Zalviso

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
  



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1. NAME OF THE MEDICINAL PRODUCT 
 
Zalviso 15 micrograms sublingual tablets  
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each sublingual tablet contains 15 micrograms sufentanil (as citrate). 
 
Excipient(s) with known effect:  
Each sublingual tablet contains 0.074 mg sunset yellow FCF Aluminium Lake (E110). 
Each sublingual tablet contains 0.013 mg sodium. 

 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Sublingual tablet.  
 
Zalviso sublingual tablets of 3 mm diameter are orange-coloured flat-faced tablets with rounded edges.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Zalviso is indicated for the management of acute moderate to severe post-operative pain in adult 
patients. 
 
 
4.2 Posology and method of administration 
 
Zalviso is to be administered in a hospital setting only. Zalviso should only be prescribed by 
physicians who are experienced in the management of opioid therapy, particularly opioid adverse 
reactions such as respiratory depression (see section 4.4).  
 
Posology 
 
Zalviso sublingual tablets are to be self-administered by the patient in response to pain using the 
Zalviso administration device. The Zalviso administration device is designed to deliver a single 
sufentanil 15 micrograms sublingual tablet, on a patient-controlled as needed basis, with a minimum 
of 20 minutes (lockout interval) between doses, over a period of up to 72 hours, which is the 
maximum recommended treatment duration. See section “Method of administration”.  
 
Elderly  
 
No special population studies were performed using sufentanil sublingual tablets in elderly patients. In 
clinical trials approximately 30 % of enrolled patients were 65 to 75 years of age. The safety and 
efficacy in elderly patients was similar to that observed in younger adults (see section 5.2). 
 
Hepatic or renal impairment 
 



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No special population studies were performed using sufentanil sublingual tablets in hepatic and renal 
impaired patients. Only limited data are available for the use of sufentanil in such patients. Zalviso 
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 Zalviso in children aged below 18 years have not been established. No data 
are available. 
 
Method of administration  
 
For sublingual use only.  
 
The Zalviso sublingual tablets are to be self-administered using the Zalviso administration device 
which should only be actuated by the patient in response to pain (see section 6.6). 
 
The dispensed sublingual tablet should dissolve under the tongue and should not be crushed, chewed, 
or swallowed. Patients should not eat or drink and minimize talking for 10 minutes after each dose of 
Zalviso. 
The maximum amount of sublingual sufentanil that can be delivered via the Zalviso administration 
device over an hour is 45 micrograms (3 doses).  
 
In the event of repeated maximal usage by the patient, one cartridge will last for a period of 13 hours 
20 minutes. Additional Zalviso cartridges may be utilized if needed.  
 
For instructions on the setup and handling of the Zalviso administration device before administration, 
see section 6.6. 
 
 
4.3 Contraindications 
 

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
- Significant respiratory depression. 

 
 
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). 
 
Sleep-related breathing disorders 
 
Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-
related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who 
present with CSA, consider decreasing the total opioid dosage. 
 
 
 
 



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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. 
 
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 Zalviso 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 the 
Zalviso administration device can deliver.  
 
Gastrointestinal effects 
 
Sufentanil as a µ-opioid receptor agonist may slow the gastrointestinal motility. Therefore, Zalviso 
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, Zalviso 
should be used with caution in patients with biliary tract disease, including acute pancreatitis. 
 
 
Risk from concomitant use of sedating medicinal products such as benzodiazepines or related 
substances 
 
Concomitant use of Zalviso and sedating medicinal products such as benzodiazepines or related 
substances may result in sedation, respiratory depression, coma and death. Because of these risks, 
concomitant prescribing with these sedating medicinal products should be reserved for patients for 
whom alternative treatment options are not possible. If a decision is made to prescribe Zalviso 
concomitantly with sedating medicinal products the duration of the concomitant treatment should be 
as short as possible. 
The patients should be followed closely for signs and symptoms of respiratory depression and 
sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware 
of these symptoms (see section 4.5). 
 
Other 
 
Before use, the health-care professional should ensure that the patients have been appropriately 
instructed on how to operate the Zalviso administration device to self-administer tablets as needed to 



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manage their pain post-operatively. Only patients who are able to understand and follow the 
instructions to operate the administration device should use Zalviso. The health-care professional 
should take into consideration the ability (e. g. visual or cognitive) of the patient to use the device 
appropriately. 
 
Excipients 
 
Zalviso sublingual tablets contain the azo colouring agent sunset yellow FCF Aluminium Lake (E110), 
which may cause allergic reactions. 
Zalviso sublingual tablets contain less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 
‘sodium free’. 

 
 
 
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. itraconazol, ritonavir) cannot be excluded. Any change in 
efficacy/tolerability associated with the increased exposure would be compensated in practice by an 
alteration in dosing frequency (see section 4.2). 
 
Central nervous system (CNS) depressants 
 
The concomitant use of CNS depressants including barbiturates, neuroleptics or other opioids, halogen 
gases or other non-selective CNS depressants (e.g. alcohol) may enhance respiratory depression.  
 
Sedating medicinal products such as benzodiazepines or related substances 
 
The concomitant use of opioids with sedating medicinal products such as benzodiazepines or related 
substances increases the risk of sedation, respiratory depression, coma and death because of additive 
CNS depressant effect. The duration of the concomitant use should be limited (see section 4.4). 
 
 
Serotonergic agents 
 
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 Zalviso 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 



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There is insufficient data on the use of sufentanil during human pregnancy to evaluate its potential 
harmful effects. There are no indications to date that the use of sufentanil during pregnancy increases 
the risk of congenital abnormalities.  
Sufentanil crosses the placenta. 
Reproductive toxicity has been shown in animal studies (see section 5.3).  
 
Zalviso is not recommended during pregnancy and in women of childbearing potential not using 
contraception. 
 
Breast-feeding 
 
Sufentanil is excreted in human milk when applied intravenously; therefore caution is advised when 
Zalviso is administered to breast-feeding women. Breastfeeding is not recommended when sufentanil 
is administered, due to the risk of opioid effects or toxicity in the breastfed newborns/infants (see 
section 4.9). 
 
Fertility 
 
There are no data on the effects of sufentanil on fertility in women or men. 
 
 
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 Zalviso. Patients should only drive and use machines if sufficient 
time has elapsed after the last administration of Zalviso. 
 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most serious adverse reaction of sufentanil is respiratory depression, potentially leading to 
apnoea and respiratory arrest (see section 4.4). 
Based on the combined safety data from these clinical studies, nausea and vomiting were the most 
frequently reported adverse reactions (≥1/10 frequency).  
 
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: 

Very common ≥1/10 
Common ≥1/100 and <1/10 
Uncommon ≥1/1,000 and <1/100 
Rare ≥1/10,000 and <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 Not known 



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Immune system 
disorders 

  Hypersensitivity* Anaphylactic shock  

Psychiatric disorders  Confusional state Apathy* 
Nervousness* 

 

Nervous system 
disorders 

 Dizziness 
Headache 
Sedation 

Somnolence 
Paraesthesia 
Ataxia* 
Dystonia* 
Hyperreflexia* 

Convulsions 
Coma  

Eye disorders   Vision 
disturbances 

Miosis 

Cardiac disorders  Heart rate increased Heart rate 
decreased* 

 

Vascular disorders  Blood pressure 
increased 
Blood pressure 
decreased 

   

Respiratory, thoracic 
and mediastinal 
disorders 

 Respiratory 
depression  

Apnoea  Respiratory arrest  

Gastrointestinal 
disorders 

Nausea 
Vomiting 

Constipation 
Dyspepsia 

Dry mouth 
 

Skin and subcutaneous 
tissue disorders 

 
Pruritus Hyperhidrosis 

Rash  
Dry skin* 

Erythema  

Musculoskeletal and 
connective tissue 
disorders 

 Involuntary muscle 
spasms  
Muscle twitching*  

  

Renal and urinary 
disorders 

 Urinary retention    

General disorders and 
administration site 
conditions 

Pyrexia 
 

Chills 
Asthenia 

Drug Withdrawal 
Syndrome 

* see “Description of selected adverse reactions” 
 
 
 
Description of selected adverse reactions 
 
After prolonged use of other substances with µ-opioid receptor activity, symptoms of withdrawal were 
observed after abrupt interruption of the treatment. 
Some adverse reactions were not observed in the clinical trials with Zalviso. Their frequencies were 
established based on data from intravenous administration of sufentanil: common – muscle twitching; 
uncommon – hypersensitivity, apathy, nervousness, ataxia, dystonia, hyperreflexia, heart rate 
decreased and dry skin. 
 
 
Reporting of suspected adverse reactions 
 



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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 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 sufentanil should be taken into account. In that case, the opioid antagonist can 
be administered repeatedly or by infusion.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Opioid anaesthetics, 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.  
 

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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.  
 
Clinical efficacy and safety 
 
Analgesia 
 
Efficacy of Zalviso for patient-controlled analgesia was demonstrated in 3 Phase III clinical trials in 
acute post-surgical nociceptive and visceral pain (post-surgical pain following major abdominal or 
orthopaedic surgery): 2 trials were double-blind placebo-controlled (Zalviso N = 430 patients; placebo 
N = 161 patients) and 1 was an open-label active-controlled (Zalviso N = 177 patients; morphine 
N = 180 patients) trial. 
 
Patients were treated using the Zalviso dosing regimen of 15 micrograms sufentanil sublingually as 
needed with a minimum 20 minute lock-out interval over a period of 72 hours. 
  
Superiority over placebo was demonstrated in the Phase III placebo-controlled trials for the primary 
endpoint time-weighted sum of pain intensity difference from baseline over 48 hours (SPID48; 
P ≤0.001), and the secondary endpoints, time-weighted SPID (P ≤0.004), total pain relief (TOTPAR; P 
≤0.004), and patients global assessment (P ≤0.007) over 24, 48 and 72 hours. After 48 hours more than 
half of the subjects in the Zalviso group had a relevant pain reduction (30 % responder rate) in these 
trials (visceral pain 60 %, nociceptive pain 54.9 %). 
 
A significantly higher proportion of patients (78.5 %) rated the method of pain control as “good” or 
“excellent” with Zalviso than with intravenous morphine patient-controlled analgesia method (65.5 %) 
(primary endpoint at 48 hours; P = 0.007). Patients reported in all the 3 Phase III trials a clinically 
meaningful pain relief within the first hour of treatment with Zalviso (pain intensity difference to 
baseline and total pain response >1 NRS). Zalviso was also considered to be easier to use by health-
care professionals (P = 0.017). 
 
As demonstrated in the active-controlled trial, the average time between Zalviso doses was 
approximately double as long as compared to intravenous morphine patient-controlled analgesia 
(approximately 80 minutes compared to approximately 45 minutes) over the first 48 hours. 
Patients who were treated with Zalviso between 48 and 72 hours in the three controlled trials used a 
wide range of the available 216 doses, with a mean of 49 doses/patient (range of 8-153 doses) with the 
majority of patients (69.7 %) using between 24 to 72 doses. 
 



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Respiratory depression 
 
Analgesic doses of Zalviso resulted in respiratory depressive effects in some patients in the clinical 
trials. In the Phase III active-controlled trial, the magnitude of decrease in oxygen saturation was 
comparable between Zalviso and i.v. patient-controlled morphine groups. However, there was a 
statistically significant lower percentage of patients who experienced oxygen desaturation episodes 
following the administration of Zalviso sublingual tablets (19.8 %) with the administration device than 
in the IV PCA morphine group (30.0 %). Clinical trials have shown that sufentanil administered 
intravenously causes less respiratory depression when compared with equianalgesic doses of fentanyl. 
 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The pharmacokinetics of sufentanil after sublingual administration can be described as a three-
compartment model with first-order absorption. This route of administration results in higher absolute 
bioavailability by avoiding intestinal and first-pass liver 3A4 enzyme metabolism.  
Mean absolute bioavailability after a single sublingual administration of Zalviso relative to a one-
minute intravenous sufentanil infusion of 15 micrograms was 59 %. This compares to a substantially 
lower bioavailability of 9 % after oral intake (swallowed). In clinical trials during repeated 
administrations the bioavailability decreased to 37.6 %. 
Buccal administration study 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 50 minutes after a single dose; this 
is shortened to approximately 20 minutes following repeat dosing. When Zalviso was administered 
every 20 minutes, steady state plasma concentrations were achieved after 13 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. 
 
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 
 
The total plasma clearance after single intravenous administration is about 917 l/min. 
Approximately 80 % of the intravenously administered dose of sufentanil is excreted within 24 hours. 
Only 2 % of the dose is excreted in unchanged form. Clearance is not affected by race, sex, renal 
parameters, hepatic parameters, or concomitant CYP3A4 substrates. 
 
Clinically relevant plasma levels are 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. After a single dose, the median CST½ was 
2.2 hours, increasing to a median value of 2.5 h after multiple dosing: the sublingual delivery route 
thus substantially extends the duration of action associated with intravenous sufentanil administration 
(CST½ of 0.14 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. 



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After single administration of a 15 micrograms sufentanil sublingual tablet, mean terminal phase half-
lives in the range of 6 to 10 hours have been observed. After multiple administrations, a longer mean 
terminal half-life of up to 18 hours was determined, 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.  
 
Special populations 
 
Renal impairment 
 
A population pharmacokinetic analysis of plasma sufentanil concentrations following usage of Zalviso 
in patients and healthy volunteers (N = 700), which included 75 patients with moderate and 7 patients 
with severe renal impairment, did not identify renal function as a significant covariate for clearance. 
However, due to the limited number of patients with severe renal impairment studied, Zalviso should 
be used with caution in such patients (see section 4.4).  
 
Hepatic impairment 
 
Based on the population pharmacokinetic analysis for Zalviso in patients and healthy volunteers 
(N = 700), which included 13 patients with moderate and 6 patients with severe hepatic impairment, 
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, Zalviso should be used with caution in 
such patients (see section 4.4).  
 
Paediatric population  
 
No pharmacokinetic data exist for the Zalviso in paediatric patients.  
There is limited pharmacokinetic data available in children after intravenous sufentanil administration. 
 
Elderly 
 
No special population studies were performed using Zalviso in the elderly. Pharmacokinetic data from 
intravenous sufentanil administration did not reveal age related differences. In the placebo-controlled 
Phase 3 trials, approximately 20 % of enrolled patients were elderly (≥ 75 years of age) and 
approximately 30 % of enrolled patients were 65 to 75 years of age. The population pharmacokinetic 
analysis showed an effect of age with a 27 % decrease in clearance in the elderly people (above 65 
years of age). Since this decrease related to age is smaller than the observed inter-subject variability of 
30-40 % in exposure parameters for sufentanil, this effect is not considered to be of clinical relevance, 
particularly given that Zalviso is only used on an ‘as-needed’ basis. 
 
Population pharmacokinetics  
 
When patients titrated themselves to analgesic effect with Zalviso, plasma sufentanil concentrations 
averaged 60-100 pg/ml over two days of use, with no effect based on age or body mass index (BMI), 
or mild to moderate renal or liver impairment.  
 
Patients with BMI > 30 kg/m2  
 
Population pharmacokinetic analysis with a BMI as covariate showed that patients with a 
BMI > 30 kg/m2 dosed more frequently. 
 
 
5.3 Preclinical safety data 
 
Repeat-dose toxicity 



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Sufentanil has been shown to induce opioid-like effects in a variety of laboratory animals (dogs, rats, 
guinea pigs, hamsters) at doses above those inducing analgesia and in two repeat-dose studies with 
sufentanil sublingual tablets administered buccally in Golden Syrian hamster.  
 
Reproductive toxicity 
 
Sufentanil was not teratogenic in rats and rabbits. Sufentanil caused embryolethality in rats and rabbits 
who were treated for 10-30 days during pregnancy with 2.5 times the maximum human dose by 
intravenous administration. The embryolethal effect was considered secondary to the toxicity for the 
mother animal. 
No negative effects were observed in another study in rats that were treated with 20times the 
maximum human dose in the period of organogenesis. The preclinical effects were only observed 
following administrations of levels significantly above the maximum human dose, which are therefore 
of little relevance for clinical use. 
 
Mutagenicity 
 
The Ames test revealed no mutagenic activity of sufentanil. In the micronucleus test in female rats, 
single intravenous doses of sufentanil as high as 80 µg/kg (approximately 2.5 times the upper human 
intravenous dose) produced no structural chromosome mutations.  
  
Carcinogenicity 
 
Carcinogenicity studies have not been conducted on 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 Zalviso sublingual tablets have no or minimal 
potential for local irritation. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol (E421) 
Calcium hydrogen phosphate, anhydrous 
Hypromellose 
Croscarmellose sodium  
Stearic acid 
Magnesium stearate 
Sunset yellow FCF Aluminium Lake (E110) 
 
6.2 Incompatibilities 
 
Not applicable.  
 
 
6.3 Shelf life 
 
3 years 
 
 



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6.4 Special precautions for storage 
 
Store in the original package in order to protect from light.  
 
 
6.5 Nature and contents of container  
 
Zalviso is provided in a polycarbonate cartridge, each of which contains 40 sublingual tablets and is 
packed in a polyester film/LDPE/aluminium foil/LDPE sachet with an oxygen absorber. Zalviso is 
available in pack sizes of 1 and 10, 20 cartridges and multipacks containing 40 (2 packs of 20), 60 
(3 packs of 20) and 100 (5 packs of 20) cartridges, equivalent to 40, 400, 800, 1,600, 2,400 and 
4,000 sublingual tablets, respectively.  
Not all pack sizes may be marketed. 
 
 
6.6 Special precautions for disposal and other handling 
 
The cartridge should be used only with the Zalviso administration device, consisting of a controller 
and a dispenser to ensure the proper use of this system.  
After removing from the sachet, the cartridge should be placed into the Zalviso administration device 
immediately. 
 
The device should be used as recommended in the information provided by the device manufacturer. 
The instructions for setting up the Zalviso administration device by a healthcare professional must be 
followed carefully. 
The Zalviso administration device should not be used if any component is visibly damaged. 
 
The fully charged Zalviso administration device will operate without recharging for up to 72 hours.  
 
After treatment discontinuation the health-care professional has to remove the cartridge from the 
device and any unused and/or not completely empty cartridges have to be disposed by the health-care 
professional in accordance with local laws and requirements for controlled substances. Any other 
waste material must be discarded in accordance to the institutional policies and local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Grünenthal GmbH 
Zieglerstr. 6 
52078 Aachen 
Germany 
Tel.: +49-241-569-0 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
EU/1/15/1042/001 
EU/1/15/1042/002 
EU/1/15/1042/003 
EU/1/15/1042/004 
EU/1/15/1042/005 
EU/1/15/1042/006 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 18 September 2015 



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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. 
 
 
  

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ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 



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A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturer responsible for batch release 

Grunenthal GmbH 
Zieglerstr. 6 
D-52078 Aachen 
GERMANY 

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. 

The marketing authorisation holder shall submit the first periodic safety update report for this 
product within 6 months following authorisation. 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

• Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new 
information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached.  

• Additional risk minimisation measures  
 

Prior to launch of Zalviso in each Member State the Marketing Authorisation Holder (MAH) must 
agree about the content and format of the educational programme, including communication media, 
distribution modalities, and any other aspects of the programme, with the National Competent 
Authority.  

The MAH shall ensure that, following discussions and agreement with the National Competent 
Authorities in each Member State where Zalviso is launched all healthcare professionals who are 
expected to prescribe Zalviso are informed through an information letter on having access to / are 
provided with the following items: 



17 

• Summary of Product Characteristics (SmPC) and Package Leaflet 

• Educational materials for the healthcare professionals 

 

The Educational material shall contain the following key messages: 

- Inform about the indication and how to appropriately select patients;  

- Use Zalviso according to the guidance in the SmPC to ensure appropriate use and minimize risks. 

 
 
 
 
 
 
 
 
 
 
  



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



20 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON for 1, 10 and 20 cartridges 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zalviso 15 micrograms sublingual tablets  
Sufentanil  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sublingual tablet contains 15 micrograms sufentanil (as citrate). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sunset yellow FCF Aluminium Lake (E110), contains sodium. See leaflet for further 
information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
1 cartridge of 40 sublingual tablets 
10 cartridges of 40 sublingual tablets each 
20 cartridges of 40 sublingual tablets each 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Sublingual use. 
To be used only with the Zalviso administration device. 
Place immediately into the Zalviso administration device after removal from sachet. 
Do not crush, chew, or swallow the tablet. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
 
8. EXPIRY DATE 
 
EXP 
 



21 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light 
 
 
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 
 
Grünenthal GmbH 
Zieglerstr. 6 
52078 Aachen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1042/001 1 cartridge of 40 sublingual tablets 
EU/1/15/1042/002 10 cartridges of 40 sublingual tablets each 
EU/1/15/1042/003 20 cartridges of 40 sublingual tablets each 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN: 



22 

 
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
INTERMEDIATE CARTON COMPONENT OF A MULTIPACK (WITHOUT BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zalviso 15 micrograms sublingual tablets  
Sufentanil  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sublingual tablet contains 15 micrograms sufentanil (as citrate). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sunset yellow FCF Aluminium Lake (E110), contains sodium. See leaflet for further 
information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
800 sublingual tablets (20 cartridges of 40 sublingual tablets each). Component of multipack, can’t be 
sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Sublingual use. 
To be used only with the Zalviso administration device. 
Place immediately into the Zalviso administration device after removal from sachet. 
Do not crush, chew, or swallow the tablet. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



23 

 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light 
 
 
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 
 
Grünenthal GmbH 
Zieglerstr. 6 
52078 Aachen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN: 
  



24 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER LABEL (WITH BLUE BOX) 
MULTIPACKS ONLY 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zalviso 15 micrograms sublingual tablets  
Sufentanil  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sublingual tablet contains 15 micrograms sufentanil (as citrate). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sunset yellow FCF Aluminium Lake (E110), contains sodium. See leaflet for further 
information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Multipack: 1600 sublingual tablets [40 (2 packs of 20) cartridges of 40 sublingual tablets each]  
Multipack: 2400 sublingual tablets [60 (3 packs of 20) cartridges of 40 sublingual tablets each] 
Multipack: 4000 sublingual tablets [100 (5 packs of 20) cartridges of 40 sublingual tablets each] 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Sublingual use. 
To be used only with the Zalviso administration device. 
Place immediately into the Zalviso administration device after removal from sachet. 
Do not crush, chew, or swallow the tablet. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



25 

9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light 
 
 
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 
 
Grünenthal GmbH 
Zieglerstr. 6 
52078 Aachen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1042/004 2 x 20 cartridges of 40 sublingual tablets each 
EU/1/15/1042/005 3 x 20 cartridges of 40 sublingual tablets each 
EU/1/15/1042/006 5 x 20 cartridges of 40 sublingual tablets each 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
  



26 

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



27 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
SACHET 
 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zalviso 15 micrograms sublingual tablets  
Sufentanil  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sublingual tablet contains 15 micrograms sufentanil (as citrate). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sunset yellow FCF Aluminium Lake (E110), contains sodium. See leaflet for further 
information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
1 cartridge of 40 sublingual tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Sublingual use. 
To be used only with the Zalviso administration device. 
Place immediately into the Zalviso administration device after removal from sachet. 
Do not crush, chew, or swallow the tablet. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP see page 1 
EXP see reverse 
 



28 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light 
 
 
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 
 
Grünenthal GmbH 
Zieglerstr. 6 
52078 Aachen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
 
 
13. BATCH NUMBER 
 
Lot 
Lot see page 1 
Lot see reverse 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
  



29 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
CARTRIDGE 
 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Zalviso 15 micrograms sublingual tablets  
Sufentanil  
Sublingual use 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
40 sublingual tablets 
 
 
6. OTHER 
 
 
 
 
 
  



30 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



31 

Package leaflet: Information for the patient 
 

Zalviso 15 micrograms sublingual tablets 
Sufentanil 

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

not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Zalviso is and what it is used for  
2. What you need to know before you take Zalviso  
3. How to take Zalviso  
4. Possible side effects  
5. How to store Zalviso  
6. Contents of the pack and other information 
 
 
1. What Zalviso is and what it is used for 
 
The active substance of Zalviso is sufentanil, which belongs to a group of strong pain-relieving 
medicines called opioids. 
 
Zalviso is used to treat acute moderate to severe pain after an operation in adults. 
 
 
2. What you need to know before you take Zalviso  
 
Do not take Zalviso: 
- if you are allergic to sufentanil or any of the other ingredients of this medicine (listed in section 

6).  
-  if you have severe breathing problems. 
 
 
Warnings and precautions  
Talk to your doctor or nurse before taking Zalviso.  
 
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 Zalviso 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 heart beats, low 

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

way in which your body breaks down and eliminates the medicine; 
- have a history of medicine or alcoholabuse; 
- are regularly using a prescribed opioid medicine (e.g. codeine, fentanyl, hydromorphone, 

oxycodone); 
- have abnormally slow bowel movements; 
- have a disease of the gall bladder or pancreas. 
 
 



32 

Sleep-related breathing disorders 
Zalviso contains an active substance that belongs to the group of opioids. Opioids can cause sleep-
related breathing disorders, for example central sleep apnea (shallow/pause of breathing during sleep) 
and sleep-related hypoxemia (low level of oxygen in the blood).  
The risk of experiencing central sleep apnea is dependent on the dose of opioids. Your doctor may 
consider decreasing your total opioid dosage if you experience central sleep apnea. 
 
Taking the sublingual tablets with the device 
Before you start using Zalviso, your doctor or nurse will show you how to use the Zalviso 
administration device. You will then be able to take a tablet as needed to relieve your pain. Follow the 
instructions carefully. Talk to your doctor or nurse if you did not fully understand the instructions or 
are unsure about the correct handling of the administration device.  
 
Children and adolescents 
Zalviso should not be used in children and adolescents below 18 years. 
 
Other medicines and Zalviso 
Tell your doctor if you are taking, have recently taken or might take any other medicines. In particular, 
tell your doctor if you are taking any of the following: 
- Any medicines that might have an effect on the way in which your body breaks down Zalviso e.g. 

ketoconazole, which is used for the treatment of fungal infections.  
- Any medicines to treat anxiety, tranquillisers or other opioid medicines, as they can increase the 

risk of severe breathing problems. 
- 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 Zalviso 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 Zalviso. 

- Other medicines which are also taken sublingually (medicines that are placed under the tongue 
where they dissolve) or medicines which dilute or 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 Zalviso has not 
been studied.  

 
Concomitant use of Zalviso and sedating medicines such as benzodiazepines or related drugs  
increases the risk of drowsiness, difficulties in breathing (respiratory depression), coma and may be 
life-threatening. Because of this, concomitant use should only be considered when other treatment 
options are not possible.  
However if your doctor prescribes Zalviso together with sedating medicines the duration of 
concomitant treatment should be limited by your doctor.  
Please tell your doctor about all sedating medicines you are taking, and follow your doctor’s dose 
recommendation closely. It could be helpful to inform friends or relatives to be aware of the signs and 
symptoms stated above. Contact your doctor when experiencing such symptoms. 

 
Zalviso with alcohol 
Do not drink alcohol while using Zalviso. 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. 
 
Zalviso should not be used during pregnancy or if you are a woman of childbearing potential not using 
contraception. 
 
Sufentanil passes into breast milk and can cause side effects in the breast-fed child. Breastfeeding is 
not recommended when you take Zalviso. 
 



33 

Driving and using machines 
Zalviso 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 Zalviso. You should only drive and use machines if sufficient time as 
elapsed after your last dose of Zalviso.  
 
Zalviso contains sunset yellow FCF Aluminium Lake (E110) 
Zalviso contains the colouring agent sunset yellow FCF Aluminium Lake (E110), which may cause 
allergic reactions. 
 
Zalviso contains sodium 
Zalviso contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium free’.  
 
 
 
3. How to take Zalviso 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. 
 
The sublingual tablets are taken using the Zalviso administration device, which is a system that 
delivers a single dose upon activation. After receiving a dose you will not be able to release another 
dose for 20 minutes and you will not be able to take more than 3 doses in one hour. 
 
The device will work for 3 days (72 hours), which is also the maximum recommended duration of 
your treatment. 
 
Zalviso is placed under the tongue using the Zalviso administration device. You can control your 
treatment and should only activate the device when in need of pain relief. 
 
The tablets dissolve under your tongue and should not be crushed, chewed, or swallowed. You should 
not eat or drink and should talk as little as possible for 10 minutes after each dose. 
 
Zalviso is only to be taken in a hospital setting. It is only prescribed by physicians who are 
experienced in the use of strong pain killers like Zalviso and know the effects it may have on you, in 
particular on your breathing (see “Warnings and precautions” above).  
 
Do not use the device if any component is visibly damaged. 
 
After your treatment the medical staff will take the Zalviso administration device and dispose of any 
unused tablets accordingly. The device is constructed so that you will not be able to open it.  
 
If you take more Zalviso than you should 
The administration device will make you wait 20 minutes between doses to prevent you from taking 
more Zalviso than you should. However, symptoms of overdose include severe breathing problems 
like slow and shallow breathing, loss of conciousness, extreme 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. 
 
The most serious side effects are severe breathing problems like slow and shallow breathing, which 
may even lead to stopping breathing or inability to breathe.  



34 

In case you experience any of the above mentioned side effects, stop taking Zalviso and tell your 
doctor or nurse immediately. 
 
Very common side effects (may affect more than 1 in 10 people): nausea, vomiting, fever.  
 
Common side effects (may affect up to 1 in 10 people): 
confusion, dizziness, headache, drowsiness, increased heart rate, high blood pressure, low blood 
pressure, constipation, indigestion, itching of the skin, involuntary muscle cramps, muscle twitching, 
difficulty passing urine.  
 
Uncommon side effects (may affect up to 1 in 100 people): allergic reactions, lack of interest or 
emotion, nervousness, sleepiness, abnormal sensation of the skin, problems coordinating muscle 
movements, muscle contractions, exaggeration of reflexes, vision disturbances, decreased heart rate, 
dry mouth, excessive sweating, rash, dry skin, chills, weakness.  
 
Frequency not known (frequency cannot be estimated from the available data): severe allergic 
reactions (anaphylactic shock), convulsion (fits), coma, small pupil size, redness of the skin, 
withdrawal syndrome.   
 
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 
Appendix V.  
By reporting side effects, you can help provide more information on the safety of this medicine. 
 
 
 
 
 
5. How to store Zalviso 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and sachet after EXP. 
 
Store in the original package in order to protect from light. 
 
Do not throw away any medicines via wastewater or household waste. Ask the medical staff how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Zalviso contains  
- The active substance is sufentanil. Each sublingual tablet contains 15 micrograms sufentanil (as 

citrate). 
- The other ingredients are mannitol (E421), calcium hydrogen phosphate (anhydrous), 

hypromellose, croscarmellose sodium, stearic acid, magnesium stearate, sunset yellow FCF 
Aluminium Lake (E110) (see section 2 “What you need to know before you take Zalviso”) 

 
What Zalviso looks like and contents of the pack 
Zalviso sublingual tablets are orange-coloured flat-faced tablets with rounded edges. The sublingual 
tablets measure 3 mm in diameter. 
 
The sublingual tablets are supplied in cartridges; each cartridge contains 40 sublingual tablets. One 
cartridge is packed in a sachet including an oxygen absorber. 

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


35 

Zalviso sublingual tablets are available in pack sizes of 1, 10 and 20 cartridges and in multipacks 
containing 40 (2 packs of 20), 60 (3 packs of 20) and 100 (5 packs of 20) cartridges, equivalent to 40, 
400, 800, 1,600, 2,400 and 4,000 sublingual tablets, respectively. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Grünenthal GmbH 
Zieglerstraße 6 
52078 Aachen 
Germany 
Tel.: +49-241-569-0 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Luxemburg/Luxembourg 
S.A. Grünenthal N.V.  
Lenneke Marelaan 8 
1932 Sint-Stevens-Woluwe 
België/Belgique/Belgien 
Tél/Tel: + 32 (0)2 290 52 00 
beinfo@grunenthal.com 
 

Lietuva 
Grünenthal GmbH 
Tel: + 49 241 569-0 
 
 

България 
Grünenthal GmbH 
Teл.: + 49 241 569-0 
 

Magyarország 
Grünenthal GmbH 
Tel.: + 49 241 569-0 
 

Česká republika 
Grünenthal GmbH 
Tel: + 49 241 569-0 

Malta 
Grünenthal GmbH 
Tel.: + 49 241 569-0 
 

Danmark 
Grünenthal Denmark ApS 
Arne Jacobsens Allé 7 
2300 København S 
Tlf: +45 88883200 
 

Nederland 
Grünenthal B.V. 
De Corridor 21K 
NL-3621 ZA Breukelen 
Tel:+31 (0)30 6046370  
info.nl@grunenthal.com 
 

Deutschland 
Grünenthal GmbH 
Zieglerstr. 6 
DE-52078 Aachen 
Tel: + 49 241 569-1111 
service@grunenthal.com 
 

Norge 
Grünenthal Norway AS 
C.J. Hambros Plass 2C 
0164 Oslo 
Tlf: +47 22996054 
 

Eesti 
Grünenthal GmbH 
Tel: + 49 241 569-0 
 

Österreich 
Grünenthal GmbH 
Campus 21, Liebermannstraße A01/501 
2345 Brunn am Gebirge 
Tel: +43(0)2236 379 550-0 
 

Ελλάδα 
Grünenthal GmbH 
Τηλ: + 49 241 569-0 
 

Polska 
Grünenthal GmbH 
Tel.: + 49 241 569-0 
 

España Portugal 



36 

Grünenthal Pharma, S.A. 
C/Dr. Zamenhof, 36 
E-28027 Madrid 
Tel: +34 (91) 301 93 00  
 

Grünenthal, S.A. 
Alameda Fernão Lopes, 12-8.º A 
P-1495 - 190 Algés 
Tel: +351 / 214 72 63 00 

France 
Laboratoires Grünenthal SAS 
Immeuble Eurêka 
19 rue Ernest Renan 
CS 90001 
F- 92024 Nanterre Cedex 
Tél: + 33 (0)1 41 49 45 80 
 

România 
Grünenthal GmbH 
Tel: + 49 241 569-0 

Hrvatska 
Grünenthal GmbH 
Tel: + 49 241 569-0 
 

Slovenija 
Grünenthal GmbH 
Tel: + 49 241 569-0 
 

Ireland 
Grünenthal Pharma Ltd 
4045 Kingswood Road,  
Citywest Business Park 
IRL – Citywest Co., Dublin 
Tel: +44 (0)870 351 8960 
medicalinformationie@grunenthal.com 
 

Slovenská republika 
Grünenthal GmbH 
Tel: + 49 241 569-0 
 

Ísland 
Grünenthal GmbH 
Sími: + 49 241 569-0 
 

Suomi/Finland 
Grünenthal GmbH 
Puh/Tel: + 49 241 569-0 
 

Italia 
Grünenthal Italia S.r.l.I 
Tel: +39 02 4305 1 
 

Sverige 
Grunenthal Sweden AB 
Tel: +46 (0)86434060 
 

Κύπρος 
Grünenthal GmbH 
Τηλ: + 49 241 569-0 
 

United Kingdom 
Grünenthal Ltd 
1 Stokenchurch Business Park 
Ibstone Road, HP14 3FE – UK 
Tel: +44 (0)870 351 8960 
medicalinformationuk@grunenthal.com 
 

Latvija 
Grünenthal GmbH 
Tel: + 49 241 569-0 
 

 

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

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

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