Effentora

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 
Effentora 100 micrograms buccal tablets 
Effentora 200 micrograms buccal tablets 
Effentora 400 micrograms buccal tablets 
Effentora 600 micrograms buccal tablets 
Effentora 800 micrograms buccal tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Effentora 100 micrograms buccal tablets 
Each buccal tablet contains 100 micrograms fentanyl (as citrate). 
Excipient with known effect: Each tablet contains 10 mg of sodium. 
 
Effentora 200 micrograms buccal tablets 
Each buccal tablet contains 200 micrograms fentanyl (as citrate).  
Excipient with known effect: Each tablet contains 20 mg of sodium. 
 
Effentora 400 micrograms buccal tablets 
Each buccal tablet contains 400 micrograms fentanyl (as citrate). 
Excipient with known effect: Each tablet contains 20 mg of sodium. 
 
Effentora 600 micrograms buccal tablets 
Each buccal tablet contains 600 micrograms fentanyl (as citrate). 
Excipient with known effect: Each tablet contains 20 mg of sodium. 
 
Effentora 800 micrograms buccal tablets 
Each buccal tablet contains 800 micrograms fentanyl (as citrate). 
Excipient with known effect: Each tablet contains 20 mg of sodium. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Buccal tablet. 
 
Effentora 100 micrograms buccal tablets 
Flat-faced, white, round bevelled-edge tablet, embossed on one side with a “C” and on the other side 
with “1”. 
 
Effentora 200 micrograms buccal tablets 
Flat-faced, white, round bevelled-edge tablet, embossed on one side with a “C” and on the other side 
with “2”. 
 
Effentora 400 micrograms buccal tablets 
Flat-faced, white, round bevelled-edge tablet, embossed on one side with a “C” and on the other side 
with “4”. 
 
Effentora 600 micrograms buccal tablets 
Flat-faced, white, round bevelled-edge tablet, embossed on one side with a “C” and on the other side 
with “6”. 
 



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Effentora 800 micrograms buccal tablets 
Flat-faced, white, round bevelled-edge tablet, embossed on one side with a “C” and on the other side 
with “8”. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Effentora is indicated for the treatment of breakthrough pain (BTP) in adults with cancer who are 
already receiving maintenance opioid therapy for chronic cancer pain. 
BTP is a transitory exacerbation of pain that occurs on a background of otherwise controlled persistent 
pain. 
Patients receiving maintenance opioid therapy are those who are taking at least 60 mg of oral 
morphine daily, at least 25 micrograms of transdermal fentanyl per hour, at least 30 mg of oxycodone 
daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week 
or longer. 
 
4.2 Posology and method of administration 
 
Treatment should be initiated by and remain under the guidance of a physician experienced in the 
management of opioid therapy in cancer patients. Physicians should keep in mind the potential of 
abuse of fentanyl. Patients should be instructed not to use two different formulations of fentanyl 
concurrently for the treatment of breakthrough pain, and to dispose of any fentanyl product prescribed 
for BTP when switching to Effentora. The number of tablet strengths available to the patients at any 
time should be minimised to prevent confusion and potential overdose. 
 
Posology 
 
Dose titration 
 
Effentora should be individually titrated to an “effective” dose that provides adequate analgesia and 
minimises adverse reactions. In clinical studies, the effective dose of Effentora for BTP was not 
predictable from the daily maintenance dose of opioid. 
Patients should be carefully monitored until an effective dose is reached. 
 
Titration in patients not switching from other fentanyl containing products 
The initial dose of Effentora should be 100 micrograms, titrating upwards as necessary through the 
range of available tablets strengths (100, 200, 400, 600, 800 micrograms).  
 
Titration in patients switching from other fentanyl containing products 
Due to different absorption profiles, switching must not be done at a 1:1 ratio. If switching from 
another oral fentanyl citrate product, independent dose titration with Effentora is required as 
bioavailability between products differs significantly. However, in these patients, a starting dose 
higher than 100 micrograms may be considered. 
 
Method of titration 
 
During titration, if adequate analgesia is not obtained within 30 minutes after the start of 
administration of a single tablet, a second Effentora tablet of the same strength may be used.  
 
If treatment of a BTP episode requires more than one tablet, an increase in dose to the next higher 
available strength should be considered to treat the next BTP episode. 
 
During titration, multiple tablets may be used: up to four 100 micrograms or up to four 200 
micrograms tablets may be used to treat a single episode of BTP during dose titration according to the 
following schedule: 



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• If the initial 100 micrograms tablet is not efficacious, the patient can be instructed to treat the next 
episode of BTP with two 100 micrograms tablets. It is recommended that one tablet should be 
placed in each side of the mouth. If this dose is considered to be the effective dose, treatment of 
successive episodes of BTP may be continued with a single 200 micrograms tablet of Effentora. 

• If a single 200 micrograms tablet of Effentora (or two 100 micrograms tablets) is not considered to 
be efficacious the patient can be instructed to use two 200 micrograms tablets (or four 100 
micrograms tablets) to treat the next episode of BTP. It is recommended that two tablets should be 
placed in each side of the mouth. If this dose is considered to be the effective dose, treatment of 
successive episodes of BTP may be continued with a single 400 micrograms tablet of Effentora. 

• For titration to 600 micrograms and 800 micrograms, tablets of 200 micrograms should be used. 
 
Doses above 800 micrograms were not evaluated in clinical studies. 
 
No more than two tablets should be used to treat any individual BTP episode, except when titrating 
using up to four tablets as described above. 
Patients should wait at least 4 hours before treating another BTP episode with Effentora during 
titration. 
 
Maintenance therapy 
 
Once an effective dose has been established during titration, patients should continue to take this dose 
as a single tablet of that given strength. Breakthrough pain episodes may vary in intensity and the 
required Effentora dose might increase over time due to progression of the underlying cancer disease. 
In these cases, a second tablet of the same strength may be used. If a second tablet of Effentora was 
required for several consecutive times, the usual maintenance dose is to be readjusted (see below). 
Patients should wait at least 4 hours before treating another BTP episode with Effentora during 
maintenance therapy. 
 
Dose readjustment 
 
The maintenance dose of Effentora should be increased when a patient requires more than one tablet 
per BTP episode for several consecutive BTP episodes. For dose-readjustment the same principles 
apply as outlined for dose titration (see above). 
Dose readjustment of the background opioid therapy may be required if patients consistently 
present with more than four BTP episodes per 24 hours. 
 
In absence of adequate pain control, the possibility of hyperalgesia, tolerance and progression of 
underlying disease should be considered (see section 4.4). 
 
Discontinuation of therapy 
 
Effentora should be discontinued immediately if the patient no longer experiences breakthrough pain 
episodes. The treatment for the persistent background pain should be kept as prescribed.  
If discontinuation of all opioid therapy is required, the patient must be closely followed by the doctor 
in order to manage the risk of abrupt withdrawal effects. 
 
Hepatic or renal impairment 
 
Effentora should be administered with caution to patients with moderate or severe hepatic or renal 
impairment (see section 4.4). 
 
Patients with xerostomia 
 
Patients experiencing xerostomia are advised to drink water to moisten the buccal cavity prior to 
administration of Effentora. If this recommendation does not result in an appropriate effervescence, 
then a switch of therapy may be advised. 
 



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Use in the elderly (older than 65 years) 
 
In clinical studies patients older than 65 years tended to titrate to a lower effective dose than younger 
patients. It is recommended that increased caution should be exercised in titrating the dose of 
Effentora in elderly patients. 
 
Paediatric population 
 
The safety and efficacy of Effentora in children aged 0 to 18 years have not been established. No data 
are available.  
 
Method of administration 
 
Effentora tablet once exposed to moisture utilises an effervescent reaction to deliver the active 
substance. Therefore patients should be instructed not to open the blister until ready to place the tablet 
in the buccal cavity. 
 
Opening the blister package 
 
Patients should be instructed NOT to attempt to push the tablet through the blister because this could 
damage the buccal tablet. The correct method of releasing the tablet from the blister is: 
One of the blister units should be separated from the blister card by tearing it apart at the perforations. 
The blister unit should then be flexed along the line printed on the backing foil where indicated. The 
backing foil should be peeled back to expose the tablet. 
Patients should be instructed not to attempt to crush or split the tablet. 
 
The tablet should not be stored once removed from the blister package as the tablet integrity cannot be 
guaranteed and a risk of accidental exposure to a tablet can occur. 
 
Tablet administration 
 
Patients should remove the tablet from the blister unit and immediately place the entire Effentora 
tablet in the buccal cavity (near a molar between the cheek and gum).   
 
The Effentora tablet should not be sucked, chewed or swallowed, as this will result in lower plasma 
concentrations than when taken as directed.  
 
Effentora should be placed and retained within the buccal cavity for a period sufficient to allow 
disintegration of the tablet which usually takes approximately 14-25 minutes. 
Alternatively, the tablet could be placed sublingually (see section 5.2). 
 
After 30 minutes, if remnants from the Effentora tablet remain, they may be swallowed with a glass of 
water. 
 
The length of time that the tablet takes to fully disintegrate following oromucosal administration does 
not appear to affect early systemic exposure to fentanyl. 
 
Patients should not consume any food and drink when a tablet is in the buccal cavity. 
In case of buccal mucosa irritation, a change in tablet placement within the buccal cavity should be 
recommended. 
 
4.3 Contraindications 
 
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
• Patients without maintenance opioid therapy as there is an increased risk of respiratory 

depression. 
• Severe respiratory depression or severe obstructive lung conditions. 



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• Treatment of acute pain other than breakthrough pain  
 
4.4 Special warnings and precautions for use 
 
Accidental use in children 
Patients and their carers must be instructed that Effentora contains an active substance in an amount 
that can be fatal, especially to a child. Therefore they must keep all tablets out of the sight and reach of 
children. 
 
Monitoring 
In order to minimise the risks of opioid-related undesirable effects and to identify the effective dose, it 
is imperative that patients be monitored closely by health professionals during the titration process. 
 
Maintenance opioid treatment 
It is important that the maintenance opioid treatment used to treat the patient’s persistent pain has been 
stabilised before Effentora therapy begins and that the patient continues to be treated with the 
maintenance opioid treatment whilst taking Effentora. The product must not be given to patients 
without maintenance opioid therapy as there is an increased risk of respiratory depression and death. 
 
Respiratory depression  
As with all opioids, there is a risk of clinically significant respiratory depression associated with the 
use of fentanyl. Improper patient selection (e.g., use in patients without maintenance opioid therapy) 
and/or improper dosing have resulted in fatal outcome with Effentora as well as with other fentanyl 
products.  
Effentora should only be used for conditions specified in section 4.1. 
 
Chronic obstructive pulmonary disease 
Particular caution should be used when titrating Effentora in patients with non-severe chronic 
obstructive pulmonary disease or other medical conditions predisposing them to respiratory 
depression, as even normally therapeutic doses of Effentora may further decrease respiratory drive to 
the point of respiratory failure. 
 
Alcohol 
The concomitant use of alcohol with fentanyl can produce increased depressant effects which may 
result in a fatal outcome (see section 4.5). 
 
Risks of concomitant administration with benzodiazepines or related drugs 
Concomitant use of opioids, including Effentora, with benzodiazepines or related drugs may result in 
profound sedation, respiratory depression, coma, and death. Because of these risks, concomitant 
prescribing of opioids and benzodiazepines or related drugs should be made only in patients for whom 
alternative treatment options are inadequate.  
If a decision is made to prescribe Effentora concomitantly with benzodiazepines or related drugs, the 
lowest effective dosages and minimum durations of concomitant use should be chosen. Patients should 
be closely monitored for signs and symptoms of respiratory depression and sedation (see section 4.5). 
 
Increased intracranial pressure, impaired consciousness 
Effentora should only be administered with extreme caution in patients who may be particularly 
susceptible to the intracranial effects of CO2 retention, such as those with evidence of increased 
intracranial pressure or impaired consciousness. Opioids may obscure the clinical course of a patient 
with a head injury and should be used only if clinically warranted. 
 
Bradyarrhythmias 
Fentanyl may produce bradycardia. Fentanyl should be used with caution in patients with previous or 
pre-existing bradyarrythmias. 
 
Hepatic or renal impairment 



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In addition, Effentora should be administered with caution to patients with hepatic or renal 
impairment. The influence of hepatic and renal impairment on the pharmacokinetics of the medicinal 
product has not been evaluated, however, when administered intravenously the clearance of fentanyl 
has been shown to be altered in hepatic and renal impairment due to alterations in metabolic clearance 
and plasma proteins. After administration of Effentora, impaired hepatic and renal function may both 
increase the bioavailability of swallowed fentanyl and decrease its systemic clearance, which could 
lead to increased and prolonged opioid effects. Therefore, special care should be taken during the 
titration process in patients with moderate or severe hepatic or renal impairment. 
 
Careful consideration should be given to patients with hypovolaemia and hypotension. 
 
Serotonin Syndrome 
Caution is advised when Effentora is co-administered with drugs that affect the serotoninergic 
neurotransmitter systems. 
 
The development of a potentially life-threatening serotonin syndrome may occur with the concomitant 
use of serotonergic drugs such as Selective Serotonin Re-uptake Inhibitors (SSRIs) and Serotonin 
Norepinephrine Re-uptake Inhibitors (SNRIs), and with drugs which impair metabolism of serotonin 
(including Monoamine Oxidase Inhibitors [MAOIs]). This may occur within the recommended dose. 
 
Serotonin syndrome may include mental-status changes (e.g., agitation, hallucinations, coma), 
autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular 
abnormalities (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., 
nausea, vomiting, diarrhoea). 
 
If serotonin syndrome is suspected, treatment with Effentora should be discontinued. 
 
Drug dependence and potential for abuse 
Tolerance, physical dependence and psychological dependence may develop upon repeated 
administration of opioids. Iatrogenic addiction following opioid administration may occur. Fentanyl 
can be abused in a manner similar to other opioids and all patients treated with opioids require 
monitoring for signs of abuse and addiction. Patients with a prior history of drug dependence/alcohol 
abuse are more at risk to develop dependence and abuse in opioid treatment. Patients at increased risk 
of opioid abuse may still be appropriately treated with opioids; however, these patients will require 
additional monitoring for signs of misuse, abuse, or addiction. Abuse or intentional misuse of fentanyl 
buccal tablets may result in overdose and/or death.  
 
Endocrine effects 
Opioids may influence the hypothalamic-pituitary-adrenal or gonadal axes. Some changes that can be 
seen include an increase in serum prolactin and decrease in plasma cortisol and testosterone. Clinical 
signs and symptoms may manifest from these hormonal changes. 
 
Hyperalgesia 
As with other opioids, in case of insufficient pain control in response to an increased dose of fentanyl, 
the possibility of opioid-induced hyperalgesia should be considered. A fentanyl dose reduction or 
discontinuation of fentanyl treatment or treatment review may be indicated. 
 
Anaphylaxis and hypersensitivity 
Anaphylaxis and hypersensitivity have been reported in association with the use of oral transmucosal 
fentanyl products (see Section 4.8). 
 
Excipient(s) 
 
Sodium 
 
Effentora 100 micrograms buccal tablets 
This medicinal product contains 10 mg sodium per buccal tablet, equivalent to 0.5 % of the WHO 



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recommended maximum daily intake of 2 g sodium for an adult. 
 
Effentora 200  micrograms buccal tablets 
Effentora 400  micrograms buccal tablets 
Effentora 600  micrograms buccal tablets 
Effentora 800  micrograms buccal tablets 
This medicinal product contains 20 mg sodium per per buccal tablet, equivalent to 1 % of the WHO 
recommended maximum daily intake of 2 g sodium for an adult. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Agents that affect CYP3A4 activity 
Fentanyl is metabolised mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4), 
therefore potential interactions may occur when Effentora is given concurrently with agents that affect 
CYP3A4 activity. 
 
CYP3A4 inducers 
Co-administration with agents that induce 3A4 activity may reduce the efficacy of Effentora.  
 
CYP3A4 inhibitors 
The concomitant use of Effentora with strong CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, 
itraconazole, troleandomycin, clarithromycin, and nelfinavir) or moderate CYP3A4 inhibitors (e.g., 
amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, and 
verapamil) may result in increased fentanyl plasma concentrations, potentially causing serious adverse 
drug reactions including fatal respiratory depression. Patients receiving Effentora concomitantly with 
moderate or strong CYP3A4 inhibitors should be carefully monitored for an extended period of time. 
Dosage increase should be done with caution. 
 
Agents that can increase CNS depressant effects 
Co-administration of fentanyl with other central nervous system depressants, including other opioids, 
sedatives or hypnotics, (including benzodiazepines), general anaesthetics, phenothiazines, 
tranquillisers, skeletal muscle relaxants, sedating antihistamines and alcohol can produce additive 
depressant effects which may result in a fatal outcome (see section 4.4). 
 
Sedative medicines such as benzodiazepines or related drugs 
The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs 
increases the risk of sedation, respiratory depression, coma and death because of additive CNS 
depressant effect. The dose and duration of concomitant use should be limited (see section 4.4). 
 
Partial opioid agonists/antagonists 
The concomitant use of partial opioid agonists/antagonists (e.g. buprenorphine, nalbuphine, 
pentazocine) is not recommended. They have high affinity to opioid receptors with relatively low 
intrinsic activity and therefore partially antagonise the analgesic effect of fentanyl and may induce 
withdrawal symptoms in opioid dependant patients. 
 
Serotoninergic agents 
Co-administration of fentanyl with a serotoninergic agent, such as a Selective Serotonin Re-uptake 
Inhibitor (SSRI) or a Serotonin Norepinephrine Re-uptake Inhibitor (SNRI) or a Monoamine Oxidase 
Inhibitor (MAOI), may increase the risk of serotonin syndrome, a potentially life-threatening 
condition. Effentora is not recommended for use in patients who have received MAOIs within 14 days 
because severe and unpredictable potentiation by MAOIs has been reported with opioid analgesics. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 



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There are no adequate data from the use of fentanyl in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Effentora 
should not be used in pregnancy unless clearly necessary. 
 
With long-term use of fentanyl during pregnancy, there is a risk of neonatal opioid withdrawal 
syndrome which may be life-threatening if not recognized and treated, and requires management 
according to protocols developed by neonatology experts. If opioid use is required for a prolonged 
period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and 
ensure that appropriate treatment will be available (see section 4.8). 
 
It is advised not to use fentanyl during labour and delivery (including caesarean section) because 
fentanyl passes through the placenta and may cause respiratory depression in the foetus. If Effentora is 
administered, an antidote for the child should be readily available. 
 
Breast-feeding 
Fentanyl passes into breast milk and may cause sedation and respiratory depression in the breast-fed 
child. Fentanyl should not be used by breastfeeding women and breastfeeding should not be restarted 
until at least 5 days after the last administration of fentanyl. 
 
Fertility 
There are no human data on fertility available. In animal studies, male fertility was impaired (See 
Section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
No studies of the effects on the ability to drive and use machines have been performed. However, 
opioid analgesics impair the mental and/or physical ability required for the performance of potentially 
dangerous tasks (e.g., driving a car or operating machinery). Patients should be advised not to drive or 
operate machinery if they experience somnolence, dizziness, or visual disturbance while taking 
Effentora and not to drive or operate machinery until they know how they react. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
Typical opioid adverse reactions are to be expected with Effentora. Frequently, these will cease or 
decrease in intensity with continued use of the medicinal product, as the patient is titrated to the most 
appropriate dose. However, the most serious adverse reactions are respiratory depression (potentially 
leading to apnoea or respiratory arrest), circulatory depression, hypotension and shock and all patients 
should be closely monitored for these. 
 
The clinical studies of Effentora were designed to evaluate safety and efficacy in treating BTP and all 
patients were also taking concomitant opioids, such as sustained-release morphine or transdermal 
fentanyl, for their persistent pain. Therefore it is not possible to definitively separate the effects of 
Effentora alone. 
 
Tabulated list of adverse reactions 
The following adverse reactions have been reported with Effentora and/or other fentanyl-containing 
compounds during clinical studies and post marketing experience. Adverse reactions are listed below 
as MedDRA preferred term by system organ class and frequency (frequencies are defined as: very 
common ≥1/10, common ≥1/100 to <1/10, uncommon ≥ 1/1,000 to <1/100, rare (≥1/10,000 to 
<1/1,000), not known (cannot be estimated from the available data); within each frequency group, 
undesirable effects are presented in order of decreasing seriousness: 
 
 Very common Common Uncommon Rare Not known 

Infections and 
infestations 

 Oral candidiasis Pharyngitis Oral pustule  



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 Very common Common Uncommon Rare Not known 
Blood and 
lymphatic 
system 
disorders 

 Anaemia 
Neutropenia 

Thrombocyto-
penia 

  

Immune 
system 
disorders 

   Hypersensitivit
y* 

 

Endocrine 
disorders 

   Hypogonadism Adrenal 
insufficiency 
Androgen 
deficiency 

Metabolism 
and nutrition 
disorders 

 Anorexia    

Psychiatric 
disorders 

 Depression 
Anxiety 
Confusional 
state 
Insomnia 

Euphoric 
mood  
Nervousness 
Hallucination 
Visual 
hallucination 
Mental status 
changes 
Disorientation 

 Drug 
dependence 
(addiction)* 
Drug abuse 
(see 
section 4.4), 
Delirium 

Nervous 
system 
disorders 

Dizziness 
Headache 

Dysgeusia 
Somnolence 
Lethargy 
Tremor 
Sedation 
Hypoaesthesia  
Migraine 

Depressed 
level of 
consciousness 
Disturbance in 
attention 
Balance 
disorder 
Dysarthria 

Cognitive 
disorder 
Motor 
dysfunction 

Loss of 
consciousness
* 
Convulsion 

Eye 
disorders 

  Visual 
disturbance 
Ocular 
hyperaemia 
Blurred vision 
Visual acuity 
reduced 

Abnormal 
sensation in 
eye 
Photopsia 
 

 

Ear and 
labyrinth 
disorders 

  Vertigo 
Tinnitus 
Ear discomfort 

  

Cardiac 
disorders 

 Tachycardia Bradycardia   

Vascular 
disorders 

 Hypotension 
Hypertension 

Flushing 
Hot flush 

  

Respiratory, 
thoracic and 
mediastinal 
disorders 

 Dyspnoea  
Pharyngolaryn-
geal pain 

Respiratory 
depression 
Sleep apnoea 
syndrome  

 Respiratory 
arrest* 

Gastro-
intestinal 
disorders 

Nausea  
Vomiting 

Constipation 
Stomatitis 
Dry mouth 
Diarrhoea 
Abdominal pain  
Gastro-
oesophageal 

Ileus 
Mouth 
ulceration 
Oral 
hypoaesthesia 
Oral 
discomfort 

Oral mucosal 
blistering 
Dry lip 

 



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 Very common Common Uncommon Rare Not known 
reflux disease 
Stomach 
discomfort 
Dyspepsia 
Toothache 

Oral mucosal 
discolouration 
Oral soft tissue 
disorder 
Glossodynia 
Tongue 
blistering 
Gingival pain 
Tongue 
ulceration 
Tongue 
disorder 
Oesophagitis 
Chapped lips 
Tooth disorder 

Hepatobiliary 
disorders 

  Biliary 
dilatation 

  

Skin and 
subcutaneous 
tissue 
disorders 

 Pruritus 
Hyperhidrosis 
Rash 

Cold sweat 
Facial swelling 
Generalised 
pruritus 
Alopecia 

Onychorrhexis  

Musculoskel
etal and 
connective 
tissue 
disorders 

 Myalgia  
Back pain 

Muscle 
twitching 
Muscular 
weakness 

  

Renal and 
urinary 
disorders 

  Urinary 
retention 
 

  

General 
disorders and 
administration 
site conditions 

Application 
site reactions 
including 
bleeding, pain, 
ulcer, 
irritation, 
paraesthesia, 
anaesthesia, 
erythema, 
oedema, 
swelling and 
vesicles 

Peripheral 
oedema  
Fatigue 
Asthenia 
Drug 
withdrawal 
syndrome* 
Chills 

Malaise 
Sluggishness 
Chest 
discomfort 
Feeling 
abnormal 
Feeling jittery 
Thirst 
Feeling cold 
Feeling hot 
 

 Pyrexia 
Neonatal 
withdrawal 
syndrome 
(see 
section 4.6) 

Investigations  Weight 
decreased 

Platelet count 
decreased 
Heart rate 
increased 
Haematocrit 
decreased 
Haemoglobin 
decreased 

  

Injury, 
poisoning and 
procedural 
complications 

 Fall    

* See section Description of selected adverse reactions 
 



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Description of selected adverse reactions 
Tolerance, physical and/or psychological dependence may develop upon repeated administration of 
opioids such as fentanyl (see section 4.4). 
 
Opioid withdrawal symptoms such as nausea, vomiting, diarrhoea, anxiety, chills, tremor and sweating 
have been observed with transmucosal fentanyl. 
 
Loss of consciousness and respiratory arrest have been observed in the context of overdose (see 
section 4.9). 
 
Hypersensitivity reactions have been reported in post-marketing experience, including rash, erythema, 
lip and face swelling, and urticaria (see section 4.4). 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Symptoms 
 
The symptoms of fentanyl overdose are expected to be similar in nature to those of intravenous 
fentanyl and other opioids, and are an extension of its pharmacological actions, with the most serious 
significant effects being altered mental status, loss of consciousness, hypotension, respiratory 
depression, respiratory distress, and respiratory failure, which have resulted in death. 
 
Management 
 
Immediate management of opioid overdose includes removal of the Effentora buccal tablet, if still in 
the mouth, ensuring a patent airway, physical and verbal stimulation of the patient, assessment of the 
level of consciousness, ventilatory and circulatory status, and assisted ventilation (ventilatory support) 
if necessary. 
 
Overdose (accidental ingestion) in the opioid-naive person 
For treatment of overdose (accidental ingestion) in the opioid-naive person, intravenous access should 
be obtained and naloxone or other opioid antagonists should be employed as clinically indicated. The 
duration of respiratory depression following overdose may be longer than the effects of the opioid 
antagonist’s action (e.g., the half-life of naloxone ranges from 30 to 81 minutes) and repeated 
administration may be necessary. Consult the Summary of Product Characteristics of the individual 
opioid antagonist for details about such use. 
 
Overdose in opioid-maintained patients 
For treatment of overdose in opioid-maintained patients, intravenous access should be obtained. The 
judicious use of naloxone or another opioid antagonist may be warranted in some instances, but it is 
associated with the risk of precipitating an acute withdrawal syndrome. 
 
Although muscle rigidity interfering with respiration has not been seen following the use of Effentora, 
this is possible with fentanyl and other opioids. If it occurs, it should be managed by the use of 
assisted ventilation, by an opioid antagonist, and as a final alternative, by a neuromuscular blocking 
agent. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 

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5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: analgesics; opioids; ATC code N02AB03. 
 
Mechanism of action and pharmacodynamic effects 
Fentanyl is an opioid analgesic, interacting predominantly with the opioid µ-receptor. Its primary 
therapeutic actions are analgesia and sedation. Secondary pharmacological effects are respiratory 
depression, bradycardia, hypothermia, constipation, miosis, physical dependence and euphoria. 
 
The analgesic effects of fentanyl are related to its plasma level. In general, the effective concentration 
and the concentration at which toxicity occurs increase with increasing tolerance to opioids. The rate 
of development of tolerance varies widely among individuals. As a result, the dose of Effentora should 
be individually titrated to achieve the desired effect (see section 4.2). 
 
All opioid µ-receptor agonists, including fentanyl, produce dose dependent respiratory depression. The 
risk of respiratory depression is less in patients receiving chronic opioid therapy as these patients will 
develop tolerance to respiratory depressant effects. 
 
Opioids may influence the hypothalamic-pituitary-adrenal or –gonadal axes. Some changes that can be 
seen include an increase in serum prolactin, and decreases in plasma cortisol and testosterone. Clinical 
signs and symptoms may be manifest from these hormonal changes (see also section 4.8). 
 
Clinical efficacy and safety 
The safety and efficacy of Effentora have been evaluated in patients taking the drug at the onset of the 
breakthrough pain episode. Pre-emptive use of Effentora for predictable pain episodes was not 
investigated in the clinical trials. Two double-blind, randomized, placebo-controlled crossover studies 
have been conducted involving a total of 248 patients with BTP and cancer who experienced on 
average 1 to 4 episodes of BTP per day while taking maintenance opioid therapy. During an initial 
open-label phase, patients were titrated to an effective dose of Effentora. Patients who identified an 
effective dose entered the double-blind phase of the study. The primary efficacy variable was the 
patient’s assessment of pain intensity. Patients assessed pain intensity on a 11-point scale. For each 
BTP episode, pain intensity was assessed prior to and at several time points after treatment. 
 
Sixty-seven percent of the patients were able to be titrated to an effective dose. 
 
In the pivotal clinical study (study 1), the primary endpoint was the average sum of differences in pain 
intensity scores from dosing to 60 minutes, inclusive (SPID60), which was statistically significant 
compared to placebo (p<0.0001). 
 



14 

 
 

 
 
In the second pivotal study (study 2), the primary endpoint was SPID30, which was also statistically 
significant compared to placebo (p<0.0001). 
 



15 

Statistically significant improvement in pain intensity difference was seen with Effentora versus 
placebo as early as 10 minutes in Study 1 and as early as 15 minutes (earliest time point measured) in 
Study 2. These differences continued to be significant at each subsequent time point in each individual 
study. 
 
5.2 Pharmacokinetic properties 
 
General introduction 
Fentanyl is highly lipophilic and can be absorbed very rapidly through the oral mucosa and more 
slowly by the conventional gastrointestinal route. It is subject to first-pass hepatic and intestinal 
metabolism and the metabolites do not contribute to fentanyl’s therapeutic effects. 
 
Effentora employs a delivery technology which utilises an effervescent reaction which enhances the 
rate and extent of fentanyl absorbed through the buccal mucosa. Transient pH changes accompanying 
the effervescent reaction may optimise dissolution (at a lower pH) and membrane permeation (at a 
higher pH).  
 
Dwell time (defined as the length of time that the tablet takes to fully disintegrate following buccal 
administration), does not affect early systemic exposure to fentanyl. A comparison study between one 
400 mcg Effentora tablet administered either buccally (i.e., between the cheek and the gum) or 
sublingually met the criteria of bioequivalence. 
 
The effect of renal or hepatic impairment on the pharmacokinetics of Effentora has not been studied. 
 
Absorption: 
Following oromucosal administration of Effentora, fentanyl is readily absorbed with an absolute 
bioavailability of 65%. The absorption profile of Effentora is largely the result of an initial rapid 
absorption from the buccal mucosa, with peak plasma concentrations following venous sampling 
generally attained within an hour after oromucosal administration. Approximately 50% of the total 
dose administered is rapidly absorbed transmucosally and becomes systemically available. The 
remaining half of the total dose is swallowed and slowly absorbed from the gastrointestinal tract. 
About 30% of the amount swallowed (50% of the total dose) escapes hepatic and intestinal first-pass 
elimination and becomes systemically available. 
 
The main pharmacokinetic parameters are shown in the following table. 
 
Pharmacokinetic Parameters* in Adult Subjects Receiving Effentora  
 

Pharmacokinetic 
parameter (mean) 

Effentora 400 micrograms 
 

Absolute 
bioavailability 
 

65% (±20%) 
 

Fraction 
absorbed transmucosally 
 

48% (±31.8%) 
 

Tmax (minute) ** 
 

46.8 (20-240) 
 

Cmax (ng/ml) 
 

1.02 (± 0.42) 
 

AUC0-tmax (ng.hr/ml) 
 

0.40 (± 0.18) 
 

AUC0-inf (ng.hr/ml) 
 

6.48 (± 2.98) 
 



16 

*    Based on venous blood samples (plasma). Fentanyl concentrations obtained in serum were higher 
than in plasma: Serum AUC and Cmax were approximately 20% and 30% higher than plasma AUC 
and Cmax, respectively. The reason of this difference is unknown.  
** Data for Tmax presented as median (range). 
 
In pharmacokinetic studies that compared the absolute and relative bioavailability of Effentora and 
oral transmucosal fentanyl citrate (OTFC), the rate and extent of fentanyl absorption in Effentora 
demonstrated exposure that was between 30% to 50% greater than that for oral transmucosal fentanyl 
citrate. If switching from another oral fentanyl citrate product, independent dose titration with 
Effentora is required as bioavailability between products differs significantly. However, in these 
patients, a starting dose higher than 100 micrograms may be considered. 
 

 
 
Differences in exposure with Effentora were observed in a clinical study with patients with grade 1 
mucositis. Cmax and AUC0-8 were 1% and 25% higher in patients with mucositis compared to those 
without mucositis, respectively. The differences observed were not clinically significant. 
 
Distribution 
Fentanyl is highly lipophilic and is well distributed beyond the vascular system, with a large apparent 
volume of distribution. After buccal administration of Effentora, fentanyl undergoes initial rapid 
distribution that represents an equilibration of fentanyl between plasma and the highly perfused tissues 
(brain, heart and lungs). Subsequently, fentanyl is redistributed between the deep tissue compartment 
(muscle and fat) and the plasma. 
 
The plasma protein binding of fentanyl is 80% to 85%. The main binding protein is alpha-1-acid 
glycoprotein, but both albumin and lipoproteins contribute to some extent. The free fraction of 
fentanyl increases with acidosis. 
 

 

0.0

0.2

0.4

0.6

0.8

1.0

0 5 10 15 20 25

0.0

0.2

0.4

0.6

0.8

1.0

0 1 2 3 4 5 6

Time after Dose Administration (hours) 

Mean Plasma Concentration Versus Time 
Profiles Following Singles Doses of EFFENTORA and OTFC in Healthy Subjects 

Pl
as

ma
 F

en
tan

yl 
Co

nc
en

tra
tio

n (
ng

/m
L)

 

OTFC data was dose adjusted (800 mcg to 400 mcg) 

400 mcg EFFENTORA 
OTFC (normalized to 400 mcg) 

 



17 

Biotransformation 
The metabolic pathways following buccal administration of Effentora have not been characterised in 
clinical studies. Fentanyl is metabolised in the liver and in the intestinal mucosa to norfentanyl by 
CYP3A4 isoform. Norfentanyl is not pharmacologically active in animal studies. More than 90% of 
the administered dose of fentanyl is eliminated by biotransformation to N-dealkylated and 
hydroxylated inactive metabolites. 
 
Elimination 
Following the intravenous administration of fentanyl, less than 7% of the administered dose is 
excreted unchanged in the urine, and only about 1% is excreted unchanged in the faeces. The 
metabolites are mainly excreted in the urine, while faecal excretion is less important. 
 
Following the administration of Effentora, the terminal elimination phase of fentanyl is the result of 
the redistribution between plasma and a deep tissue compartment. This phase of elimination is slow, 
resulting in a median terminal elimination half-life t1/2 of approximately 22 hours following buccal 
administration of the effervescent formulation and approximately 18 hours following intravenous 
administration. The total plasma clearance of fentanyl following intravenous administration is 
approximately 42 L/h. 
 
Linearity/non-linearity 
Dose proportionality from 100 micrograms to 1000 micrograms has been demonstrated. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity and carcinogenicity.  
 
 Embryo-foetal developmental toxicity studies conducted in rats and rabbits revealed no compound-
induced malformations or developmental variations when administered during the period of 
organogenesis.   
 
In a fertility and early embryonic development study in rats, a male-mediated effect was observed at 
high doses (300 mcg/kg/day, s.c.) and is considered secondary to the sedative effects of fentanyl in 
animal studies. 
In studies on pre and postnatal development in rats the survival rate of offspring was significantly 
reduced at doses causing severe maternal toxicity. Further findings at maternally toxic doses in F1 
pups were delayed physical development, sensory functions, reflexes and behaviour. These effects 
could either be indirect effects due to altered maternal care and/or decreased lactation rate or a direct 
effect of fentanyl on the pups. 
 
Carcinogenicity studies (26-week dermal alternative bioassay in Tg.AC transgenic mice; two-year 
subcutaneous carcinogenicity study in rats) with fentanyl did not reveal any findings indicative of 
oncogenic potential. Evaluation of brain slides from the carcinogenicity study in rats revealed brain 
lesions in animals administered high doses of fentanyl citrate. The relevance of these findings to 
humans is unknown. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol  
Sodium starch glycolate type A 
Sodium hydrogen carbonate 
Sodium carbonate 
Citric acid 
Magnesium stearate 



18 

 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Store in the original package in order to protect from moisture. 
 
6.5 Nature and contents of container 
 
Aluminium laminated blister of PVC/Al foil/Polyamide/PVC with paper/polyester lidding. 
 
Blister packs are supplied in cartons of 4 or 28 tablets. Not all pack-sizes may be marketed. 
 
6.6 Special precautions for disposal  
 
Patients and carers must be advised to dispose of any unopened tablets remaining from a prescription 
as soon as they are no longer needed. 
 
Any used or unused but no longer required medicinal product or waste material should be disposed of 
in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
TEVA B.V. 
Swensweg 5 
2031 GA Haarlem  
Netherlands  
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
Effentora 100 micrograms buccal tablets 
EU/1/08/441/001-002  
 
Effentora 200 micrograms buccal tablets 
EU/1/08/441/003-004 
 
Effentora 400 micrograms buccal tablets 
EU/1/08/441/005-006 
 
Effentora 600 micrograms buccal tablets 
EU/1/08/441/007-008 
 
Effentora 800 micrograms buccal tablets 
EU/1/08/441/009-010 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 04 April 2008 



19 

Date of latest renewal: 20 February 2013 
 
 
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. 
 



20 

  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

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



21 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Teva Pharmaceuticals Europe B.V. 
Swensweg 5  
2031 GA HAARLEM 
Netherlands 
 
 
B. CONDITIONS OR RESTRICTION(S) REGARDING SUPPLY AND USE 
 
Medicinal product subject to special and 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. 

 
If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 
 
• Additional risk minimisation measures 
 
In each Member State where EFFENTORA is marketed the Marketing Authorisation Holder (MAH) 
shall agree an updated educational programme with the National Competent Authority. The MAH 
shall ensure that, following discussions and agreement with the National Competent Authorities in 
each Member State where EFFENTORA is marketed all healthcare professionals who are expected to 
prescribe EFFENTORA are provided with an information pack containing the following items: 
 

• Summary of Product Characteristics (SmPC) and Package Leaflet 
• Educational material for the healthcare professionals  
• Educational material for the patients 

 
The educational material for healthcare professionals shall consist of four items: 

• Opioid prescribing guide 



22 

• Brochure on breakthrough pain 
• EFFENTORA prescribing guide 
• Titration guide tool  

Key elements to be included in the educational material for healthcare professionals: 
- Prescription of EFFENTORA only by physicians experienced in the management of opioid 

therapy in cancer patients 
- Prescription of EFFENTORA only to critically selected patients with close following on  

• Instructions for use of fentanyl buccal tablet and how to place the tablet  
• Instructions on how to open the child-resistant blister  
• Information on the correct indication and the risk for abuse  
• Information on the titration process as indicated in the labelling  

- Instructions on the safe use (to avoid the risk of overdosing), on storage (to avoid the risk 
of accidental exposure), and disposal of fentanyl buccal tablet  

- Boxed statements as follows:  
 

1. Effentora must not be prescribed in pain other than breakthrough cancer pain 
2. Effentora must not be prescribed in patients with short term pain only 
3. Effentora must not be prescribed in patients without around-the-clock opioid pain 

medication 
4. Effentora must not be prescribed in patients below 18 years of age 

 
The educational material for patients shall consist of the following three items:  
 
1. A document explaining the titration process and the dosing recommendations after treatment 
initiation 
 
2. A Q&A document, providing answers to potential questions on the following topics: 

• What is Breakthrough pain? 
• What is EFFENTORA for? 
• How to use EFFENTORA (how to take it, how to reach the effective dose during the 

titration process)? 
• Possible side effects (the most likely ones, how to recognise them and when to alert 

physicians) 
• Risk of interactions with other medications 
• Main precautions for use: How to prevent main risks (take the drug as prescribed; remain 

on maintenance opioid therapy; keep EFFENTORA out of the reach and the sight of 
children; prevent theft and misuse) 

• Safe use, storage and disposal of EFFENTORA. 
 
3. A Daily Pain Journal to record daily pain levels, providing patients and physicians 
with a follow-up tool for daily symptoms and treatment efficacy. 
  



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



25 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Effentora 100 micrograms buccal tablets 
Fentanyl 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each buccal tablet contains 100 micrograms fentanyl (as citrate) 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sodium. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
4 buccal tablets 
28 buccal tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oromucosal use. 
Place in buccal cavity. Not to be sucked, chewed or swallowed whole. Read the package leaflet before 
use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
This product must only be used by patients already receiving maintenance opioid therapy for chronic 
cancer pain. Read enclosed leaflet for important warnings and directions.  
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. 
 



26 

 
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 
 
TEVA B.V. Swensweg 5 2031 GA Haarlem Netherlands  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/08/441/001  
EU/1/08/441/002 
 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Effentora 100 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 
  



27 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER OF 4 TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Effentora 100 micrograms buccal tablets 
Fentanyl 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
TEVA B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. OTHER 
 
1. Tear 
2. Bend 
3. Peel 
  



28 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Effentora 200 micrograms buccal tablets 
Fentanyl 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each buccal tablet contains 200 micrograms fentanyl (as citrate) 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sodium. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
4 buccal tablets 
28 buccal tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oromucosal use. 
Place in buccal cavity. Not to be sucked, chewed or swallowed whole. Read the package leaflet before 
use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
This product must only be used by patients already receiving maintenance opioid therapy for chronic 
cancer pain. Read enclosed leaflet for important warnings and directions. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. 
 



29 

 
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 
 
TEVA B.V. Swensweg 5 2031 GA Haarlem Netherlands  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/08/441/003  
EU/1/08/441/004  
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Effentora 200 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 
  



30 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER OF 4 TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Effentora 200 micrograms buccal tablets 
Fentanyl 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
TEVA B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. OTHER 
 
1. Tear 
2. Bend 
3. Peel 
  



31 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Effentora 400 micrograms buccal tablets 
Fentanyl 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each buccal tablet contains 400 micrograms fentanyl (as citrate) 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sodium. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
4 buccal tablets 
28 buccal tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oromucosal use. 
Place in buccal cavity. Not to be sucked, chewed or swallowed whole. Read the package leaflet before 
use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
This product must only be used by patients already receiving maintenance opioid therapy for chronic 
cancer pain. Read enclosed leaflet for important warnings and directions.  
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. 
 



32 

 
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 
 
TEVA B.V. Swensweg 5 2031 GA Haarlem Netherlands  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/08/441/005  
EU/1/08/441/006  
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Effentora 400 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 
  



33 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER OF 4 TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Effentora 400 micrograms buccal tablets 
Fentanyl 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
TEVA B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. OTHER 
 
1. Tear 
2. Bend 
3. Peel 
  



34 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Effentora 600 micrograms buccal tablets 
Fentanyl 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each buccal tablet contains 600 micrograms fentanyl (as citrate) 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sodium. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
4 buccal tablets 
28 buccal tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oromucosal use. 
Place in buccal cavity. Not to be sucked, chewed or swallowed whole. Read the package leaflet before 
use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
This product must only be used by patients already receiving maintenance opioid therapy for chronic 
cancer pain. Read enclosed leaflet for important warnings and directions.  
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. 
 
 



35 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
TEVA B.V. Swensweg 5 2031 GA Haarlem Netherlands  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/08/441/007  
EU/1/08/441/008  
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Effentora 600 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 
  



36 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER OF 4 TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Effentora 600 micrograms buccal tablets 
Fentanyl 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
TEVA B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. OTHER 
 
1. Tear 
2. Bend 
3. Peel 
  



37 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Effentora 800 micrograms buccal tablets 
Fentanyl 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each buccal tablet contains 800 micrograms fentanyl (as citrate) 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sodium. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
4 buccal tablets 
28 buccal tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oromucosal use. 
Place in buccal cavity. Not to be sucked, chewed or swallowed whole. Read the package leaflet before 
use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
This product must only be used by patients already receiving maintenance opioid therapy for chronic 
cancer pain. Read enclosed leaflet for important warnings and directions.  
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. 
 



38 

 
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 
 
TEVA B.V. Swensweg 5 2031 GA Haarlem Netherlands  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/08/441/009  
EU/1/08/441/010 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Effentora 800 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 
  



39 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER OF 4 TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Effentora 800 micrograms buccal tablets 
Fentanyl 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
TEVA B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. OTHER 
 
1. Tear 
2. Bend 
3. Peel 
  



40 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



41 

Package leaflet: Information for the user 
 

Effentora 100 micrograms buccal tablets 
Effentora 200 micrograms buccal tablets 
Effentora 400 micrograms buccal tablets 
Effentora 600 micrograms buccal tablets 
Effentora 800 micrograms buccal tablets 

 
Fentanyl 

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

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

effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet  
1. What Effentora is and what it is used for 
2. What you need to knowbefore you use Effentora 
3. How to use Effentora 
4. Possible side effects 
5. How to store Effentora 
6. Contents of the pack and other information 
 
 
1. What Effentora is and what it is used for 
 
The active substance of Effentora is fentanyl citrate. Effentora is a pain-relieving medicine known as 
an opioid, which is used to treat breakthrough pain in adult patients with cancer who are already taking 
other opioid pain medicines for their persistent (around-the-clock) cancer pain. 
Breakthrough pain is additional, sudden pain that occurs in spite of you having taken your usual opioid 
pain-relieving medicines. 
 
 
2. What you need to know before you use Effentora 
 
Do NOT use Effentora: 
• If you are not regularly using a prescribed opioid medicine (e.g codeine, fentanyl, hydromorphone, 

morphine, oxycodone, pethidine), every day on a regular schedule, for at least a week, to control 
your persistent pain. If you have not been using these medicines you must not use Effentora, 
because it may increase the risk that breathing could become dangerously slow and/or shallow, or 
even stop. 

• If you are allergic to fentanyl or any of the other ingredients of this medicine (listed in section 6). 
• If you suffer from severe breathing problems or severe obstructive lung conditions. 
• If you suffer from short-term pain other than breakthrough pain 
 
Warnings and precautions 
Keep using the opioid pain medicine you take for your persistent (around-the-clock) cancer pain 
during your Effentora treatment. 
Whilst you are being treated with Effentora, do not use other fentanyl treatments previously prescribed 
for your breakthrough pain. If you still have some of these fentanyl treatments at home, contact your 
pharmacist to check how to dispose of them. 



42 

Repeated use of the product may result in the drug being less effective (you become accustomed to it) 
or becoming dependent on it. 
 
Talk to your doctor or pharmacist BEFORE using Effentora if: 
• Your other opioid pain medicine taken for your persistent (around-the-clock) cancer pain is not 

stabilised yet. 
• You are suffering from any condition that has an effect on your breathing (such as asthma, 

wheezing, or shortness of breath). 
• You have a head injury. 
• You have an exceptionally slow heart rate or other heart problems. 
• You have liver or kidney problems, as these organs have an effect on the way in which your 

system breaks down the medicine. 
• You have low amount of fluid in the circulation or low blood pressure. 
• You are over 65 years old - you may need a lower dose and any dose increase will be reviewed 

very carefully by your doctor. 
• You have problems with your heart especially slow heart rate. 
• You use benzodiazepines (see section 2 under “Other medicines and Effentora”). Using 

benzodiazepines can increase the chances of getting serious side effects including death 
• You use antidepressants or antipsychotics (selective serotonin reuptake inhibitors [SSRIs], 

serotonin norepinephrine reuptake inhibitors [SNRIs], monoamine oxidase (MAO) inhibitors; see 
section 2 under “Do not use Effentora” and “Other medicines and Effentora”)The use of these 
medicines with Effentora can lead to a serotonin syndrome a potentially life-threatening 
condition (see section 2 under “Other medicines and Effentora”). 

• You have ever developed adrenal insufficiency, a condition in which the adrenal glands do not 
produce enough hormones or lack of sex hormones (androgen deficiency) with opioid use (see 
section 4 under “Serious side effects”). 

• You have ever abused or been dependent on opioids or any other drug, alcohol or illegal drugs. 
• You drink alcohol; please refer to section Effentora with food, drink and alcohol. 
 
Consult your doctor WHILE using Effentora if: 
• You experience pain or increased sensitivity to pain (hyperalgesia) which does not respond to a 

higher dosage of your medicine as prescribed by your doctor. 
• You experience a combination of the following symptoms: nausea, vomiting, anorexia, fatigue, 

weakness, dizziness and low blood pressure. Together these symptoms may be a sign of a 
potentially life-threatening condition called adrenal insufficiency, a condition in which the adrenal 
glands do not produce enough hormones. 

 
Seek URGENT medical advice if: 
• You experience symptoms such as difficulty in breathing or dizziness, swelling of the tongue, lip 

or throat while using Effentora. These might be early symptoms of a serious allergic reaction 
(anaphylaxis, hypersensitivity; see section 4 under “Serious side effects”) 

 
What to do if someone accidentally takes Effentora 
If you think someone has accidentally taken Effentora please seek immediate medical assistance. Try 
to keep the person awake until emergency help arrives. 
 
If someone has accidentally taken Effentora, they may have the same side effects as described in the 
section 3 “If you use more Effentora than you should”. 
 
Children and adolescents 
Do not give this medicine to children and adolescents below18 years of age. 
 
Other medicines and Effentora 
Tell your doctor or pharmacist before starting Effentora if you are taking or have recently taken or 
might take any of the following medicines: 



43 

• Concomitant use of Effentora and sedative medicines such as benzodiazepines or related drugs 
increases the risk of drowsiness, difficulties in breathing (respiratory depression), coma and may 
be life-threatening. Because of this, concomitant use should only be considered when other 
treatment options are not possible.  

 However if your doctor does prescribe Effentora together with sedative medicines the dose and 
duration of concomitant treatment should be limited by your doctor.  

 Please tell your doctor about all sedative medicines you are taking (such as sleeping pills, 
medicines to treat anxiety, some medicines to treat allergic reactions (antihistamines), or 
tranquillisers) and follow your doctor’s dose recommendation closely. It could be helpful to 
inform friends or relatives to be aware of the signs and symptoms stated above. Contact your 
doctor when experiencing such symptoms. 

• Some muscle relaxants - such as baclofen, diazepam (see also section “Warnings and 
precautions”. 

• Any medicines that might have an effect on the way in which your body breaks down Effentora, 
such as ritonavir, nelfinavir, amprenavir, and fosamprenavir (medicines that help control HIV 
infection) or other so-called CYP3A4 inhibitors such as ketoconazole, itraconazole, or fluconazole 
(used for treatment of fungal infections), troleandomycine, clarithromycine, or erythromycine 
(medicines for treatment of bacterial infections), aprepitant (used for severe nausea) and diltiazem 
and verapamil (medicines for treatment of high blood pressure or heart diseases). 

• Medicines called monoamine-oxidase (MAO) inhibitors (used for severe depression) or have done 
so in the past 2 weeks. 

• Certain type of strong pain killers, calledpartial agonist/antagonists e.g. buprenorphine, nalbuphine 
and pentazocine (medicines for treatment of pain). You could experience symptoms of withdrawal 
syndrom (nausea, vomiting, diarrhoea, anxiety, chills, tremor, and sweating) while using these 
medicines. 

• The risk of side effects increases if you are taking medicines such as certain antidepressants or 
antipsychotics. Effentora may interact with these medicines and you may experience mental status 
changes (e.g. agitation, hallucinations, coma), and other effects such as body temperature above 
38°C, increase in heart rate, unstable blood pressure, and exaggeration of reflexes, muscular 
rigidity, lack of coordination and/or gastrointestinal symptoms (e.g nausea, vomiting, diarrhoea). 
Your doctor will tell you whether Effentora is suitable for you. 

 
Tell your doctor or pharmacist if you are taking or have recently taken or might take any other 
medicines. 
 
Effentora with food, drink and alcohol 
• Effentora may be used before or after, but not during, meals. You may drink some water before 

using Effentora to help moisten your mouth, but you should not drink or eat anything while taking 
the medicine.  

• You should not drink grapefruit juice while using Effentora because it may affect the way your 
body breaks down Effentora. 

• Do not drink alcohol while using Effentora. It can increase the risk of experiencing serious side 
effects including death. 

 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before using this medicine. 
 
Pregnancy 
Effentora should not be used during pregnancy unless you have discussed this with your doctor. 
If Effentora is used for a long time during pregnancy, there is also a risk of the new-born child having 
withdrawal symptoms which might be life-threatening if not recognized and treated by a doctor. 
 
You should not use Effentora during childbirth because fentanyl may cause respiratory depression in 
the new-born child.  



44 

 
Breast-feeding 
Fentanyl can get into breast milk and may cause side effects in the breast-fed infant. Do not use 
Effentora if you are breast-feeding. You should not start breast-feeding until at least 5 days after the 
last dose of Effentora. 
 
Driving and using machines 
You should discuss with your doctor whether it is safe for you to drive, or operate machinery after 
taking Effentora. Do not drive or operate machinery if you: are feeling sleepy or dizzy; have blurred or 
double vision; or have difficulty in concentrating. It is important you know how you react to Effentora 
before driving or operating machinery. 
 
Effentora contains sodium 
 
Effentora 100 micrograms 
This medicine contains 10 mg sodium (main component of cooking/table salt) in each buccal tablet. 
This is equivalent to 0.5 % of the recommended maximum daily dietary intake of sodium for an adult. 
 
Effentora 200 micrograms, Effentora 400 micrograms, Effentora 600 micrograms, 
Effentora 800 micrograms 
This medicine contains 20 mg sodium (main component of cooking/table salt) in each buccal tablet. 
This is equivalent to 1 % of the recommended maximum daily dietary intake of sodium for an adult. 
 
 
3. How to use Effentora 
 
Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if 
you are not sure.  
 
Dosage and frequency 
When you first start using Effentora, your doctor will work with you to find the dose that will relieve 
your breakthrough pain. It is very important that you use Effentora exactly as the doctor tells you The 
initial dose is 100 micrograms. During determination of your right dose, your doctor may instruct you 
to take more than one tablet per episode. If your breakthrough pain is not relieved after 30 minutes, 
use only 1 more tablet of Effentora during the titration period. 
 
Once the right dose has been determined with your doctor, use 1 tablet for an episode of breakthrough 
pain as a general rule. In the further course of treatment your requirement for analgesic therapy may 
change. Higher doses may be necessary. If your breakthrough pain is not relieved after 30 minutes, use 
only 1 more tablet of Effentora during this dose-readjustment period. 
Contact your doctor if your right dose of Effentora does not relieve your breakthrough pain. Your 
doctor will decide if your dose needs to be changed. 
 
Wait at least 4 hours before treating another episode of breakthrough pain with Effentora. 
 
You must let your doctor know immediately if you are using Effentora more than four times per day, 
as a change may be required to your treatment regimen. Your doctor may change the treatment for 
your persistent pain; when your persistent pain is controlled, your doctor may need to change the dose 
of Effentora. If your doctor suspects Effentora-related increased sensitivity to pain (hyperalgesia), a 
reduction of your Effentora dose may be considered (see section 2 under “Warnings and precautions”). 
For the most effective relief, let your doctor know about your pain and how Effentora is working for 
you, so that the dose can be changed if needed. 
 
Do not change doses of Effentora or your other pain medicines on your own. Any change in dosage 
must be prescribed and monitored by your doctor. 
 



45 

If you are not sure about the right dose, or if you have questions about taking this medicine, you 
should contact your doctor. 
 
Method of administration 
Effentora buccal tablets are for oromucosal use. When you place a tablet in your mouth, it dissolves 
and the medicine is absorbed through the lining of your mouth, into the blood system. Taking the 
medicine in this way allows it to be absorbed quickly to relieve your breakthrough pain. 
 
Taking the medicine 
• Open the blister only when you are ready to use the tablet. The tablet must be used immediately 

once removed from the blister. 
• Separate one of the blister units from the blister card by tearing apart at the perforations. 
• Bend the blister unit along the line where indicated. 
• Peel the blister backing to expose the tablet. Do NOT attempt to push the tablet through the blister, 

because this can damage the tablet. 

 
 
• Remove the tablet from the blister unit and immediately place the entire tablet near a molar tooth 

between the gum and the cheek (as shown in the picture). Sometimes, your doctor may tell you to 
place the tablet under your tongue instead. 

• Do not attempt to crush or split the tablet. 

 
 
• Do not bite, suck, chew, or swallow the tablet, as this will result in less pain relief than when taken 

as directed. 
• The tablet should be left between the cheek and gum until dissolved, which usually takes 

approximately 14 to 25 minutes. 
• You may feel a gentle bubbling sensation between your cheek and gum as the tablet dissolves. 
• In case of irritation, you may change the placement of the tablet on the gum. 
• After 30 minutes, if pieces of the tablet remain, they may be swallowed with a glass of water. 
 
If you use more Effentora than you should 
• The most common side effects are feeling sleepy, sick or dizzy. If you begin to feel very dizzy, or 

very sleepy before the tablet is completely dissolved, rinse your mouth with water and spit the 
remaining pieces of the tablet into a sink or toilet right away. 

• A serious side effect of Effentora is slow and/or shallow breathing. This can occur if your dose of 
Effentora is too high or if you take too much Effentora. If this occurs, please seek immediate 
medical assistance. 

 
If you forget to use Effentora 
If the breakthrough pain is still ongoing, you may take Effentora as prescribed by your physician. If 
the breakthrough pain has stopped, do not take Effentora until the next breakthrough pain episode. 



46 

 
If you stop using Effentora 
You should discontinue Effentora when you no longer have any breakthrough pain. You must 
however continue to take your usual opioid pain relieving medicine to treat your persistent cancer pain 
as advised by your doctor. You may experience withdrawal symptoms similar to the possible side 
effects of Effentora when discontinuing Effentora. If you experience withdrawal symptoms or if you 
are concerned about your pain relief, you should contact your doctor. Your doctor will evaluate if you 
need medicine to reduce or eliminate the withdrawal symptoms.  
 
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. If you 
notice any of these, contact your doctor.  
 
Serious side effects 
 
• The most serious side effects are shallow breathing, low blood pressure and shock. 

Effentora like other fentanyl products can cause very severe breathing problems which can 
lead to death. If you become very sleepy or have slow and/or shallow breathing, you or your 
carer should contact your doctor immediately and call for emergency help. 

 
• Contact your doctor immediately if you experience a combination of the following 

symptoms 
- Nausea, vomiting, anorexia, fatigue, weakness, dizziness and low blood pressure 

Together these symptoms may be a sign of a potentially life-threatening condition called adrenal 
insufficiency. A condition in which the adrenal glands do not produce enough hormones. 

 
Other side effects 
 
Very common: may affect more than 1 in 10 people 
• Dizziness, headache 
• feeling nauseous, vomiting 
• at the site of tablet application: pain, ulcer, irritation, bleeding, numbness, loss of sensation, 

redness, swelling or spots 
 
Common: may affect up to 1 in 10 people 
• feeling anxious or confused, depression, insomnia  
• abnormal taste, weight decreased 
• sleepiness, sedation, excessive tiredness, weakness, migraine, numbness, swelling of arms or legs, 

drug withdrawal syndrome (may manifest by the occurrence of the following side effects nausea, 
vomiting, diarrhoea, anxiety, chills, tremor, and sweating), shaking, falls, chills 

• constipation, inflammation of the mouth, dry mouth, diarrhoea, heartburn, loss of appetite, 
stomach pain, uncomfortable stomach, indigestion, toothache, oral thrush 

• itching, excessive sweating, rash 
• shortness of breath, painful throat 
• decrease in white cells in the blood, decrease in red blood cells, decreased or raised blood 

pressure, unusually fast heart rate 
• muscle pain, back pain 
• fatigue 
 
Uncommon: may affect up to 1 in 100 people 
• sore throat 
• decrease in cells that help the blood to clot, 



47 

• feeling elated, nervous, abnormal, jittery or slow; seeing or hearing things that are not really there 
(hallucinations), reduced consciousness, change in mental state, dependence (reliance on the 
medicine, addiction), disorientation, lack of concentration, loss of balance, vertigo, problem with 
speaking, ringing in the ear, ear discomfort 

• disturbed or blurred vision, red eye 
• unusually low heart rate, feeling very warm (hot flushes),  
• severe breathing problems, trouble breathing during sleep, 
• one or more of the following problems in the mouth: ulcer, loss of sensation, discomfort, unusual 

colour, soft tissue disorder, tongue disorder, painful or blistered or ulcerated tongue, gum pain, 
chapped lips, tooth disorder 

• inflammation of the oesophagus, paralysis of the gut, gall bladder disorder 
• cold sweat, swollen face, generalised itching, hair loss, muscle twitching, muscular weakness, 

feeling unwell, chest discomfort, thirst, feeling cold, feeling hot, difficulty passing urine 
• malaise 
• flushing 
 
Rare: may affect up to 1 in 1,000 people 
• disturbance in thinking, movements disturbance 
• blisters in the mouth, dry lips, collection of pus under the skin in the mouth 
• lack of testosterone, abnormal sensation in eye, observing flashes of light, brittle nails 
• Allergic reactions such as rash, redness, swollen lip and face, hives 
 
Not known: frequency cannot be estimated from the available data 
• loss of consciousness, stop in breathing, convulsion (fits) 
• lack of sex hormones (androgen deficiency) 
• drug dependence (addiction) 
• drug abuse 
• delirium (symptoms may include a combination of agitation, restlessness, disorientation, 

confusion, fear, seeing or hearing things that are not really there, sleep disturbance, nightmares) 
• prolonged treatment with fentanyl during pregnancy may cause withdrawal symptoms in the 

newborn which can be life-threatening (see section 2) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Effentora 
 
The pain-relieving medicine in Effentora is very strong and could be life-threatening if taken 
accidentally by a child. This medicine must be kept out of the sight and reach of children. 
• Do not use this medicine after the expiry/use before date which is stated on the blister package 

label and the carton. The expiry date refers to the last day of that month. 
• Store in the original package in order to protect from moisture.  
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how 

to throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Effentora contains 
The active substance is fentanyl. Each tablet contains either: 
• 100 micrograms fentanyl (as citrate) 
• 200 micrograms fentanyl (as citrate) 
• 400 micrograms fentanyl (as citrate) 

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


48 

• 600 micrograms fentanyl (as citrate) 
• 800 micrograms fentanyl (as citrate) 
The other ingredients are mannitol, sodium starch glycolate type A, sodium hydrogen carbonate, 
sodium carbonate, citric acid, magnesium stearate. 
 
What Effentora looks like and contents of the pack 
The buccal tablets are flat-faced, round bevelled-edge tablet, embossed one side with a “C” and on the 
other side with “1” for Effentora 100 micrograms, with “2” for Effentora 200 micrograms, with “4” 
for Effentora 400 micrograms, with “6” for Effentora 600 micrograms, with “8” for Effentora 
800 micrograms. 
 
Each blister contains 4 buccal tablets, supplied in cartons of 4 or 28 buccal tablets. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
TEVA B.V. 
Swensweg 5 
2031 GA Haarlem  
Netherlands  
 
Manufacturer 
Teva Pharmaceuticals Europe B.V. 
Swensweg 5  
2031 GA HAARLEM 
Netherlands 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder or call the following number: 
 
België/Belgique/Belgien 
Teva Pharma Belgium N.V./S.A./AG 
Tel/Tél: +32 3 820 73 73 
 

Lietuva 
UAB Teva Baltics 
Tel: +370 5 266 02 03 

България 
Актавис ЕАД 
Teл.: +359 2 489 95 85 
 

Luxembourg/Luxemburg 
Teva Pharma Belgium N.V./S.A./AG. 
Tél: +32 3 820 73 73 

Česká republika 
Teva Pharmaceuticals CR, s.r.o. 
Tel: +420 251 007 111 
 

Magyarország 
Teva Gyógyszergyár Zrt. 
Tel.: (+ 36) 1 288 6400 

Danmark 
Teva Denmark A/S 
Tlf: +45 44 98 55 11 
 

Malta 
Teva Pharmaceuticals Ireland 
Tel: +353 19630330 

Deutschland 
TEVA GmbH 
Tel: +49 731 402 08 
 

Nederland 
Teva Nederland B.V. 
Tel: +31 (0) 800 0228 400 

Eesti 
UAB Teva Baltics Eesti filiaal 
Tel: + 372 661 0801 
 

Norge 
Teva Norway AS 
Tlf: +47 66 77 55 90 
 

Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 2118805000 
 

Österreich 
ratiopharm Arzneimittel Vertriebs-GmbH 
Tel: +43 197007 0 



49 

España 
Teva Pharma, S.L.U.  
Tel: + 34 91 387 32 80 
 

Polska 
Teva Pharmaceuticals Polska Sp. z o.o. 
Tel.: +48 22 345 93 00  
 

France 
Teva Santé 
Tél: +33 1 55 91 78 00 
 
Hrvatska 
Pliva Hrvatska d.o.o 
Tel: + 385 1 37 20 000 
 

Portugal 
Teva Pharma - Produtos Farmacêuticos, Lda. 
Tel: +351 21 476 75 50 
 
România 
Teva Pharmaceuticals S.R.L. 
Tel: +4021 230 65 24 
 

Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 1912-7700 
 

Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 1 58 90 390 

Ísland 
Teva Finland Oy 
Finnland 
Sími: +358 201805900 
 

Slovenská republika 
TEVA Pharmaceuticals Slovakia s.r.o. 
Tel: +421257267911 
 

Italia 
Teva Italia S.r.l. 
Tel: +39 028917981 
 

Suomi/Finland 
Teva Finland Oy 
Puh/Tel: +358 20 180 5900 

Κύπρος 
Teva Ελλάς Α.Ε. 
Τηλ: +30 2118805000 
 

Sverige 
Teva Sweden AB 
Tel: +46 (0)42 12 11 00 

Latvija 
UAB Teva Baltics filiāle Latvijā 
Tel: +371 67 323 666 
 

United Kingdom 
Teva UK Limited 
Tel: +44 1977628500 

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

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

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