PecFent

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



 2 

1. NAME OF THE MEDICINAL PRODUCT 
 
PecFent 100 micrograms/spray nasal spray, solution 
PecFent 400 micrograms/spray nasal spray, solution 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
PecFent 100 micrograms/spray nasal spray, solution 
Each ml of solution contains 1,000 micrograms fentanyl (as citrate) 
1 spray (100 microlitres) contains 100 micrograms fentanyl (as citrate) 
 
Bottles contain: 
0.95 ml (950 micrograms fentanyl) -  2 spray bottle 
or 
1.55 ml (1,550  micrograms fentanyl) - 8 spray bottle 
 
PecFent 400 micrograms/spray nasal spray, solution 
Each ml of solution contains 4,000 micrograms fentanyl (as citrate) 
1 spray (100 microlitres) contains 400 micrograms fentanyl (as citrate) 
 
Each bottle contains 1.55 ml (6,200 micrograms fentanyl)  
 
Excipients with known effect: 
Each spray contains 0.02 mg propylparahydroxybenzoate (E216). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Nasal spray, solution (nasal spray). 
 
A clear to practically clear colourless aqueous solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
PecFent is indicated for the management of breakthrough pain (BTP) in adults who are already 
receiving maintenance opioid therapy for chronic cancer pain. Breakthrough pain 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 supervision of a physician experienced in the 
management of opioid therapy in cancer patients. Physicians should keep in mind the potential for 
abuse of fentanyl. 
 



 3 

Posology 
PecFent should be titrated to an “effective” dose that provides adequate analgesia and minimises 
adverse reactions without causing undue (or intolerable) adverse reactions, for two consecutively 
treated episodes of BTP. The efficacy of a given dose should be assessed over the ensuing 30 minute 
period.  
 
Patients should be carefully monitored until an effective dose is reached. 
 
 
 
PecFent is available in two strengths: 100 micrograms/spray and 400 micrograms/spray. 
 
One dose of PecFent may include administration of 1 spray (100 microgram or 400 microgram doses) 
or 2 sprays (200 microgram or 800 microgram doses) of the same strength (either 100 microgram or 
400 microgram strength).   
 
Patients should not  use more than 4 doses per day. Patients should wait at least 4 hours after a dose 
before treating another BTP episode with PecFent. 
 
PecFent can deliver 100, 200, 400 and 800 microgram doses as follows: 
 

Dose required  
(micrograms)  

Product strength 
(micrograms) 

Amount 

100 100 One spray administered into one 
nostril 

200 100 One spray administered into each 
nostril 

400 400 One spray administered into one 
nostril 

800 400 One spray administered into each 
nostril 

 
Initial dose 
• The initial dose of PecFent to treat episodes of BTP is always 100 micrograms (one spray), even 

in patients switching from other fentanyl containing products for their BTP. 
• Patients must wait at least 4 hours before treating another episode of BTP with PecFent. 
 
Method of titration 
• Patients should be prescribed an initial titration supply of one bottle (2 sprays or 8 sprays) of 

PecFent 100 micrograms/spray. 
• Patients whose initial dose is 100 micrograms and who need to titrate to a higher dose due to a 

lack of effect can be instructed to use two 100 microgram sprays (one in each nostril) for their 
next BTP episode. If this dose is not successful, the patient may be prescribed a bottle of 
PecFent 400 micrograms/spray and instructed to change to one 400 microgram spray for their 
next episode of pain. If this dose is not successful, the patient may be instructed to increase to 
two 400 microgram sprays (one in each nostril). 

• From treatment initiation, patients should be closely followed and the dose titrated until an 
effective dose is reached and confirmed for two consecutively treated episodes of BTP.  

 
Titration in patients switching between immediate-release fentanyl containing products  
Substantial differences may exist in the pharmacokinetic profile of immediate-release fentanyl 
medicinal products, which result in clinically important differences in the rate and extent of absorption 
of fentanyl.  Therefore, when switching between fentanyl containing medicinal products indicated for 
treatment of breakthrough pain, including intranasal formulations, it is essential that patients are again 
titrated with the new medicinal product, and not switched on a dose-for-dose (microgram-for-
microgram) basis. 
 



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Maintenance therapy 
Once an effective dose has been established during titration, patients should continue to take this dose 
up to a maximum of 4 doses per day.  
 
Dose readjustment 
Generally, the maintenance dose of PecFent should be increased only where the current dose fails to 
adequately treat the BTP for several consecutive episodes. 
 
A review of the dose 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). 
 
If adverse reactions are intolerable or persistent, the dose should be reduced or treatment with PecFent 
replaced by another analgesic. 
 
Discontinuation of therapy 
PecFent should be discontinued immediately if the patient no longer experiences breakthrough pain 
episodes. The treatment for persistent backgound pain should be kept as prescribed. 
If discontinuation of all opioid therapy is required, the patient must be closely followed by the doctor 
as gradual downward opioid titration therapy is necessary in order to avoid the possibility of abrupt 
withdrawal effects.   
 
Special populations 
 
Elderly (older than 65 years) 
In the PecFent clinical trial programme, 104 (26.1%) of patients were over 60 years of age, 67 (16.8%) 
over 65 years and 15 (3.8%) over 75 years.  There was no indication that older patients tended to 
titrate to lower doses or experience more adverse reactions. Nevertheless, in view of the importance of 
renal and hepatic function in the metabolism and clearance of fentanyl, additional care should be 
exercised in the use of PecFent in the elderly. No data on the pharmacokinetics of PecFent in elderly 
patients are available.   
 
Hepatic or renal impairment 
PecFent should be administered with caution to patients with moderate or severe hepatic or renal 
impairment (see section 4.4). 
 
Paediatric population 
The safety and efficacy of PecFent in children and adolescents aged below 18 years have not yet been 
established.  
 
No data are available.  
 
Method of administration 
PecFent is for  nasal  use only. 
 
The bottle should be removed from the child resistant container immediately prior to use and the 
protective cap removed. The bottle must be primed before first use by holding upright and simply 
pressing and releasing the finger grips either side of the nozzle until a green bar appears in the 
counting window (should occur after four sprays).  
 
2 spray bottle: 
The 2 spray bottle cannot be re-primed and once both doses are used, or if longer than 5 days since 
priming, the bottle and contents should be discarded as described in section 6.6. 
 



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8 spray bottle: 
If the product has not been used for 5 days, it should be re-primed by spraying once.   
 
The patient should be advised to write the date of first use in the space provided on the label of the 
child resistant container. 
 
To administer PecFent the nozzle is placed a short distance (about 1 cm) into the nostril and pointed 
slightly towards the bridge of the nose. A spray is then administered by pressing and releasing the 
finger grips either side of the nozzle. An audible click will be heard and the number displayed on the 
counter will advance by one.   
 
Patients must be advised that they may not feel the spray being administered, and that they should, 
therefore, rely on the audible click and the number on the counter advancing to confirm that a spray 
has been delivered.  
 
The PecFent spray droplets form a gel in the nose. Patients should be advised not to blow their nose 
immediately after PecFent administration.  
 
The protective cap should be replaced after each use and the bottle returned to the child resistant 
container for safe storage. 
 
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. 
 
Treatment of acute pain other than breakthrough pain. 
 
4.4 Special warnings and precautions for use 
 
Patients and their carers must be instructed that PecFent contains an active substance in an amount that 
can be fatal to a child. 
 
In order to minimise the risks of opioid-related adverse reactions and to identify the effective dose, it 
is imperative that patients be monitored closely by health professionals during the titration process. 
 
It is important that the long acting opioid treatment used to treat the patient’s persistent pain has been 
stabilised before PecFent therapy begins. 
 
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. 
 
Respiratory depression 
There is a risk of clinically significant respiratory depression associated with the use of fentanyl. 
Patients with pain who receive chronic opioid therapy develop tolerance to respiratory depression and 
hence the risk of respiratory depression in these patients is reduced. The use of concomitant central 
nervous system depressants may increase the risk of respiratory depression (see section 4.5). 
 
Chronic pulmonary disease 
In patients with chronic obstructive pulmonary diseases, fentanyl may cause more serious adverse 
reactions. In these patients, opioids may decrease respiratory drive and increase airway resistance. 
 



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Increased intracranial pressure 
PecFent 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 patients 
with a head injury and should be used only if clinically warranted. 
 
Cardiac disease 
Fentanyl may produce bradycardia. PecFent should, therefore, be used with caution in patients with 
previous or pre-existing bradyarrhythmias. 
 
Impaired hepatic or renal function 
In addition, PecFent 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. 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. 
 
Abuse potential and tolerance 
Tolerance and physical and/or psychological dependence may develop upon repeated administration 
of opioids such as fentanyl. However, iatrogenic addiction following therapeutic use of opioids is 
known to occur. 
 
Athletes should be informed that treatment with fentanyl could lead to positive doping tests. 
 
Serotonin Syndrome 
Caution is advised when PecFent is coadministered with medicinal products that affect the 
serotoninergic neurotransmitter systems. 
 
The development of a potentially life-threatening serotonin syndrome may occur with the concomitant 
use of serotonergic medicinal products such as Selective Serotonin Re-uptake Inhibitors (SSRIs) and 
Serotonin Norepinephrine Re-uptake Inhibitors (SNRIs), and with medicinal products which impair 
metabolism of serotonin (including Monoamine Oxidase Inhibitors [MAOIs]). This may occur within 
the recommended dose (see section 4.5). 
 
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 PecFent should be discontinued. 
 
Route of administration 
PecFent is only intended for nasal use, and must not be administered by any other route.  Due to 
physico-chemical properties of excipients included in the formulation, intravenous or intra-arterial 
injection must be avoided in particular. 
 
Nasal conditions 
If the patient experiences recurrent episodes of epistaxis or nasal discomfort while taking PecFent, an 
alternative method of administration for treatment of breakthrough pain should be considered. 
 



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PecFent excipients 
PecFent contains propylparahydroxybenzoate (E216). Propylparahydroxybenzoate  may cause allergic 
reactions (possibly delayed) and, exceptionally, bronchospasm (if the medicinal product is not 
correctly administered). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Fentanyl is metabolised mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4), 
therefore potential interactions may occur when PecFent is given concurrently with  medicinal 
products that affect CYP3A4 activity. Coadministration with medicinal products that induce 3A4 
activity may reduce the efficacy of PecFent. The concomitant use of PecFent 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 PecFent concomitantly with moderate or strong CYP3A4 inhibitors 
should be carefully monitored for an extended period of time. Dose increase should be undertaken 
with caution. 
 
The concomitant use of other central nervous system depressants, including other opioids, sedatives or 
hypnotics, general anaesthetics, phenothiazines, tranquillisers, skeletal muscle relaxants, sedating 
antihistamines and alcohol may produce additive depressant effects. 
 
Serotoninergic medicinal products: 
Coadministration of fentanyl with a serotoninergic medicinal product, 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. 
 
PecFent is not recommended for use in patients who have received monoamine oxidase (MAO) 
inhibitors within the previous 14 days because severe and unpredictable potentiation by MAO 
inhibitors has been reported with opioid analgesics. 
 
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 dependent patients. 
 
Concomitant use of nasally administered oxymetazoline has been shown to decrease the absorption of 
PecFent (see section 5.2). The concomitant use of nasally administered vasoconstrictive decongestants 
during titration is, therefore, not recommended as this may lead to patients titrating to a dose that is 
higher than required. PecFent maintenance treatment may also be less effective in patients with rhinitis 
when administered concomitantly with a nasal vasoconstrictive decongestant. If this occurs, patients 
should be advised to discontinue their decongestant. 
 
Concomitant use of PecFent and other medicinal products (other than oxymetazoline) administered via 
the nose has not been evaluated in the clinical trials. Other nasally administered treatments should be 
avoided within 15 minutes of dosing with PecFent. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy  
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. PecFent 
should not be used during pregnancy unless clearly necessary. 
 



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Following long-term treatment, fentanyl may cause withdrawal in the new-born infant. 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 PecFent is administered, an 
antidote for the child should be readily available. 
 
Breastfeeding 
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 breast-feeding should not be restarted 
until at least 5 days after the last administration of fentanyl. 
 
Fertility 
There are no clinical data on the effects of fentanyl on fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Opioid analgesics may impair the mental and/or physical ability required for driving or operating 
machinery.  
 
Patients should be advised not to drive or operate machinery if they experience somnolence, dizziness, 
or visual disturbance or other adverse reactions which can impair their ability to drive or operate 
machinery. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
Typical opioid adverse reactions are to be expected with PecFent. 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 monitored for these. 
 
The clinical studies of PecFent were designed to evaluate safety and efficacy in treating BTP and all 
patients were also on background opioid therapies, such as sustained-release morphine or transdermal 
fentanyl, for their persistent pain. Therefore it is not possible to definitively separate the effects of 
PecFent alone. 
 
Tabulated list of adverse reactions 
The following adverse reactions have been reported with PecFent and/or other fentanyl-containing 
compounds during clinical studies and post marketing experience (frequencies 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); very rare (<1/10,000); unknown (cannot be estimated from available data)). 
 

 Common Uncommon Unknown 
Infections and 
infestations 
 
 

 Pneumonia 
Nasopharyngitis 
Pharyngitis 
Rhinitis 

 

Blood and lymphatic 
system disorders 

 Neutropenia  

Immune system 
disorders 

 Hypersensitivity  

Metabolism and 
nutrition disorders 

 Dehydration 
Hyperglycaemia 
Decreased appetite 
Increased appetite 

 



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 Common Uncommon Unknown 
Psychiatric disorders Disorientation 

 
Delirium 
Hallucination 
Confusional state 
Depression 
Attention 
deficit/hyperactivity 
disorder 
Anxiety 
Euphoric mood 
Nervousness 

Insomnia 
Drug dependence 
(addiction) 
Drug abuse 

Nervous system 
disorders 

Dysgeusia 
Dizziness 
Somnolence 
Headache 

Loss of consciousness 
Depressed level of 
consciousness 
Convulsion 
Ageusia 
Anosmia 
Memory impairment 
Parosmia 
Speech disorder 
Sedation 
Lethargy 
Tremor 

 

Ear and labyrinth 
disorders 

 Vertigo  

Cardiac disorders  Cyanosis  
Vascular disorders  Cardiovascular 

insufficiency 
Lymphoedema 
Hypotension 
Hot flush 

Flushing 
 

Respiratory, thoracic 
and mediastinal 
disorders 

Epistaxis 
Rhinorrhoea 
Nasal discomfort 
 

Upper airway 
obstruction 
Pharyngolaryngeal pain 
Rhinalgia 
Nasal mucosal disorder 
Cough 
Dyspnoea 
Sneezing 
Upper respiratory tract 
congestion 
Nasal congestion 
Intranasal hypoaesthesia 
Throat irritiation 
Postnasal drip 
Nasal dryness 

Respiratory depression 

Gastrointestinal 
disorders 

Vomiting 
Nausea 
Constipation 

Intestinal perforation 
Peritonitis 
Oral hypoaesthesia 
Oral paraesthesia 
Diarrhoea 
Retching 
Abdominal pain 
Tongue disorder 
Mouth ulceration 
Dyspepsia 
Dry mouth 

 



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 Common Uncommon Unknown 
Skin and subcutaneous 
tissue disorders 

Pruritus 
 

Hyperhydrosis 
Urticaria 

 

Musculoskeletal and 
connective tissue 
disorders 

 Arthralgia 
Muscle twitching 

 

Renal and urinary 
disorders 

 Anuria 
Dysuria 
Proteinuria 
Urinary hesitation 

 

Reproductive system 
and breast disorders 

 Vaginal haemorrhage  

General disorders and 
administration site 
conditions 

 Non-cardiac chest pain 
Asthenia 
Chills 
Face oedema 
Peripheral oedema 
Gait disturbance 
Pyrexia 
Fatigue 
Malaise 
Thirst 

Withdrawal syndrome* 
Neonatal withdrawal 
syndrome 

Investigations 
 

 Platelet count decreased 
Weight increased 

 

Injury, poisoning and 
procedural 
complications 

 Fall 
Intentional drug misuse 
Medication error 

 

*See next section below 
 
Description of selected adverse reactions 
Opioid withdrawal symptoms such as nausea, vomiting, diarrhoea, anxiety, chills, tremor, and 
sweating have been observed with transmucosal fentanyl. 
 
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 
 
The symptoms of fentanyl overdose via the nasal route 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 effect being respiratory depression. Coma is also known to occur. 
 
Immediate management of opioid overdose includes 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. 
 
For treatment of overdose (accidental ingestion) in the opioid-naïve 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. For details about such use the Summary of Product Characteristics 
of the individual opioid antagonist should be consulted. 
 

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


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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. 
 
It should be noted that although statistically significant increases in Cmax levels were seen following a 
second dose of PecFent given either one or two hours after the initial dose, this increase is not 
considered to be large enough to suggest that clinically concerning accumulation or over-exposure 
would occur, providing a wide safety margin for the recommended dose interval of four hours. 
 
Although muscle rigidity interfering with respiration has not been seen following the use of PecFent, 
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 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Analgesics; opioids; phenylpiperidine derivatives;  
ATC code: N02AB03. 
 
Mechanism of action 
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. 
 
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. 

 
Pharmacodynamic effects 
A double-blind, randomised, placebo-controlled crossover study has been conducted in which 114 
patients who experienced on average 1 to 4 episodes of break through pain (BTP) per day while taking 
maintenance opioid therapy were entered into an initial open-label titration phase in order to identify 
an effective dose of PecFent (Study CP043). The patients entering the double-blind phase treated up to 
10 episodes of BTP with either PecFent (7 episodes) or placebo (3 episodes) in a random order. 
 
Of the patients entering the titration phase, only 7 (6.1 %) were unable to be titrated to an effective 
dose due to lack of efficacy and 6 (5.3 %) withdrew due to adverse events. 
   
The primary endpoint was the comparison between the summed pain intensity difference at 30 minutes 
after dosing (SPID30), which was 6.57 in the PecFent-treated episodes compared to 4.45 for placebo 
(p<0.0001 ). The SPID for PecFent-treated episodes was also significantly different to placebo at 10 
15, 45 and 60 minutes after administration. 
 
The mean pain intensity scores (73 patients) for all PecFent-treated episodes (459 episodes) compared 
to those treated with placebo (200 episodes) were significantly lower at 5, 10, 15, 30, 45 and 
60 minutes following administration (see Figure 1). 
 



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Figure 1: Mean (± SE) Pain Intensity Scores at Each Time Point (mITT Population) 

PecFent

PecFent 
PecFent 
PecFent 

 
 
The superior  efficacy of PecFent over placebo was supported by data from secondary endpoints 
including the number of BTP episodes with clinically meaningful pain relief, defined as a reduction in 
pain intensity score of at least 2 (Figure 2). 
 
Figure 2: Clinically Meaningful Pain Relief – PecFent vs placebo: % Patients’ Episodes With ≥2 Point 
Reduction in Pain Intensity 
 

 
In a double-blind, randomized comparator-controlled study (Study 044) of similar design to Study 043 
conducted in opioid-tolerant patients with breakthrough cancer pain on stable doses of regularly 
scheduled opioids, PecFent was shown to be superior to immediate-release morphine sulfate (IRMS). 
Superiority was demonstrated by the primary endpoint, Pain Intensity Difference within 15 minutes, 
which was 3.02 in patients treated with PecFent compared to 2.69 in patients treated with IRMS 
(p=0.0396). 



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In a long-term, open-label, safety study (Study 045), 355 patients entered the 16-week treatment 
phase, during which 42,227 episodes of breakthrough cancer pain (BTP) were treated with PecFent. 
One hundred of these patients continued treatment for up to 26 months in an extension phase. Of the 
355 patients treated in the open-label treatment phase, 90 % required no increase in dose.   
 
In the randomised, placebo-controlled study (CP043) 9.4% of 459 PecFent-treated BTP episodes in 73 
patients required use of any further (rescue) medicinal products within 60 minutes of dosing.  During 
the longer-term, open-label study (CP045) this was 6.0 % of 42,227 episodes in 355 patients treated 
with PecFent during up to 159 days of treatment. 
 
5.2 Pharmacokinetic properties 
 
General introduction 
Fentanyl is highly lipophilic and can be absorbed very rapidly through the nasal mucosa and more 
slowly by the gastrointestinal route. It is subject to first pass hepatic and intestinal metabolism and the 
metabolites do not contribute to fentanyl’s therapeutic effects. 
 
PecFent utilises the PecSys nasal drug delivery system to modulate the delivery and absorption of 
fentanyl. The PecSys system allows the product to be sprayed into the front area of the nasal cavity as 
a fine mist of droplets, which gel on contact with the calcium ions present in the nasal mucosa. 
Fentanyl diffuses from the gel and is absorbed through the nasal mucosa; this gel-modulated 
absorption of fentanyl restrains the peak in plasma concentration (Cmax) whilst allowing the attainment 
of an early time to that peak (Tmax). 
 
Absorption 
In a pharmacokinetic study comparing PecFent (100, 200, 400 and 800 micrograms) with oral 
transmucosal fentanyl citrate (OTFC, 200 micrograms), fentanyl was shown to be rapidly absorbed 
following single dose intranasal administration of PecFent, with median Tmax ranging from 15 to 
21 minutes (Tmax for OTFC was approximately 90 minutes). The variability of the pharmacokinetics of 
fentanyl was considerable following treatment with both PecFent and OTFC. Relative bioavailability 
of fentanyl from the PecFent treatment compared to the 200 microgram OTFC was approximately 
120 %. 
 
The main pharmacokinetic parameters are shown in the following table. 
 
Pharmacokinetic parameters in adult subjects receiving PecFent and OTFC 
Pharmacokinetic 
parameters  
(mean (%CV)) 

PecFent OTFC 
100 

micrograms 
200 

micrograms 
400 

micrograms 
800 

micrograms 
200 

micrograms 
Tmax (hours)* 0.33 (0.08-

1.50) 
0.25 (0.17-

1.60) 
0.35 (0.25-

0.75) 
0.34 (0.17-

3.00) 
1.50 (0.50 

-8.00) 
Cmax (pg/ml) 351.5 (51.3) 780.8 (48.4) 1552.1 (26.2) 2844.0 (56.0) 317.4 (29.9) 
AUC (pg.hour/ml) 2460.5 (17.9 4359.9 (29.8) 7513.4 (26.7) 17272 (48.9) 3735.0 (32.8) 
t1/2 (hour) 21.9 (13.6) 24.9 (51.3) 15.0 (24.7) 24.9 (92.5) 18.6 (31.4) 

*Data for Tmax presented as median (range). 
 
The curves for each dose level are similar in shape with increasing dose levels producing increasing 
plasma fentanyl levels. Dose-proportionality was demonstrated for Cmax and area under the curve 
(AUC) in the dose range 100 micrograms to 800 micrograms (see Figure 3). If switching to PecFent 
from another fentanyl product for BTP, independent dose titration with PecFent is required as the 
bioavailability between products differs significantly. 
 



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Figure 3: Mean plasma fentanyl concentrations following single doses of PecFent and OTFC in 
healthy subjects 

 
 
A pharmacokinetic study was conducted to evaluate the absorption and tolerability of a single dose of 
PecFent in patients with pollen-induced seasonal allergic rhinitis, comparing the un-challenged, 
acutely challenged (rhinitic) and acutely challenged and then treated with oxymetazoline, states. 
 
There was no clinically significant effect of acute rhinitis on Cmax, Tmax or overall exposure to 
fentanyl, comparing the unchallenged with the acutely challenged states. Following treatment of the 
acute rhinitic state with oxymetazoline, there were reductions in Cmax and exposure, and increases in 
Tmax that were statistically, and possibly clinically, significant. 
 
Distribution 
Fentanyl is highly lipophilic and is well distributed beyond the vascular system, with a large apparent 
volume of distribution. Animal data have shown that, following absorption, fentanyl is rapidly 
distributed to the brain, heart, lungs, kidneys and spleen followed by a slower redistribution to muscles 
and fat. 
 
The plasma protein binding of fentanyl is 80 – 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. 
 
Biotransformation 
The metabolic pathways following nasal administration of PecFent have not been characterised in 
clinical studies. Fentanyl is metabolised in the liver to norfentanyl by cytochrome CYP3A4 isoform. 
Norfentanyl is not pharmacologically active in animal studies. It is more than 90 % eliminated by 
biotransformation to N-dealkylated and hydroxylated inactive metabolites. 
 
Elimination 
Disposition of fentanyl following intranasal administration of PecFent has not been characterised in a 
mass balance study. Less than 7 % of an administered dose of fentanyl 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. 
 
The total plasma clearance of fentanyl following intravenous administration is approximately 42 L/h. 
 
Linearity/non-linearity 
Dose-proportionality was demonstrated for Cmax and AUC in the dose range 100 micrograms to 
800 micrograms. 

0

500

1000

1500

2000

2500

3000

3500

4000

4500

0 0.5 1 1.5 2 2.5 3 3.5 4

Pl
as

m
a 

Fe
nt

an
yl

 (p
g/

m
l)

Time (hours)

A.  PecFent 100 µg dose B.  PecFent 200 µg dose

C.  PecFent 400 µg dose D.  PecFent 800 µg dose

E.  OTFC 200 µg dose



 15 

The effect of renal or hepatic impairment on the pharmacokinetics of PecFent has not been studied. 
 
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 consistent with 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 induce any findings indicative of 
oncogenic potential.  Evaluation of brain slides from the carciogenicity 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 
 
Pectin (E440) 
Mannitol (E421) 
Phenylethyl alcohol 
Propylparahydroxybenzoate (E216) 
Sucrose 
Hydrochloric acid (0.36%) or sodium hydroxide (for pH adjustment) 
Purified water 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
2 spray bottle:  
18 months 
After priming, use within 5 days. 
 
8 spray bottle:  
3 years 
After first use: 60 days 
 



 16 

6.4 Special precautions for storage 
 
Do not store above 25 °C. 
Do not freeze. 
Keep the bottle in the child resistant container in order to protect from light.  
Store the bottle in the child resistant container at all times, even when finished. 
 
6.5 Nature and contents of container 
 
Bottle (clear Type I glass) with an attached metering pump incorporating an audible dose counter and 
a protective cap (solid white cap for the 2 spray and translucent cap for the 8 spray). In each case the 
product is packed in a clam-shell-like child resistant container. 
 
Bottles contain:  
0.95 ml ensuring delivery of 2 full sprays  
or 
1.55 ml ensuring delivery of 8 full sprays. 
 
Bottles in their child resistant containers are supplied in cartons containing: 
For 2 spray bottle: 1 bottle. 
For 8 spray bottle: 1, 4 or 12 bottles. 
 
Not all presentations or pack sizes may be marketed. 
 
6.6 Special precautions for disposal  
 
Partially used PecFent bottles may contain enough medicine to be harmful or life-threatening to a 
child.  Even if there is little or no medicine left in the bottle, PecFent must be disposed of properly, 
according to the following steps: 
o Patients and caregivers must be instructed to properly dispose of all unused, partially used and 

used PecFent bottles. The patient should be instructed how to do this correctly.  
o If there are any unwanted therapeutic sprays remaining in the bottle, the patient should be 

instructed to expel these as follows: 
 

2 spray bottle: 
o Aim the spray away from themselves (and any other people) and expel remaining spray until the 

red number “2” appears in the counting window and there are no more full therapeutic sprays 
obtainable from the bottle. 

o After the counter has advanced to “2”, the patient should continue to push down on the finger 
grips (there will be some increased resistance) a total of four times in order to expel any residual 
medicine from the bottle.  

o After the 2 therapeutic sprays have been emitted, the patient will not hear a click and the counter 
will not advance beyond “2”; further sprays emitted will not be full sprays and should not be 
used therapeutically. 

 
8 spray bottle: 
o Aim the spray away from themselves (and any other people) and expel remaining spray until the 

red number “8” appears in the counting window and there are no more full therapeutic sprays 
obtainable from the bottle. 

o  After the counter has advanced to “8”, the patient should continue to push down on the finger 
grips (there will be some increased resistance) a total of four times in order to expel any residual 
medicine from the bottle.  

o After the 8 therapeutic sprays have been emitted, the patient will not hear a click and the counter 
will not advance beyond “8”; further sprays emitted will not be full sprays and should not be 
used therapeutically. 

 



 17 

As soon as PecFent is no longer needed, patients and members of their household must be advised to 
systematically dispose of any bottles remaining from a prescription as soon as possible by returning 
them to their child-resistant container and discarding them, according to local requirements or by 
returning them to the pharmacy. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Kyowa Kirin Holdings B.V. 
Bloemlaan 2,  
2132NP Hoofddorp 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/644/007 
 
EU/1/10/644/001 
EU/1/10/644/002 
EU/1/10/644/005 
 
EU/1/10/644/003 
EU/1/10/644/004 
EU/1/10/644/006 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 31 August 2010 
Date of latest renewal: 17 July 2015 
 
 
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/


 18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURERRESPONSIBLE 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 
 



 19 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
L. Molteni & C dei F. LLi Alitti Societá di Esercizio S.p.A 
Strada Statale 67  
Tosco Romagnola 
Fraz. Granatieri  
IT-50018 Scandicci (FI) 
Italy 
 
 
B. CONDITIONS OR RESTRICTIONS 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 OR THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports  
 
The marketing authorisation holder shall submit periodic safety update reports for this product 
in accordance with the requirements set out in the list of Union reference dates (EURD list) 
provided for under Article 107c(7) of Directive 2001/83/EC and 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 signficant 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  
 
Prior to launch in each member State the MAH shall agree the final educational material with the 
National Competent Authority. 
 
The MAH shall ensure that, at launch, all physicians, pharmacists and patients expected to 
prescribe/use PecFent are provided with educational material informing about the correct and safe use 
of the product. 
 



 20 

Educational material for patients should highlight the following: 
• Instructions for use of the nasal spray device 
• Instructions for opening and closing of the child-resistant box 
• Information on the correct indication 
• Only use PecFent nasal spray if you are using other opioid pain medicine on a daily basis 
• Only use PecFent nasal spray if you have been experiencing breakthrough cancer pain episodes 
• Do not use PecFent nasal spray to treat any other short-term pain or pain status 
• Do not use PecFent nasal spray for treatment of more than four breakthrough cancer pain 

episodes a day 
• Only use PecFent nasal spray if you have received the proper information regarding the use of 

the device and the safety precautions from the prescriber and/or the pharmacist 
• All unused devices or empty containers should be returned systematically according to the local 

regulation 
 
Educational material for physicians should highlight the following: 
• PecFent nasal spray should be prescribed only by physicians experienced in the management of 

opioid therapy in cancer patients. 
• The prescribers of PecFent nasal spray must critically select the patients and closely follow 

o Instructions for use of the nasal spray device 
o Instructions for opening and closing of the child-resistant box 
o Information on the correct indication 

• PecFent nasal spray should not be used to treat any other short-term pain or pain status. 
• All unused devices or empty containers should be returned systematically according to the local 

regulation. 
• The prescriber must make use of the checklist for prescribers 
 
Educational material for pharmacists should highlight the following: 
• PecFent nasal spray is only indicated for the management of breakthrough pain in adults already 

receiving maintenance opioid therapy for chronic cancer pain 
• PecFent nasal spray should not be used to treat any other short-term pain or pain status 
• The pharmacist must be familiar with the educational material of PecFent nasal spray before 

using it in his/her organization 
• The PecFent nasal spray dose strengths can not be compared with other PecFent products 
• Instructions for use of the nasal spray device 
• Instructions for opening and closing of the child-resistant box 
• The pharmacist must inform the patients that in order to prevent theft and misuse of PecFent 

nasal spray they have to keep it in a safe place to avoid misuse and diversion 
• All unused devices or empty containers should be returned systematically according to the local 

regulation 
• The pharmacist must make use of the checklist for pharmacist 

  



 21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



 22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



 23 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
PecFent 100 micrograms/spray nasal spray solution 
Fentanyl 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each spray contains 100 micrograms of fentanyl (as citrate)  
Each ml of solution contains 1,000 micrograms fentanyl (as citrate) 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: pectin (E440), mannitol (E421), phenylethyl alcohol, propylparahydroxybenzoate 
(E216), sucrose, purified water and hydrochloric acid (0.36%) or sodium hydroxide for pH 
adjustment. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Nasal spray, solution 
 
[2 spray bottle:] 
1 bottle – 0.95 ml (2 sprays) per bottle 
 
[8 spray bottle:] 
1 bottle –  1.55 ml (8 sprays) per bottle 
4 bottles –  1.55 ml (8 sprays) per bottle 
12 bottles  1.55 ml (8 sprays) per bottle 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Nasal use 
 
[2 spray bottle:] 
If the spray has not been used within 5 days after priming it should be discarded. 
 
[8 spray bottle:] 
If PecFent has not been used for 5 days, re-prime by spraying once. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHTAND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 



 24 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
This medicine should only be used by patients taking other opioids. 
 
 
8. EXPIRY DATE 
 
EXP 
 
[2 spray bottle:] 
After priming, use within 5 days. 
 
[8 spray bottle:] 
After first-use, use within 60 days 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Do not freeze. 
Keep the bottle in the child resistant container in order to protect from light.  
Store the PecFent bottle in the child resistant container at all times, even when finished. 
 
 
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 
 
Kyowa Kirin Holdings B.V. 
Bloemlaan 2,  
2132NP Hoofddorp 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/644/007 100 micrograms, 2 sprays, 1 bottle 
 
EU/1/10/644/001 100 micrograms, 8 sprays, 1 bottle 
EU/1/10/644/002 100 micrograms, 8 sprays, 4 bottles 
EU/1/10/644/005 100 micrograms, 8 sprays, 12 bottles 
 
 
13. BATCH NUMBER 
 
Lot 
 
 



 25 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
PecFent 100  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 



 26 

PARTICULARS TO APPEAR ON THE CHILD RESISTANT CONTAINER (CRC) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
PecFent 100 micrograms/spray nasal spray  
Fentanyl 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each spray contains 100 micrograms of fentanyl (as citrate)  
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: pectin (E440), mannitol (E421), phenylethyl alcohol, propylparahydroxybenzoate 
(E216), sucrose, purified water and hydrochloric acid (0.36%) or sodium hydroxide for pH 
adjustment. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Nasal use 
Read the package leaflet before use. 
 
[2 spray bottle:] 
If the spray has not been used within 5 days after priming it should be discarded. 
 
[8 spray bottle:] 
If PecFent has not been used for 5 days, re-prime by spraying once. 
 
 
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 medicine should only be used by patients taking other opioids. 
 
 
8. EXPIRY DATE 
 
2 spray bottle: 
After priming, use within 5 days.  
Date of priming: ………. 
 



 27 

8 spray bottle: 
After first-use, use within 60 days 
Date of first use: ………. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Do not freeze. 
Keep the bottle in the child resistant container in order to protect from light.  
Store the PecFent bottle in the child resistant container at all times, even when finished. 
 
 
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 
 
Kyowa Kirin Holdings B.V. 
Bloemlaan 2,  
2132NP Hoofddorp 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
 



 28 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
BOTTLE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
PecFent 100 micrograms/spray nasal spray  
Fentanyl  
Nasal use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
0.95 ml – 2 sprays 
1.55 ml - 8 sprays 
 
 
6. OTHER 
 
 



 29 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
PecFent 400 micrograms/spray nasal spray solution 
Fentanyl 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each spray contains 400 micrograms of fentanyl (as citrate)  
Each ml of solution contains 4,000 micrograms fentanyl (as citrate) 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: pectin (E440), mannitol (E421), phenylethyl alcohol, propylparahydroxybenzoate 
(E216), sucrose, purified water and hydrochloric acid (0.36%) or sodium hydroxide for pH 
adjustment. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Nasal spray, solution 
1 bottle – 1.55 ml (8 sprays) per bottle 
4 bottles – 1.55 ml (8 sprays) per bottle 
12 bottles – 1.55 ml (8 sprays) per bottle 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Nasal use 
If PecFent has not been used for 5 days, re-prime by spraying once. 
 
 
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 medicine should only be used by patients taking other opioids. 
 
 



 30 

8. EXPIRY DATE 
 
EXP 
After first-use, use within 60 days. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Do not freeze. 
Keep the bottle in the child resistant container in order to protect from light.  
Store the PecFent bottle in the child resistant container at all times, even when finished. 
 
 
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 
 
Kyowa Kirin Holdings B.V. 
Bloemlaan 2,  
2132NP Hoofddorp 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/644/003 400 micrograms, 8 sprays, 1 bottle 
EU/1/10/644/004 400 micrograms, 8 sprays, 4 bottles 
EU/1/10/644/006 400 micrograms, 8 sprays, 12 bottles 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
PecFent 400  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 



 31 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 



 32 

PARTICULARS TO APPEAR ON THE CHILD RESISTANT CONTAINER (CRC) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
PecFent 400 micrograms/spray nasal spray  
Fentanyl 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each spray contains 400 micrograms of fentanyl (as citrate)  
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: pectin (E440), mannitol (E421), phenylethyl alcohol, propylparahydroxybenzoate 
(E216), sucrose, purified water and hydrochloric acid (0.36%) or sodium hydroxide for pH 
adjustment. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Nasal use 
Read the package leaflet before use. 
If PecFent has not been used for 5 days, re-prime by spraying once. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THESIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
This medicine should only be used by patients taking other opioids. 
 
 
8. EXPIRY DATE 
 
After first-use, use within 60 days 
Date of first use: ………. 
 
 



 33 

9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Do not freeze. 
Keep the bottle in the child resistant container in order to protect from light.  
Store the PecFent bottle in the child resistant container at all times, even when finished. 
 
 
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 
 
Kyowa Kirin Holdings B.V. 
Bloemlaan 2,  
2132NP Hoofddorp 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 



 34 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
BOTTLE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
PecFent 400 micrograms/spray nasal spray  
Fentanyl  
Nasal use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1.55 ml - 8 sprays 
 
 
6. OTHER 
 
 

  



 35 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
  



 36 

 
 

Package leaflet: Information for the user 
 

PecFent 100 micrograms/spray nasal spray, solution 
PecFent 400 micrograms/spray nasal spray, solution 

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 doctoror 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 PecFent is and what it is used for 
2. What you need to know before you use PecFent 
3. How to use PecFent 
4.  Possible side effects 
5. How to store PecFent 
6. Contents of the pack and other information 
 
 
1. What PecFent is and what it is used for 
 
What PecFent is 
PecFent contains fentanyl, which is a strong pain-relieving medicine known as an opioid pain killer.  
 
What PecFent is used for 
PecFent is used in adults with cancer for a type of pain called ‘breakthrough’ pain.  
• Breakthrough pain comes on suddenly.  
• It comes on even though you have taken your usual opioid pain killer (such as morphine, 

fentanyl, oxycodone or hydromorphone) to control your constant background pain.  
 
PecFent is only to be used by adults who are already taking other opioid medicines daily for their 
constant cancer pain. 
 
How PecFent works 
PecFent is a nasal spray, solution  
• When you spray PecFent into your nose the very small spray droplets form a thin gel.  
• Fentanyl is absorbed quickly through the lining of your nose and into the blood stream.  
• This means the medicine gets into your system quickly to relieve your breakthrough pain. 
 
 
2. What you need to know before you use PecFent 
 
Do not use PecFent if: 
• you are allergic to fentanyl or any of the other ingredients of this medicine (listed in Section 6). 
• 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 PecFent, 
because it may increase the risk that breathing could become dangerously slow and/or shallow, 
or even stop. 



 37 

• you suffer from short-term pain other than breakthrough pain. 
• you have a serious breathing or lung problem. 
 
Do not use PecFent if any of the above applies to you. If you are not sure, talk to your doctor or 
pharmacist before using PecFent. 
 
Warnings and precautions 
 
Keeping PecFent safe from children 
• You must keep PecFent in the child resistant storage container when you are not using it, even if 

you have used all 8 sprays. This is because PecFent could be life-threatening if taken by a child 
by accident.  

 
Check with your doctor or pharmacist before using PecFent if: 
• you have not been taking the same dose of your daily opioid medicine for your constant pain for 

some time 
• you have breathing problems such as asthma, wheezing or shortness of breath 
• you suffer a severe blow to the head 
• you have problems with your heart especially slow heart rate 
• you have low blood pressure or a low amount of fluid in your circulation 
• you have liver or kidney problems. This is because it may affect the way in which your body 

breaks down the medicine. 
• you take antidepressants or antipsychotics, please refer to the section ‘Other medicines and 

PecFent’. 
 
If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist before using 
PecFent. 
• If you are an athlete, using PecFent may result in positive doping-tests. 
 
Consult your doctor while using PecFent if: 
• you suffer from recurrent nose bleeding - he may advise an alternative treatment 
• you feel that PecFent is becoming less effective in treating your episodes of breakthrough pain 
• 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 think you are becoming dependent on PecFent 
• 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 

• you have ever developed adrenal insufficiency or lack of sex hormones (androgen deficiency) 
with opioid use 
 

 
Children and adolescents 
PecFent is not approved for use in children under 18 years of age. 
 
Other medicines and PecFent 
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.  
In particular tell your doctor or pharmacist before using PecFent if you are taking or have recently 
taken any of the following medicines: 
• medicines that might make you sleepy such as sleeping tablets, tranquilisers, muscle relaxants, 

medicines for anxiety or medicines for allergies (anti-histamines) 
• medicines for depression called ‘monoamine-oxidase inhibitors’ (MAOI). Tell your doctor or 

pharmacist if you have taken an MAOI medicine in the past 2 weeks before using PecFent. 
The risk of side effects increases if you are taking medicines such as certain antidepressants or 
antipsychotics. PecFent may interact with these medicines and you may experience mental 



 38 

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 PecFent is suitable for you. 

• nasal sprays to treat a stuffy nose (containing a decongestant such as oxymetazoline) 
• medicines that might have an effect on the way your body breaks down PecFent. These include:  

o medicines for HIV infection (such as ritonavir, nelfinavir, amprenavir or fosamprenavir)  
o medicines for fungal infections (such as ketoconazole, itraconazole or fluconazole) 
o medicines for bacterial infections (such as troleandomycin, clarithromycin or 

erythromycin)  
o ‘aprepitant’ - used to stop you feeling sick 
o ‘diltiazem’ and ‘verapamil’ - used for high blood pressure or heart problems. 
o other pain killers called partial agonist/antagonist like buprenorphine, nalbuphine, 

pentazocine. You could experience symptoms of withdrawal syndrome (nausea, 
vomiting, diarrhoea, anxiety, chills, tremor, and sweating) while using these medicines. 

If any of the above applies to you (or you are not sure), talk to your doctor or pharmacist before using 
PecFent. 
 
Don’t use any other kind of nasal spray for at least 15 minutes after using PecFent. 
 
PecFent with food, drink and alcohol 
• Do not drink alcohol while using PecFent. It can increase the risk of getting serious side effects. 
• Do not drink grapefruit juice while using PecFent. It may affect the way your body breaks down 

PecFent. 
 
Pregnancy, breast-feeding and fertility 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
• Do not use PecFent if you are pregnant or might get pregnant, unless your doctor has told you 

to. 
• Do not use PecFent during child birth. This is because it may cause breathing problems in your 

baby. 
• Do not use PecFent if you are breast-feeding. This is because the medicine can get into your 

breast milk and may cause side effects in the breast-fed child. 
• You should not start breast-feeding within 5 days after the last dose of PecFent. 
 
Driving and using machines 
• Talk to your doctor about whether it will be safe for you to drive or use tools or machines after 

using PecFent. 
• You may feel sleepy, dizzy or have problems with your eyesight after using PecFent. If this 

happens, do not drive or use any tools or machines.  
• Do not drive or use tools or machines until you know how this medicine makes you feel.  
 
PecFent contains propylparahydroxybenzoate (E216). 
May cause allergic reactions (possibly delayed), and exceptionally, bronchospasm (if you do not use 
the nasal spray correctly).  
 
 
3. How to use PecFent 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
PecFent comes in two different strengths: a 100 microgram per spray bottle and a 400 microgram 
per spray bottle. Make sure that you use the strength that your doctor has prescribed for you. 
 



 39 

How much to use 
• A dose to treat a breakthrough pain episode might be either 1 spray or 2 sprays (one in each 

nostril). Your doctor will tell you how many sprays (1 or 2) you should use to treat your 
breakthrough pain episode. 

• Do not use more than the dose your doctor prescribes for any single breakthrough pain 
episode. 

• Do not use PecFent more than 4 times daily 
• Wait at least 4 hours to take the next dose of PecFent. 
Starting dose 
• The starting dose is 100 micrograms. 
• This is a single spray into one nostril from the 100 microgram per spray bottle.  
• See ‘Using the PecFent bottle’ for instructions on how to use a dose. 
 
Finding the right dose 
• Your doctor will then help you find the right dose to relieve your breakthrough pain. It is very 

important to follow your doctor’s instructions. 
• Tell your doctor about your pain and how PecFent is working. Your doctor will decide if your 

PecFent dose needs to be changed.  
• Do not change the dose yourself. 
 
Once you have found the right dose 
• Tell your doctor if your dose of PecFent does not relieve your breakthrough pain. Your doctor 

will decide if your dose needs to be changed. Do not change the dose of PecFent or your 
other pain medicines yourself. 

• Tell your doctor straight away if you have more than 4 episodes of breakthrough pain a day. 
Your doctor may change the medicine for your constant pain. Once your constant pain is 
controlled, your doctor may then change your dose of PecFent. 

If you are not sure about the right dose or how much PecFent to use, ask your doctor. 
 
Using the PecFent bottle 
 

 
 
Preparing the PecFent bottle for use  
Before you use a new bottle of PecFent you need to prepare it for use. This is called ‘priming’.  
To prime the bottle, please follow the instructions below: 
1. A new bottle of PecFent will show two red lines in the counting window in the white plastic top 

on the bottle (Figure 1 and Figure 3a).  
2. Take off the clear plastic protective cap from the nozzle (Figure 1). 
3. Aim the nasal spray away from you (and any other people). 
4. Hold the PecFent nasal spray upright with your thumb on the bottom of the bottle, and your first 

and middle fingers on the finger grips each side of the nozzle (Figure 2).  



 40 

5. Firmly press down on the finger grips until a ‘click’ is heard and then let go of the grips (Figure 
2). You will hear a second ‘click’ and there should now be a single large red bar in the counting 
window (Figure 3b). 

6. Repeat step 5 three times. As you repeat step 5, the red bar will become smaller and smaller 
until you see a green bar in the counting window (Figure 3b-e).  The green bar means the 
PecFent nasal spray is ready to use.  

7. Wipe the nozzle with a tissue and flush the tissue down the toilet. 
8. If you are not going to use your medicine straight away, put the protective cap back on. Then 

put the PecFent bottle in the child-resistant storage container.   If PecFent has not been used for 
5 days, re-prime by spraying once. 

 

 
 
 
 
 
 
 
 
Using PecFent 
 
PecFent is only to be used by spraying into your nostril.  
 
1. Check that there is a green bar or a number showing in the counting window (Figure 4): this 

confirms that the PecFent bottle has been primed (see ‘Preparing the PecFent bottle for use’ 
above). 

2. Blow your nose if you feel you need to.  
3. Sit down with your head upright. 
4. Take off the protective cap from the nozzle. 
5. Hold the PecFent bottle with your thumb on the bottom of the bottle and your first and middle 

fingers on the finger grips (Figure 4).  
6. Put the nozzle a short distance (about 1 cm) into your nostril. Point it inwards towards the wall 

of your nose. This will tilt the bottle slightly (Figure 5). 
7. Close the other nostril with a finger from your other hand (Figure 5). 
8. Firmly press down on the finger grips so that PecFent sprays into your nostril. When you hear a 

click let go of the grips. Note: You may not feel anything happen in your nose at all – do not 
trust this to mean the spray did not operate – rely on the click and number counter.  

9. Breathe in gently through your nose and out through your mouth.  
10. The number counter will move forward after each use and show how many sprays have been 

used. 
11. If your doctor has prescribed a second spray, repeat steps 5 to 9, using the other nostril.  

 
Do not use more than the dose that your doctor prescribes to treat any single pain episode. 
12. Put the bottle back in the child-resistant container after each use. Keep out of the sight and reach 

of children (Figure 6) 



 41 

13. Stay sitting for at least 1 minute after using the nasal spray. 
 

 
Number of sprays in a PecFent bottle 
There are 8 full sprays in each PecFent bottle. 
• After the first spray, number 1 will appear in the counting window. This will go up each time 

the spray is used.  
• When you see a red 8 in the counting window, the bottle is finished and you will no longer be 

able to get a full spray from it. 
 

Disposal of unused PecFent 
If you can see a number, other than 8 in the counting window, you have NOT used all 8 sprays in the 
bottle. There are still doses of PecFent left in the bottle. 
 
You must empty the remaining doses of PecFent from the bottle by aiming the nasal spray away 
from you (and any other people) and pressing and releasing the grips until the red number “8” appears 
in the counting window. 
 
When you see the number “8” in the counting window, there is still medicine in the bottle that 
you must empty. 
•  You will need to press down and release the finger grips 4 more times while aiming the nasal 

spray away from you (and any other people). 
• You will feel some increased resistance when you press down and the finger grips will only 

move a small amount. 
• You will NOT hear a click when you press down . 
• The counter will stay on the number “8”. 
• Put the protective cap back on the spray bottle.  
• Put the bottle back in the child resistant container. 
• Speak to your local pharmacy about disposal of empty bottles (see ‘How to store PecFent’) 

 
If the PecFent nasal spray is blocked or does not spray properly 
• If the spray is blocked, aim the spray away from you (and any other people) and push firmly 

down on the pump. This should clear any blockage. 
• If your nasal spray is still not working properly, dispose of the faulty bottle and start a new one. 

Tell your doctor what happened. Never try to fix the nasal spray yourself or take it apart. 
This is because it may then give you the wrong dose. 

 
Dispose of the PecFent bottle and start a new one if: 

It has been 60 days or more since you primed or used your bottle for the first time. 
 



 42 

If you use more PecFent than you should 
• If you use more PecFent than you should, you may feel sleepy, sick, dizzy or have slow or 

shallow breathing. In severe cases taking too much PecFent may also lead to coma. If you feel 
very dizzy, very sleepy or have slow or shallow breathing, call an ambulance or ask someone 
else to call one straight away. 

 
If you stop using PecFent 
If you no longer have breakthrough pain, talk to your doctor before stopping PecFent and follow 
his/her advice. However, you should keep taking your other opioid medicine to treat your constant 
pain. Your doctor may need to check the dose. 
 
You may experience withdrawal symptoms similar to the possible side effects of PecFent when 
discontinuing PecFent. If you experience withdrawal symptoms, 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.  
 
Call an ambulance or ask someone else to call one straight away if you: 
• feel very dizzy or faint  
• feel very sleepy 
• get slow or shallow breathing  
• get cold clammy skin, look pale, have a weak pulse or other signs of shock.  
 
If you or your carer notice any of the side effects above, call an ambulance straight away. 
 
Common side effects (may affect up to 1 in 10 people):  
• not knowing where you are (disorientated)  
• change in taste  
• feeling dizzy 
• feeling or being sick 
• feeling sleepy, headache 
• nose bleed, discomfort in the nose, runny nose  
• constipation 
• itchy skin 
 
Uncommon side effects: (may affect up to 1 in 100 people): 
• chest infection 
• painful, sore or inflamed throat or nose 
• cough, sneezing, catarrh or cold, changes in the fluid produced by your nose  
• allergic reaction, rash 
• loss of or increase in appetite, weight increase 
• dehydration, feeling thirsty 
• misusing the medicine 
• seeing or hearing things that are not really there (hallucinations/delirium), feeling confused  
• feeling depressed, worried, slow or nervous 
• a lack of concentration or increased activity 
• memory loss 
• feeling “high” 
• being less aware or responsive, losing consciousness 
• convulsion (fits) 



 43 

• muscle convulsions or trembling 
• loss of taste, loss or change in sense of smell 
• difficulty in speaking 
• blue skin colour 
• vertigo, falling over, malaise 
• heat and circulation not working properly, hot flush or fever, chills, excessive sweating 
• swelling of the soft tissue 
• low blood pressure 
• blockage in the wind-pipe 
• shortness of breath 
• vaginal bleeding 
• tear in the intestine or inflammation of the stomach lining 
• numbness or tingling in the mouth, tongue, or nose, or other tongue problems, mouth ulcers, dry 

mouth 
• diarrhoea 
• retching, stomach pains, indigestion 
• sore or painful joints 
• difficulty in or inability to pass water 
• chest pain 
• feeling tired or weak, problems moving 
• changes in blood cells (detected by laboratory tests) 
• increased blood sugar  
• protein in the urine  
 
Other side effects (frequency not known (frequency cannot be estimated from the available data)) 
• Severe breathing problems 
• Flushing 
• Insomnia 
• Withdrawal syndrome (may manifest by the occurrence of the following side effects nausea, 

vomiting, diarrhoea, anxiety, chills, tremor, and sweating) 
• Drug dependence (addiction) 
• Drug abuse 
 
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 PecFent 
 
Keep this medicine out of the sight and reach of children. PecFent could be life-threatening if 
taken by a child by accident.  
• Do not use this medicine after the expiry date which is stated on the carton and bottle after EXP. 

The expiry date refers to the last day of that month.  
• Do not store PecFent above 25°C.  
• Do not freeze. 
• Keep the bottle in its child resistant container in order to protect from light. 
• Store the PecFent bottle in the child resistant container at all times, even when finished. 

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


 44 

• Do not use for more than 60 days after first use (either priming or using to treat a breakthrough 
pain episode). 

• PecFent that has passed the expiry date or is no longer required may still contain enough 
medicine to be harmful to other people, especially children. PecFent should not be disposed of 
via wastewater or household waste. Any unwanted PecFent should be disposed of as soon as 
possible following the instructions under Disposal of unused PecFent. Any empty bottles 
should be returned to their child resistant container and discarded by taking them back to the 
pharmacy or according to local requirements. 

6. Contents of the pack and other information 
 
What PecFent contains 
 
The active substance is fentanyl.  
• PecFent 100 micrograms/spray nasal spray, solution 

Each ml of solution contains 1,000 micrograms  fentanyl (as citrate). 
1 spray (100 microlitres) contains 100 micrograms fentanyl (as citrate). 

• PecFent 400 micrograms/spray nasal spray, solution 
Each ml of solution contains 4,000 micrograms fentanyl (as citrate). 
1 spray (100 microlitres) contains 400 micrograms fentanyl (as citrate). 
 

The other ingredients (excipients) are pectin (E440), mannitol (E421), phenylethyl alcohol, 
propylparahydroxybenzoate (E216), sucrose, purified water and hydrochloric acid or sodium 
hydroxide for pH adjustment. 
 
What PecFent looks like and contents of the pack 
The medicine is a clear to almost clear, colourless nasal spray, solution. It is contained in a clear glass 
bottle, fitted with a metering pump. The pump has a spray counter that clicks, so you can hear as well 
as see that the spray has been given and a protective cap. After the PecFent bottle has been primed 
(prepared for use) it delivers 8 full sprays. Each PecFent bottle is supplied in a child resistant 
container. 
 
PecFent bottles in their child resistant containers are supplied in cartons containing 1, 4 or 12 bottles. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Kyowa Kirin Holdings B.V. 
Bloemlaan 2,  
2132NP Hoofddorp 
The Netherlands 
 
Manufacturer 
L. Molteni & C. dei F.lli Alitti Società di Esercizio S.p.A 
Strada Statale 67 Tosco Romagnola,  
Fraz. Granatieri – 50018 Scandicci (FI) 
Italy 
 
This leaflet was last revised  
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 
 
  

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


 45 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
  



 46 

 
 

Package leaflet: Information for the user 
 

PecFent 100 micrograms/spray nasal spray, solution - two-spray bottle 
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 doctoror 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 PecFent is and what it is used for 
3. What you need to know before you use PecFent 
3. How to use PecFent 
4.  Possible side effects 
5. How to store PecFent 
6. Contents of the pack and other information 
 
 
1. What PecFent is and what it is used for 
 
What PecFent is 
PecFent contains fentanyl, which is a strong pain-relieving medicine known as an opioid pain killer.  
 
What PecFent is used for 
PecFent is used in adults with cancer for a type of pain called ‘breakthrough’ pain.  
• Breakthrough pain comes on suddenly.  
• It comes on even though you have taken your usual opioid pain killer (such as morphine, 

fentanyl, oxycodone or hydromorphone) to control your constant background pain.  
 
PecFent is only to be used by adults who are already taking other opioid medicines daily for their 
constant cancer pain. 
 
How PecFent works 
PecFent is a nasal spray, solution  
• When you spray PecFent into your nose the very small spray droplets form a thin gel.  
• Fentanyl is absorbed quickly through the lining of your nose and into the blood stream.  
• This means the medicine gets into your system quickly to relieve your breakthrough pain. 
 
 
2. What you need to know before you use PecFent 
 
Do not use PecFent if: 
• you are allergic to fentanyl or any of the other ingredients of this medicine (listed in Section 6). 
• 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 PecFent, 
because it may increase the risk that breathing could become dangerously slow and/or shallow, 
or even stop. 

• you suffer from short-term pain other than breakthrough pain. 



 47 

• you have a serious breathing or lung problem. 
Do not use PecFent if any of the above applies to you. If you are not sure, talk to your doctor or 
pharmacist before using PecFent. 
 
Warnings and precautions 
Keeping PecFent safe from children 
• You must keep PecFent in the child resistant storage container when you are not using it, even if 

you have used all 2 sprays. This is because PecFent could be life-threatening if taken by a child 
by accident.  

 
Check with your doctor or pharmacist before using PecFent if: 
• you have not been taking the same dose of your daily opioid medicine for your constant pain for 

some time 
• you have breathing problems such as asthma, wheezing or shortness of breath 
• you suffer a severe blow to the head 
• you have problems with your heart especially slow heart rate 
• you have low blood pressure or a low amount of fluid in your circulation 
• you have liver or kidney problems. This is because it may affect the way in which your body 

breaks down the medicine. 
• you take antidepressants or antipsychotics, please refer to the section ‘Other medicines and 

PecFent’. 
 
If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist before using 
PecFent. 
• If you are an athlete, using PecFent may result in positive doping-tests. 
 
Consult your doctor while using PecFent if: 
• you suffer from recurrent nose bleeding - he may advise an alternative treatment 
• you feel that PecFent is becoming less effective in treating your episodes of breakthrough pain 
• 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 think you are becoming dependent on PecFent 
• 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 

• you have ever developed adrenal insufficiency or lack of sex hormones (androgen deficiency) 
with opioid use 
 

 
Children and adolescents 
PecFent is not approved for use in children under 18 years of age. 
 
Other medicines and PecFent 
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.  
In particular tell your doctor or pharmacist before using PecFent if you are taking or have recently 
taken any of the following medicines: 
• medicines that might make you sleepy such as sleeping tablets, tranquilisers, muscle relaxants, 

medicines for anxiety or medicines for allergies (anti-histamines) 
• medicines for depression called ‘monoamine-oxidase inhibitors’ (MAOI). Tell your doctor or 

pharmacist if you have taken an MAOI medicine in the past 2 weeks before using PecFent. 
The risk of side effects increases if you are taking medicines such as certain antidepressants or 
antipsychotics. PecFent 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, 



 48 

muscular rigidity, lack of coordination and/or gastrointestinal symptoms (e.g. nausea, vomiting, 
diarrhoea). Your doctor will tell you whether PecFent is suitable for you. 

• nasal sprays to treat a stuffy nose (containing a decongestant such as oxymetazoline) 
• medicines that might have an effect on the way your body breaks down PecFent. These include:  

o medicines for HIV infection (such as ritonavir, nelfinavir, amprenavir or fosamprenavir)  
o medicines for fungal infections (such as ketoconazole, itraconazole or fluconazole) 
o medicines for bacterial infections (such as troleandomycin, clarithromycin or 

erythromycin)  
o ‘aprepitant’ - used to stop you feeling sick 
o ‘diltiazem’ and ‘verapamil’ - used for high blood pressure or heart problems. 
o other pain killers called partial agonist/antagonist like buprenorphine, nalbuphine, 

pentazocine. You could experience symptoms of withdrawal syndrome (nausea, 
vomiting, diarrhoea, anxiety, chills, tremor, and sweating) while using these medicines. 

If any of the above applies to you (or you are not sure), talk to your doctor or pharmacist before using 
PecFent. 
 
Don’t use any other kind of nasal spray for at least 15 minutes after using PecFent. 
 
PecFent with food, drink and alcohol 
• Do not drink alcohol while using PecFent. It can increase the risk of getting serious side effects. 
• Do not drink grapefruit juice while using PecFent. It may affect the way your body breaks down 

PecFent. 
 
Pregnancy, breast-feeding and fertility 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
• Do not use PecFent if you are pregnant or might get pregnant, unless your doctor has told you 

to. 
• Do not use PecFent during child birth. This is because it may cause breathing problems in your 

baby. 
• Do not use PecFent if you are breast-feeding. This is because the medicine can get into your 

breast milk and may cause side effects in the breast-fed child. 
• You should not start breast-feeding within 5 days after the last dose of PecFent. 
 
Driving and using machines 
• Talk to your doctor about whether it will be safe for you to drive or use tools or machines after 

using PecFent. 
• You may feel sleepy, dizzy or have problems with your eyesight after using PecFent. If this 

happens, do not drive or use any tools or machines.  
• Do not drive or use tools or machines until you know how this medicine makes you feel.  
 
PecFent contains propylparahydroxybenzoate (E216). 
May cause allergic reactions (possibly delayed), and exceptionally, bronchospasm (if you do not use 
the nasal spray correctly).  
 
 
3. How to use PecFent 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
PecFent comes in two different strengths: a 100 microgram per spray bottle and a 400 microgram 
per spray bottle. Make sure that you use the strength that your doctor has prescribed for you. 
 
How much to use 



 49 

• A dose to treat a breakthrough pain episode might be either 1 spray or 2 sprays (one in each 
nostril). Your doctor will tell you how many sprays (1 or 2) you should use to treat your 
breakthrough pain episode. 

• Do not use more than the dose your doctor prescribes for any single breakthrough pain 
episode. 

• Do not use PecFent more than 4 times daily 
• Wait at least 4 hours to take the next dose of PecFent. 
 
Starting dose 
• The starting dose is 100 micrograms. 
• This is a single spray into one nostril from the 100 microgram per spray bottle.  
• See ‘Using the PecFent bottle’ for instructions on how to use a dose. 
 
Finding the right dose 
• Your doctor will then help you find the right dose to relieve your breakthrough pain. It is very 

important to follow your doctor’s instructions. 
• Tell your doctor about your pain and how PecFent is working. Your doctor will decide if your 

PecFent dose needs to be changed.  
• Do not change the dose yourself. 
 
Once you have found the right dose 
• Tell your doctor if your dose of PecFent does not relieve your breakthrough pain. Your doctor 

will decide if your dose needs to be changed. Do not change the dose of PecFent or your 
other pain medicines yourself. 

• Tell your doctor straight away if you have more than 4 episodes of breakthrough pain a day. 
Your doctor may change the medicine for your constant pain. Once your constant pain is 
controlled, your doctor may then change your dose of PecFent. 

If you are not sure about the right dose or how much PecFent to use, ask your doctor. 
 
Using the PecFent bottle 
 

 
 
Preparing the PecFent bottle for use  
Before you use a new bottle of PecFent you need to prepare it for use. This is called ‘priming’. It is 
recommended that you prime the bottle immediately before use rather than in advance (Note: This 2 
spray bottle cannot be re-primed. If the spray has not been used within 5 days after priming, the bottle 
should be discarded.) 
 
To prime the bottle, please follow the instructions below: 
1. A new bottle of PecFent will show two red lines in the counting window in the white plastic top 

on the bottle (Figure 1 and Figure 3a).  
2. Take off the white plastic protective cap from the nozzle (Figure 1). 



 50 

3. Aim the nasal spray away from you (and any other people). 
4. Hold the PecFent nasal spray upright with your thumb on the bottom of the bottle, and your first 

and middle fingers on the finger grips each side of the nozzle (Figure 2).  
5. Firmly press down on the finger grips until a ‘click’ is heard and then let go of the grips (Figure 

2). You will hear a second ‘click’ and there should now be a single large red bar in the counting 
window (Figure 3b). 

6. Repeat step 5 three times. As you repeat step 5, the red bar will become smaller and smaller 
until you see a green bar in the counting window (Figure 3b-e).  The green bar means the 
PecFent nasal spray is ready to use.  

7. Wipe the nozzle with a tissue and flush the tissue down the toilet.  
 

 
 
 
 
 
 
 
 
Using PecFent 
 
PecFent is only to be used by spraying into your nostril.  
 
1. Check that there is a green bar or a number showing in the counting window (Figure 4): this 

confirms that the PecFent bottle has been primed (see ‘Preparing the PecFent bottle for use’ 
above). 

2. Blow your nose if you feel you need to.  
3. Sit down with your head upright. 
4. Take off the protective cap from the nozzle. 
5. Hold the PecFent bottle with your thumb on the bottom of the bottle and your first and middle 

fingers on the finger grips (Figure 4).  
6. Put the nozzle a short distance (about 1 cm) into your nostril. Point it inwards towards the wall 

of your nose. This will tilt the bottle slightly (Figure 5). 
7. Close the other nostril with a finger from your other hand (Figure 5). 
8. Firmly press down on the finger grips so that PecFent sprays into your nostril. When you hear a 

click let go of the grips. Note: You may not feel anything happen in your nose at all – do not 
trust this to mean the spray did not operate – rely on the click and number counter.  

9. Breathe in gently through your nose and out through your mouth.  
10. The number counter will move forward after each use and show how many sprays have been 

used. 
11. If your doctor has prescribed a second spray, repeat steps 5 to 9, using the other nostril.  
 
Do not use more than the dose that your doctor prescribes to treat any single pain episode. 
12. Put the bottle back in the child-resistant container after each use. Keep out of the sight and reach 

of children (Figure 6) 



 51 

13. Stay sitting for at least 1 minute after using the nasal spray. 
 

 
Number of sprays in this PecFent bottle 
There are 2 full sprays in each PecFent bottle. 
• After the first spray, number 1 will appear in the counting window. This will go up to the 

number 2 when the spray is used again.  
• When you see the red 2 in the counting window, the bottle is finished and you will no longer be 

able to get a full spray from it. 
 
Disposal of unused PecFent 
• If you can see a number, other than 2 in the counting window, you have NOT used all 2 sprays 

in the bottle. There are still doses of PecFent left in the bottle. 
 

• You must empty this remaining dose of PecFent from the bottle by aiming the nasal spray 
away from you (and any other people) and pressing and releasing the grips until the red number 
“2” appears in the counting window. 
 

When you see the number “2” in the counting window, there is still medicine in the bottle that 
you must empty. 
•  You will need to press down and release the finger grips 4 more times while aiming the nasal 

spray away from you (and any other people). 
• You will feel some increased resistance when you press down and the finger grips will only 

move a small amount. 
• You will NOT hear a click when you press down . 
• The counter will stay on the number “2”. 
• Put the protective cap back on the spray bottle.  
• Put the bottle back in the child resistant container. 
• Speak to your local pharmacy about disposal of empty bottles (see ‘How to store PecFent’) 
 
If the PecFent nasal spray is blocked or does not spray properly 
• If the spray is blocked, aim the spray away from you (and any other people) and push firmly 

down on the pump. This should clear any blockage. 
• If your nasal spray is still not working properly, dispose of the faulty bottle and start a new one. 

Tell your doctor what happened. Never try to fix the nasal spray yourself or take it apart. 
This is because it may then give you the wrong dose. 

 
Dispose of the PecFent bottle and start a new one if: 
• It is more than 5 days since you primed your bottle for the first time. 
 



 52 

If you use more PecFent than you should 
• If you use more PecFent than you should, you may feel sleepy, sick, dizzy or have slow or 

shallow breathing. In severe cases taking too much PecFent may also lead to coma. If you feel 
very dizzy, very sleepy or have slow or shallow breathing, call an ambulance or ask someone 
else to call one straight away. 
 

If you stop using PecFent 
If you no longer have breakthrough pain, talk to your doctor before stopping PecFent and follow 
his/her advice. However, you should keep taking your other opioid medicine to treat your constant 
pain. Your doctor may need to check the dose. 
 
You may experience withdrawal symptoms similar to the possible side effects of PecFent when 
discontinuing PecFent. If you experience withdrawal symptoms, 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.  
 
Call an ambulance or ask someone else to call one straight away if you: 
• feel very dizzy or faint  
• feel very sleepy 
• get slow or shallow breathing  
• get cold clammy skin, look pale, have a weak pulse or other signs of shock.  
 
If you or your carer notice any of the side effects above, call an ambulance straight away. 
 
Common side effects (may affect up to 1 in 10 people):  
• not knowing where you are (disorientated)  
• change in taste  
• feeling dizzy 
• feeling or being sick 
• feeling sleepy, headache 
• nose bleed, discomfort in the nose, runny nose  
• constipation 
• itchy skin 
 
Uncommon side effects: (may affect up to 1 in 100 people): 
• chest infection 
• painful, sore or inflamed throat or nose 
• cough, sneezing, catarrh or cold, changes in the fluid produced by your nose  
• allergic reaction, rash 
• loss of or increase in appetite, weight increase 
• dehydration, feeling thirsty 
• misusing the medicine 
• seeing or hearing things that are not really there (hallucinations/delirium), feeling confused  
• feeling depressed, worried, slow or nervous 
• a lack of concentration or increased activity 
• memory loss 
• feeling “high” 
• being less aware or responsive, losing consciousness 
• convulsion (fits) 



 53 

• muscle convulsions or trembling 
• loss of taste, loss or change in sense of smell 
• difficulty in speaking 
• blue skin colour 
• vertigo, falling over, malaise 
• heat and circulation not working properly, hot flush or fever, chills, excessive sweating 
• swelling of the soft tissue 
• low blood pressure 
• blockage in the wind-pipe 
• shortness of breath 
• vaginal bleeding 
• tear in the intestine or inflammation of the stomach lining 
• numbness or tingling in the mouth , tongue, or nose, or other tongue problems, mouth ulcers, 

dry mouth 
• diarrhoea 
• retching, stomach pains, indigestion 
• sore or painful joints 
• difficulty in or inability to pass water 
• chest pain 
• feeling tired or weak, problems moving 
• changes in blood cells (detected by laboratory tests) 
• increased blood sugar  
• protein in the urine  
 
Other side effects (frequency not known (frequency cannot be estimated from the available data)) 
• Severe breathing problems 
• Flushing 
• Insomnia 
• Withdrawal syndrome (may manifest by the occurrence of the following side effects nausea, 

vomiting, diarrhoea, anxiety, chills, tremor, and sweating) 
• Drug dependence (addiction) 
• Drug abuse 
 
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 PecFent 
 
Keep this medicine out of the sight and reach of children. PecFent could be life-threatening if 
taken by a child by accident.  
• Do not use this medicine after the expiry date which is stated on the carton and bottle after EXP. 

The expiry date refers to the last day of that month.  
• Do not store PecFent above 25°C.  
• Do not freeze. 
• Keep the bottle in its child resistant container in order to protect from light. 
• Store the PecFent bottle in the child resistant container at all times, even when finished. 

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


 54 

• Do not use for more than 5 days after first use (either priming or using to treat a breakthrough 
pain episode). 

• PecFent that has passed the expiry date or is no longer required may still contain enough 
medicine to be harmful to other people, especially children. PecFent should not be disposed of 
via wastewater or household waste. Any unwanted PecFent should be disposed of as soon as 
possible following the instructions under Disposal of unused PecFent. Any empty bottles 
should be returned to their child resistant container and discarded by taking them back to the 
pharmacy or according to local requirements. 

6. Contents of the pack and other information 
 
What PecFent contains 
 
The active substance is fentanyl.  
• PecFent 100 micrograms/spray nasal spray, solution 

Each ml of solution contains 1,000 micrograms  fentanyl (as citrate). 
1 spray (100 microlitres) contains 100 micrograms fentanyl (as citrate). 

 
The other ingredients (excipients) are pectin (E440), mannitol (E421), phenylethyl alcohol, 
propylparahydroxybenzoate (E216), sucrose, purified water and hydrochloric acid or sodium 
hydroxide for pH adjustment. 
 
What PecFent looks like and contents of the pack 
The medicine is a clear to almost clear, colourless nasal spray, solution. It is contained in a clear glass 
bottle, fitted with a metering pump and a protective cap. The pump has a spray counter that clicks, so 
you can hear as well as see that the spray has been given. After the PecFent bottle has been primed 
(prepared for use) it delivers 2 full sprays. Each PecFent bottle is supplied in a child resistant 
container. 
 
PecFent 2 spray bottles in their child resistant containers are supplied in a carton containing 1 bottle. 
 
Marketing Authorisation Holder 
Kyowa Kirin Holdings B.V. 
Bloemlaan 2,  
2132NP Hoofddorp 
The Netherlands 
 
Manufacturer 
L. Molteni & C. dei F.lli Alitti Società di Esercizio S.p.A 
Strada Statale 67 Tosco Romagnola,  
Fraz. Granatieri – 50018 Scandicci (FI) 
Italy 
 
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/

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