Farydak

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
  



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1. NAME OF THE MEDICINAL PRODUCT 
 
Farydak 10 mg hard capsules 
Farydak 15 mg hard capsules 
Farydak 20 mg hard capsules 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Farydak 10 mg hard capsules 
 
Each hard capsule contains panobinostat lactate anhydrous equivalent to 10 mg panobinostat. 
 
Farydak 15 mg hard capsules 
 
Each hard capsule contains panobinostat lactate anhydrous equivalent to 15 mg panobinostat. 
 
Farydak 20 mg hard capsules 
 
Each hard capsule contains panobinostat lactate anhydrous equivalent to 20 mg panobinostat. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Hard capsule (capsule). 
 
Farydak 10 mg hard capsules 
 
Light green opaque hard gelatin capsule (15.6–16.2 mm) containing white to almost white powder, 
with radial marking “LBH 10 mg” in black ink on cap and two radial bands in black ink on body. 
 
Farydak 15 mg hard capsules 
 
Orange opaque hard gelatin capsule (19.1–19.7 mm) containing white to almost white powder, with 
radial marking “LBH 15 mg” in black ink on cap and two radial bands in black ink on body. 
 
Farydak 20 mg hard capsules 
 
Red opaque hard gelatin capsule (19.1–19.7 mm) containing white to almost white powder, with radial 
marking “LBH 20 mg” in black ink on cap and two radial bands in black ink on body. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Farydak, in combination with bortezomib and dexamethasone, is indicated for the treatment of adult 
patients with relapsed and/or refractory multiple myeloma who have received at least two prior 
regimens including bortezomib and an immunomodulatory agent. 
 
4.2 Posology and method of administration 
 
Treatment with Farydak should be initiated by a physician experienced in the use of anti-cancer 



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therapies. 
 
Posology 
 
The recommended starting dose of panobinostat is 20 mg, taken orally once a day, on days 1, 3, 5, 8, 
10 and 12 of a 21-day cycle. Patients should be treated initially for eight cycles. It is recommended 
that patients with clinical benefit continue the treatment for eight additional cycles. The total duration 
of treatment is up to 16 cycles (48 weeks). 
 
Panobinostat is administered in combination with bortezomib and dexamethasone, as shown in 
Tables 1 and 2. The bortezomib and dexamethasone prescribing information should be consulted prior 
to the start of the combination treatment to assess whether a dose reduction is required. 
 
The recommended dose of bortezomib is 1.3 mg/m2 given as an injection. The recommended dose of 
dexamethasone is 20 mg taken orally on a full stomach. 
 
Table 1 Recommended dosing schedule of panobinostat in combination with bortezomib and 

dexamethasone (cycles 1-8) 
 

Cycles 1-8 
(3-week cycles) 

Week 1 
Days 

Week 2 
Days 

Week 3 

Farydak 1  3  5   8  10  12   Rest period 
Bortezomib 1   4    8   11    Rest period 
Dexamethasone 1 2  4 5   8 9  11 12   Rest period 

 
Table 2 Recommended dosing schedule of panobinostat in combination with bortezomib and 

dexamethasone (cycles 9-16) 
 

Cycles 9-16 
(3-week cycles) 

Week 1 
Days 

Week 2 
Days 

Week 3 

Farydak 1  3  5   8  10  12   Rest period 
Bortezomib 1       8       Rest period 
Dexamethasone 1 2      8 9      Rest period 

 
Monitoring recommendations 
 
Blood cell counts 
A complete blood cell count must be performed before initiating treatment with panobinostat. The 
baseline platelet count should be ≥100 x 109/l and the baseline absolute neutrophil count (ANC) 
≥1.0 x 109/l. Complete blood counts should be frequently monitored during treatment (in particular 
before each injection of bortezomib, i.e. on days 1, 4, 8 and 11 of cycles 1 to 8 and on days 1 and 8 of 
cycles 9 to 16), especially for thrombocytopenia (see section 4.4). Prior to initiating any cycle of 
therapy with panobinostat in combination with bortezomib and dexamethasone, platelet count should 
be at least ≥100 x 109/l (see section 4.4). Additional blood counts should be considered during the 
“rest period” – e.g. on days 15 and/or 18, especially in patients ≥65 years and patients with a baseline 
platelet count below 150 x 109/l. 
 
ECG 
Panobinostat may increase the QTc interval (see section 4.4). Therefore an ECG should be recorded 
prior to the start of therapy and repeated periodically before each treatment cycle. QTcF should be 
<480 msec prior to initiation of treatment with panobinostat (see below section on dose adjustments 
and section 4.4). 
 
Blood electrolytes 
Blood electrolytes, especially potassium, magnesium and phosphorus, should be measured at baseline 
and monitored periodically as clinically indicated, especially in patients with diarrhoea. Abnormal 
values should be corrected as clinically indicated (see section 4.4). 



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Liver function tests 
Liver function should be monitored prior to treatment and regularly during treatment as clinically 
indicated, especially in patients with hepatic impairment (see section 4.4). 
 
Thyroid function tests 
Mild hypothyroidism was reported in patients treated with panobinostat + bortezomib + 
dexamethasone in Study D2308; some patients required treatment (see section 4.4). Thyroid and 
pituitary function should be monitored by measuring hormone levels (e.g. free T4 and TSH) as 
clinically indicated. 
 
Dose adjustments 
Modification of the treatment dose and/or schedule may be required based on individual tolerability. 
Clinical judgement on how to continue the treatment should be exercised when a patient experiences 
an adverse drug reaction. 
 
If a dose reduction is required, the dose of panobinostat should be reduced by decrements of 5 mg (i.e. 
from 20 mg to 15 mg or from 15 mg to 10 mg). The dose should not be reduced below 10 mg and the 
same treatment schedule (3-week treatment cycle) should be kept. 
 
Thrombocytopenia 
Platelet counts should be monitored prior to each dose of bortezomib (i.e. on days 1, 4, 8 and 11 of 
cycles 1-8, see Table 1, and on days 1 and 8 of cycles 9-16, see Table 2). If patients experience 
thrombocytopenia, panobinostat may need to be temporarily withheld and the subsequent dose may 
need to be reduced (see Table 3). In patients with platelet count <50 x 109/l (complicated by bleeding) 
or <25 x 109/l, Farydak therapy should be withheld and resumed at a reduced dose upon recovery to 
platelet count ≥50 x 109/l. Platelet counts should be monitored at least twice a week until ≥50 x 109/l. 
Platelet transfusions may be required, if clinically indicated (see section 4.4). Discontinuation of 
treatment may be considered if thrombocytopenia does not improve despite the treatment 
modifications described below and/or the patient requires repeated platelet transfusions. Additionally, 
dose adjustment of bortezomib may be considered (see bortezomib SmPC and Table 3). 
 
Table 3 Recommended dose modifications for thrombocytopenia 
 

Thrombocytopenia 
grade on day of 
treatment 

Modification 
of 
panobinostat 
starting dose 

Panobinostat dose 
on recovery to 
grade 2 
thrombocytopenia 
(≥50 x 109/l) 

Modification 
of 
bortezomib 
starting dose 

Bortezomib dose on 
recovery to grade 2 
thrombocytopenia 
(≥50 x 109/l) 
1 dose 
omitted 

More 
than 
1 dose 
omitted 

Grade 3 
Platelets <50 x 109/l 
with bleeding 

Omit dose Resume at reduced 
dose 

Omit dose Resume 
at same 
dose 

Resume at 
reduced 
dose 

Grade 4 
Platelets <25 x 109/l 

Omit dose Resume at reduced 
dose 

Omit dose Resume 
at same 
dose 

Resume at 
reduced 
dose 

 
Gastrointestinal toxicity 
Gastrointestinal toxicity is very common in patients treated with panobinostat. Patients who 
experience diarrhoea and nausea or vomiting may require temporary dose discontinuation or dose 



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reduction as outlined in Table 4. 
 
Table 4 Recommended dose modifications for gastrointestinal toxicity 
 

Adverse 
drug 
reaction 

Grade on day of 
treatment 

Modification of 
panobinostat 
starting dose 

Panobinostat 
dose on 
recovery to 
≤ grade 1 

Modification 
of 
bortezomib 
starting dose 

Bortezomib 
dose on 
recovery to 
≤ grade 1 

Diarrhoea Grade 2 despite 
anti-diarrhoeal 
medicinal product 

Omit dose Resume at the 
same dose 

Omit dose Resume at 
reduced dose 
or change to 
once weekly 

Grade 3 despite 
anti-diarrhoeal 
medicinal product 

Omit dose Resume at 
reduced dose 

Omit dose Resume at 
reduced dose 
or with the 
same dose 
but with a 
once-weekly 
schedule 

Grade 4 despite 
anti-diarrhoeal 
medicinal product 

Permanently 
discontinue 

 Permanently 
discontinue 

 

 
At the first sign of abdominal cramping, loose stools or onset of diarrhoea, it is recommended that the 
patient be treated with an anti-diarrhoeal medicinal product (e.g. loperamide). 
 
In the event of grade 3 nausea or grade 3 or 4 vomiting despite administration of an anti-emetic, 
panobinostat should be temporarily discontinued and resumed at a reduced dose on recovery to 
grade 1. 
 
Prophylactic anti-emetics should be administered at the discretion of the physician and in accordance 
with local medical practice (see section 4.4). 
 
Neutropenia 
Neutropenia may require temporary or permanent dose reduction. Instructions for dose interruptions 
and reductions for panobinostat are outlined in Table 5. 
 
Table 5 Recommended dose modifications for neutropenia 
 

Neutropenia grade 
on day of treatment 

Modification of 
panobinostat 
starting dose 

Panobinostat dose 
on recovery to 
grade 2 neutropenia 
(<1.5-1.0 x 109/l) 

Modification 
of 
bortezomib 
starting dose 

Bortezomib 
dose on 
recovery to 
grade 2 
neutropenia 
(<1.5-1.0 x 109/l) 

Grade 3 neutropenia 
(<1.0-0.5 x 109/l) 

Omit dose Resume at same dose Omit dose Resume at same 
dose 

Grade 4 neutropenia 
(<0.5 x 109/l) or 
febrile neutropenia 
(<1.0 x 109/l and 
fever ≥38.5°C) 

Omit dose Resume at reduced 
dose 

Omit dose Resume at same 
dose 

 
In the event of grade 3 or 4 neutropenia, physicians should consider the use of growth factors (e.g. 
G-CSF) according to local guidelines. Discontinuation of treatment may be considered if neutropenia 
does not improve despite the dose modifications and/or despite the addition of granulocyte colony 
stimulating factor therapy according to local medical practice and treatment guidelines, and/or in the 



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event of severe secondary infections. 
 
QTc prolongation 
In the event of long QT interval prior to initiation of panobinostat (QTcF ≥480 msec at baseline), the 
start of treatment should be delayed until pre-dose average QTcF has returned to <480 msec. In 
addition any abnormal serum potassium, magnesium or phosphorus values should be corrected prior to 
initiation of Farydak therapy (see section 4.4). In the event of QT prolongation during treatment: 
• The dose should be omitted, if QTcF is ≥480 msec or above 60 msec from baseline. 
• If QT prolongation is resolved within 7 days, resume treatment at prior dose for initial 

occurrence or at reduced dose if QT prolongation is recurrent. 
• If QT prolongation is unresolved within 7 days, treatment should be discontinued. 
• If any QTcF value is above 500 msec, Farydak therapy should be permanently discontinued. 
 
Other adverse drug reactions 
For patients experiencing severe adverse drug reactions other than thrombocytopenia, gastrointestinal 
toxicity, neutropenia or QTc prolongation, the recommendation is the following: 
• CTC grade 2 toxicity recurrence or CTC grades 3 and 4 - omit the dose until recovery to CTC 

grade ≤1 and resume treatment at a reduced dose. 
• CTC grade 3 or 4 toxicity recurrence - a further dose reduction may be considered once the 

adverse reaction has resolved to CTC grade <1. 
 
Special populations 
Patients with renal impairment 
Plasma exposure of panobinostat is not altered in cancer patients with mild to severe renal impairment. 
Therefore, starting dose adjustments are not necessary. Panobinostat has not been studied in patients 
with end-stage renal disease (ESRD) or patients on dialysis (see section 5.2). 
 
Patients with hepatic impairment 
A clinical study in cancer patients with impaired hepatic function showed that plasma exposure of 
panobinostat increased by 43% (1.4-fold) and 105% (2-fold) in patients with mild and moderate 
hepatic impairment, respectively. Patients with mild hepatic impairment should be started on 
panobinostat at a reduced dose of 15 mg during the first treatment cycle. A dose escalation from 
15 mg to 20 mg may be considered based on patient tolerability. Patients with moderate hepatic 
impairment should be started on panobinostat at a reduced dose of 10 mg during the first treatment 
cycle. A dose escalation from 10 mg to 15 mg may be considered based on patient tolerability. 
Frequency of monitoring of these patients should be increased during treatment with panobinostat, 
particularly during the dose escalation phase. Panobinostat should not be administered in patients with 
severe hepatic impairment due to lack of experience and safety data in this population. Adjustment of 
bortezomib dose should also be considered (see bortezomib SmPC and Table 6). 
 



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Table 6 Recommended starting dose modification for patients with hepatic impairment 
 

Grade of 
hepatic 
impairment* 

Bilirubin level SGOT 
(AST) levels 

Modification of 
panobinostat starting 
dose 

Modification of 
bortezomib starting 
dose 

Mild ≤1.0 x ULN >ULN Reduce panobinostat 
dose to 15 mg in the 
first treatment cycle. 
Consider dose 
escalation up to 20 mg 
in subsequent cycles 
based on patient 
tolerability. 

None 
>1.0 x ULN and 
≤1.5 x ULN 

Any 

Moderate >1.5 x ULN and 
≤3.0 x ULN 

Any Reduce panobinostat 
dose to 10 mg in the 
first treatment cycle. 
Consider dose 
escalation up to 15 mg 
in subsequent cycles 
based on patient 
tolerability. 

Reduce bortezomib 
dose to 0.7 mg/m2 in 
the first treatment 
cycle. Consider dose 
escalation to 
1.0 mg/m2 or further 
dose reduction to 
0.5 mg/m2 in 
subsequent cycles 
based on patient 
tolerability. 

SGOT = serum glutamic oxaloacetic transaminase; 
AST = aspartate aminotransferase 
ULN = upper limit of the normal range 
* Based on NCI-CTEP classification 

 
Elderly population 
Patients over 65 years of age had a higher frequency of selected adverse reactions and of 
discontinuation of treatment because of adverse reactions. It is recommended to monitor patients over 
65 years of age more frequently, especially for thrombocytopenia and gastrointestinal toxicity (see 
sections 4.4 and 4.8). 
 
For patients >75 years of age, depending on the patient’s general condition and concomitant diseases, 
an adjustment of the starting doses or schedule of the components of the combination regimen may be 
considered. Panobinostat may be started at a dose of 15 mg, and if tolerated in the first cycle escalated 
to 20 mg in the second cycle. Bortezomib may be started at 1.3 mg/m2 once weekly on days 1 and 8, 
and dexamethasone at 20 mg on days 1 and 8. 
 
Paediatric population 
There is no relevant use of panobinostat in paediatric patients below the age of 18 years in the 
indication multiple myeloma (see section 5.2). 
 
Strong CYP3A4 inhibitors 
In patients who take concomitant medicinal products which are strong CYP3A and/or Pgp inhibitors, 
including, but not limited to, ketoconazole, itraconazole, voriconazole, ritonavir, saquinavir, 
telithromycin, posaconazole and nefazodone, the dose of panobinostat should be reduced to 10 mg 
(see section 4.5). If continuous treatment with a strong CYP3A4 inhibitor is required, a dose escalation 
from 10 mg to 15 mg panobinostat may be considered based on patient tolerability. 
 
In patients with hepatic impairment receiving concomitant medicinal products which are strong 
CYP3A4 inhibitors, treatment with panobinostat should be avoided due to lack of experience and 
safety data in this patient population. 
 
Strong CYP3A inhibitors should not be started in patients who have already received a reduced dose 



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of panobinostat due to adverse reactions. If this is unavoidable, patients should be closely monitored 
and further dose reduction or discontinuation may be considered as clinically indicated (see 
section 4.5). 
 
Method of administration 
 
Farydak should be administered orally once daily on scheduled days only, at the same time each day. 
The capsules should be swallowed whole with water, with or without food (see section 5.2), and they 
should not be opened, crushed or chewed. If a dose is missed, it can be taken up to 12 hours after the 
specified dose time. If vomiting occurs the patient should not take an additional dose, but should take 
the next usual prescribed dose. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
Breast-feeding (see section 4.6). 
 
4.4 Special warnings and precautions for use 
 
Panobinostat is used in combination treatment, therefore the prescribing information of bortezomib 
and dexamethasone should be consulted prior to initiation of treatment with panobinostat. 
 
Decrease in blood cell count 
 
Haematological adverse drug reactions, including severe thrombocytopenia, neutropenia and anaemia 
(CTC grade 3 to 4) were reported in patients treated with panobinostat. Therefore a complete blood 
count must be performed before initiating therapy with panobinostat, with frequent monitoring during 
treatment (in particular before each injection of bortezomib as per bortezomib SmPC). 
 
The platelet count should be ≥100 x 109/l and the absolute neutrophil count ≥1.0 x 109/l prior to 
initiation of treatment. Platelet count should be ≥100 x 109/l prior to initiating any cycle of treatment 
(see section 4.2). 
 
In the phase III study, thrombocytopenia typically recovered to baseline by the start of the next 21-day 
cycle (see Figure 1). The median time to onset for grade 3 and 4 thrombocytopenia was one month and 
the median time to recovery was 12 days. 



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Figure 1 Median platelet counts over time (Study D2308, Safety set, cycles 1-8) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PAN=panobinostat  
BTZ= bortezomib 
Dex = dexamethasone 
 
In patients with CTC grade 3 thrombocytopenia (platelet count <50 x 109/l with bleeding) 
panobinostat may need to be temporarily withheld and/or the subsequent dose may need to be reduced. 
Platelet transfusions may be required as clinically indicated (see sections 4.2 and 4.8). 
 
Haemorrhage 
 
Haemorrhage has been reported in patients during treatment with panobinostat. CTC grade 3 or 4 
haemorrhage was reported in 4.2% of patients, including cases of gastrointestinal and pulmonary 
haemorrhage with fatal outcomes. Therefore, physicians and patients should be aware of the increased 
risk of thrombocytopenia and the potential for haemorrhage, especially in patients with coagulation 
disorders or in those who are receiving chronic anti-coagulation therapy. 
 
Infection 
 
Localised and systemic infections, including pneumonia, other bacterial infections, invasive fungal 
infections such as aspergillosis or candidiasis, and viral infections including hepatitis B virus and 
herpes simplex, have been reported in patients taking panobinostat. Some of these infections (e.g. 
pneumonia) have been severe (e.g. leading to sepsis, or respiratory or multi-organ failure) and have 
had fatal outcomes (see section 4.8). Of note, whereas grade 3 and grade 4 neutropenia were observed 
in 28% and 7% of patients, respectively, febrile neutropenia was observed in 1% of patients (see 
section 4.8). Physicians and patients should be aware of the increased risk of infection with 
panobinostat. 
 
Farydak treatment should not be initiated in patients with active infections. Pre-existing infections 
should be treated prior to initiation of the therapy. Patients should be monitored for signs and 
symptoms of infections during treatment with panobinostat; if a diagnosis of infection is made, 
appropriate anti-infective treatment should be instituted promptly and interruption or discontinuation 
of Farydak considered. 
 
If a diagnosis of invasive systemic fungal infection is made, panobinostat should be discontinued and 
appropriate anti-fungal therapy instituted. 
 

(BL) 1:4  1:8  1:11 2:1 2:4  2:8  2:11 3:1 3:4  3:8 3:11 4:1  4:4  4:8 4:11 5:1  5:4  5:8 5:11 6:1  6:4 6:8 6:11 7:1  7:4  7:8 7:11 8:1  8:4  8:8  8:11  

100 

200 

300 

400 

500 

0 

PAN+BTZ+Dex PBO+BTZ+Dex 
PAN+BTZ+Dex   n=       381    370    367    363    351   342    335    320    323    310   298     283   285     265    268    250   253    232   238    225    230    206   206  199    205    183    188    175    185   159    170     155 
PBO+BTZ+Dex  n=        377    364    368    365   357   349    340    339     335    325   313     302   308     292    292    279   275    255   259    241    251    234   242   203   233    209    217    204     211   192   194     188  

Cycle:Day 

 
Pl

at
el

et
s 

10
 x

 1
09

/l 



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Gastrointestinal disorders 
 
Severe nausea, diarrhoea, constipation and vomiting, sometimes requiring the use of anti-emetic and 
anti-diarrhoeal medicinal products, have been reported in patients treated with Farydak (see 
section 4.8). Fluid and electrolyte blood levels, especially potassium, magnesium and phosphate, 
should be monitored periodically during therapy and corrected as clinically indicated to prevent 
potential dehydration and electrolyte disturbances (see section 4.2). 
 
Prophylactic anti-emetics (e.g. prochlorperazine) may be considered at the discretion of the physician 
and in accordance with local medical practice. Anti-emetic medicinal products with a known risk of 
QT prolongation such as dolasetron, granisetron, ondansetron and tropisetron should be used with 
caution (see section 4.5). 
 
At the first sign of abdominal cramping, loose stools or onset of diarrhoea, it is recommended that the 
patient be treated with anti-diarrhoeal medicinal product (e.g. loperamide) or any additional treatment 
in accordance with local treatment guidelines. Replacement intravenous fluids and electrolytes may be 
used as appropriate. Medicinal products with laxative properties should be used with caution because 
of the potential for exacerbation of diarrhoea. Patients should be advised to contact their physician to 
discuss the use of any laxative product. 
 
Electrocardiographic changes 
 
Panobinostat may prolong cardiac ventricular repolarisation (QT interval). 
 
No episodes of QTcF prolongation >500 msec were reported with the dose of 20 mg Farydak in the 
phase III clinical study, in combination with bortezomib and dexamethasone. Pooled clinical data from 
over 500 patients treated with panobinostat alone in multiple indications and at different dose levels 
have shown that the incidence of CTC grade 3 QTc prolongation (QTcF >500 msec) was 
approximately 1% overall and 5% or more at a dose of 60 mg or higher; no episodes of torsades de 
pointes were observed. 
 
Additional analysis suggests that the risk of QTc prolongation does not increase over time (see 
section 4.2). 
 
QTcF should be <480 msec prior to initiation of treatment with Farydak. 
 
Appropriate monitoring of electrolytes (e.g. potassium, magnesium and phosphorus) and ECG should 
be performed at baseline and periodically during treatment, particularly in patients with severe 
gastrointestinal adverse drug reaction (see section 4.2). 
 
Farydak should be used with caution in patients who already have or who are at significant risk of 
developing QTc prolongation. This includes patients: 
• with long QT syndrome. 
• with uncontrolled or significant cardiac disease, including recent myocardial infarction, 

congestive heart failure, unstable angina or clinically significant bradycardia. 
 
Concomitant administration of medicinal products that are known to cause QTc prolongation should 
be used with caution (see section 4.5). 
 
In case of concomitant use of agents that may increase panobinostat plasma concentrations, such as 
strong CYP3A4 inhibitors, dose adjustment is required (see sections 4.5 and 4.2). 
 
Hepatotoxicity 
 
Hepatic dysfunction, primarily mild transient elevations in aminotransferases and total bilirubin, has 
been reported in patients during treatment with panobinostat. 
 



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Liver function should be monitored prior to treatment and regularly during treatment. If results of liver 
function tests show abnormalities according to the NCI-CTEP classification, dose adjustments for 
patients with mild and moderate hepatic impairment are recommended and the patient should be 
followed until values return to normal or pre-treatment levels. Panobinostat should not be administered 
in patients with severe hepatic impairment due to lack of experience and safety data in this population. 
Adjustment of bortezomib dose should also be considered (see bortezomib SmPC and Table 6). 
 
Elderly population 
 
It is recommended to monitor patients over 65 years of age more frequently, especially for 
thrombocytopenia and gastrointestinal toxicity (see section 4.8 and section 4.2). 
 
For patients >75 years of age, depending on the patient’s general condition and concomitant diseases, 
an adjustment of the starting doses or schedule of the components of the combination regimen may be 
considered (see section 4.2). 
 
Strong CYP3A4 inducers 
 
Strong inducers may reduce the efficacy of panobinostat, therefore the concomitant use of strong 
CYP3A4 inducers including, but not limited to, carbamazepine, phenobarbital, phenytoin, rifabutin, 
rifampicin and St. John’s Wort (Hypericum perforatum), should be avoided (see section 4.5). 
 
Women of childbearing potential 
 
Women of childbearing potential taking panobinostat in combination with bortezomib and 
dexamethasone must use highly effective contraception for three months after stopping treatment (see 
sections 4.5 and 4.6 and bortezomib and dexamethasone SmPC). Women using hormonal 
contraceptives should additionally use a barrier method of contraception. 
 
Hypothyroidism 
 
Hypothyroidism events were reported in 8 of 381 patients treated with panobinostat + bortezomib + 
dexamethasone in Study D2308, of whom 2 required treatment. Thyroid and pituitary function should 
be monitored by measuring hormone levels (e.g. free T4 and TSH) as clinically indicated (see 
section 4.2). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Farydak metabolism is through both non-CYP and CYP mediated routes. Approximately 40% of 
panobinostat is metabolised through CYP3A4. Metabolism via CYP2D6 and 2C19 was minor. 
Therefore, medicinal products that can influence CYP3A4 enzyme activity may alter the 
pharmacokinetics of panobinostat. Panobinostat is a P-gp substrate. 
 
Agents that may increase panobinostat plasma concentrations 
 
Co-administration of a single 20 mg panobinostat dose with ketoconazole, a strong CYP3A inhibitor, 
increased the Cmax and AUC of panobinostat by 1.6- and 1.8-fold, respectively, compared to when 
panobinostat was given alone. 
 
In patients who take concomitant medicinal products which are strong CYP3A and/or Pgp inhibitors, 
including, but not limited to, ketoconazole, itraconazole, voriconazole, ritonavir, saquinavir, 
telithromycin, posaconazole and nefazodone, the dose of panobinostat should be reduced (see 
section 4.2). 
 
Patients should be instructed to avoid star fruit, grapefruit, grapefruit juice, pomegranates and 
pomegranate juice, as these are known to inhibit cytochrome P450 3A enzymes and may increase the 
bioavailability of panobinostat. 



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Agents that are predicted to decrease panobinostat concentrations 
 
The panobinostat fraction metabolised through CYP3A4 is approximately 40%. In clinical studies in 
multiple myeloma, the exposure of panobinostat was decreased by approximately 20% by the 
concomitant use of dexamethasone, which is a dose-dependent mild/moderate CYP3A4 inducer. 
Strong inducers are expected to have greater effects, and may reduce the efficacy of panobinostat, 
therefore the concomitant use of strong CYP3A4 inducers including, but not limited to, 
carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin and St. John’s Wort (Hypericum 
perforatum), should be avoided. 
 
Agents whose plasma concentrations may be increased by panobinostat 
 
Panobinostat increased the Cmax and the AUC of dextromethorphan (a substrate of CYP2D6) by 
1.8- and 1.6-fold, respectively, and it cannot be excluded that the effect may be larger on a more 
sensitive CYP2D6 substrate. Avoid panobinostat use in patients who are taking CYP2D6 substrates 
with a narrow therapeutic index (including, but not limited to, pimozide). When Farydak is 
co-administered with sensitive CYP2D6 substrates (e.g. atomoxetine, dextromethorphan, metoprolol, 
nebivolol, perphenazine and pimozide), dose titrate individual CYP2D6 substrates based on 
tolerability and frequently monitor patients for adverse reactions. 
 
Agents whose plasma exposure can be decreased by panobinostat 
 
Hormonal contraceptives 
It is currently unknown whether panobinostat may reduce the effectiveness of hormonal 
contraceptives. In addition, when panobinostat is administered together with dexamethasone, which is 
known to be a weak to moderate inducer of CYP3A4 as well as other enzymes and transporters, the 
risk for reduced efficacy of contraceptives needs to be considered. Women using hormonal 
contraceptives should additionally use a barrier method of contraception. 
 
No data is available that can be used to exclude the risk that panobinostat could be a weak inducer of 
the enzyme CYP3A4 in the gastrointestinal tract. This could potentially lead to slightly decreased 
exposure to sensitive CYP3A4 substrates. 
 
Anticipated pharmacodynamic interactions 
 
Prolongation of QT interval 
Based on preclinical and clinical data, panobinostat has the potential to prolong the QT interval. 
Concomitant use of anti-arrhythmic medicinal products (including, but not limited to, amiodarone, 
disopyramide, procainamide, quinidine and sotalol) and other substances that are known to prolong the 
QT interval (including, but not limited to, chloroquine, halofantrine, clarithromycin, methadone, 
moxifloxacin, bepridil and pimozide) is not recommended. Anti-emetic medicinal products with a 
known risk of QT prolongation such as dolasetron, granisetron, ondansetron and tropisetron should be 
used with caution (see section 4.4). 
 
4.6 Fertility, pregnancy and lactation 
 
Women of child-bearing potential/Contraception in males and females 
 
Based on findings in animals, the likelihood of panobinostat increasing the risk of both foetal death 
and developmental skeletal abnormalities when administered to pregnant women is predicted to be 
high. Women of child-bearing potential should have a pregnancy test prior to the initiation of 
treatment with Farydak and must use a highly effective method of contraception during treatment and 
for three months after the last dose of Farydak. Women using hormonal contraceptives should 
additionally use a barrier method of contraception. 
 



13 

Due to its cytostatic/cytotoxic mode of action, panobinostat can influence the quality of sperm formed 
during treatment. Sexually active men taking Farydak and their female partners should use a highly 
effective method of contraception during the man’s treatment and for six months after his last dose of 
Farydak. 
 
When panobinostat is administered together with dexamethasone, which is known to be a weak to 
moderate inducer of CYP3A4 as well as other enzymes and transporters, the risk for reduced efficacy 
of hormonal contraceptives needs to be considered. In addition, it is currently unknown whether 
panobinostat may reduce the effectiveness of hormonal contraceptives, and therefore women using 
hormonal contraceptives should additionally use a barrier method of contraception. 
 
Pregnancy 
 
There are no clinical studies on the use of Farydak in pregnant patients. Studies in animals have shown 
reproductive and embryo-foetal toxicity (see section 5.3). Given panobinostat’s cytostatic/cytotoxic 
mode of action, the potential risk to the foetus is high. Farydak should only be used during pregnancy 
if the expected benefits outweigh the potential risks to the foetus. If it is used during pregnancy or if 
the patient becomes pregnant while using it, the patient must be informed of the potential risk to the 
foetus. 
 
Breast-feeding 
 
It is unknown whether panobinostat is excreted in human milk. Given its cytostatic/cytotoxic mode of 
action, breast-feeding is contraindicated during Farydak treatment (see section 4.3). 
 
Fertility 
 
Based on non-clinical findings, male fertility may be compromised by treatment with Farydak (see 
section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Farydak has a minor influence on the ability to drive and use machines. Dizziness may occur 
following administration of Farydak (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The safety data of panobinostat have been assessed from a total of 451 patients with multiple myeloma 
treated with panobinostat in combination with bortezomib and dexamethasone and from a total of 
278 patients treated with panobinostat as a single agent. 
 
The safety data reported below are based on the phase III clinical study (Panorama 1) in 381 patients 
with multiple myeloma treated with 20 mg panobinostat once a day three times per week, on a 
2 weeks on and 1 week off dosing regimen in combination with bortezomib and dexamethasone. 
The median duration of exposure in the study was 5.0 months. 15.7% of patients were exposed to 
study treatment for ≥48 weeks. 
 
The most common non-haematological adverse reactions were diarrhoea, fatigue, nausea and 
vomiting. 
 
Treatment-emergent haematological toxicities included thrombocytopenia, anaemia, neutropenia and 
lymphopenia. 
 
QTcF >480 and <500 msec was recorded in 1.3% of patients and change from baseline of >60 msec 
was observed in 0.8% of patients. No patient had an absolute QTcF >500 msec. 



14 

 
Cardiac events (most frequently atrial fibrillation, tachycardia, palpitation and sinus tachycardia) were 
reported in 17.6% of panobinostat + bortezomib + dexamethasone-treated patients versus 9.8% of 
placebo + bortezomib + dexamethasone-treated patients and syncope events were reported in 6.0% 
versus 2.4%, respectively. 
 
Discontinuation due to adverse events, regardless of causality, was observed in 36.2% of patients. The 
most common adverse events (AEs) leading to treatment discontinuation were diarrhoea (4.5%), 
asthenia and fatigue (2.9% each) and pneumonia (1.3%). 
 
On-treatment deaths not due to the study indication (multiple myeloma) were reported in 6.8% of 
panobinostat + bortezomib + dexamethasone-treated patients versus 3.2% of placebo + bortezomib + 
dexamethasone-treated patients. 
 
Tabulated list of adverse drug reactions from clinical studies 
 
Adverse drug reactions from the phase III study (Panorama 1) are shown in Table 7. Adverse drug 
reactions are listed according to system organ classes in MedDRA. Within each system organ class, 
the adverse drug reactions are ranked by frequency, with the most frequent reactions first. Within each 
frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In 
addition, the corresponding frequency category for each adverse drug reaction is based on the 
following convention (CIOMS III): 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 available data). 
 
Table 7 includes adverse drug reactions that occur due to the addition of panobinostat to the 
bortezomib and dexamethasone combination. The frequency category reflects the combination of all 
the medicinal products i.e. panobinostat + bortezomib + dexamethasone. For adverse drug reactions 
that are related to bortezomib or dexamethasone treatment, please refer to the relevant SmPC. 
 
Table 7 Panobinostat adverse drug reactions observed in multiple myeloma patients in the 

phase III study 
 

System Organ Class Frequency Adverse reaction 
Infections and infestations Very common Upper respiratory tract infection, pneumonia 

Common Septic shock, urinary tract infection, viral 
infection, oral herpes, Clostridium difficile 
colitis, otitis media, cellulitis, sepsis, 
gastroenteritis, lower respiratory tract infection, 
candidiasis 

Uncommon Pneumonia fungal, hepatitis B, aspergillosis 
Blood and lymphatic 
system disorders a 

Very common Pancytopenia, thrombocytopenia, anaemia, 
leukopenia, neutropenia, lymphopenia 

Endocrine disorders Common Hypothyroidism 
Metabolism and nutrition 
disorders 

Very common Decreased appetite, hypophosphataemia a, 
hyponatraemia a, hypokalaemia a 

Common Hyperglycaemia, dehydration, 
hypoalbuminaemia, fluid retention, 
hyperuricaemia, hypocalcaemia, 
hypomagnesaemia 

Psychiatric disorders Very common Insomnia 
Nervous system disorders Very common Dizziness, headache 

Common Haemorrhage intracranial, syncope, tremor, 
dysgeusia 

Eye disorders Common Conjunctival haemorrhage 



15 

Cardiac disorders Common Bradycardia, atrial fibrillation, sinus tachycardia, 
tachycardia, palpitation 

Uncommon Myocardial infarction 
Vascular disorders Very common Hypotension 

Common Hypertension, haematoma, orthostatic 
hypotension 

Uncommon Shock haemorrhagic 
Respiratory, thoracic and 
mediastinal disorders 

Very common Cough, dyspnoea 
Common Respiratory failure, rales, wheezing, epistaxis 
Uncommon Pulmonary haemorrhage, haemoptysis 

Gastrointestinal disorders Very common Diarrhoea, nausea, vomiting, abdominal pain, 
dyspepsia 

Common Gastrointestinal haemorrhage, haematochezia, 
gastritis, cheilitis, abdominal distension, dry 
mouth, flatulence 

Uncommon Colitis, haematemesis, gastrointestinal pain 
Hepatobiliary disorders Common Hepatic function abnormal, 

hyperbilirubinaemia a 
Skin and subcutaneous 
disorders 

Common Skin lesions, rash, erythema 
Uncommon Petechiae 

Musculoskeletal and 
connective tissue disorders 

Common Joint swelling 

Renal and urinary 
disorders 

Common Renal failure, haematuria, urinary incontinence 

General disorders and 
administration site 
conditions 

Very common Fatigue, oedema peripheral, pyrexia, asthenia 
Common Chills, malaise 

Investigations Very common Weight decreased 
Common Blood urea increased, glomerular filtration rate 

decreased, blood alkaline phosphatase increased, 
electrocardiogram QT prolonged, blood 
creatinine increased a, SGPT alanine 
transaminase (ALT) increased a, SGOT aspartate 
transaminase (AST) increased a 

a Frequency is based on laboratory values 
 
Description of selected adverse drug reactions 
 
Gastrointestinal 
Gastrointestinal toxicity, primarily diarrhoea, nausea and vomiting, is among the most frequently 
reported adverse reactions. However, treatment discontinuation due to these reactions was reported in 
a relatively small proportion of patients, with diarrhoea at 4.5% and nausea and vomiting at 0.5% 
each. Patients should be advised to contact their physician if severe gastrointestinal toxicity occurs and 
dose adjustment or discontinuation may be required (see section 4.4). 
 
Thrombocytopenia 
Due to the nature of multiple myeloma and the known haematotoxicity for panobinostat and its 
combination agent bortezomib, thrombocytopenia, often severe, has been frequently observed. CTC 
grade 3 or 4 thrombocytopenia occurred in 256 patients, with a median onset time of one month. 
However, thrombocytopenia is reversible (median time to recovery of 12 days) and can usually be 
managed by dose adjustment and interruption with or without platelet transfusion (see section 4.4). 
33.3% patients in the panobinostat + bortezomib + dexamethasone arm and 10.3% patients in the 
placebo + bortezomib + dexamethasone arm received platelet transfusions during treatment. 
 
Thrombocytopenia rarely leads to treatment discontinuation (1.6% of patients). Most patients with 
thrombocytopenia did not experience haemorrhage. 20.7% of patients experienced haemorrhage, most 



16 

frequently epistaxis (4.7%), haematoma (2.6%), and conjunctival haemorrhage (2.1%). CTC grade 3 
or 4 haemorrhage was reported in 4.2% of patients, mostly commonly involving gastrointestinal 
haemorrhage. Five patients (1.3%) died of events associated with haemorrhage. Amongst the patients 
who died of haemorrhage, one patient had thrombocytopenia grade 4, three patients had 
thrombocytopenia grade 3 and 1 patient had thrombocytopenia grade 1. 
 
Neutropenia 
Neutropenia was frequently reported on the basis of laboratory findings determined during the study 
(all grades: 75%). Most newly occurring severe neutropenia was grade 3 (28%), with considerably 
fewer cases of grade 4 (6.6%). While many patients developed neutropenia, febrile neutropenia only 
occurred in a fraction of treated patients (1.0%, both for CTC all grades and for grades 3 and 4). 
Patients with neutropenia are prone to infection, mostly upper respiratory tract infection or pneumonia. 
Only 0.3% of the patients were discontinued from the treatment due to neutropenia. 
 
Fatigue and asthenia 
Fatigue and asthenia were reported in 41.2% and 22.0% of patients, respectively. CTC grade 3 fatigue 
was reported in 15.7% of the patients, and grade 4 in 1.3%. Grade 3 asthenia was observed in 9.4% of 
the patients, with no patients experiencing asthenia at CTC grade 4. The treatment was discontinued in 
2.9% of patients due to fatigue and asthenia. 
 
Infections 
Relapsed or refractory multiple myeloma patients are at risk of infections. Potential contributing 
factors may include prior history of chemotherapy, stem cell transplant, the nature of the disease and 
neutropenia or lymphopenia associated with Farydak treatment. The most frequently reported 
infections include upper respiratory tract infection, pneumonia and nasopharyngitis. Fatalities 
involving either pneumonia or sepsis were reported. Treatment discontinuation due to infections was 
reported in 5% of patients. 
 
QT prolongation and ECG abnormalities 
QTc prolongation was observed and was mostly mild in degree: QTcF interval >450 msec and 
≤480 msec was reported in 10.8% of patients, with maximum increase from baseline >30 msec and 
≤60 msec in 14.5% of patients. QTcF >500 msec was not reported in any patient. 
 
ECG (electrocardiogram) abnormalities have been reported in patients treated with panobinostat + 
bortezomib + dexamethasone, mainly involving ST-T depression (21.7%) and T wave changes 
(39.6%). Regardless of events chronology, syncope was reported in 9% of patients with ST-T 
depression and 7.2% of patients with T wave change and 4.9% of patients with neither of these ECG 
abnormalities. Likewise ischaemic heart disease (including myocardial infarction and ischaemia) were 
reported in 4.5% of patients with ST-T depression and 4.8% of patients with T wave change and 2.7% 
of patients with neither of these ECG abnormalities. 
 
Special populations 
 
Elderly population 
The incidence of deaths not related to study indication was 8.8% in patients ≥65 years of age 
compared to 5.4% in patients <65 years of age. 
 
Adverse reactions leading to permanent discontinuation occurred in 30%, 44% and 47% of patients 
aged <65 years, 65-75 years and ≥75 years, respectively. Grade 3-4 events more frequently observed 
in patients included the following (percentages presented for patients <65 years, 65-75 years and 
≥75 years of age, respectively): thrombocytopenia (60%, 74%, and 91%), anaemia (16%, 17% and 
29%), diarrhoea (21%, 27% and 47%), and fatigue (18%, 28% and 47%). 
 
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 



17 

professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Limited experience with overdose has been reported during clinical studies. Adverse reactions 
observed were consistent with the safety profile, with events primarily involving haematological and 
gastrointestinal disorders such as thrombocytopenia, pancytopenia, diarrhoea, nausea, vomiting and 
anorexia. Cardiac monitoring and assessment of electrolytes and platelet counts should be undertaken 
and supportive care given as necessary in the event of overdose. It is not known whether panobinostat 
is dialysable. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other antineoplastic agents, ATC code: L01XX42 
 
Mechanism of action 
 
Farydak is a histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDACs at 
nanomolar concentrations. HDACs catalyse the removal of acetyl groups from the lysine residues of 
histones and some non-histone proteins. Inhibition of HDAC activity results in increased acetylation 
of histone proteins, an epigenetic alteration that results in a relaxing of chromatin, leading to 
transcriptional activation. In vitro, panobinostat caused the accumulation of acetylated histones and 
other proteins, inducing cell cycle arrest and/or apoptosis of some transformed cells. Increased levels 
of acetylated histones were observed in xenografts from mice that were treated with panobinostat. 
Panobinostat shows more cytotoxicity towards tumour cells compared to normal cells. 
 
Pharmacodynamic effects 
 
Treatment of tumour cells with panobinostat resulted in a dose-dependent increase in acetylation of 
histones H3 and H4 both in vitro and in xenograft animal pre-clinical models, demonstrating target 
inhibition. In addition, increased expression of the tumour suppressor gene p21CDKNIA (cyclin 
dependent kinase inhibitor 1/p21) gene, a key mediator of G1 arrest and differentiation, was triggered 
with panobinostat exposure. 
 
Clinical efficacy and safety 
 
Clinical efficacy in patients with relapsed and relapsed and refractory multiple myeloma 
(Study D2308 – Panorama 1) 
The efficacy and safety of panobinostat in combination with bortezomib and dexamethasone were 
evaluated in a randomised, double-blind, placebo-controlled, multicentre phase III study in patients 
with relapsed or relapsed and refractory multiple myeloma who had received 1-3 prior lines of 
therapies. 
 
Patients received panobinostat (20 mg taken orally once a day, three times per week, on a 2 weeks on 
and 1 week off dosing regimen), in combination with bortezomib (1.3 mg/m2 injected intravenously) 
and dexamethasone (20 mg). Treatment was administered for a maximum of 16 cycles (see Tables 1 
and 2). 
 
A total of 768 patients were randomised in a 1:1 ratio to either the panobinostat + bortezomib + 
dexamethasone (n=387) or the placebo + bortezomib + dexamethasone (n=381) arm, stratified by prior 
use of bortezomib [Yes (n=336 (43.8%)), No (n=432 (56.3%))] and number of prior lines of 
anti-myeloma therapy [1 prior line (n=352 (45.8%)), 2 to 3 prior lines (n=416 (54.2%))]. 
Demographics and baseline disease characteristics were balanced and comparable between the study 

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


18 

arms. 
 
The median age was 63 years, range 28-84; 42.1% of patients were older than 65 years. A total of 
53.0% of patients were male. Caucasians comprised 65.0% of the study population, Asians 30.2% and 
blacks 2.9%. ECOG performance status was 0-1 in 93% of patients. The median number of prior 
therapies was 1.0. More than half (57.2%) of the patients had undergone prior stem cell transplantation 
and 62.8% of the patients were relapsed after previous anti-neoplastic therapies (e.g. melphalan 
79.6%, dexamethasone 81.1%, thalidomide 51.2%, cyclophosphamide 45.3%, bortezomib 43.0%, 
combined bortezomib and dexamethasone 37.8%, lenalidomide 20.4%). More than one third (35.8%) 
of the patients were relapsed and refractory to prior treatment. 
 
The median duration of follow-up was 28.75 months in the panobinostat + bortezomib + 
dexamethasone arm and 29.04 months in the placebo + bortezomib + dexamethasone arm. 
 
The primary endpoint was progression free survival (PFS) as per modified European Bone Marrow 
Transplant Group (mEBMT) criteria and as assessed by the investigator. In the overall patient 
population PFS based on the full analysis set (FAS) was statistically significantly different between 
the treatment arms (stratified Log-rank test p<0.0001, with an estimated 37% risk reduction in the 
panobinostat + bortezomib + dexamethasone arm compared to the placebo + bortezomib + 
dexamethasone arm (Hazard ratio: 0.63 (95% CI: 0.52, 0.76)). The median PFS (95% CI) was 
12.0 months (10.3, 12.9) and 8.1 months (7.6, 9.2), respectively. 
 
Overall survival (OS) was the key secondary endpoint. OS was not statistically significantly different 
between the two treatment groups. The median OS was 40.3 months in the panobinostat + bortezomib 
+ dexamethasone arm and 35.8 months in the placebo + bortezomib + dexamethasone arm (Hazard 
ratio: 0.94 (95% CI: 0.78, 1.14)). 
 
Out of the pre-specified subgroup of patients with prior treatment with bortezomib and an 
immunomodulatory agent (N=193), 76% of patients had received at least two prior regimens. In this 
subset of patients (N=147), the median duration of treatment was 4.5 months in the panobinostat + 
bortezomib + dexamethasone arm and 4.8 months in the placebo + bortezomib + dexamethasone arm. 
The median PFS (95% CI) was 12.5 months (7.26, 14.03) in the panobinostat + bortezomib + 
dexamethasone arm and 4.7 months (3.71, 6.05) in the placebo + bortezomib + and dexamethasone 
arm [HR: 0.47 (0.31, 0.72)]. These patients had a median of 3 prior therapies. Efficacy results are 
summarised in Table 8 and the Kaplan-Meier curves for PFS are provided in Figure 2. 
 
Table 8 Progression-free survival in patients who received at least two prior regimens 

including bortezomib and an immunomodulating agent 
 

 

Farydak 
bortezomib and dexamethasone 

N=73 

Placebo 
bortezomib and dexamethasone 

N=74 
Progression-free survival   
Median, months [95% CI] 12.5 [7.26, 14.03] 4.7 [3.71, 6.05] 
Hazard ratio [95% CI]1 0.47 (0.31, 0.72) 

1 Hazard ratio obtained from stratified Cox model 



19 

 
Figure 2 Kaplan-Meier plot of progression-free survival in patients with multiple myeloma 

who received at least two prior regimens including bortezomib and an 
immunomodulatory agent 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PAN= panobinostat 
PBO= placebo 
BTZ= bortezomib 
Dex = dexamethasone 
 
In the subgroup of patients who had received at least two prior regimens including bortezomib and an 
immunomodulatory agent (n=147), the overall response rate using modified EBMT criteria was 59% 
in the panobinostat + bortezomib + dexamethasone arm and 39% in the placebo + bortezomib + 
dexamethasone arm. Response rates are summarised in Table 9. 
 
Table 9 Response rates in patients with multiple myeloma who received at least two prior 

regimens including bortezomib and an immunomodulatory agent 
 

 

Farydak 
bortezomib and dexamethasone 

N=73 

Placebo 
 bortezomib and 
dexamethasone 

N=74 
Overall response 43 (59%) 29 (39%) 
[95% CI] (46.8, 70.3) (28, 51.2) 
Complete response 6 (8%) 0 
Near complete response 10 (14%) 6 (8%) 
Partial response 27 (37%) 23 (31%) 

 
Clinical efficacy in patients with bortezomib-refractory multiple myeloma (Study DUS71 – 
Panorama 2) 
 
Study DUS71 was a two-stage, single-arm, open-label multicentre phase II study of oral panobinostat 
(20 mg) in combination with bortezomib (1.3 mg/m2) and dexamethasone (20 mg) in 55 patients with 
relapsed and refractory multiple myeloma, who were bortezomib-refractory and had received at least 
two prior lines of therapy. Patients had to be exposed to an IMiD (lenalidomide or thalidomide). 
Refractoriness to bortezomib was defined as disease progression on or within 60 days of the last 
bortezomib-containing line of therapy. 
 
The primary endpoint of the study was to assess overall response rate (ORR) after 8 cycles of therapy 

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 

PAN+BTZ+Dex 
PBO+BTZ+Dex   

6 
36 
23 

8 
32 
11 

10 
25 
9 

12 
20 
5 

14 
15 
4 

16 
10 
2 

18 
6 
2 

20 
4 
2 

22 
3 
2 

24 
2 
2 

26 
2 
0 

28 
1 
0 

30 
0 
0 

0 
73 
74 

2 
57 
54 

4 
42 
37 

0 

20 

40 

60 

80 

100 

 P
ro

gr
es

si
on

-fr
ee

 s
ur

vi
va

l P
ro

ba
bi

lit
y 

(%
)  

Number of patients at risk 
 

Time (months) 
 

Time (months) 

Hazard Ratio= 0.47 
95% CI [0.31; 0.72] 
  Logrank p-value=0.0003 
  Kaplan Meier medians 
PAN+BTZ+Dex: 12.48 months 
PBO+BTZ+Dex: 4.70 months 

Censoring Times 
 PAN+BTZ+Dex (n/N=44/73) PBO+BTZ+Dex (n/N=54/74) 



20 

as per mEBMT criteria. 
 
Patients were heavily pre-treated and had received multiple prior regimens (median: 4; range: 2-11). 
All 55 patients were previously treated with bortezomib and at least one IMiD (lenalidomide: 98.2%, 
thalidomide: 69.1%). The majority of patients had received prior transplant (63.6%). 
 
The median duration of exposure to study treatment was 4.6 months (range: 0.1-24.1 months). Patients 
achieved an ORR (≥PR (partial response)) of 34.5% and 52.7% (≥MR (minimal response)). The 
median time to response was 1.4 months and the median duration of response was 6.0 months. The 
median OS was 17.5 months. 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Farydak in all subsets of the paediatric population in multiple myeloma (see section 4.2 for 
information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Panobinostat is rapidly and almost completely absorbed with Tmax reached within 2 hours of oral 
administration in patients with advanced cancer. The absolute oral bioavailability of panobinostat was 
approximately 21%. After oral administration, panobinostat pharmacokinetics appear to be linear in 
the dose range 10-30 mg, but AUC increases less than proportionally with dose at higher doses. 
 
Overall panobinostat exposure and inter-patient variability remained unchanged with or without food, 
whereas Cmax was reduced by <45% and Tmax prolonged by 1 to 2.5 hours with food (i.e. both normal 
and high-fat breakfasts). Since food did not alter overall bioavailability (AUC), panobinostat can be 
administered regardless of food in cancer patients. 
 
Distribution 
 
Panobinostat is moderately (approximately 90%) bound to human plasma proteins. Its fraction in the 
erythrocyte is 0.60 in vitro, independent of the concentration. The volume of distribution of 
panobinostat at steady state (Vss) is approximately 1,000 litres based on final parameter estimates in 
the population pharmacokinetic analysis. 
 
Biotransformation 
 
Panobinostat is extensively metabolised, and a large fraction of the dose is metabolised before 
reaching the systemic circulation. Pertinent metabolic pathways involved in the biotransformation of 
panobinostat are reduction, hydrolysis, oxidation and glucuronidation processes. Oxidative 
metabolism of panobinostat played a less prominent role, with approximately 40% of the dose 
eliminated by this pathway. Cytochrome P450 3A4 (CYP3A4) is the main oxidation enzyme, with 
potential minor involvement of CYP2D6 and 2C19. 
 
Panobinostat represented 6 to 9% of the drug-related exposure in plasma. The parent substance is 
deemed to be responsible for the overall pharmacological activity of panobinostat. 
 
Elimination 
 
After a single oral dose of [14C] panobinostat in patients, 29 to 51% of administered radioactivity is 
excreted in the urine and 44 to 77% in the faeces. Unchanged panobinostat accounted for <2.5% of the 
dose in urine and <3.5% of the dose in faeces. The remainders are metabolites. Apparent panobinostat 
renal clearance (CLR/F) was found to range from 2.4 to 5.5 l/h. Panobinostat has a terminal elimination 
half-life of approximately 37 hours based on final parameters estimate in the population PK analysis. 



21 

 
Special populations 
 
Paediatric population 
Panobinostat was not evaluated in multiple myeloma patients under 18 years of age. 
 
Elderly population 
In the phase III clinical study 162 out of 387 patients were aged 65 years or over. Plasma exposure of 
panobinostat in patients aged 65 years or younger was similar to those older than 65 years in the 
pooling of single-agent panobinostat studies between the dose range of 10 mg and 80 mg. 
 
Patients with hepatic impairment 
The effect of hepatic impairment on the pharmacokinetics of panobinostat was evaluated in a phase I 
study, in 24 patients with solid tumours and with varying degrees of hepatic impairment. Mild and 
moderate hepatic impairment as per NCI-CTEP classification increased panobinostat plasma exposure 
by 43% and 105%, respectively. No pharmacokinetic data are available for patients with severe 
hepatic impairment. 
 
Patients with renal impairment 
The effect of renal impairment on the pharmacokinetics of panobinostat was assessed in a phase I 
study in 37 patients with advanced solid tumours with varying degrees of renal function. Mild, 
moderate and severe renal impairment based on baseline urinary creatinine clearance did not increase 
the panobinostat plasma exposure in mild, moderate and severe groups. 
 
5.3 Preclinical safety data 
 
Repeated dose toxicity studies 
 
The primary target organs of toxicity following administration of panobinostat in rats and dogs were 
identified as the erythropoietic, myelopoietic and lymphatic systems. The thyroid changes including 
hormones in dogs (decrease triodothyronine (T3)) and rats (decrease in triodothyronine (T3), 
tetraiodothyronine (T4) (males) and thyroid stimulating hormone (TSH)) were observed at exposures 
corresponding to 0.07-2.2 of the human AUC observed clinically. 
 
Carcinogenesis and mutagenesis 
 
 
Carcinogenicity studies have not been performed with panobinostat. Panobinostat has demonstrated 
mutagenic potential in the Ames assay, endo reduplication effects in human peripheral blood 
lymphocytes in vitro. Additionally, in vivo DNA damage was observed in a COMET study in mouse 
lymphoma L5178Y cells and a dose-dependent molecular mechanisms study in murine bone marrow 
cells. The in vitro and in vivo findings are attributed to the pharmacological mode of action. 
 
 
Reproduction toxicity 
 
An increase in early resorptions was observed in female rats (doses ≥30 mg/kg). Prostatic atrophy 
accompanied by reduced secretory granules, testicular degeneration, oligospermia and increased 
epididymal debris were observed in dogs at exposures corresponding to 0.41-0.69 of the human 
clinical AUC and not fully reversible after a 4 week recovery period. 
 
Based on animal data, the likelihood of panobinostat increasing the risk of foetal death and 
developmental skeletal abnormalities is predicted to be high. Embryo foetal lethality and increases in 
skeletal anomalies (extra sternabrae, extra ribs, increases in minor skeletal variations, delayed 
ossification and variations of the sternabrae) were seen above exposures corresponding to 0.25 of the 
human clinical AUC. 
 



22 

The effects of panobinostat on labour and post-natal growth and maturation were not evaluated in 
animal studies. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Capsule content 
 
Magnesium stearate 
Mannitol 
Microcrystalline cellulose 
Pregelatinised starch (maize) 
 
Capsule shell 
 
Farydak 10 mg hard capsules 
Gelatin 
Titanium dioxide (E171) 
Brilliant blue FCF (E133) 
Iron oxide, yellow (E172) 
 
Farydak 15 mg hard capsules 
Gelatin 
Titanium dioxide (E171) 
Iron oxide, yellow (E172) 
Iron oxide, red (E172) 
 
Farydak 20 mg hard capsules 
Gelatin 
Titanium dioxide (E171) 
Iron oxide, red (E172) 
 
Printing ink 
 
Iron oxide, black (E172) 
Propylene glycol (E1520) 
Shellac glaze 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
4 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  
 
PVC/PCTFE/Alu blister containing 6 capsules. 
 



23 

Packs containing 6, 12 or 24 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 
 
Secura Bio Limited 
32 Molesworth Street 
Dublin 2 
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
Farydak 10 mg hard capsules 
 
EU/1/15/1023/001-003 
 
Farydak 15 mg hard capsules 
 
EU/1/15/1023/004-006 
 
Farydak 20 mg hard capsules 
 
EU/1/15/1023/007-009 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 28 August 2015 
Date of latest renewal: 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 
 
  

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


24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 
 



25 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Novartis Pharma GmbH 
Roonstrasse 25 
90429 Nuremberg 
Germany 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• 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. 

 
• Additional risk minimisation measures 
 
Prior to launch of Farydak in each Member State the Marketing Authorisation Holder (MAH) must 
agree about the content and format of the educational programme, including communication media, 
distribution modalities, and any other aspects of the programme, with the National Competent 
Authority. 
 
The educational programme is aimed to address the risk of medication error. 
 



26 

The MAH shall ensure that in each Member State where Farydak is marketed, all patients/carers who 
are expected to use Farydak have access to/are provided with the following educational package: 
 
• Patient information pack 
 
The patient information pack should contain: 
o Patient information leaflet 
o A patient compliance card 
 

• The patient compliance card shall contain instructions on the following key messages: 
o How to become familiar with the compliance card: this section provides a general 

overview of the compliance card and its purpose. 
o How to use the compliance card: this section provides a general overview on how 

to use the compliance card. 
o How to take medication according to the prescription: this section provides 

guidance on how to fill in the compliance card. 
o Recommendation to bring compliance card to each visit: this section reminds the 

patient to bring the compliance card to the HCP at each visit. 
o A table describing the treatment regimen for each day of the cycle with space for 

the patient to note what medication they took. 
 
  



27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



28 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 
  



29 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Farydak 10 mg hard capsules 
panobinostat 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each hard capsule contains panobinostat lactate anhydrous equivalent to 10 mg panobinostat. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Hard capsule 
 
6 capsules 
12 capsules 
24 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 
 
Cytotoxic: handle with caution. 
 
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. 
 
 



30 

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

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Secura Bio Limited 
32 Molesworth Street 
Dublin 2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1023/001 6 capsules 
EU/1/15/1023/002 12 capsules 
EU/1/15/1023/003 24 capsules 

 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Farydak 10 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



31 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Farydak 10 mg capsules 
panobinostat 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Secura Bio Limited 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Week 1 
Week 2 
Week 3 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8 
Day 9 
Day 10 
Day 11 
Day 12 
Day 13 
Day 14 
Day 15 
Day 16 
Day 17 
Day 18 
Day 19 
Day 20 
Day 21 
 
  



32 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Farydak 15 mg hard capsules 
panobinostat 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each hard capsule contains panobinostat lactate anhydrous equivalent to 15 mg panobinostat. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Hard capsule 
 
6 capsules 
12 capsules 
24 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 
 
Cytotoxic: handle with caution. 
 
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. 
 
 



33 

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

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Secura Bio Limited 
32 Molesworth Street 
Dublin 2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1023/004 6 capsules 
EU/1/15/1023/005 12 capsules 
EU/1/15/1023/006 24 capsules 

 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Farydak 15 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



34 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Farydak 15 mg capsules 
panobinostat 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Secura Bio Limited 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Week 1 
Week 2 
Week 3 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8 
Day 9 
Day 10 
Day 11 
Day 12 
Day 13 
Day 14 
Day 15 
Day 16 
Day 17 
Day 18 
Day 19 
Day 20 
Day 21 
 
  



35 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Farydak 20 mg hard capsules 
panobinostat 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each hard capsule contains panobinostat lactate anhydrous equivalent to 20 mg panobinostat. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Hard capsule 
 
6 capsules 
12 capsules 
24 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 
 
Cytotoxic: handle with caution. 
 
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. 
 
 



36 

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 
 
Secura Bio Limited 
32 Molesworth Street 
Dublin 2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1023/007 6 capsules 
EU/1/15/1023/008 12 capsules 
EU/1/15/1023/009 24 capsules 

 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Farydak 20 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



37 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Farydak 20 mg capsules 
panobinostat 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Secura Bio Limited 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Week 1 
Week 2 
Week 3 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8 
Day 9 
Day 10 
Day 11 
Day 12 
Day 13 
Day 14 
Day 15 
Day 16 
Day 17 
Day 18 
Day 19 
Day 20 
Day 21 
 
 
  



38 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



39 

Package leaflet: Information for the patient 
 

Farydak 10 mg hard capsules 
Farydak 15 mg hard capsules 
Farydak 20 mg hard capsules 

panobinostat 
 
 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Farydak is and what it is used for 
2. What you need to know before you take Farydak 
3. How to take Farydak 
4. Possible side effects 
5. How to store Farydak 
6. Contents of the pack and other information 
 
1. What Farydak is and what it is used for 
 
What Farydak is 
Farydak is an anti-cancer medicine that contains the active substance panobinostat, which belongs to a 
group of medicines called pan-deacetylase inhibitors. 
 
What Farydak is used for 
Farydak is used to treat adult patients with a rare type of blood cancer called multiple myeloma. 
Multiple myeloma is a disorder of plasma cells (a type of blood cell) that grow out of control in the 
bone marrow. 
 
Farydak blocks the growth of cancerous plasma cells and reduces the number of cancer cells. 
 
Farydak is always used together with two other medicines: bortezomib and dexamethasone. 
 
If you have any questions about how Farydak works or why you have been given it, ask your doctor or 
pharmacist. 
 
 
2. What you need to know before you take Farydak 
 
Do not take Farydak: 
- if you are allergic to panobinostat or any of the other ingredients of this medicine (listed in 

section 6). 
- if you are breast-feeding 
 
Warnings and precautions 
Follow all your doctor’s instructions carefully. 
 



40 

Talk to your doctor or pharmacist before taking Farydak: 
- if you have liver problems or have ever had liver disease. 
- if you have heart or heartbeat problems, such as irregular heartbeat or a condition called long 

QT syndrome. 
- if you have a bacterial, viral or fungal infection. 
- if you have gastrointestinal problems such as diarrhoea, nausea or vomiting. 
- if you have blood clotting problems (coagulation disorder). 
 
Tell your doctor or pharmacist straight away during treatment with Farydak: 
- if you notice any signs of a gastrointestinal problem. 
- if you notice any signs of a liver problem. 
- if you notice any signs of an infection. 
- if you notice any signs of a heart problem. 
The list of associated symptoms is provided in section 4, Possible side effects. 
 
Your doctor may need to change your dose, temporarily stop or completely stop your treatment with 
Farydak in case you experience side effects. 
 
Monitoring during your treatment with Farydak 
You will have regular blood tests during treatment with Farydak. These are to: 
- check how well your liver is working (by measuring your blood levels of bilirubin and 

transaminase, which are substances made by the liver). 
- check the amounts of certain cells of your blood (white blood cells, red blood cells, platelets). 
- check the amount of electrolytes (such as potassium, magnesium, phosphate) in your body. 
- check how well your thyroid and pituitary gland are working (by measuring your blood levels of 

thyroid hormones). 
 
Your heart rate will also be checked using a machine that measures the electrical activity of the heart 
(called an ECG). 
 
Children and adolescents 
Farydak is not to be used in children or adolescents under 18 years of age. 
 
Other medicines and Farydak 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines, including medicines obtained without a prescription, such as vitamins or herbal 
supplements, because they might interact with Farydak. 
 
In particular tell your doctor or pharmacist if you are taking any of the following medicines: 
- medicines used to treat infections, including fungal infections (such as ketoconazole, 

itraconazole, voriconazole or posaconazole) and some bacterial infections (such as antibiotics 
like clarithromycin or telithromycin). Medicines used to treat tuberculosis, such as rifabutin or 
rifampicin. 

- medicines used to stop seizures or fits (anti-epileptics such as carbamazepine, pherphenazine, 
phenobarbital or phenytoin). 

- medicines used to treat HIV, such as ritonavir or saquinavir. 
- medicines used to treat depression, such as nefazodone. 
- St. John’s wort, a herbal medicine used to treat depression. 
- medicines to prevent blood clotting called anti-coagulants, such as warfarin or heparin. 
- medicines used to treat cough, such as dextromethorphan. 
- medicines used to treat irregular heartbeat, such as amiodarone, disopyramide, procainamide, 

quinidine, propafenone or sotalol. 
- medicines that may have an unwanted effect on the heart (called QT prolongation), such as 

chloroquine, halofantrine, methadone, moxifloxacin, bepridil or pimozide. 
- medicines used to treat hypertension, such as metoprolol or nebivolol. 
- medicines used to treat severe mental health problems, such as risperidone. 
- medicines used to treat breast cancer, such as tamoxifen. 



41 

- medicines used to treat nausea and vomiting such as dolasetron, granisetron, ondansetron or 
tropisetron; these may also have an unwanted effect on the heart (QT prolongation). 

- atomoxetine, a medicine used to treat attention deficit hyperactivity disorder. 
 
These medicines should be used with care or may need to be avoided during your treatment with 
Farydak. If you are taking any of these medicines, your doctor might prescribe a different medicine for 
you during your treatment with Farydak. 
 
Ask your doctor or pharmacist if you are not sure whether your medicine is one of the medicines listed 
above. 
 
During Farydak treatment, you should also tell your doctor or your pharmacist if you are prescribed 
another medicine that you have not already been taking. 
 
Farydak with food and drink 
You should not eat star fruit, pomegranate or grapefruit or drink pomegranate or grapefruit 
juice during your treatment with Farydak, as they may increase the amount of the medicine that passes 
into your blood. 
 
Pregnancy and breast-feeding 
Due to the potential risk of death or malformation to the foetus, Farydak should not be taken during: 
 
- Pregnancy 
Farydak should not be taken during pregnancy, unless the potential benefit to the mother is greater 
than the potential risk to the baby. If you are pregnant, think you might be pregnant or plan to become 
pregnant, ask your doctor for advice. Your doctor will discuss with you the possible risks of taking 
Farydak during pregnancy. 
 
- Breast-feeding 
You must not take Farydak if you are breast-feeding. 
 
Contraception for women and men 
Due to the potential risk of death or malformation to the foetus, you should use the following methods 
of contraception while taking Farydak: 
 
- For women taking Farydak 
If you are a sexually active woman, you should have a pregnancy test before starting Farydak 
treatment and you must use a highly effective method of contraception during treatment with Farydak. 
You must also use this for three months after you have stopped taking Farydak. Your doctor will 
discuss with you which is the best method for you to use. If you use a hormonal contraceptive you 
must also use a barrier method of contraception (such as condom or diaphragm) in addition. 
 
- For men taking Farydak 
If you are a sexually active man, you should use condoms during treatment with Farydak. You should 
also do this for six months after you have stopped taking Farydak. If your partner is able to become 
pregnant she should also use a highly effective method of contraception during your treatment and for 
six months after. Tell your doctor straight away if your partner becomes pregnant while you are taking 
Farydak or during the six months following your treatment with Farydak. 
 
Driving and using machines 
Farydak may have a minor influence on the ability to drive and use machines. If you feel dizzy while 
taking this medicine, do not drive a vehicle or use any tools or machines. 
 
 
3. How to take Farydak 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or your 



42 

pharmacist if you are not sure. 
 
How much to take 
- Farydak is taken over 21 days (2 weeks on and 1 week off) – this is called a treatment cycle. 
- You do not take the medicine every day. 
- Based on the recommendation of your doctor, the dose of Farydak is either 20 mg or 15 mg or 

10 mg, to be taken once a day on days 1, 3, 5, 8, 10 and 12 of the 21-day cycle. 
- Do not take Farydak in Week 3. 
- After Week 3 you start a new cycle again as shown in Tables 1 and 2 below. 

Please refer to Table 1 for cycles 1 to 8 and Table 2 for cycles 9-16. 
 
Table 1 Recommended schedule for taking Farydak in combination with bortezomib and 

dexamethasone (cycles 1-8) 
 

Cycles 1-8 
(3-week cycles) 

Week 1 
Days 

Week 2 
Days 

Week 3 

Farydak 1  3  5   8  10  12   Rest period 
Bortezomib 1   4    8   11    Rest period 
Dexamethasone 1 2  4 5   8 9  11 12   Rest period 

 
Table 2 Recommended schedule for taking Farydak in combination with bortezomib and 

dexamethasone (cycles 9-16). 
 

Cycles 9-16 
(3-week cycles) 

Week 1 
Days 

Week 2 
Days 

Week 3 

Farydak 1  3  5   8  10  12   Rest period 
Bortezomib 1       8       Rest period 
Dexamethasone 1 2      8 9      Rest period 

 
Your doctor will tell you exactly how many capsules of Farydak you need to take. Do not change the 
dose without talking to your doctor. 
 
Take Farydak once a day at the same time each day only on the scheduled days. 
 
Taking this medicine 
- Swallow the capsules whole with a glass of water. 
- The medicine can be taken with or without food. 
- Do not chew or crush the capsules. 
 
If you  vomit after you swallow the Farydak capsules, do not take any more capsules until your next 
scheduled dose. 
  



43 

 
How to use the Farydak blister 
 

 

One Farydak blister = 3 weeks = 1 cycle 

 

The days of the cycle are numbered on the blister. 
 
Take Farydak on days 1, 3 and 5 and on days 8, 10 and 12. 

 

Push the Farydak capsule through the pocket on days 1, 3 and 
5 of week 1 and days 8, 10 and 12 of week 2. 

 

On days when you do not have to take Farydak, including the 
rest period in week 3, scratch the relevant empty cavities with 
your finger nail to help you keep track of your medicine 
schedule. 

 
How long to take Farydak 
Keep taking Farydak for as long as your doctor tells you. This is a long-term treatment with 16 cycles 
(48 weeks). Your doctor will monitor your condition to see if the treatment is working. If you have 
questions about how long to take Farydak, talk to your doctor or pharmacist. 
 
If you take more Farydak than you should 
If you accidentally take more capsules than you should, or if someone else accidentally takes your 
medicine, talk to a doctor or go to a hospital straight away. Take the pack and this leaflet with you. 
You may need medical treatment. 
 
If you forget to take Farydak 
- If it is less than 12 hours since you should have taken the medicine, take the missed dose as 

soon as you remember. Then continue taking the medicine as normal. 
- If it is more than 12 hours since you should have taken the medicine, skip the missed dose. Then 

continue taking the medicine as normal. 
 
Do not take a double dose to make up for a forgotten dose. 
 
Never take a missed dose of Farydak on one of the “off” days when no Farydak dose is planned. 
 
Tell your doctor about all the doses that you have missed during any 21-day cycle of treatment. 
 



44 

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. 
 
Some side effects could be serious 
STOP taking Farydak and seek medical help immediately if you experience any of the following: 
• difficulty in breathing or swallowing, swelling of the face, lips, tongue or throat, severe itching 

of the skin, with a red rash or raised bumps (potential signs of an allergic reaction) 
• severe headache, feeling weak or paralysis of limbs or face, difficulty speaking, sudden loss of 

consciousness (potential signs of nervous system problems such as bleeding or swelling in the 
skull or brain) 

• fast breathing, feeling dizzy 
• sudden and crushing chest pain, feeling tired, irregular heartbeat (potential signs of a heart 

attack) 
• coughing up blood, oozing of bloody fluid from the nose (signs of bleeding in the lungs) 
• vomiting blood, black or bloody stools, passage of fresh blood through the anus, usually in or 

with stools (signs of gastrointestinal bleeding) 
• difficulty in breathing with blueness around the mouth, which could lead to loss of 

consciousness (sign of serious lung problems) 
• fever, chest pain, increased heart rate, decreased blood pressure, shortness of breath or rapid 

breathing (signs of blood poisoning, which is also known as sepsis) 
• chest pain or discomfort, changes in heartbeat (faster or slower), palpitations, light-headedness, 

fainting, dizziness, blue discolouration of your lips, shortness of breath, swelling of lower limbs 
or skin (signs of heart problems) 

 
Tell a doctor or a pharmacist straight away if you notice any of these side effects: 
• stomach or abdominal pain, nausea, diarrhoea, vomiting, black or bloody stools, constipation, 

heartburn, swelling or bloating of the abdomen (signs of a gastrointestinal problem) 
• new or worsening symptoms such as cough with or without mucus, fever, difficult or painful 

breathing, wheezing, pain in chest when breathing, shortness of breath or, difficulty breathing, 
pain or burning feeling when passing urine, exaggerated sense of needing to pass urine, blood in 
urine (signs of an infection in the lungs or urinary tract) 

• fever, sore throat, or mouth ulcers due to infections (signs of a low level of white blood cells) 
• sudden bleeding or bruising underneath the skin (signs of low level of blood platelets) 
• diarrhoea, abdominal pain, fever (signs of an inflamed colon) 
• light-headedness, particularly when standing up (a sign of low blood pressure) 
• feeling thirsty, low urine output, weight loss, dry flushed skin, irritability (signs of dehydration) 
• swollen ankles (a sign of a low level of albumin in the blood which is known as 

hypoalbuminaemia) 
• feeling tired, itching, yellowing of the skin and whites of the eyes, nausea or vomiting, loss of 

appetite, pain on the right side of your stomach, dark or brown urine, bleeding or bruising more 
easily than normal (signs of a liver problem) 

• severely decreased urine output, swelling of the legs (signs of a kidney problem) 
• muscle weakness, muscle spasms, unusual heartbeat (signs of changes in the level of potassium 

in the blood) 
 
Other possible side effects 
If any of the side effects below becomes severe, tell your doctor, or your pharmacist. 
 
Very common (may affect more than 1 in 10 people) 
• feeling tired (fatigue), pale skin. These could be signs of a low level of red blood cells. 
• decreased appetite or weight loss 
• difficulty falling or staying asleep (insomnia) 
• headache 



45 

• feeling dizzy, tired or weak 
• vomiting, nausea, upset stomach, indigestion 
• swelling of the legs or arms 
• reduced blood level of phosphate or sodium 
 
Common (may affect up to 1 in 10 people) 
• rash of small fluid-filled blisters, appearing on reddened skin, mouth or gums (signs of a 

potentially severe viral infection) 
• inflamed ear, nose bleed or bleeding in the white of the eye, bruising, inflamed skin caused by 

infection (rash, red skin, which is also known as erythema) 
• abdominal pain, diarrhoea, swelling or bloating of the abdomen (signs of inflamed stomach 

lining) 
• oral thrush (yeast infection of the mouth) 
• feeling thirsty, high urine output, increased appetite with weight loss (signs of a high level of 

sugar in the blood) 
• fast weight gain, swelling of hands, ankles, feet or face (signs of water retention) 
• reduced level of calcium in the blood, sometimes leading to cramps 
• uncontrolled shaking of the body 
• palpitations 
• clicking, rattling or crackling noise made by the lungs when breathing 
• cracked, chapped lips  
• dry mouth or changes to your sense of taste 
• flatulence 
• joint pain or inflammation 
• blood in urine (a sign of a kidney problem) 
• being unable to control the flow of urine because of loss of or weak bladder control 
• chills 
• weight gain, feeling tired, hair loss, muscle weakness, feeling cold (signs of an underactive 

thyroid gland, which is known as hypothyroidism) 
• generally feeling unwell 
• increased blood level of uric acid 
• reduced blood level of magnesium 
• increased blood level of the waste product creatinine 
• increased blood levels of the liver enzymes alanine aminotransferase (ALT), aspartate 

aminotransferase (AST) or alkaline phosphatase (ALP). 
 
Uncommon (may affect up to 1 in 100 people) 
• red or purple, flat pinhead spots under the skin 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Farydak 
 
- Keep this medicine out of the sight and reach of children. 
- Do not take this medicine after the expiry date, which is stated on the carton and blister foil. 
- Do not store above 30°C. 
- Store in the original package in order to protect from moisture. 
- Do not take this medicine if you notice any damage to the packaging or if there are any signs of 

tampering. 
- Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away 

medicines you no longer use. These measures will help to protect the environment. 
 

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


46 

 
6. Contents of the pack and other information 
 
What Farydak contains 
- The active substance of Farydak is panobinostat. 
- Each Farydak 10 mg hard capsule contains panobinostat lactate anhydrous equivalent to 10 mg 

panobinostat. The other ingredients are: magnesium stearate, mannitol, microcrystalline 
cellulose, pregelatinised starch, gelatin, titanium dioxide (E171), brilliant blue FCF (E133), 
yellow iron oxide (E172), black iron oxide (E172), propylene glycol (E1520), shellac glaze. 

- Each Farydak 15 mg hard capsule contains panobinostat lactate anhydrous equivalent to 15 mg 
panobinostat. The other ingredients are: magnesium stearate, mannitol, microcrystalline 
cellulose, pregelatinised starch, gelatin, titanium dioxide (E171), yellow iron oxide (E172), red 
iron oxide (E172), black iron oxide (E172), propylene glycol (E1520), shellac glaze. 

- Each Farydak 20 mg hard capsule contains panobinostat lactate anhydrous equivalent to 20 mg 
panobinostat. The other ingredients are: magnesium stearate, mannitol, microcrystalline 
cellulose, pregelatinised starch, gelatin, titanium dioxide (E171), red iron oxide (E172), black 
iron oxide (E172), propylene glycol (E1520), shellac glaze. 

 
What Farydak looks like and contents of the pack 
Farydak 10 mg hard capsules are light green opaque capsules (15.6–16.2 mm) containing white to 
almost white powder, with radial marking “LBH 10 mg” in black ink on the cap and two radial bands 
in black ink on the body, provided in blisters. 
Farydak 15 mg hard capsules are orange opaque capsules (19.1–19.7 mm) containing white to almost 
white powder, with radial marking “LBH 15 mg” in black ink on the cap and two radial bands in black 
ink on the body, provided in blisters. 
Farydak 20 mg hard capsules are red opaque capsules (19.1–19.7 mm) containing white to almost 
white powder, with radial marking “LBH 20 mg” in black ink on the cap and two radial bands in black 
ink on the body, provided in blisters. 
 
The following pack sizes are available: blister packs containing 6, 12 or 24 capsules. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Secura Bio Limited 
32 Molesworth Street 
Dublin 2 
Ireland 
 
Manufacturer 
Novartis Pharma GmbH 
Roonstrasse 25 
90429 Nuremberg 
Germany 
 
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 
  

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


47 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Annex IV 

Scientific conclusions and grounds for the variation to the terms of the marketing 
authorisation(s) 

 



48 

Scientific conclusions 
 
Taking into account the PRAC Assessment Report on the PSUR(s) for panobinostat, the scientific 
conclusions of CHMP are as follows:  
 
In view of available data from the literature regarding DNA damage in an in vivo dose-dependent 
molecular mechanisms study in murine bone marrow cells, the PRAC concluded that the existing 
wording in section 5.3 of the Summary of Product Characteristics of products containing 
panobinostat should be amended to include this information. 
 
The CHMP agrees with the scientific conclusions made by the PRAC. 
 
 
Grounds for the variation to the terms of the marketing authorisation(s) 
 
On the basis of the scientific conclusions for panobinostat the CHMP is of the opinion that the 
benefit-risk balance of the medicinal product(s) containing panobinostat is unchanged subject to the 
proposed changes to the product information. 
 
The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER 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
	LABELLING AND PACKAGE LEAFLET
	A. LABELLING
	B. PACKAGE LEAFLET
	Scientific conclusions and grounds for the variation to the terms of the marketing authorisation(s)