

 

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 

 

 



89 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/422/003 PVC/PVDC/Alu [in wallet] 112 hard capsules 

EU/1/07/422/004 PA/Alu/PVC/Alu [in wallet] 112 hard capsules 

EU/1/07/422/008 PVC/PVDC/Alu [in carton] 112 hard capsules 

EU/1/07/422/012 PVC/PVDC/Alu [in carton] 120 hard capsules 

EU/1/07/422/014 PVC/PVDC/Alu [in carton] 392 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Tasigna 200 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

  



90 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



91 

Package leaflet: Information for the user 

 

Tasigna 50 mg hard capsules 

nilotinib 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What Tasigna is and what it is used for 

2. What you need to know before you take Tasigna 

3. How to take Tasigna 

4. Possible side effects 

5. How to store Tasigna 

6. Contents of the pack and other information 

 

 

1. What Tasigna is and what it is used for 

 

What Tasigna is 
Tasigna is a medicine containing an active substance called nilotinib. 

 

What Tasigna is used for 

Tasigna is used to treat a type of leukaemia called Philadelphia chromosome positive chronic myeloid 

leukaemia (Ph-positive CML). CML is a cancer of the blood which makes the body produce too many 

abnormal white blood cells. 

 

Tasigna is used in adult and paediatric patients with newly diagnosed CML or in patients with CML 

who are no longer benefiting from previous treatment including imatinib. It is also used in adult and 

paediatric patients who experienced serious side effects with previous treatment and are not able to 

continue taking it. 

 

How Tasigna works 

In patients with CML, a change in DNA (genetic material) triggers a signal that tells the body to 

produce abnormal white blood cells. Tasigna blocks this signal, and thus stops the production of these 

cells. 

 

Monitoring during Tasigna treatment 

Regular tests, including blood tests, will be performed during treatment. These tests will monitor: 

- the amount of blood cells (white blood cells, red blood cells and platelets) in the body to see 
how Tasigna is tolerated. 

- pancreas and liver function in the body to see how Tasigna is tolerated. 
- the electrolytes in the body (potassium, magnesium). These are important in the functioning of 

the heart. 

- the level of sugar and fats in the blood. 
The heart rate will also be checked using a machine that measures electrical activity of the heart (a test 

called an “ECG”). 

 



92 

Your doctor will regularly evaluate your treatment and decide whether you should continue to take 

Tasigna. If you are told to discontinue this medicine, your doctor will continue to monitor your CML 

and may tell you to re-start Tasigna if your condition indicates that this is necessary. 

 

If you have any questions about how Tasigna works or why it has been prescribed for you or your 

child, ask your doctor. 

 

 

2. What you need to know before you take Tasigna 

 

Follow all the doctor’s instructions carefully. They may differ from the general information contained 

in this leaflet. 

 

Do not take Tasigna 
- if you are allergic to nilotinib or any of the other ingredients of this medicine (listed in 

section 6). 

If you think you may be allergic, tell your doctor before taking Tasigna. 

 

Warnings and precautions 

Talk to your doctor or pharmacist before taking Tasigna: 

- if you have suffered prior cardiovascular events such as a heart attack, chest pain (angina), 
problems with the blood supply to your brain (stroke) or problems with the blood flow to your 

leg (claudication) or if you have risk factors for cardiovascular disease such as high blood 

pressure (hypertension), diabetes or problems with the level of fats in your blood (lipid 

disorders). 

- if you have a heart disorder, such as an abnormal electrical signal called “prolongation of the 
QT interval”. 

- if you are being treated with medicines that affect the heart beat (anti-arrhythmics) or the liver 
(see Other medicines and Tasigna). 

- if you suffer from lack of potassium or magnesium. 
- if you have a liver or pancreas disorder. 
- if you have symptoms such as easy bruising, feeling tired or short of breath or have experienced 

repeated infections. 

- if you have had a surgical procedure involving the removal of the entire stomach (total 
gastrectomy). 

- if you have ever had or might now have a hepatitis B infection. This is because Tasigna could 
cause hepatitis B to become active again, which can be fatal in some cases. Patients will be 

carefully checked by their doctor for signs of this infection before treatment is started. 

If any of these apply to you or your child, tell your doctor. 

 

During treatment with Tasigna 

- if you faint (loss of consciousness) or have an irregular heart beat while taking this medicine, 
tell your doctor immediately as this may be a sign of a serious heart condition. Prolongation of 

the QT interval or an irregular heart beat may lead to sudden death. Uncommon cases of sudden 

death have been reported in patients taking Tasigna. 

- if you have sudden heart palpitations, severe muscle weakness or paralysis, seizures or sudden 
changes in your thinking or level of alertness, tell your doctor immediately as this may be a 

sign of a fast breakdown of cancer cells called tumour lysis syndrome. Rare cases of tumour 

lysis syndrome have been reported in patients treated with Tasigna. 

- if you develop chest pain or discomfort, numbness or weakness, problems with walking or with 
your speech, pain, discolouration or a cool feeling in a limb, tell your doctor immediately as 

this may be a sign of a cardiovascular event. Serious cardiovascular events including problems 

with the blood flow to the leg (peripheral arterial occlusive disease), ischaemic heart disease and 

problems with the blood supply to the brain (ischaemic cerebrovascular disease) have been 

reported in patients taking Tasigna. Your doctor should assess the level of fats (lipids) and sugar 

in your blood before initiating treatment with Tasigna and during treatment. 

  



93 

- if you develop swelling of the feet or hands, generalised swelling or rapid weight gain tell your 
doctor as these may be signs of severe fluid retention. Uncommon cases of severe fluid 

retention have been reported in patients treated with Tasigna. 

If you are the parent of a child who is being treated with Tasigna, tell the doctor if any of the above 

conditions apply to your child. 

 

Children and adolescents 

Tasigna is a treatment for children and adolescents with CML. There is no experience with the use of 

this medicine in children below 2 years of age. There is no experience with the use of Tasigna in 

newly diagnosed children below 10 years of age and limited experience in patients below 6 years of 

age who are no longer benefiting from previous treatment for CML. The long-term effects of treating 

children with Tasigna for long periods of time are not known. 

 

Some children and adolescents taking Tasigna may have slower than normal growth. The doctor will 

monitor growth at regular visits. 

 

Other medicines and Tasigna 
Tasigna may interfere with some other medicines. 

 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. This includes in particular: 

- anti-arrhythmics – used to treat irregular heart beat; 
- chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin - medicines 

that may have an unwanted effect on the electrical activity of the heart; 

- ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin – used to treat 
infections; 

- ritonavir – a medicine from the class “ antiproteases” used to treat HIV; 
- carbamazepine, phenobarbital, phenytoin – used to treat epilepsy; 
- rifampicin – used to treat tuberculosis; 
- St. John’s Wort – a herbal product used to treat depression and other conditions (also known as 

Hypericum perforatum); 

- midazolam – used to relieve anxiety before surgery; 

- alfentanil and fentanyl – used to treat pain and as a sedative before or during surgery or medical 
procedures; 

- cyclosporine, sirolimus and tacrolimus – medicines that suppress the “self-defence” ability of 
the body and fight infections and are commonly used to prevent the rejection of transplanted 

organs such as the liver, heart and kidney; 

- dihydroergotamine and ergotamine – used to treat dementia; 
- lovastatin, simvastatin – used to treat high level of fats in blood; 
- warfarin – used to treat blood coagulation disorders (such as blood clots or thromboses); 
- astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil or ergot alkaloids (ergotamine, 

dihydroergotamine). 

 

These medicines should be avoided during your treatment with Tasigna. If you are taking any of these, 

your doctor might prescribe other alternative medicines. 

 

In addition, tell your doctor or pharmacist before taking Tasigna if you are taking any antacids, which 

are medicines against heartburn. These medicines need to be taken separately from Tasigna: 

- H2 blockers, which decrease the production of acid in the stomach. H2 blockers should be taken 

approximately 10 hours before and approximately 2 hours after you take Tasigna; 

- antacids such as those containing aluminium hydroxide, magnesium hydroxide and simethicone, 

which neutralise high acidity in the stomach. These antacids should be taken approximately 

2 hours before or approximately 2 hours after you take Tasigna. 

 

You should also tell your doctor if you are already taking Tasigna and you are prescribed a new 

medicine that you have not taken previously during Tasigna treatment. 

 



94 

Tasigna with food and drink 
Do not take Tasigna with food. Food may enhance the absorption of Tasigna and therefore increase 

the amount of Tasigna in the blood, possibly to a harmful level. Do not drink grapefruit juice or eat 
grapefruit. It may increase the amount of Tasigna in the blood, possibly to a harmful level. 

 

Pregnancy and breast-feeding 

- Tasigna is not recommended during pregnancy unless clearly necessary. If you are pregnant 
or think that you may be, tell your doctor who will discuss with you whether you can take this 

medicine during your pregnancy. 

- Women who might get pregnant are advised to use highly effective contraception during 
treatment and for up to two weeks after ending treatment. 

- Breast-feeding is not recommended during treatment with Tasigna and for two weeks after the 
last dose. Tell your doctor if you are breast-feeding. 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor or pharmacist for advice before taking this medicine. 

 

Driving and using machines 
If you experience side effects (such as dizziness or visual disorders) with a potential impact on the 

ability to safely drive or use any tools or machines after taking this medicine, you should refrain from 

these activities until the effect has disappeared. 

 

Tasigna contains lactose 

This medicine contains lactose (also known as milk sugar). If you have been told by your doctor that 

you have an intolerance to some sugars, contact your doctor before taking this medicine. 

 

 

3. How to take Tasigna 

 

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 

or pharmacist if you are not sure. 

 

How much Tasigna to take 

 

Use in adults 

- Patients newly diagnosed with CML: The recommended dose is 600 mg per day. This dose is 
achieved by taking two hard capsules of 150 mg twice a day. 

- Patients who are no longer benefiting from previous treatment for CML: The 
recommended dose is 800 mg per day. This dose is achieved by taking two hard capsules of 

200 mg twice a day. 

 

Use in children and adolescents 

- The dose given to your child will depend on your child’s body weight and height. The doctor 
will calculate the correct dose to use and tell you which and how many capsules of Tasigna to 

give to your child. The total daily dose you give to your child must not exceed 800 mg. 

 

Your doctor may prescribe a lower dose depending on how you respond to treatment. 

 

Older people (age 65 years and over) 

Tasigna can be used by people aged 65 years and over at the same dose as for other adults. 

 

When to take Tasigna 
Take the hard capsules: 

- twice a day (approximately every 12 hours); 
- at least 2 hours after any food; 
- then wait 1 hour before eating again. 
If you have questions about when to take this medicine, talk to your doctor or pharmacist. Taking 

Tasigna at the same time each day will help you remember when to take your hard capsules. 



95 

 

How to take Tasigna 
- Swallow the hard capsules whole with water. 
- Do not take any food together with the hard capsules. 
- Do not open the hard capsules unless you are unable to swallow them. If so, you may sprinkle 

the content of each hard capsule in one teaspoon of apple sauce and take it immediately. Do not 

use more than one teaspoon of apple sauce for each hard capsule and do not use any food other 

than apple sauce. 

 

How long to take Tasigna 
Continue taking Tasigna every day for as long as your doctor tells you. This is a long-term treatment. 

Your doctor will regularly monitor your condition to check that the treatment is having the desired 

effect. 

Your doctor may consider discontinuing your treatment with Tasigna based on specific criteria. 

If you have questions about how long to take Tasigna, talk to your doctor. 

 

If you take more Tasigna than you should 
If you have taken more Tasigna than you should have, or if someone else accidentally takes your hard 

capsules, contact a doctor or hospital for advice straight away. Show them the pack of hard capsules 

and this package leaflet. Medical treatment may be necessary. 

 

If you forget to take Tasigna 
If you miss a dose, take your next dose as scheduled. Do not take a double dose to make up for a 

forgotten hard capsule. 

 

If you stop taking Tasigna 

Do not stop taking this medicine unless your doctor tells you to do so. Stopping Tasigna without your 

doctor’s recommendation places you at risk for worsening of your disease which could have 

life-threatening consequences. Be sure to discuss with your doctor, nurse, and/or pharmacist if you are 

considering stopping Tasigna. 

 

If your doctor recommends that you discontinue treatment with Tasigna 

Your doctor will regularly evaluate your treatment with a specific diagnostic test and decide whether 

you should continue to take this medicine. If you are told to discontinue Tasigna, your doctor will 

continue to carefully monitor your CML before, during and after you have discontinued Tasigna and 

may tell you to re-start Tasigna if your condition indicates that this is necessary. 

 

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

 

 

4. Possible side effects 
 

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

the side effects are mild to moderate and will generally disappear after a few days to a few weeks of 

treatment. 

 

Some side effects could be serious. 

These side effects are very common (may affect more than 1 in 10 people), common (may affect up to 1 

in 10 people), uncommon (may affect up to 1 in 100 people) or have been reported with frequency not 

known (cannot be estimated from the available data). 

- rapid weight gain, swelling of hands, ankles, feet or face (signs of water retention) 
- chest pain or discomfort, high or low blood pressure, irregular heart rhythm (fast or slow), 

palpitations (sensation of rapid heartbeat), fainting, blue discolouration of the lips, tongue or 

skin (signs of heart disorders) 

- difficulty breathing or painful breathing, cough, wheezing with or without fever, swelling of the 
feet or legs (signs of lung disorders) 

  



96 

- fever, easy bruising or unexplained bleeding, severe or frequent infections, unexplained 
weakness (signs of blood disorders) 

- weakness or paralysis of the limbs or face, difficulty speaking, severe headache, seeing, feeling 
or hearing things that are not there, changes in eyesight, loss of consciousness, confusion, 

disorientation, trembling, sensation of tingling, pain or numbness in fingers and toes (signs of 

nervous system disorders) 

- thirst, dry skin, irritability, dark urine, decreased urine output, difficulty and pain when 
urinating, exaggerated sense of needing to urinate, blood in urine, abnormal urine colour (signs 

of kidney or urinary tract disorders) 

- visual disturbances including blurred vision, double-vision or perceived flashes of light, 
decreased sharpness or loss of vision, blood in eye, increased sensitivity of the eyes to light, eye 

pain, redness, itching or irritation, dry eye, swelling or itching of the eyelids (signs of eye 

disorders) 

- swelling and pain in one part of the body (signs of clotting within a vein) 
- abdominal pain, nausea, vomiting of blood, black or bloody stools, constipation, heartburn, 

stomach acid reflux, swollen abdomen (signs of gastrointestinal disorders) 

- severe upper (middle or left) abdominal pain (sign of pancreatitis) 
- yellow skin and eyes, nausea, loss of appetite, dark-coloured urine (signs of liver disorders) 
- painful red lumps, skin pain, skin reddening, peeling or blisters (signs of skin disorders) 
- pain in joints and muscles (signs of musculoskeletal pain) 
- excessive thirst, high urine output, increased appetite with weight loss, tiredness (signs of high 

level of sugar in the blood) 

- fast heartbeat, bulging eyes, weight loss, swelling at the front of the neck (signs of overactive 
thyroid gland) 

- weight gain, tiredness, hair loss, muscle weakness, feeling cold (signs of underactive thyroid 
gland) 

- severe headache often accompanied by nausea, vomiting and sensitivity to light (signs of 
migraine) 

- dizziness or spinning sensation (signs of vertigo) 
- nausea, shortness of breath, irregular heartbeat, clouding of urine, tiredness and/or joint 

discomfort associated with abnormal results of blood tests (such as high levels of potassium, 

uric acid and phosphorous and low levels of calcium) 

- pain, discomfort, weakness or cramping in the leg muscles, which may be due to decreased 
blood flow, ulcers on the legs or arms that heal slowly or not at all and noticeable changes in 

colour (blueness or paleness) or temperature (coolness) of the legs or arms, as these symptoms 

could be signs of artery blockage in the affected limb (leg or arm) and digits (toes or fingers) 

- recurrence (reactivation) of hepatitis B infection when you have had hepatitis B in the past (a 
liver infection). 

 

Some side effects are very common (may affect more than 1 in 10 people) 

- diarrhoea 
- headache 
- tiredness, lack of energy 
- muscle pain 
- itching, rash 
- nausea 
- abdominal pain 
- constipation 
- vomiting 
- hair loss 
- musculoskeletal pain, muscle pain, pain in extremity, pain in joints, bone pain and spinal pain 

upon discontinuing treatment with Tasigna 

- slowing of growth in children and adolescents 
 

  



97 

Some side effects are common (may affect up to 1 in 10 people) 

- upper respiratory tract infections 
- stomach discomfort after meals, flatulence, swelling or bloating of the abdomen 
- bone pain, pain in joints, muscle spasms, muscle weakness 
- pain including back pain, neck pain and pain in extremity, pain or discomfort in the side of the 

body 

- dry skin, acne, wart, decreased skin sensitivity, hives 
- loss of appetite, disturbed sense of taste, weight decrease or increase 
- insomnia, depression, anxiety 
- night sweats, excessive sweating 
- generally feeling unwell 
- voice disorder 
- nose bleed 
- frequent urine output 
 

Some side effects are uncommon (may affect up to 1 in 100 people) 

- increased skin sensitivity 
- dry mouth, sore throat, mouth sores 
- breast pain 
- painful and swollen joints (gout) 
- increased appetite 
- attention disorder 
- inability to achieve or maintain an erection 
- breast enlargement in men 
- flu-like symptoms 
- pneumonia, bronchitis 
- urinary tract infection 
- herpes virus infection 
- oral or vaginal thrush 
- muscle and joint stiffness, joint swelling 
- feeling body temperature change (including feeling hot, feeling cold) 
- sensitive teeth 
 

The following other side effects have been reported with frequency not known (cannot be 

estimated from the available data): 

- allergy (hypersensitivity to Tasigna) 
- memory loss, disturbed mood 
- skin cyst, thinning or thickening of the skin, thickening of the outermost layer of the skin, skin 

discolouration, fungal infection of the feet 

- thickened patches of red/silver skin (signs of psoriasis) 
- bleeding, tender or enlarged gums 
- oral warts 
- reddening and/or swelling and possibly peeling on the palms and soles (so called hand-foot 

syndrome) 

- increased sensitivity of the skin to light 
- difficulty hearing, ear pain, noises (ringing) in the ears 
- joint inflammation 
- urinary incontinence 
- enterocolitis (inflammation of the bowel) 
- haemorrhoids, anal abscess 
- feeling of hardening in the breasts, heavy periods, nipple swelling 
- symptoms of restless legs syndrome (an irresistable urge to move a part of the body, usually the 

leg, accompanied by uncomfortable sensations) 

 

  



98 

During Tasigna treatment, you may also have some abnormal blood test results such as: 

- low level of blood cells (white cells, red cells, platelets) or haemoglobin 
- increase in the number of platelets or white cells, or specific types of white cells (eosinophils) in 

the blood 

- high blood level of lipase or amylase (pancreas function) 
- high blood level of bilirubin or liver enzymes (liver function) 
- high blood level of creatinine or urea (kidney function) 
- low or high blood level of insulin (a hormone regulating blood sugar level) 
- low or high level of sugar, or high level of fats (including cholesterol) in the blood 
- high blood level of parathyroid hormone (a hormone regulating calcium and phosphorus level) 
- change in blood proteins (low level of globulins or presence of paraprotein) 
- high blood levels of enzymes (alkaline phosphatase, lactate dehydrogenase or creatine 

phosphokinase) 

- high blood level of potassium, calcium, phosphorus or uric acid 
- low blood level of magnesium, potassium, sodium, calcium, or phosphorus 
 

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 Tasigna 
 

- 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 carton and blister. The 

expiry date refers to the last day of that month. 

- Do not store above 30°C. 
- Store in the original package in order to protect from moisture. 
- 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. 

 

 

6. Contents of the pack and other information 

 

What Tasigna contains 
- The active substance is nilotinib. Each hard capsule contains 50 mg nilotinib (as hydrochloride 

monohydrate). 

- The other ingredients are lactose monohydrate, crospovidone type A, poloxamer 188, colloidal 
anhydrous silica, magnesium stearate. The hard capsule shell is composed of gelatin, titanium 

dioxide (E171), red iron oxide (E172), yellow iron oxide (E172) and, shellac, black iron oxide 

(E172), propylene glycol and ammonium hydroxide for stamping of the imprint. 

 

  



99 

What Tasigna looks like and contents of the pack 

Tasigna is supplied as hard capsules. The hard capsules are red/light yellow. A black imprint is 

stamped on each hard capsule (“NVR/ABL”). 

 

Tasigna is available in a pack containing 120 hard capsules (3 packs of 40 hard capsules). 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Farmacéutica SA 

Ronda de Santa Maria, 158 

08210 Barberà del Vallès (Barcelona) 

Spain 

 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

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

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 555 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 



100 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

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/. There are also links to other websites about rare diseases and treatments. 

 



101 

Package leaflet: Information for the user 

 

Tasigna 150 mg hard capsules 

nilotinib 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What Tasigna is and what it is used for 

2. What you need to know before you take Tasigna 

3. How to take Tasigna 

4. Possible side effects 

5. How to store Tasigna 

6. Contents of the pack and other information 

 

 

1. What Tasigna is and what it is used for 

 

What Tasigna is 
Tasigna is a medicine containing an active substance called nilotinib. 

 

What Tasigna is used for 

Tasigna is used to treat a type of leukaemia called Philadelphia chromosome positive chronic myeloid 

leukaemia (Ph-positive CML). CML is a cancer of the blood which makes the body produce too many 

abnormal white blood cells. 

 

Tasigna is used in adult and paediatric patients with newly diagnosed CML. It is also used in 

paediatric patients with CML who are no longer benefiting from previous treatment including imatinib 

or who experienced serious side effects with previous treatment and are not able to continue taking it. 

 

How Tasigna works 

In patients with CML, a change in DNA (genetic material) triggers a signal that tells the body to 

produce abnormal white blood cells. Tasigna blocks this signal, and thus stops the production of these 

cells. 

 

Monitoring during Tasigna treatment 

Regular tests, including blood tests, will be performed during treatment. These tests will monitor: 

- the amount of blood cells (white blood cells, red blood cells and platelets) in the body to see 
how Tasigna is tolerated. 

- pancreas and liver function in the body to see how Tasigna is tolerated. 
- the electrolytes in the body (potassium, magnesium). These are important in the functioning of 

the heart. 

- the level of sugar and fats in the blood. 
The heart rate will also be checked using a machine that measures electrical activity of the heart (a test 

called an “ECG”). 

 

Your doctor will regularly evaluate your treatment and decide whether you should continue to take 

Tasigna. If you are told to discontinue this medicine, your doctor will continue to monitor your CML 

and may tell you to re-start Tasigna if your condition indicates that this is necessary. 



102 

 

If you have any questions about how Tasigna works or why it has been prescribed for you or your 

child, ask your doctor. 

 

 

2. What you need to know before you take Tasigna 

 

Follow all the doctor’s instructions carefully. They may differ from the general information contained 

in this leaflet. 

 

Do not take Tasigna 
- if you are allergic to nilotinib or any of the other ingredients of this medicine (listed in 

section 6). 

If you think you may be allergic, tell your doctor before taking Tasigna. 

 

Warnings and precautions 

Talk to your doctor or pharmacist before taking Tasigna: 

- if you have suffered prior cardiovascular events such as a heart attack, chest pain (angina), 
problems with the blood supply to your brain (stroke) or problems with the blood flow to your 

leg (claudication) or if you have risk factors for cardiovascular disease such as high blood 

pressure (hypertension), diabetes or problems with the level of fats in your blood (lipid 

disorders). 

- if you have a heart disorder, such as an abnormal electrical signal called “prolongation of the 
QT interval”. 

- if you are being treated with medicines that affect the heart beat (anti-arrhythmics) or the liver 
(see Other medicines and Tasigna). 

- if you suffer from lack of potassium or magnesium. 
- if you have a liver or pancreas disorder. 
- if you have symptoms such as easy bruising, feeling tired or short of breath or have experienced 

repeated infections. 

- if you have had a surgical procedure involving the removal of the entire stomach (total 
gastrectomy). 

- if you have ever had or might now have a hepatitis B infection. This is because Tasigna could 
cause hepatitis B to become active again, which can be fatal in some cases. Patients will be 

carefully checked by their doctor for signs of this infection before treatment is started. 

If any of these apply to you or your child, tell your doctor. 

 

During treatment with Tasigna 

- if you faint (loss of consciousness) or have an irregular heart beat while taking this medicine, 
tell your doctor immediately as this may be a sign of a serious heart condition. Prolongation of 

the QT interval or an irregular heart beat may lead to sudden death. Uncommon cases of sudden 

death have been reported in patients taking Tasigna. 

- if you have sudden heart palpitations, severe muscle weakness or paralysis, seizures or sudden 
changes in your thinking or level of alertness, tell your doctor immediately as this may be a 

sign of a fast breakdown of cancer cells called tumour lysis syndrome. Rare cases of tumour 

lysis syndrome have been reported in patients treated with Tasigna. 

- if you develop chest pain or discomfort, numbness or weakness, problems with walking or with 
your speech, pain, discolouration or a cool feeling in a limb, tell your doctor immediately as 

this may be a sign of a cardiovascular event. Serious cardiovascular events including problems 

with the blood flow to the leg (peripheral arterial occlusive disease), ischaemic heart disease and 

problems with the blood supply to the brain (ischaemic cerebrovascular disease) have been 

reported in patients taking Tasigna. Your doctor should assess the level of fats (lipids) and sugar 

in your blood before initiating treatment with Tasigna and during treatment. 

- if you develop swelling of the feet or hands, generalised swelling or rapid weight gain tell your 
doctor as these may be signs of severe fluid retention. Uncommon cases of severe fluid 

retention have been reported in patients treated with Tasigna. 

  



103 

If you are the parent of a child who is being treated with Tasigna, tell the doctor if any of the above 

conditions apply to your child. 

 

Children and adolescents 

Tasigna is a treatment for children and adolescents with CML. There is no experience with the use of 

this medicine in children below 2 years of age. There is no experience with the use of Tasigna in 

newly diagnosed children below 10 years of age and limited experience in patients below 6 years of 

age who are no longer benefiting from previous treatment for CML. The long-term effects of treating 

children with Tasigna for long periods of time are not known. 

 

Some children and adolescents taking Tasigna may have slower than normal growth. The doctor will 

monitor growth at regular visits. 

 

Other medicines and Tasigna 
Tasigna may interfere with some other medicines. 

 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. This includes in particular: 

- anti-arrhythmics – used to treat irregular heart beat; 
- chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin - medicines 

that may have an unwanted effect on the electrical activity of the heart; 

- ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin – used to treat 
infections; 

- ritonavir – a medicine from the class “ antiproteases” used to treat HIV; 
- carbamazepine, phenobarbital, phenytoin – used to treat epilepsy; 
- rifampicin – used to treat tuberculosis; 
- St. John’s Wort – a herbal product used to treat depression and other conditions (also known as 

Hypericum perforatum); 

- midazolam – used to relieve anxiety before surgery; 
- alfentanil and fentanyl – used to treat pain and as a sedative before or during surgery or medical 

procedures; 

- cyclosporine, sirolimus and tacrolimus – medicines that suppress the “self-defence” ability of 
the body and fight infections and are commonly used to prevent the rejection of transplanted 

organs such as the liver, heart and kidney; 

- dihydroergotamine and ergotamine – used to treat dementia; 
- lovastatin, simvastatin – used to treat high level of fats in blood; 
- warfarin – used to treat blood coagulation disorders (such as blood clots or thromboses); 
- astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil or ergot alkaloids (ergotamine, 

dihydroergotamine). 

 

These medicines should be avoided during your treatment with Tasigna. If you are taking any of these, 

your doctor might prescribe other alternative medicines. 

 

In addition, tell your doctor or pharmacist before taking Tasigna if you are taking any antacids, which 

are medicines against heartburn. These medicines need to be taken separately from Tasigna: 

- H2 blockers, which decrease the production of acid in the stomach. H2 blockers should be taken 

approximately 10 hours before and approximately 2 hours after you take Tasigna; 

- antacids such as those containing aluminium hydroxide, magnesium hydroxide and simethicone, 

which neutralise high acidity in the stomach. These antacids should be taken approximately 

2 hours before or approximately 2 hours after you take Tasigna. 

 

You should also tell your doctor if you are already taking Tasigna and you are prescribed a new 

medicine that you have not taken previously during Tasigna treatment. 

 

  



104 

Tasigna with food and drink 
Do not take Tasigna with food. Food may enhance the absorption of Tasigna and therefore increase 

the amount of Tasigna in the blood, possibly to a harmful level. Do not drink grapefruit juice or eat 
grapefruit. It may increase the amount of Tasigna in the blood, possibly to a harmful level. 

 

Pregnancy and breast-feeding 

- Tasigna is not recommended during pregnancy unless clearly necessary. If you are pregnant 
or think that you may be, tell your doctor who will discuss with you whether you can take this 

medicine during your pregnancy. 

- Women who might get pregnant are advised to use highly effective contraception during 
treatment and for up to two weeks after ending treatment. 

- Breast-feeding is not recommended during treatment with Tasigna and for two weeks after the 
last dose. Tell your doctor if you are breast-feeding. 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor or pharmacist for advice before taking this medicine. 

 

Driving and using machines 
If you experience side effects (such as dizziness or visual disorders) with a potential impact on the 

ability to safely drive or use any tools or machines after taking this medicine, you should refrain from 

these activities until the effect has disappeared. 

 

Tasigna contains lactose 

This medicine contains lactose (also known as milk sugar). If you have been told by your doctor that 

you have an intolerance to some sugars, contact your doctor before taking this medicine. 

 

 

3. How to take Tasigna 

 

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 

or pharmacist if you are not sure. 

 

How much Tasigna to take 

 

Use in adults 

- The recommended dose is 600 mg per day. This dose is achieved by taking two hard capsules of 
150 mg twice a day. 

 

Use in children and adolescents 

- The dose given to your child will depend on your child’s body weight and height. The doctor 
will calculate the correct dose to use and tell you which and how many capsules of Tasigna to 

give to your child. The total daily dose you give to your child must not exceed 800 mg. 

 

Your doctor may prescribe a lower dose depending on how you respond to treatment. 

 

Older people (age 65 years and over) 

Tasigna can be used by people aged 65 years and over at the same dose as for other adults. 

 

When to take Tasigna 
Take the hard capsules: 

- twice a day (approximately every 12 hours); 
- at least 2 hours after any food; 
- then wait 1 hour before eating again. 
If you have questions about when to take this medicine, talk to your doctor or pharmacist. Taking 

Tasigna at the same time each day will help you remember when to take your hard capsules. 

 



105 

How to take Tasigna 
- Swallow the hard capsules whole with water. 
- Do not take any food together with the hard capsules. 
- Do not open the hard capsules unless you are unable to swallow them. If so, you may sprinkle 

the content of each hard capsule in one teaspoon of apple sauce and take it immediately. Do not 

use more than one teaspoon of apple sauce for each hard capsule and do not use any food other 

than apple sauce. 

 

How long to take Tasigna 
Continue taking Tasigna every day for as long as your doctor tells you. This is a long-term treatment. 

Your doctor will regularly monitor your condition to check that the treatment is having the desired 

effect. 

Your doctor may consider discontinuing your treatment with Tasigna based on specific criteria. 

If you have questions about how long to take Tasigna, talk to your doctor. 

 

If you take more Tasigna than you should 
If you have taken more Tasigna than you should have, or if someone else accidentally takes your hard 

capsules, contact a doctor or hospital for advice straight away. Show them the pack of hard capsules 

and this package leaflet. Medical treatment may be necessary. 

 

If you forget to take Tasigna 
If you miss a dose, take your next dose as scheduled. Do not take a double dose to make up for a 

forgotten hard capsule. 

 

If you stop taking Tasigna 

Do not stop taking this medicine unless your doctor tells you to do so. Stopping Tasigna without your 

doctor’s recommendation places you at risk for worsening of your disease which could have 

life-threatening consequences. Be sure to discuss with your doctor, nurse, and/or pharmacist if you are 

considering stopping Tasigna. 

 

If your doctor recommends that you discontinue treatment with Tasigna 

Your doctor will regularly evaluate your treatment with a specific diagnostic test and decide whether 

you should continue to take this medicine. If you are told to discontinue Tasigna, your doctor will 

continue to carefully monitor your CML before, during and after you have discontinued Tasigna and 

may tell you to re-start Tasigna if your condition indicates that this is necessary. 

 

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

 

 

4. Possible side effects 
 

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

the side effects are mild to moderate and will generally disappear after a few days to a few weeks of 

treatment. 

 

Some side effects could be serious. 

These side effects are very common (may affect more than 1 in 10 people), common (may affect up to 1 

in 10 people), uncommon (may affect up to 1 in 100 people) or have been reported with frequency not 

known (cannot be estimated from the available data). 

- rapid weight gain, swelling of hands, ankles, feet or face (signs of water retention) 
- chest pain or discomfort, high blood pressure, irregular heart rhythm (fast or slow), palpitations 

(sensation of rapid heartbeat), fainting, blue discolouration of the lips, tongue or skin (signs of 

heart disorders) 

- difficulty or painful breathing, cough, wheezing with or without fever, swelling of the feet or 
legs (signs of lung disorders) 

- fever, easy bruising or unexplained bleeding, frequent infections, unexplained weakness (signs 
of blood disorders) 



106 

- weakness or paralysis of the limbs or face, difficulty speaking, severe headache, seeing, feeling 
or hearing things that are not there, loss of consciousness, confusion, disorientation, trembling, 

sensation of tingling, pain or numbness in fingers and toes (signs of nervous system disorders) 

- difficulty and pain when passing urine, abnormal urine colour (signs of kidney or urinary tract 
disorders) 

- visual disturbances including blurred vision, perceived flashes of light, loss of vision, blood in 
eye, eye pain, redness, itching or irritation, dry eye, swelling or itching of the eyelids (signs of 

eye disorders) 

- abdominal pain, nausea, vomiting of blood, bloody stools, constipation, heartburn, stomach acid 
reflux, swollen abdomen (signs of gastrointestinal disorders) 

- severe upper (middle or left) abdominal pain (sign of pancreatitis) 
- yellow skin and eyes, nausea, loss of appetite, dark-coloured urine (signs of liver disorders) 
- painful red lumps, skin pain, skin reddening, peeling or blisters (signs of skin disorders) 
- pain in joints and muscles (signs of musculoskeletal pain) 
- excessive thirst, high urine output, increased appetite with weight loss, tiredness (signs of high 

level of sugar in the blood) 

- severe headache often accompanied by nausea, vomiting and sensitivity to light (signs of 
migraine) 

- dizziness or spinning sensation (signs of vertigo) 
- nausea, shortness of breath, irregular heartbeat, clouding of urine, tiredness and/or joint 

discomfort associated with abnormal results of blood tests (such as high levels of potassium, 

uric acid and phosphorous and low levels of calcium) 

- pain, discomfort, weakness or cramping in the leg muscles, which may be due to decreased 
blood flow, ulcers on the legs or arms that heal slowly or not at all and noticeable changes in 

colour (blueness or paleness) or temperature (coolness) of the legs or arms, as these symptoms 

could be signs of artery blockage in the affected limb (leg or arm) and digits (toes or fingers) 

- recurrence (reactivation) of hepatitis B infection when you have had hepatitis B in the past (a 
liver infection). 

 

Some side effects are very common (may affect more than 1 in 10 people) 

- headache 
- tiredness 
- muscle pain 
- itching, rash 
- nausea 
- hair loss 
- musculoskeletal pain, muscle pain, pain in extremity, pain in joints, bone pain and spinal pain 

upon discontinuing treatment with Tasigna 

- slowing of growth in children and adolescents 
 

Some side effects are common (may affect up to 1 in 10 people) 

- diarrhoea, vomiting, abdominal pain, stomach discomfort after meals, flatulence, swelling or 
bloating of the abdomen, constipation 

- bone pain, pain in joints, muscle spasms, muscle weakness, pain in extremity, back pain, pain or 
discomfort in the side of the body 

- upper respiratory tract infections 
- dry skin, acne, wart, decreased skin sensitivity 
- loss of appetite, disturbed sense of taste, weight increase 
- insomnia, anxiety, depression 
- night sweats, excessive sweating 
 

Some side effects are uncommon (may affect up to 1 in 100 people) 

- generally feeling unwell 
- painful and swollen joints (gout) 
- inability to achieve or maintain an erection 
- feeling body temperature change (including feeling hot, feeling cold) 



107 

- sensitive teeth 
 

The following other side effects have been reported with frequency not known (cannot be 

estimated from the available data): 

- allergy (hypersensitivity to Tasigna) 
- memory loss, disturbed or depressed mood, lack of energy 
- oral thrush 
- skin cyst, thinning or thickening of the skin, thickening of the outermost layer of the skin, skin 

discolouration, hives, fungal infection of the feet 

- thickened patches of red/silver skin (signs of psoriasis) 
- increased skin sensitivity 
- bleeding, tender or enlarged gums 
- nose bleed 
- dry mouth, sore throat, mouth sores 
- frequent urine output 
- haemorrhoids, anal abscess 
- enterocolitis (inflammation of the bowel) 
- herpes virus infection 
- feeling of hardening in the breasts, heavy periods, nipple swelling 
- appetite disorder, weight decreased 
- breast enlargement in men 
- symptoms of restless legs syndrome (an irresistable urge to move a part of the body, usually the 

leg, accompanied by uncomfortable sensations) 

 

During Tasigna treatment, you may also have some abnormal blood test results such as: 

- low level of blood cells (white cells, red cells, platelets) or haemoglobin 
- increase in the number of platelets or white cells, or specific types of white cells (eosinophils) in 

the blood 

- high blood level of lipase or amylase (pancreas function) 
- high blood level of bilirubin or liver enzymes (liver function) 
- low or high blood level of insulin (a hormone regulating blood sugar level) 
- low or high level of sugar, or high level of fats (including cholesterol) in the blood 
- high blood level of parathyroid hormone (a hormone regulating calcium and phosphorus level) 
- change in blood proteins (low level of globulins or presence of paraprotein) 
- high blood level of alkaline phosphatase 
- high blood level of potassium, calcium, phosphorus or uric acid 
- low blood level of potassium or calcium 
 

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 Tasigna 
 

- 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 carton and blister. The 

expiry date refers to the last day of that month. 

- Do not store above 30°C. 
- Store in the original package in order to protect from moisture. 
- 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. 

 



108 

 

6. Contents of the pack and other information 

 

What Tasigna contains 
- The active substance is nilotinib. Each hard capsule contains 150 mg nilotinib (as hydrochloride 

monohydrate). 

- The other ingredients are lactose monohydrate, crospovidone type A, poloxamer 188, colloidal 
anhydrous silica, magnesium stearate. The hard capsule shell is composed of gelatin, titanium 

dioxide (E171), red and yellow iron oxide (E172) and, shellac, black iron oxide (E172), n-butyl 

alcohol, propylene glycol, dehydrated ethanol, isopropylalcohol and ammoniumhydroxide for 

stamping of the imprint. 

 

What Tasigna looks like and contents of the pack 

Tasigna is supplied as hard capsules. The hard capsules are red. A black imprint is stamped on each 

hard capsule (“NVR/BCR”). 

 

Tasigna is available in packs containing 28 or 40 hard capsules and in multipacks of 112 hard capsules 

(comprising 4 cartons, each containing 28 hard capsules), 120 hard capsules (comprising 3 cartons, 

each containing 40 hard capsules) or 392 hard capsules (comprising 14 cartons, each containing 

28 hard capsules). 

 

Not all packs may be marketed in your country. 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Lek d.d., PE PROIZVODNJA LENDAVA 

Trimlini 2D 

Lendava, 9220 

Slovenia 

 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

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

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 



109 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 555 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

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/. There are also links to other websites about rare diseases and treatments. 

 



110 

Package leaflet: Information for the user 

 

Tasigna 200 mg hard capsules 

nilotinib 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What Tasigna is and what it is used for 

2. What you need to know before you take Tasigna 

3. How to take Tasigna 

4. Possible side effects 

5. How to store Tasigna 

6. Contents of the pack and other information 

 

 

1. What Tasigna is and what it is used for 

 

What Tasigna is 
Tasigna is a medicine containing an active substance called nilotinib. 

 

What Tasigna is used for 

Tasigna is used to treat a type of leukaemia called Philadelphia chromosome positive chronic myeloid 

leukaemia (Ph-positive CML). CML is a cancer of the blood which makes the body produce too many 

abnormal white blood cells. 

 

Tasigna is used in adult and paediatric patients with newly diagnosed CML or in patients with CML 

who are no longer benefiting from previous treatment including imatinib. It is also used in adult and 

paediatric patients who experienced serious side effects with previous treatment and are not able to 

continue taking it. 

 

How Tasigna works 

In patients with CML, a change in DNA (genetic material) triggers a signal that tells the body to 

produce abnormal white blood cells. Tasigna blocks this signal, and thus stops the production of these 

cells. 

 

Monitoring during Tasigna treatment 

Regular tests, including blood tests, will be performed during treatment. These tests will monitor: 

- the amount of blood cells (white blood cells, red blood cells and platelets) in the body to see 
how Tasigna is tolerated. 

- pancreas and liver function in the body to see how Tasigna is tolerated. 
- the electrolytes in the body (potassium, magnesium). These are important in the functioning of 

the heart. 

- the level of sugar and fats in the blood. 
The heart rate will also be checked using a machine that measures electrical activity of the heart (a test 

called an “ECG”). 

 



111 

Your doctor will regularly evaluate your treatment and decide whether you should continue to take 

Tasigna. If you are told to discontinue this medicine, your doctor will continue to monitor your CML 

and may tell you to re-start Tasigna if your condition indicates that this is necessary. 

 

If you have any questions about how Tasigna works or why it has been prescribed for you or your 

child, ask your doctor. 

 

 

2. What you need to know before you take Tasigna 

 

Follow all the doctor’s instructions carefully. They may differ from the general information contained 

in this leaflet. 

 

Do not take Tasigna 
- if you are allergic to nilotinib or any of the other ingredients of this medicine (listed in 

section 6). 

If you think you may be allergic, tell your doctor before taking Tasigna. 

 

Warnings and precautions 

Talk to your doctor or pharmacist before taking Tasigna: 

- if you have suffered prior cardiovascular events such as a heart attack, chest pain (angina), 
problems with the blood supply to your brain (stroke) or problems with the blood flow to your 

leg (claudication) or if you have risk factors for cardiovascular disease such as high blood 

pressure (hypertension), diabetes or problems with the level of fats in your blood (lipid 

disorders). 

- if you have a heart disorder, such as an abnormal electrical signal called “prolongation of the 
QT interval”. 

- if you are being treated with medicines that affect the heart beat (anti-arrhythmics) or the liver 
(see Other medicines and Tasigna). 

- if you suffer from lack of potassium or magnesium. 
- if you have a liver or pancreas disorder. 
- if you have symptoms such as easy bruising, feeling tired or short of breath or have experienced 

repeated infections. 

- if you have had a surgical procedure involving the removal of the entire stomach (total 
gastrectomy). 

- if you have ever had or might now have a hepatitis B infection. This is because Tasigna could 
cause hepatitis B to become active again, which can be fatal in some cases. Patients will be 

carefully checked by their doctor for signs of this infection before treatment is started. 

If any of these apply to you or your child, tell your doctor. 

 

During treatment with Tasigna 

- if you faint (loss of consciousness) or have an irregular heart beat while taking this medicine, 
tell your doctor immediately as this may be a sign of a serious heart condition. Prolongation of 

the QT interval or an irregular heart beat may lead to sudden death. Uncommon cases of sudden 

death have been reported in patients taking Tasigna. 

- if you have sudden heart palpitations, severe muscle weakness or paralysis, seizures or sudden 
changes in your thinking or level of alertness, tell your doctor immediately as this may be a 

sign of a fast breakdown of cancer cells called tumour lysis syndrome. Rare cases of tumour 

lysis syndrome have been reported in patients treated with Tasigna. 

- if you develop chest pain or discomfort, numbness or weakness, problems with walking or with 
your speech, pain, discolouration or a cool feeling in a limb, tell your doctor immediately as 

this may be a sign of a cardiovascular event. Serious cardiovascular events including problems 

with the blood flow to the leg (peripheral arterial occlusive disease), ischaemic heart disease and 

problems with the blood supply to the brain (ischaemic cerebrovascular disease) have been 

reported in patients taking Tasigna. Your doctor should assess the level of fats (lipids) and sugar 

in your blood before initiating treatment with Tasigna and during treatment. 

  



112 

- if you develop swelling of the feet or hands, generalised swelling or rapid weight gain tell your 
doctor as these may be signs of severe fluid retention. Uncommon cases of severe fluid 

retention have been reported in patients treated with Tasigna. 

If you are the parent of a child who is being treated with Tasigna, tell the doctor if any of the above 

conditions apply to your child. 

 

Children and adolescents 

Tasigna is a treatment for children and adolescents with CML. There is no experience with the use of 

this medicine in children below 2 years of age. There is no experience with the use of Tasigna in 

newly diagnosed children below 10 years of age and limited experience in patients below 6 years of 

age who are no longer benefiting from previous treatment for CML. The long-term effects of treating 

children with Tasigna for long periods of time are not known. 

 

Some children and adolescents taking Tasigna may have slower than normal growth. The doctor will 

monitor growth at regular visits. 

 

Other medicines and Tasigna 
Tasigna may interfere with some other medicines. 

 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. This includes in particular: 

- anti-arrhythmics – used to treat irregular heart beat; 
- chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin - medicines 

that may have an unwanted effect on the electrical activity of the heart; 

- ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin – used to treat 
infections; 

- ritonavir – a medicine from the class “ antiproteases” used to treat HIV; 
- carbamazepine, phenobarbital, phenytoin – used to treat epilepsy; 
- rifampicin – used to treat tuberculosis; 
- St. John’s Wort – a herbal product used to treat depression and other conditions (also known as 

Hypericum perforatum); 

- midazolam – used to relieve anxiety before surgery; 

- alfentanil and fentanyl – used to treat pain and as a sedative before or during surgery or medical 
procedures; 

- cyclosporine, sirolimus and tacrolimus – medicines that suppress the “self-defence” ability of 
the body and fight infections and are commonly used to prevent the rejection of transplanted 

organs such as the liver, heart and kidney; 

- dihydroergotamine and ergotamine – used to treat dementia; 
- lovastatin, simvastatin – used to treat high level of fats in blood; 
- warfarin – used to treat blood coagulation disorders (such as blood clots or thromboses); 
- astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil or ergot alkaloids (ergotamine, 

dihydroergotamine). 

 

These medicines should be avoided during your treatment with Tasigna. If you are taking any of these, 

your doctor might prescribe other alternative medicines. 

 

In addition, tell your doctor or pharmacist before taking Tasigna if you are taking any antacids, which 

are medicines against heartburn. These medicines need to be taken separately from Tasigna: 

- H2 blockers, which decrease the production of acid in the stomach. H2 blockers should be taken 

approximately 10 hours before and approximately 2 hours after you take Tasigna; 

- antacids such as those containing aluminium hydroxide, magnesium hydroxide and simethicone, 

which neutralise high acidity in the stomach. These antacids should be taken approximately 

2 hours before or approximately 2 hours after you take Tasigna. 

 

You should also tell your doctor if you are already taking Tasigna and you are prescribed a new 

medicine that you have not taken previously during Tasigna treatment. 

 



113 

Tasigna with food and drink 
Do not take Tasigna with food. Food may enhance the absorption of Tasigna and therefore increase 

the amount of Tasigna in the blood, possibly to a harmful level. Do not drink grapefruit juice or eat 
grapefruit. It may increase the amount of Tasigna in the blood, possibly to a harmful level. 

 

Pregnancy and breast-feeding 

- Tasigna is not recommended during pregnancy unless clearly necessary. If you are pregnant 
or think that you may be, tell your doctor who will discuss with you whether you can take this 

medicine during your pregnancy. 

- Women who might get pregnant are advised to use highly effective contraception during 
treatment and for up to two weeks after ending treatment. 

- Breast-feeding is not recommended during treatment with Tasigna and for two weeks after the 
last dose. Tell your doctor if you are breast-feeding. 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor or pharmacist for advice before taking this medicine. 

 

Driving and using machines 
If you experience side effects (such as dizziness or visual disorders) with a potential impact on the 

ability to safely drive or use any tools or machines after taking this medicine, you should refrain from 

these activities until the effect has disappeared. 

 

Tasigna contains lactose 

This medicine contains lactose (also known as milk sugar). If you have been told by your doctor that 

you have an intolerance to some sugars, contact your doctor before taking this medicine. 

 

 

3. How to take Tasigna 

 

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 

or pharmacist if you are not sure. 

 

How much Tasigna to take 

 

Use in adults 

- The recommended dose is 800 mg per day. This dose is achieved by taking two hard capsules of 
200 mg twice a day. 

 

Use in children and adolescents 

- The dose given to your child will depend on your child’s body weight and height. The doctor 
will calculate the correct dose to use and tell you which and how many capsules of Tasigna to 

give to your child. The total daily dose you give to your child must not exceed 800 mg. 

 

Your doctor may prescribe a lower dose depending on how you respond to treatment. 

 

Older people (age 65 years and over) 

Tasigna can be used by people aged 65 years and over at the same dose as for other adults. 

 

When to take Tasigna 
Take the hard capsules: 

- twice a day (approximately every 12 hours); 
- at least 2 hours after any food; 
- then wait 1 hour before eating again. 
If you have questions about when to take this medicine, talk to your doctor or pharmacist. Taking 

Tasigna at the same time each day will help you remember when to take your hard capsules. 

 



114 

How to take Tasigna 
- Swallow the hard capsules whole with water. 
- Do not take any food together with the hard capsules. 
- Do not open the hard capsules unless you are unable to swallow them. If so, you may sprinkle 

the content of each hard capsule in one teaspoon of apple sauce and take it immediately. Do not 

use more than one teaspoon of apple sauce for each hard capsule and do not use any food other 

than apple sauce. 

 

How long to take Tasigna 
Continue taking Tasigna every day for as long as your doctor tells you. This is a long-term treatment. 

Your doctor will regularly monitor your condition to check that the treatment is having the desired 

effect. 

Your doctor may consider discontinuing your treatment with Tasigna based on specific criteria. 

If you have questions about how long to take Tasigna, talk to your doctor. 

 

If you take more Tasigna than you should 
If you have taken more Tasigna than you should have, or if someone else accidentally takes your hard 

capsules, contact a doctor or hospital for advice straight away. Show them the pack of hard capsules 

and this package leaflet. Medical treatment may be necessary. 

 

If you forget to take Tasigna 
If you miss a dose, take your next dose as scheduled. Do not take a double dose to make up for a 

forgotten hard capsule. 

 

If you stop taking Tasigna 

Do not stop taking this medicine unless your doctor tells you to do so. Stopping Tasigna without your 

doctor’s recommendation places you at risk for worsening of your disease which could have 

life-threatening consequences. Be sure to discuss with your doctor, nurse, and/or pharmacist if you are 

considering stopping Tasigna. 

 

If your doctor recommends that you discontinue treatment with Tasigna 

Your doctor will regularly evaluate your treatment with a specific diagnostic test and decide whether 

you should continue to take this medicine. If you are told to discontinue Tasigna, your doctor will 

continue to carefully monitor your CML before, during and after you have discontinued Tasigna and 

may tell you to re-start Tasigna if your condition indicates that this is necessary. 

 

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

 

 

4. Possible side effects 
 

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

the side effects are mild to moderate and will generally disappear after a few days to a few weeks of 

treatment. 

 

Some side effects could be serious. 

These side effects are very common (may affect more than 1 in 10 people), common (may affect up to 1 

in 10 people), uncommon (may affect up to 1 in 100 people) or have been reported with frequency not 

known (cannot be estimated from the available data). 

- rapid weight gain, swelling of hands, ankles, feet or face (signs of water retention) 
- chest pain or discomfort, high or low blood pressure, irregular heart rhythm (fast or slow), 

palpitations (sensation of rapid heartbeat), fainting, blue discolouration of the lips, tongue or 

skin (signs of heart disorders) 

- difficulty breathing or painful breathing, cough, wheezing with or without fever, swelling of the 
feet or legs (signs of lung disorders) 

- fever, easy bruising or unexplained bleeding, severe or frequent infections, unexplained 
weakness (signs of blood disorders) 



115 

- weakness or paralysis of the limbs or face, difficulty speaking, severe headache, seeing, feeling 
or hearing things that are not there, changes in eyesight, loss of consciousness, confusion, 

disorientation, trembling, sensation of tingling, pain or numbness in fingers and toes (signs of 

nervous system disorders) 

- thirst, dry skin, irritability, dark urine, decreased urine output, difficulty and pain when 
urinating, exaggerated sense of needing to urinate, blood in urine, abnormal urine colour (signs 

of kidney or urinary tract disorders) 

- visual disturbances including blurred vision, double-vision or perceived flashes of light, 
decreased sharpness or loss of vision, blood in eye, increased sensitivity of the eyes to light, eye 

pain, redness, itching or irritation, dry eye, swelling or itching of the eyelids (signs of eye 

disorders) 

- swelling and pain in one part of the body (signs of clotting within a vein) 
- abdominal pain, nausea, vomiting of blood, black or bloody stools, constipation, heartburn, 

stomach acid reflux, swollen abdomen (signs of gastrointestinal disorders) 

- severe upper (middle or left) abdominal pain (sign of pancreatitis) 
- yellow skin and eyes, nausea, loss of appetite, dark-coloured urine (signs of liver disorders) 
- painful red lumps, skin pain, skin reddening, peeling or blisters (signs of skin disorders) 
- pain in joints and muscles (signs of musculoskeletal pain) 
- excessive thirst, high urine output, increased appetite with weight loss, tiredness (signs of high 

level of sugar in the blood) 

- fast heartbeat, bulging eyes, weight loss, swelling at the front of the neck (signs of overactive 
thyroid gland) 

- weight gain, tiredness, hair loss, muscle weakness, feeling cold (signs of underactive thyroid 
gland) 

- severe headache often accompanied by nausea, vomiting and sensitivity to light (signs of 
migraine) 

- dizziness or spinning sensation (signs of vertigo) 
- nausea, shortness of breath, irregular heartbeat, clouding of urine, tiredness and/or joint 

discomfort associated with abnormal results of blood tests (such as high levels of potassium, 

uric acid and phosphorous and low levels of calcium) 

- pain, discomfort, weakness or cramping in the leg muscles, which may be due to decreased 
blood flow, ulcers on the legs or arms that heal slowly or not at all and noticeable changes in 

colour (blueness or paleness) or temperature (coolness) of the legs or arms, as these symptoms 

could be signs of artery blockage in the affected limb (leg or arm) and digits (toes or fingers) 

- recurrence (reactivation) of hepatitis B infection when you have had hepatitis B in the past (a 
liver infection). 

 

Some side effects are very common (may affect more than 1 in 10 people) 

- diarrhoea 
- headache 
- tiredness, lack of energy 
- muscle pain 
- itching, rash 
- nausea 
- abdominal pain 
- constipation 
- vomiting 
- hair loss 
- musculoskeletal pain, muscle pain, pain in extremity, pain in joints, bone pain and spinal pain 

upon discontinuing treatment with Tasigna 

- slowing of growth in children and adolescents 
 

  



116 

Some side effects are common (may affect up to 1 in 10 people) 

- upper respiratory tract infections 
- stomach discomfort after meals, flatulence, swelling or bloating of the abdomen 
- bone pain, pain in joints, muscle spasms, muscle weakness 
- pain including back pain, neck pain and pain in extremity, pain or discomfort in the side of the 

body 

- dry skin, acne, wart, decreased skin sensitivity, hives 
- loss of appetite, disturbed sense of taste, weight decrease or increase 
- insomnia, depression, anxiety 
- night sweats, excessive sweating 
- generally feeling unwell 
- voice disorder 
- nose bleed 
- frequent urine output 
 

Some side effects are uncommon (may affect up to 1 in 100 people) 

- increased skin sensitivity 
- dry mouth, sore throat, mouth sores 
- breast pain 
- painful and swollen joints (gout) 
- increased appetite 
- attention disorder 
- inability to achieve or maintain an erection 
- breast enlargement in men 
- flu-like symptoms 
- pneumonia, bronchitis 
- urinary tract infection 
- herpes virus infection 
- oral or vaginal thrush 
- muscle and joint stiffness, joint swelling 
- feeling body temperature change (including feeling hot, feeling cold) 
- sensitive teeth 
 

The following other side effects have been reported with frequency not known (cannot be 

estimated from the available data): 

- allergy (hypersensitivity to Tasigna) 
- memory loss, disturbed mood 
- skin cyst, thinning or thickening of the skin, thickening of the outermost layer of the skin, skin 

discolouration, fungal infection of the feet 

- thickened patches of red/silver skin (signs of psoriasis) 
- bleeding, tender or enlarged gums 
- oral warts 
- reddening and/or swelling and possibly peeling on the palms and soles (so called hand-foot 

syndrome) 

- increased sensitivity of the skin to light 
- difficulty hearing, ear pain, noises (ringing) in the ears 
- joint inflammation 
- urinary incontinence 
- enterocolitis (inflammation of the bowel) 
- haemorrhoids, anal abscess 
- feeling of hardening in the breasts, heavy periods, nipple swelling 
- symptoms of restless legs syndrome (an irresistable urge to move a part of the body, usually the 

leg, accompanied by uncomfortable sensations) 

 

  



117 

During Tasigna treatment, you may also have some abnormal blood test results such as: 

- low level of blood cells (white cells, red cells, platelets) or haemoglobin 
- increase in the number of platelets or white cells, or specific types of white cells (eosinophils) in 

the blood 

- high blood level of lipase or amylase (pancreas function) 
- high blood level of bilirubin or liver enzymes (liver function) 
- high blood level of creatinine or urea (kidney function) 
- low or high blood level of insulin (a hormone regulating blood sugar level) 
- low or high level of sugar, or high level of fats (including cholesterol) in the blood 
- high blood level of parathyroid hormone (a hormone regulating calcium and phosphorus level) 
- change in blood proteins (low level of globulins or presence of paraprotein) 
- high blood levels of enzymes (alkaline phosphatase, lactate dehydrogenase or creatine 

phosphokinase) 

- high blood level of potassium, calcium, phosphorus or uric acid 
- low blood level of magnesium, potassium, sodium, calcium, or phosphorus 
 

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 Tasigna 
 

- 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 carton and blister. The 

expiry date refers to the last day of that month. 

- Do not store above 30°C. 
- Store in the original package in order to protect from moisture. 
- 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. 

 

 

6. Contents of the pack and other information 

 

What Tasigna contains 
- The active substance is nilotinib. Each hard capsule contains 200 mg nilotinib (as hydrochloride 

monohydrate). 

- The other ingredients are lactose monohydrate, crospovidone type A, poloxamer 188, colloidal 
anhydrous silica, magnesium stearate. The hard capsule shell is composed of gelatin, titanium 

dioxide (E171), yellow iron oxide (E172) and, shellac (E904), dehydrated alcohol, isopropyl 

alcohol, butyl alcohol, propylene glycol, strong ammonia solution, potassium hydroxide and red 

iron oxide (E172) for stamping of the imprint. 

 

  



118 

What Tasigna looks like and contents of the pack 

Tasigna is supplied as hard capsules. The hard capsules are light yellow. A red imprint is stamped on 

each hard capsule (“NVR/TKI”). 

 

Tasigna is available in a wallet containing 28 hard capsules and in a carton containing 28 or 40 hard 

capsules. 

 

Tasigna is also available in multipacks of: 

- 112 (4 wallets of 28) hard capsules. 
- 112 (4 packs of 28) hard capsules. 
- 120 (3 packs of 40) hard capsules. 
- 392 (14 packs of 28) hard capsules. 
 

Not all packs may be marketed in your country. 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Lek d.d., PE PROIZVODNJA LENDAVA 

Trimlini 2D 

Lendava, 9220 

Slovenia 

 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

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

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 555 



119 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

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/. There are also links to other websites about rare diseases and treatments. 

 


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