Dzuveo

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Dzuveo 30 micrograms sublingual tablet 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION  
 
Each sublingual tablet contains 30 micrograms of sufentanil (as citrate). For the full list of excipients, 
see section 6.1. 
 
3. PHARMACEUTICAL FORM 
 
Sublingual tablet. 
 
Blue-coloured flat-faced tablet with round edges and a diameter of 3 mm. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Dzuveo is indicated for the management of acute moderate to severe pain in adult patients. 
 
4.2 Posology and method of administration 
 
Dzuveo is to be administered by a healthcare professional in a medically monitored setting only. A 
medically monitored setting must have equipment and personnel trained to detect and manage 
hypoventilation, and availability of supplemental oxygen and opioid antagonists, such as naloxone. 
Dzuveo should only be prescribed and administered by healthcare professionals who are experienced 
in the management of opioid therapy; particularly opioid adverse reactions, such as respiratory 
depression (see section 4.4). 
 
Posology 
 
Dzuveo is provided in a disposable single-dose applicator, to be administered by a healthcare provider 
as needed by the individual patient, but no more than once every hour, resulting in a maximum dose of 
720 micrograms /day. Patients with a higher pain intensity at one hour after sufentanil treatment was 
initiated required more frequent redosing compared to patients with lower pain intensity scores at one 
hour. 
 
Dzuveo should not be used beyond 48 hours. 
 
Elderly 
No specific dose adjustment is required in elderly patients. However, elderly patients should be 
observed closely for adverse reactions of sufentanil (see section 5.2). 
 
Hepatic or renal impairment 
Sufentanil should be administered with caution to patients with moderate to severe hepatic or severe 
renal impairment (see section 4.4). 
 
Paediatric population 
The safety and efficacy of sufentanil in children and adolescents below 18 years have not been 
established. No data are available. 



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Method of administration 
 
For sublingual use only. 
 
Dzuveo is to be administered by a healthcare professional from a disposable single-dose applicator 
(see section 6.6). The applicator is used as a placement aid for the healthcare professional to deliver 
the tablet under the tongue, on an as needed basis, per patient request, with a minimum of 1 hour 
between doses. 
 
The dispensed sublingual tablet should dissolve under the tongue and should not be chewed or 
swallowed. If swallowed, the oral bioavailability of Dzuveo is only 9% which would result in a sub- 
therapeutic dose. Patients should not eat or drink and should minimise talking for 10 minutes after 
each dose of sufentanil 30 mcg sublingual tablet. In the case of an excessive dry mouth, patients may 
be given ice cubes. Some insoluble excipients of the tablet may remain in the mouth after dissolution 
is complete; this is normal and does not indicate lack of absorption of sufentanil from the tablet. 
 
See section 6.6 for instructions regarding handling of the Dzuveo sublingual tablet and applicator. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Significant 
respiratory depression or pulmonary compromise. 
 
4.4 Special warnings and precautions for use 
 
Respiratory depression 
 
Sufentanil may cause respiratory depression, for which the degree/severity is dose related. The 
respiratory effects of sufentanil should be assessed by clinical monitoring, e.g. respiratory rate, 
sedation level and oxygen saturation. Patients at higher risk are those with respiratory impairment or 
reduced respiratory reserve. Respiratory depression caused by sufentanil can be reversed by opioid 
antagonists. Repeat antagonist administration may be required as the duration of respiratory depression 
may last longer than the duration of the effect of the antagonist (see section 4.9). 
 
Risk from concomitant use of sedative medicines such as benzodiazepines or related medicinal 
products 
 
Concomitant use of sufentanil and sedative medicines such as benzodiazepines or related medicinal 
products may result in sedation, respiratory depression, coma and death. Because of these risks, 
concomitant prescribing with these sedative medicines should be reserved for patients for whom 
alternative treatment options are not possible, or when sufentanil is used in an emergency setting. 
 
Intracranial pressure 
 
Sufentanil should be used with caution in patients who may be particularly susceptible to the cerebral 
effects of CO2 retention, such as those with evidence of increased intracranial pressure or impaired 
consciousness. Sufentanil may obscure the clinical course of patients with head injury. Sufentanil 
should be used with caution in patients with brain tumours. 
 
Cardiovascular effects 
 
Sufentanil may produce bradycardia. Therefore, it should be used with caution in patients with 
previous or pre-existing bradyarrhythmias. 
 
Sufentanil may cause hypotension, especially in hypovolemic patients. Appropriate measures should 
be taken to maintain stable arterial pressure. 



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Impaired hepatic or renal function 
 
Sufentanil is primarily metabolised in the liver and excreted in the urine and faeces. The duration of 
activity may be prolonged in patients with severe hepatic and renal impairment. Only limited data are 
available for the use of sufentanil in such patients. Patients with moderate to severe hepatic or severe 
renal impairment should be monitored carefully for symptoms of sufentanil overdose (see section 4.9). 
 
Abuse potential and tolerance 
 
Sufentanil has potential for abuse. This should be considered when prescribing or administering 
sufentanil where there is concern about an increased risk of misuse, abuse or diversion. 
 
Patients on chronic opioid therapy or opioid addicts may require higher analgesic doses than contained 
in Dzuveo. 
 
Gastrointestinal effects 
 
Sufentanil as a μ-opioid receptor agonist may slow the gastrointestinal motility. Therefore, sufentanil 
should be used with caution in patients at risk of ileus. 
 
Sufentanil as a μ-opioid receptor agonist may cause spasm of the sphincter of Oddi. Therefore, 
sufentanil should be used with caution in patients with biliary tract disease, including acute 
pancreatitis. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Interaction with cytochrome P450-3A4 enzyme 
 
Sufentanil is primarily metabolised by the human cytochrome P450-3A4 enzyme. Ketoconazole, a 
potent CYP3A4 inhibitor, can significantly increase the systemic exposure to sublingual sufentanil 
(maximal plasma levels (Cmax) increase of 19%, overall exposure to the active substance (AUC) 
increase of 77% and prolong the time to reach maximum concentration by 41%. Similar effects with 
other potent CYP3A4 inhibitors (e. g. itraconazole, ritonavir) cannot be excluded. Any change in 
efficacy/tolerability associated with the increased exposure would be compensated in practice by an 
increase in the amount of time between doses (see section 4.2). 
 
Interaction with calcium channel and/or beta blockers 
 
The incidence and degree of bradycardia and hypotension with sufentanil may be greater in patients on 
chronic calcium channel and/or beta blocker therapy. 
 
Caution should be exercised in patients on these concomitant medicinal products and they should be 
closely monitored. 
 
Central nervous system (CNS) depressants 
 
The concomitant use of CNS depressants including barbiturates, benzodiazepines, neuroleptics or 
other opioids, halogen gases or other non-selective CNS depressants (e.g. alcohol) may enhance 
respiratory depression. 
 
When considering the use of sufentanil in a patient taking a CNS depressant, the duration of use of the 
CNS depressant and the patient’s response should be assessed, including the degree of tolerance that 
has developed to CNS depression. If the decision to begin sufentanil is made, the patient should be 
closely monitored and a lower dose of the concomitant CNS depressant should be considered. 
 



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Co-administration of sufentanil with a serotonergic agent, such as Selective Serotonin Reuptake 
Inhibitors (SSRIs), Serotonin Norepinephrine Reuptake Inhibitors (SNRIs), or Monoamine Oxidase 
Inhibitors (MAOIs), may increase the risk of serotonin syndrome, a potentially life threatening 
condition. Monoamine Oxidase Inhibitors must not be taken in the 2 weeks before or at the same time 
as Dzuveo is given. 
 
Others 
 
Interaction with other sublingually administered products or products intended to dilute/establish an 
effect in the oral cavity were not evaluated and simultaneous administration should be avoided. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data from the use of sufentanil in pregnant women. Studies in 
animals have shown reproductive toxicity (see section 5.3). Sufentanil should not be used in 
pregnancy, because it crosses the placenta and the foetal respiratory center is sensitive to opiates. If 
sufentanil is administered to the mother during this time, an antidote for the child should be readily 
available. Following long-term treatment sufentanil may cause withdrawl symptoms in the newborn. 
Sufentanil is not recommended during pregnancy and in women of childbearing potential not using 
contraception. 
 
Breast-feeding 
 
Sufentanil is excreted in human milk to such an extent that effects on the breastfed newborns/infants 
are likely. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain 
from sufentanil therapy taking into account the benefit of breast feeding for the child and the benefit of 
therapy for the woman. 
 
Fertility 
 
There are no clinical data on the effects of sufentanil on fertility. Studies in rats have revealed reduced 
fertility and enhanced embryo mortality (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Sufentanil has major influence on the ability to drive and use machines. Patients should be advised not 
to drive or operate machinery if they experience somnolence, dizziness, or visual disturbance while 
taking or after the treatment with sufentanil. Patients should only drive and use machines if sufficient 
time has elapsed after the last administration of sufentanil. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most serious adverse reaction of sufentanil is respiratory depression, which occurred at a rate of 
0.6% in sufentanil clinical trials. 
 
The most commonly reported adverse reactions seen in clinical trials and from post marketing 
experience with sufentanil containing products were nausea, vomiting and pyrexia (≥1/10 patients) 
(see section 4.4). 
 
Tabulated list of adverse reactions 
Adverse reactions identified either from clinical studies or from post marketing experience with other 
medicinal products containing sufentanil are summarised in the table below. The frequencies are 
defined as: 



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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 
Not known Cannot be estimated from the available data. 

 
MedDRA system organ 
class 

Very 
common 

Common Uncommon Unknown 

Infections and infestations   Bronchitis Conjunctivitis 
infective Pharyngitis 

 

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

  Lipoma  

Blood and lymphatic 
system disorders 

 Anaemia 
Leukocytosis 

Thrombocytopenia  

Immune system disorders  Hypersensitivity  Anaphylactic 
shock 

Metabolism and nutrition 
disorders 

 Hypocalcaemia 
Hypoalbuminaemia 
Hypokalaemia 
Hyponatraemia 

Hypomagnesaemia 
Hypoproteinaemia 
Hyperkalaemia Diabetes 
mellitus Hyperglycaemia 
Hyperlipidaemia 
Hypophosphataemia 
Hypovolaemia 

 

Psychiatric disorders  Insomnia Anxiety 
Confusional state 

Agitation Apathy 
Conversion disorder 
Disorientation Euphoric 
mood Hallucination 
Mental status changes 
Nervousness 

 

Nervous system disorders  Headache Dizziness 
Somnolence Sedation 

Tremor Ataxia Dystonia 
Hyperreflexia Tremor 
Burning sensation 
Presyncope Paraesthesia 
Hypoaesthesia Lethargy 
Memory impairment 
Migraine 
Tension headache 

Convulsions 
Coma 

Eye disorders   Eye pain 
Visual disturbance 

Miosis 

Cardiac disorders  Tachycardia 
Sinus tachycardia 

Bradycardia 
Angina pectoris Atrial 
fibrillation 
Ventricular extrasystoles 

 

Vascular disorders  Hypotension 
Hypertension 

Orthostatic hypertension 
Flushing 
Diastolic hypotension 
Orthostatic hypotension 

 



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MedDRA system organ 
class 

Very 
common 

Common Uncommon Unknown 

Respiratory, thoracic and 
mediastinal disorders 

 Hypoxia 
Pharyngolaryngeal 
pain 
Respiratory 
Depression 

Bradypnoea Epistaxis 
Hiccups Apnoea 
Atelectasis 
Hypoventilation 
Pulmonary embolism 
Pulmonary oedema 
Respiratory distress 
Respiratory failure 
Wheezing 

Respiratory 
arrest 

Gastrointestinal disorders Nausea 
Vomiting 

Constipation 
Dyspepsia Flatulence 
Dry Mouth 

Diarrhoea Eructation 
Retching 
Abdominal discomfort 
Abdominal distension 
Abdominal Pain upper 
Epigastric discomfort 
Gastritis 

 

Gastroesophageal reflux 
disease 
Hypoaesthesia oral 

Hepatobilary disorders   Hyperbilirubinaemia  
Skin and subcutaneous 
tissue disorders 

 Pruritus Hyperhidrosis 
Hypoaesthesia facial 
Pruritus generalized 
Blister 
Rash Dry Skin 

Erythema 

Musculoskeletal and 
connective tissue disorders 

 Muscle spasms 
Muscle twitching 

Back Pain 
Musculoskeletal pain 
Musculoskeletal chest 
pain 
Pain in extremity 

 

Renal and urinary 
disorders 

 Urinary retention Urinary hesitation 
Oliguria 
Renal failure Urinary tract 
pain 

 

General disorders and 
administration site 
conditions 

Pyrexia  Feeling hot Fatigue 
Asthenia Chills 
Local swelling 
Non-cardiac chest pain 
Chest discomfort 

Drug withdrawal 
syndrome 



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MedDRA system organ 
class 

Very 
common 

Common Uncommon Unknown 

Investigations  Oxygen saturation 
decreased 
Body temperature 
increased 

Blood pressure increased 
Respiratory rate decreased 
Blood glucose increased 
Blood bilirubin increased 
Urine output decreased 
Aspartate 
aminotransferase 
increased 
Blood urea increased 
Electrocardiogram T wave 
abnormal 
Electrocardiogram 
abnormal 
Hepatic enzyme increased 
Liver function test 
abnormal 

 

Injury, poisoning and 
procedural complications 

 Anaemia 
postoperative 

Procedural nausea 
Postoperative ileus 
Procedural vomiting 
Gastrointestinal stoma 
complication Procedural 
pain 

 

 
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 
 
Signs and symptoms 
 
Sufentanil overdose is manifested by an exaggeration of its pharmacological effects. Depending on 
individual sensitivity, the clinical picture is determined by the degree of respiratory depression. This 
may range from hypoventilation to respiratory arrest. Other symptoms that may occur are loss of 
consciousness, coma, cardiovascular shock and muscle rigidity. 
 
Management 
 
Management of sufentanil overdose should be focused on treating symptoms of μ-opioid receptor 
agonism, including administration of oxygen. Primary attention should be given to obstruction of 
airways and the necessity of assisted or controlled ventilation. 
 
An opiate antagonist (e.g. naloxone) should be administered in the event of respiratory depression. 
This does not rule out more direct countermeasures. The shorter duration of activity of the opiate 
antagonist compared to that of sufentanil should be taken into account. In that case, the opioid 
antagonist can be administered repeatedly or by infusion. 
 
 



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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Anesthetics, opioid anesthetics, ATC Code: N01AH03. Mechanism of 
action 
Sufentanil is a synthetic, potent opioid with highly selective binding to μ-opioid receptors. Sufentanil 
acts as a full agonist in μ-opioid receptors. Sufentanil does not induce histamine release. All effects of 
sufentanil can immediately and completely be blocked by administration of a specific antagonist such 
as naloxone. 
 
Primary pharmacodynamics effects 
 
Analgesia 
 
Analgesia induced by sufentanil is thought to be mediated via activation of μ-opioid receptors 
primarily within the CNS to alter processes affecting both the perception of and the response to pain. 
In humans the potency is 7 to 10-fold higher than fentanyl and 500 to 1,000-fold higher than morphine 
(per oral). The high lipophilicity of sufentanil allows it to be administered sublingually and achieve a 
rapid onset of analgesic effect. 
 
Secondary pharmacodynamics effects 
 
Respiratory depression 
 
Sufentanil may cause respiratory depression (see section 4.4) and also suppresses the cough reflex. 
 
Other CNS effects 
 
High doses of intravenously administered sufentanil are known to cause muscle rigidity, probably as a 
result of an effect on the substantia nigra and the striate nucleus. Hypnotic activity can be 
demonstrated by EEG alterations. 
 
Gastrointestinal effects 
 
Analgesic plasma concentrations of sufentanil may provoke nausea and vomiting by irritation of the 
chemoreceptor trigger zone. 
 
Gastrointestinal effects of sufentanil comprise decreased propulsive motility, reduced secretion and 
increased muscle tone (up to spasms) of the sphincters of the gastrointestinal tract (see section 4.4). 
 
Cardiovascular effects 
 
Low doses of intravenous sufentanil associated with likely vagal (cholinergic) activity cause mild 
bradycardia and mildly reduced systemic vascular resistance without significantly lowering blood 
pressure (see section 4.4). 
 
Cardiovascular stability is also the result of minimal effects on cardiac preload, cardiac flow rate and 
myocardial oxygen consumption. Direct effects of sufentanil on myocardial function were not 
observed. 
 



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Clinical efficacy and safety 
 
Analgesia 
The efficacy of Dzuveo was evaluated in two double-blind, placebo-controlled trials involving 
221 patients with moderate-to-severe acute postoperative pain (pain intensity of ≥ 4 on a 0-10 scale) 
after abdominal (studied up to 48-hours) or orthopedic (bunionectomy) surgery (studied up to 12 
hours). Of the 221 patients, 147 received active treatment and 74 received placebo. Patients were 
predominantly female (63%), mean age was 41 years (range 18-74 years), BMI 15.8 to 53.5 kg/m2, 
race was predominately White (69%) and Black or African American (21%). Mean (SEM) baseline 
intensity in these trials was 6.48 (0.21) for the 12-hour bunionectomy trial in the sufenatil-treated 
patients and 5.98 (0.30) for placebo-treated patients. In the abdominal surgery trial, mean baseline pain 
intensity was 5.61 (0.13) for sufentanil-treated patients and 5.48 (0.18) for placebo-treated patients. 
In both trials, the primary efficacy endpoint was the time-weighted sum of pain intensity difference 
(SPID) to baseline (measured on an 11-point NRS) over 12 hours (SPID12). Patients using Dzuveo 
had a mean SPID12 score that was superior to patients using placebo (25.8 vs. 13.1) in abdominal 
surgery patients (p<0.001) and (5.93 vs. -6.7) in bunionectomy patients (p=0.005) respectively. 
Rescue analgesia was allowed in both studies, with a higher proportion of patients in the placebo 
group requiring rescue medication due to inadequate analgesia (64.8%, 100%; abdominal, 
bunionectomy) than in the sufentanil group (27.1%, 70.0%;. abdominal, bunionectomy). Onset of 
analgesia, as measured by pain intensity difference to baseline scores, was greater (p<0.05) for 
sufentanil versus placebo by 15 minutes after the first dose in the abdominal study and 30 minutes in 
the bunionectomy study. The majority (>90%) of healthcare professionals found Dzuveo easy to use. 
In the two placebo-controlled clinical trials, the mean number of doses used in the first 6 hours of 
dosing was 2.8 tablets, with less frequent dosing in the following 6 hours (mean of 1.7 tablets). Over 
24 hours, the mean number of Dzuveo doses administered was 7.0 (210 micrograms/day). Patients 
with a higher pain intensity at one hour after Dzuveo treatment was initiated required more frequent 
redosing compared to patients with lower pain intensity scores at one hour. 
 
Respiratory depression 
Analgesic doses of sufentanil resulted in respiratory depressive effects in some patients in the clinical 
trials, however, no patient treated with Dzuveo required use of an opioid reversal drug (e.g. naloxone). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The pharmacokinetics of sufentanil after administration of Dzuveo can be described as a two- 
compartment model with first-order absorption. This route of administration results in higher absolute 
bioavailability than oral (swallowed) administration by avoiding intestinal and first-pass liver 3A4 
enzyme metabolism. Mean absolute bioavailability after a single sublingual administration of the 
sufentanil tablet relative to a one-minute intravenous sufentanil infusion of the same dose was 53%. 
 
In a study of a sufentanil 15 microgram sublingual tablet (with the same formulation as the 

30 microgram tablet), a substantially lower bioavailability of 9% after oral intake (swallowed) was 
observed. Buccal administration showed an increased bioavailability of 78% when the tablets were 
placed in front of the front lower teeth. 

 
Maximum concentrations of sufentanil are achieved approximately 60 minutes after a single dose; this 
is shortened to approximately 40 minutes following repeated hourly dosing. When Dzuveo is 
administered every hour, steady-state plasma concentrations are achieved by 7 doses. 
 
Distribution 
 
The central volume of distribution after intravenous application of sufentanil is approximately 14 litres 
and the volume of distribution at steady state is approximately 350 litres. 
 



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Biotransformation 
 
Biotransformation takes place primarily in the liver and the small intestine. Sufentanil is mainly 
metabolised in humans by the cytochrome P450-3A4 enzyme system (see section 4.5). Sufentanil is 
rapidly metabolised to a number of inactive metabolites, with oxidative N- and O-dealkylation being 
the major routes of elimination. 
 
Elimination 
 
With Dzuveo, first dose clearance in the typical patient of weight 78.5 kg and age 47 years is 84.2 
L/hr. Steady-state clearance is 129.3 L/hr. Patient weight and age are key covariates on clearance. 
 
After single administration of Dzuveo, mean terminal phase half-live of 13.4 hours (range of 2.5 to 
34.4 hours) was observed. After multiple administrations, a longer mean terminal half-life of 15.7 
hours (range 2.4 to 42.7 hours) was observed, owing to the higher plasma concentrations of sufentanil 
achieved after repeated dosing and due to the possibility to quantify these concentrations over a longer 
time period. 
 
Pharmacokinetic/Pharmacodynamic Relationship 
 
With administration of Dzuveo, clinical duration of analgesia is largely determined by the time for the 
sufentanil plasma concentration to drop from Cmax to 50% of Cmax after discontinuation of dosing 
(context sensitive half-time or CST½) rather than by the terminal half-life. Following either a single 
dose or multiple doses hourly over 12 hours, the median CST½ remained 2.3 hours: the sublingual 
delivery route thus substantially extends the duration of action associated with intravenous sufentanil 
administration (CST½ of 0.1 hours). Similar CST½ values were observed following both single and 
repeated administration, demonstrating that there is a predictable and consistent duration of action 
after multiple dosing of the sublingual tablet. 
 
Patients requested dosing with Dzuveo to maintain plasma sufentanil concentrations averaging 40- 50 
pg/ml at 12 hours, with no effect based on age or body mass index (BMI), or mild to moderate renal or 
liver impairment. 
 
Special populations 
 
Renal impairment 
 
A population pharmacokinetic analysis of plasma sufentanil concentrations following usage of Dzuveo 
did not identify renal function as a significant covariate for clearance. However, due to the limited 
number of patients with severe renal impairment studied, Dzuveo should be used with caution in such 
patients (see section 4.4). 
 
Hepatic impairment 
 
Based on the population pharmacokinetic analysis for Dzuveo, hepatic function was not identified as a 
significant covariate for clearance. Due to the limited number of patients with moderate to severe 
hepatic impairment, a potential effect of hepatic dysfunction as covariate on clearance may not have 
been detected. Therefore, Dzuveo should be used with caution in such patients (see section 4.4). 
 
Paediatric population 
 
No pharmacokinetic data exist for sufentanil in paediatric patients. 
 



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Elderly 
 
No special population studies were performed using Dzuveo in the elderly. For Dzuveo, population 
pharmacokinetic analysis showed an effect of age, with an 18% decrease in clearance in the elderly 
(above 65 years of age). 
 
Effect of BMI on dosing 
 
Population pharmacokinetic analysis with weight as a covariate showed that patients with a higher 
BMI dosed more frequently. 
 
5.3 Preclinical safety data 
 
Reproductive toxicity 
 
Fertility and early embryonic development studies were conducted in male and female rats. Increased 
mortality was noted in all treatment groups. 
 
Lower pregnancy rates were noted following treatment of males suggesting the potential for an 
adverse effect on fertility in males. Increased resorption of foetuses and reduced litter size was noted 
in the high dose females suggesting the potential for foetotoxicity, likely due to maternal toxicity. 
 
Mutagenicity 
 
The Ames test revealed no mutagenic activity of sufentanil. Carcinogenicity 
Carcinogenicity studies have not been conducted with sufentanil. Local tolerance 
Two local tolerance studies were conducted in the hamster cheek pouch with the sufentanil sublingual 
tablets. It was concluded from these studies that sufentanil sublingual tablets have no or minimal 
potential for local irritation. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol-E421 
Calcium hydrogen phosphate Hypromellose Croscarmellose sodium Indigo carmine -E132 Stearic 
acid 
Magnesium stearate 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
Store in the original package in order to protect from light and oxygen. 
 
6.5 Nature and contents of container 
 
Dzuveo is packaged in a polypropylene single-dose applicator, which is packaged in a polyester 
film/LDPE/aluminium foil/LDPE sachet with an oxygen absorber. 
Dzuveo will be available in cartons of 5 and 10. Not all pack sizes may be marketed. 



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6.6 Special precautions for disposal and other handling 
 
Instructions for use of Single Dose Applicator (SDA) 
 
Single-Use Product / Do Not Reuse 
 
Do Not Use if Pouch Seal is Broken 
 
Do not use if the Single Dose Applicator (SDA) is damaged 
 
Instruct the patient to not chew or swallow the tablet. 
 
Instruct the patient to not eat or drink and minimize talking for 10 minutes after receiving the tablet. 
 
1. When ready to administer the medicine, tear open the slit-notched pouch across the top. The 

pouch contains one clear plastic SDA with a single blue-coloured tablet housed in the tip, and 
an oxygen absorber packet. The oxygen absorber packet should be discarded. 

 
Contents of the pouch are shown below: 

 
 
 
 
 

Pusher 
 
 
 

Lock 
 
 
 
 
 
 
 
 
 
 

Tablet 



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2. Remove the white Lock from the green Pusher by squeezing the sides together and detaching 
from Pusher. Discard the Lock. 

 

 
 
3. Tell the patient to touch their tongue to the roof of their mouth if possible. 
4. Rest the SDA lightly on the patient’s teeth or lips. 
5. Place the SDA tip under the tongue and aim at the floor of the patient’s mouth. NOTE: Avoid 

direct mucosal contact with the SDA tip. 
 

 
 
6. Depress the green Pusher to deliver the tablet to the patient’s sublingual space and confirm 

tablet placement. 
 

 
 
The single-dose applicator (SDA) must be discarded in accordance to the institutional policies and 
local requirements. 
 
 



15  

7. MARKETING AUTHORISATION HOLDER 
 
FGK Representative Service GmbH, Heimeranstr. 35, 
80339 Munich, Germany. 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1284/001 EU/1/18/1284/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first utilisation: 25 June 2018 
 
 
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. 



16  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 



17  

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Propak Health Ltd 
3-4 Ballyboggan Industrial Estate Ballyboggan Road 
Finglas Dublin 11 Ireland 
 
 
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 OF THE MARKETING 

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

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

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
 
• Additional risk minimisation measures 
 
Prior to the launch of Dzuveo in each Member State (MS), the Marketing Authorisation Holder 
(MAH) must agree about the content and format of the educational materials, including 
communication media, distribution modalities, and any other aspects of the programme, with the 
National Competent Authority (NCA). 
 
The MAH shall ensure that in each MS where Dzuveo is marketed, all HCPs (i.e. physicians, hospital 
pharmacists, and nurses) who are expected to prescribe / administer the product are provided with a 
Healthcare Professional Guide, outlining critical information for the safe and effective use of Dzuveo, 
including: 
 
• The method of use of the device; 
 



18  

• The minimum dosing interval of one sublingual tablet per hour, in order to prevent / minimise 
the important identified risk of respiratory depression and the important potential risk of 
overdose; 

 
• The key message to convey during patients counselling, about possible respiratory depression / 

overdose; 
 
• Detailed instruction on how to handle overdose / respiratory depression 
 



19  

 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



20  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



21  

 

 
 
 

 
 
Dzuveo 30 micrograms sublingual tablets sufentanil 
 
 

 
 
Each sublingual tablet contains 30 micrograms sufentanil (as citrate). 
 
 

 
 
 

 
 
10 x 1sublingual tablet in a single-dose applicator. 5 x 1 sublingual tablet in a single dose applicator. 
 
 

 
 
Read the package leaflet before use. Sublingual use 
To be used only with the single-dose applicator. Do not chew or swallow the tablet. 
Minimum 1 hour dosing interval. 
 
 

 
 
Keep out of reach and sight of children. 
 
 

 
 
 

 
 
EXP 
 
 

 
 
Store in original package to protect from light and oxygen. 
 
 

 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON OF 5 OR 10 POUCHES 

1. NAME OF THE MEDICINAL PRODUCT 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

3. LIST OF EXCIPIENTS 

4. PHARMACEUTICAL FORM AND CONTENTS 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

8. EXPIRY DATE 

9. SPECIAL STORAGE CONDITIONS 

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



22  

 

 
 
FGK Representative Service GmbH, Heimeranstr. 35, 
80339 Munich, Germany. 
 
 

 
 
EU/1/18/1284/001  5 x 1 tablets in single dose applicators EU/1/18/1284/002 10 x 1 tablets in single 
dose applicators 
 
 

 
 
Lot 
 
 

 
 
 

 
 
 

 
 
Justification for not including Braille accepted. 
 
 

 
 
2D barcode carrying the unique identifier included. 
 

 
 
PC: 
SN: 
NN: 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

12. MARKETING AUTHORISATION NUMBER(S) 

13. BATCH NUMBER 

14. GENERAL CLASSIFICATION FOR SUPPLY 

15. INSTRUCTIONS ON USE 

16. INFORMATION IN BRAILLE 

17. UNIQUE IDENTIFIER – 2D BARCODE 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 



23  

 

 
 
 

 
 
Dzuveo 30 micrograms sublingual tablet sufentanil 
 
 

 
 
Each sublingual tablet contains 30 micrograms sufentanil (as citrate). 
 
 

 
 
 

 
 
1 single-dose applicator containing 1 sublingual tablet. 
 
 

 
 
Read the package leaflet before use. Sublingual use 
To be used only with the single-dose applicator. Administer product immediately after opening pouch. 
Do not chew or swallow the tablet. 
Minimum 1 hour dosing interval. 
 
 

 
 
Keep out of the sight and reach of children. 
 
 

 
 
 
 

 
 
EXP 
 
 

 
 
Store in original package to protect from light and oxygen. 
 
 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
POUCH 

1. NAME OF THE MEDICINAL PRODUCT 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

3. LIST OF EXCIPIENTS 

4. PHARMACEUTICAL FORM AND CONTENTS 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

8. EXPIRY DATE 

9. SPECIAL STORAGE CONDITIONS 



24  

 
 
 

 
 
FGK Representative Service GmbH, Heimeranstr. 35, 
80339 Munich, Germany. 
 
 

 
 
EU/1/18/1284/001 EU/1/18/1284/002 
 
 

 
 
Lot 
 
 

 
 
 

 
 
 

 
 
Justification for not including Braille accepted. 
 
 

 
 
 

 

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 

12. MARKETING AUTHORISATION NUMBER(S) 

13. BATCH NUMBER 

14. GENERAL CLASSIFICATION FOR SUPPLY 

15. INSTRUCTIONS ON USE 

16. INFORMATION IN BRAILLE 

17. UNIQUE IDENTIFIER – 2D BARCODE 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 



25  

 

 
 
 

 
 
Dzuveo 30 mcg sublingual tablet sufentanil 
 
 

 
 
 

 
 
 

 
 
Lot 
 
 

 
 
 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SINGLE-DOSE APPLICATOR 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

2. METHOD OF ADMINISTRATION 

3. EXPIRY DATE 

4. BATCH NUMBER 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

6. OTHER 



26  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



27  

Package leaflet: Information for the user 
 

Dzuveo 30 micrograms sublingual tablet 
sufentanil 

 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist or nurse. 
- If you get any side effects, talk to your doctor, or pharmacist or nurse. This includes any 

possible side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Dzuveo is and what it is used for 
2. What you need to know before you use Dzuveo 
3. How to use Dzuveo 
4. Possible side effects 
5. How to store Dzuveo 
6. Contents of the pack and other information 
 
 
1. What Dzuveo is and what it is used for 
 
The active substance of Dzuveo is sufentanil, which belongs to a group of strong painkillers called 
opioids. 
 
Sufentanil is used to treat sudden moderate-to-severe pain in adults in medically monitored settings 
such as a hospital. 
 

2. What you need to know before you use Dzuveo Do not use Dzuveo: 
 
- If you are allergic to sufentanil or any of the other ingredients of this medicine (listed in section 

6). 
- If you have a serious lung or breathing problem 
 
Warnings and precautions 
Talk to your doctor or nurse before using Dzuveo. Tell your doctor or nurse before treatment if you: 
- Are suffering from any condition that affects your breathing (such as asthma, wheezing, or 

shortness of breath). As Dzuveo may affect your breathing, your doctor or nurse will check your 
breathing during treatment; 

- Have a head injury or brain tumour; 
- Have problems with your heart and circulation, especially slow heart rate, irregular heartbeat, 

low blood volume or low blood pressure; 
- Have moderate to severe liver problems or severe kidney problems, as these organs have an 

effect on the way in which your body breaks down and eliminates the medicine; have 
abnormally slow bowel movements; 

- Have a disease of the gall bladder or pancreas; 
- Have a history of medicine or alcohol abuse; 
 
Children and adolescents 
Dzuveo should not be used in children and adolescents below 18 years. 
 
Other medicines and Dzuveo 
Tell your doctor if you are taking, have recently taken or might take any other medicines. In particular, 



28  

tell your doctor if you are taking any of the following: 
 
- Ketoconazole, which is used for the treatment of fungal infections this medicine may have an 

effect on the way in which your body breaks down sufentanil. 
- Any medicines which might make you sleepy (have a sedative effect), such as sleeping pills, 

medicines to treat anxiety (e.g. benzodiazipines), tranquillisers or other opioid medicines, as they 
can increase the risk of severe breathing problems, coma and may be life-threatening. 

-  
- Medicines for the treatment of depression known as Monoamine Oxidase Inhibitors (MAOIs). 

These medicines must not be taken in the 2 weeks before or at the same time as Dzuveo is given. 
- Medicines for the treatment of depression known as Selective Serotonin Reuptake Inhibitors 

(SSRIs) and Serotonin Norepinephrine Reuptake Inhibitors (SNRIs). It is not recommended to 
use these medicines at the same time as Dzuveo. 

- Other medicines which are also taken sublingually (placed under the tongue where they dissolve) 
or medicines which take effect in your mouth (e.g. nystatin, a liquid or pastilles you hold in your 
mouth to treat fungus infections), as the effect on Dzuveo has not been studied. 

- Regularly prescribed opioid medicine (e.g. morphine, codeine, fentanyl, hydromorphone, 
oxycodone). 

- Medicines used to treat high blood pressure or angina (chest pain) known as calcium channel or 
beta blockers e.g. diltiazem and nifedipine. 

 
Dzuveo with alcohol 
Do not drink alcohol while using Dzuveo. It can increase the risk of experiencing severe breathing 
problems. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. 
 
Dzuveo should not be used during pregnancy or in women of childbearing potential not using effective 
contraception. 
 
Dzuveo passes into breast milk and can cause side effects in the breast-fed child. Breastfeeding is not 
recommended while you are taking Dzuveo. 
 
Driving and using machines 
Dzuveo affects your ability to drive or use machines as it may cause sleepiness, dizziness or visual 
disturbances. You should not drive or operate machinery if you experience any of these symptoms 
whilst or after being treated with sufentanil. You should only drive and use machines if sufficient time 
has elapsed after your last dose of Dzuveo. 
 
 
3. How to use Dzuveo 
 
This medicine must be given to you by a doctor or a nurse using the single-dose administration device. 
You will not give yourself this medicine. 
 
Dzuveo is only used in a medically monitored setting, such as a hospital. It is only prescribed by a 
doctor who is experienced in the use of strong painkillers like sufentanil and knows the effects it may 
have on you, in particular on your breathing (see ‘Warnings and precautions’ above). 
 
The recommended dose is a maximum of one 30 microgram sublingual tablet per hour. The sublingual 
tablet will be given to you by a healthcare professional using the disposable single-dose applicator. 
The applicator will help your healthcare provider place one tablet under your tongue. The tablets 
dissolve under your tongue and should not be chewed, or swallowed because the tablet is not effective 
for pain relief unless it is allowed to dissolve under your tongue. You should not eat or drink and 
should talk as little as possible for 10 minutes after each dose. 



29  

 
After receiving a dose you will not be given another dose for at least one hour. The maximum daily 
dose is 720 micrograms (24 tablets per day). 
Dzuveo should not be used beyond 48 hours. 
After your treatment the medical staff will dispose of the applicator accordingly. 
If you use more Dzuveo than you should 
The symptoms of overdose include severe breathing problems like slow and shallow breathing, loss of 
consciousness, extremely low blood pressure, collapse and muscle rigidity. If these start to develop, 
tell a doctor or nurse immediately. 
 
If you have any further questions on the use of this medicine, ask your doctor or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects 
The most serious side effects are severe breathing problems, like slow and shallow breathing, which 
may even lead to you stopping breathing. 
 
If you experience any of the above mentioned side effects, tell your doctor or nurse immediately. 
 
Very common side effects (may affect more than 1 in 10 people): Nausea or feeling sick, vomiting or 
being sick and generally feeling hot. 
 
Common side effects (may affect up to 1 in 10 people): 
- Inability or difficulty sleeping, feeling anxious or confused, dizziness. 
- Headache, drowsiness, feeling sleepy. 
- Increased heart rate, high blood pressure, low blood pressure. 
- Low levels of oxygen in your blood, feeling pain in the lower throat, slow shallow breathing. 
- Dry mouth, flatulence (passing wind), constipation, indigestion or reflux. 
- Allergic reactions, itching of the skin. 
- Muscle twitching and spasms. 
- Inability to pass urine. 
- This medicine may also cause changes in levels of red blood cells, white blood cells, calcium, 

albumin, potassium and sodium in your blood which can only be identified through a blood test. 
If you are having a blood test ensure your doctor knows you are taking this medicine. 

 
Uncommon side effects (may affect up to 1 in 100 people): 
- Inflammation of the lungs, eye redness and inflammation, inflammation of the throat. 
- Fatty lumps underneath skin. 
- Inability to manage blood sugar (diabetes), increased cholesterol. 
- Feeling agitated, lack of interest or emotion, lack of energy, disorientation, feeling elated, 

hallucinating or seeing things that are not there, nervousness. 
- Problems coordinating muscle movements, muscle contractions, tremors or excessive shaking, 

exaggeration of reflex responses, burning sensation, feeling faint, abnormal sensation of the skin 
(tingling, skin crawling), numbness in general, tiredness, forgetfulness, migraine, tension 
headaches. 

- Vision disturbances, eye pain. 
- Decreased heart rate, irregular heartbeat, angina or other chest discomfort. 
- High blood pressure or low blood pressure when standing up, skin flushing. 
- Slow or difficult breathing (including when sleeping), Nose bleeds, hiccups. 
- Chest pain and breathing difficulties caused by a blood clot in lung, fluid in the lungs, wheezing. 
- Diarrhoea, burping or belching, inflammation of stomach lining or gastritis, bloating, acid reflux, 

retching, stomach pain or an uncomfortable stomach. 
- Developing blisters, excessive sweating, rash, dry skinnumbness of mouth or face. 



30  

- Pain in the back, chest or other body parts, pain in the extremities. 
- Difficulty urinating, strong smelling urine, pain urinating, kidney failure. 
- Swelling, uncomfortable sensations in your chest, chills, and weakness (lack of energy). 
 
This medicine may also cause changes in levels of platelets (which help your blood to clot), 
magnesium, protein, sugar, fats, phosphates and plasma in your blood which can only be identified 
through a blood test. If you are having a blood test ensure your doctor knows you are taking this 
medicine. 
 
Frequency not known (frequency cannot be estimated from the available data): 
- Severe allergic reactions (anaphylactic shock), convulsions (fits), coma, small pupil size, 

redness of the skin. 
- Withdrawal syndrome which may include symptoms such as agitation, anxiety, muscle aches, 

insomnia, sweating and yawning. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 

 
By reporting side effects, you can help provide more information on the safety of this medicine. 
 
 
5. How to store Dzuveo 
Keep this medicine out of the sight and reach of children. Your doctor or nurse will ensure that: 
- this medicine is not used after the expiry date which is stated on the label and carton after EXP. 

The expiry date refers to the last day of that month. 
- is stored in the original package in order to protect from light and oxygen. 
- this medicine is not used if there are signs of deterioration. 
 
Medicines should not be thrown away via wastewater or household waste. Your healthcare provider 
will dispose of any waste according to hospital policies. These measures will help protect the 
environment. 
 
6. Contents of the pack and other information What Dzuveo contains 
- The active substance is sufentanil. Each sublingual tablet contains 30 micrograms of sufentanil 

(as citrate). 
- The other ingredient(s) are mannitol (E421), dicalcium phosphate, hypromellose, 

croscarmellose sodium, Indigo Carmine (E132), stearic acid, and magnesium stearate. 
 
What Dzuveo looks like and contents of the pack 
Dzuveo is a blue-coloured, flat-faced sublingual tablet with round edges. It measures 3 mm in 
diameter and is enclosed within a single-dose applicator (labelled [sublingual tablet]). The applicator, 
with the tablet inside, is enclosed within a pouch. 
 
Each pouch contains one applicator and one sufentanil 30 micrograms tablet. Each pack contains 
either 5 or 10 pouches. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder  
FGK Representative Service GmbH, Heimeranstr. 35, 
80339 Munich, Germany. 
Phone:   +49 - 89-893 119 22 
Fax: +49 - 89-893 119 20 
Email:  edgar.fenzl@fgk-rs.de 
 

Appendix V 



31  

Manufacturer 
 
Propak Health Ltd, 
3-4 Ballyboggan Industrial Estate, Ballyboggan Road, 
Finglas, Dublin 11, Ireland. 
 
This leaflet was last revised in. 
 
<------------------------------------------------------------------------------------------------------------------------> 
 
The following information is intended for healthcare professionals only: 
 
Instructions for use of Single Dose Applicator (SDA) 
 
Single-Use Product / Do Not Reuse. 
 
Do Not Use if Pouch Seal is Broken. 
 
Do not use if the Single Dose Applicator (SDA) is damaged. 
 
Instruct the patient to not chew or swallow the tablet. 
 
Instruct the patient to not eat or drink and minimize talking for 10 minutes after receiving the tablet. 
 
1. When ready to administer the medicine, tear open the slit-notched pouch across the top. The 

pouch contains one clear plastic SDA with a single blue-coloured tablet housed in the tip, and 
an oxygen absorber packet. The oxygen absorber packet should be discarded. 

 
Contents of the pouch are shown below: 

 
 
 
 
 

Pusher 
 
 
 

Lock 
 
 
 
 
 
 
 
 
 
 
 
 

Tablet 



32  

2. Remove the white Lock from the green Pusher by squeezing the sides together and detaching 
from Pusher. Discard the Lock. 

 

 
 
3. Tell the patient to touch their tongue to the roof of their mouth if possible. 
4. Rest the SDA lightly on the patient’s teeth or lips. 
5. Place the SDA tip under the tongue and aim at the floor of the patient’s mouth. NOTE: Avoid 

direct mucosal contact with the SDA tip. 
 

 
 
6. Depress the green Pusher to deliver the tablet to the patient’s sublingual space and confirm 

tablet placement. 
 

 
 
The single-dose applicator (SDA) must be discarded in accordance to the institutional policies and 
local requirements. 
 
  



33  

 
 
 

Annex IV 
Scientific conclusions and grounds for the variation to the terms of the marketing 

authorisation(s) 
 
 
 
 
 
 



34  

Scientific conclusions 
Taking into account the PRAC Assessment Report on the PSUR(s) for sufentanil, the scientific 
conclusions of CHMP are as follows:  
Sufentanil may increase plasma serotonin level and its concomitant use with other serotoninergic 
agents may increase the risk of serotonin syndrome. 
 
The CHMP agrees with the scientific conclusions made by the PRAC. 
 
Grounds for the variation to the terms of the marketing authorisation(s) 
On the basis of the scientific conclusions for sufentanil the CHMP is of the opinion that the benefit-
risk balance of the medicinal product(s) containing sufentanil is unchanged subject to the proposed 
changes to the product information 
The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 
 
 
 
 


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