Prialt

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ANNEX I 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT

Prialt 25 micrograms/ml solution for infusion 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One ml solution contains 25 μg ziconotide (as acetate). 

Each 20 ml vial contains 500 μg ziconotide (as acetate). 

For the full list of excipients, see section 6.1. 

3. PHARMACEUTICAL FORM

Solution for infusion (infusion).   

Clear, colourless solution. 

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Ziconotide is indicated for the treatment of severe, chronic pain in adults who require intrathecal (IT) 
analgesia. 

4.2 Posology and method of administration 

Treatment with ziconotide should only be undertaken by physicians experienced in intrathecal (IT) 
administration of medicinal products.   

Posology 

Adults (including the elderly ≥ 65 years of age) 

Dosing of ziconotide should be initiated at 2.4 μg/day and titrated on an individual patient basis 
according to the patient’s analgesic response and adverse reactions.  Patients should be titrated in dose 
increments of ≤ 2.4 μg/day, up to a maximum dose of 21.6 μg/day.  The minimal interval between 
dose increases is 24 hours; the recommended interval, for safety reasons, is 48 hours or more.  If 
necessary the dose can be decreased by any amount (including stopping the infusion) for the 
management of adverse reactions.  Approximately 75% of patients who respond satisfactorily to 
treatment require a dose of ≤ 9.6 μg/day. 

Renal impairment

Studies have not been conducted in patients with impaired renal function.  Caution should be exercised 
when ziconotide is administered to patients with impaired renal function. 

Hepatic impairment 

Studies have not been conducted in patients with impaired hepatic function.  Caution should be 
exercised when ziconotide is administered to patients with impaired hepatic function. 



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Paediatric population 

The safety and efficacy of ziconotide in children aged 0 to 18 years have not been established. 

No data are available. 

Method of administration  

Intrathecal use. 

Ziconotide must be administered as a continuous infusion via an intrathecal catheter, using an external 
or internally implanted mechanical infusion pump capable of delivering an accurate infusion volume.  
As the risk of meningitis secondary to prolonged catheterisation of the intrathecal space is greater with 
an external catheter infusion system, internal systems are recommended to administer ziconotide for 
prolonged periods (see section 4.4).  An external catheter system should only be used when an internal 
system cannot be implanted. 

When low doses of ziconotide are required, for example when initiating titration, ziconotide must be 
diluted before use with preservative-free sodium chloride 9 mg/ml (0.9%) solution for injection. 

For instructions on dilution of the medicinal product 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. 

Combination with IT chemotherapy (see section 4.5). 

4.4 Special warnings and precautions for use

Long-term use 
Although ziconotide has been studied in long-term, open label efficacy and safety clinical trials, 
controlled studies of longer than 3 weeks duration have not been conducted (see section 5.1).  Possible 
long-term local toxic effects on the spinal cord have not been excluded and preclinical data in this 
respect are limited (see section 5.3).  Therefore, caution is needed during long-term treatment. 

Risk of infection 
The administration of medicinal products by the intrathecal (IT) route carries the risk of potentially 
serious infections, such as meningitis, which may be life threatening.  Meningitis due to the entrance 
of organisms along the catheter track or inadvertent contamination of the infusion system is a known 
complication of intrathecal medicinal product administration, especially with external systems. 

Patients and physicians must be vigilant for typical symptoms and signs of meningitis. 

The optimal intrathecal placement of the catheter tip has not been established.  Lower catheter tip 
placement, e.g. at the lumbar level, may reduce the incidence of ziconotide-related neurological 
adverse reactions.  Therefore, catheter tip placement should be carefully considered to allow adequate 
access to spinal nociceptive segments whilst minimising medicinal product concentrations at cerebral 
levels. 

Only a small number of patients have received systemic chemotherapy and IT ziconotide.  Caution 
should be exercised when ziconotide is administered to patients who are receiving systemic 
chemotherapy (see section 4.5). 



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Elevations in creatine kinase 
Elevations in creatine kinase, which are usually asymptomatic, are common amongst patients on 
intrathecal ziconotide.  Progressive elevation of the creatine kinase is uncommon.  However, 
monitoring of creatine kinase is recommended.  In the event of progressive elevation, or clinically 
significant elevation in association with clinical features of myopathy or rhabdomyolysis, 
discontinuation of ziconotide should be considered. 

Hypersensitivity reactions 
Hypersensitivity reactions, including anaphylaxis, have not been observed during clinical trials and the 
immunogenicity of ziconotide administered by the IT route appears to be low.  However, the potential 
for severe allergic reactions cannot be excluded and spontaneous reports of anaphylactic reactions 
have been received. 

Cognitive and neuropsychiatric adverse reactions 
Cognitive and neuropsychiatric adverse reactions, particularly confusion, are common in patients 
treated with ziconotide.  Cognitive impairment typically appears after several weeks of treatment.  
Episodes of acute psychiatric disturbances, such as hallucinations, paranoid reactions, hostility, 
aggressiveness, delirium, psychosis and manic reactions have been reported in patients treated with 
ziconotide.  The ziconotide dose should be reduced or discontinued if signs or symptoms of cognitive 
impairment or neuropsychiatric adverse reactions develop, but other contributing causes should also be 
considered.  The cognitive effects of ziconotide are typically reversible within 1 - 4 weeks after 
discontinuation of the medicinal product, but may persist in some cases.  It is recommended that 
patients undergo a neuropsychiatric evaluation before and after starting intrathecal ziconotide.

In patients with severe chronic pain there is a higher incidence of suicide and suicide attempts than in 
the general population.  Ziconotide may cause or worsen depression with the risk of suicide in 
susceptible patients. 

Depression of Central Nervous System (CNS) 
Patients have experienced depressed levels of consciousness while receiving ziconotide.  The patient 
usually remains conscious and breathing is not depressed.  The event may be self-limited, but 
ziconotide should be discontinued until the event resolves.  The re-introduction of ziconotide is not 
recommended in these patients.  Withdrawal of concomitant CNS depressant medicinal products 
should also be considered as they may contribute to the reduced level of arousal. 

4.5 Interaction with other medicinal products and other forms of interaction

Specific clinical medicinal product interaction studies have not been conducted with ziconotide.  
However, low plasma ziconotide concentrations, metabolism by ubiquitous peptidases and relatively 
low plasma protein binding (see section 5.2) make metabolic-based interactions or plasma protein 
displacement type interactions between ziconotide and other medicinal products unlikely. 

No clinical data are available on the interaction between IT chemotherapy and IT ziconotide.  
Ziconotide is contraindicated in combination with IT chemotherapy (see section 4.3). 

Only a small number of patients have received systemic chemotherapy and IT ziconotide.  Caution 
should be exercised when ziconotide is administered to patients who are receiving systemic 
chemotherapy (see section 4.4). 

Medicinal products that affect specific peptidases/proteases would not be expected to impact upon 
ziconotide plasma exposure.  Based on very limited clinical investigations, both angiotensin 
converting enzyme inhibitors (e.g., benazepril, lisinopril and moexipril) and HIV protease inhibitors 
(e.g., ritonavir, saquinavir, indinavir), have no readily apparent effect on plasma ziconotide exposure. 

Ziconotide does not interact with opiate receptors. If discontinuing opiates when initiating ziconotide 
therapy, opiate withdrawal should be gradual. For patients being withdrawn from IT opiates, the IT 



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opiate infusion dose should be gradually tapered over a few weeks and replaced with a 
pharmacologically equivalent dose of oral opiates.  Adding IT ziconotide to stable doses of IT 
morphine (see section 5.1), is possible but requires special attention, as a high rate of neuropsychiatric 
adverse reactions (confusion/thinking abnormal, paranoid reactions and hallucinations, and abnormal 
gait), some of them serious, was observed in Study 202 despite a low dose of ziconotide. Vomiting and 
anorexia, and peripheral oedema were also observed when IT ziconotide was added to IT morphine.  
The addition of IT morphine to stable doses of IT ziconotide is better tolerated (pruritis has been 
reported) (see section 5.1). 

An increased incidence of somnolence has been observed when ziconotide is administered 
concomitantly with systemic baclofen, clonidine, bupivacaine or propofol thus for the time being their 
simultaneous use is discouraged. 

No data are available regarding the concomitant use of partial opioid agonists (e.g. buprenorphine) 
with ziconotide. 

4.6 Fertility, pregnancy and lactation 

Pregnancy 

There are no or limited amount of data from the use of ziconotide in pregnant women.   

Studies in animals have shown reproductive toxicity (see section 5.3).   

Ziconotide is not recommended during pregnancy and in women of childbearing potential not using 
contraception.  

Breast-feeding 

It is unknown whether ziconotide/metabolites are excreted in human milk. 

A risk to newborns/infants cannot be excluded.  

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from 
ziconotide therapy taking into account the benefit of breast-feeding for the child and the benefit of 
therapy for the woman. 

Fertility 

No specific studies with ziconotide in humans have been conducted to evaluate effects on fertility. In a 
study on male and female fertility in rats no effects in males while reductions in corpora lutea; 
implantation sites and number of live embryos were observed in females (see section 5.3). 

4.7 Effects on ability to drive and use machines

Ziconotide has moderate influence on the ability to drive and use machines. 

Ziconotide may cause confusion, somnolence and other neurological adverse reactions, therefore 
patients must be advised not to drive or operate machines if affected. 

4.8 Undesirable effects 

Summary of the safety profile 
The safety of ziconotide administered as a continuous intrathecal infusion has been evaluated in more 
than 1,400 patients participating in acute and chronic pain clinical trials.  The duration of treatment has 
ranged from one-hour bolus infusion to continuous use for more than 6 years.  The median exposure 



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time was 43 days.  The infusion dose rate ranged from 0.03 - 912 μg/day, with a median final dose rate 
of 7.2 μg/day. 

In clinical trials, 88% of patients experienced adverse reactions.  The most common adverse reactions  
reported in long-term clinical trials were dizziness (42%), nausea (30%), nystagmus (23%), 
confusional state (25%), gait abnormal (16%), memory impairment (13%), vision blurred (14%), 
headache (12%), asthenia (13%), vomiting (11%), and somnolence (10%).  Most adverse reactions 
were mild to moderate in severity and resolved over time. 

Tabulated list of adverse reactions 
Unless otherwise noted the table shows the incidence rates of adverse reactions  reported in the 
intrathecal clinical trials with ziconotide (short- and long-term exposure). Within each frequency 
grouping undesirable effects are presented in order of decreasing frequency.  

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) 

System Organ 
Class 

Very common Common Uncommon Not Known 

Infections and 
infestations 

sepsis, meningitis  

Immune system 
disorders 

Anaphylactic 
reactiona

Metabolism and 
nutrition 
disorders 

appetite decreased, 
anorexia 

Psychiatric 
disorders 

confusional 
state 

anxiety, auditory 
hallucination, 
insomnia, agitation, 
disorientation, 
hallucination, visual 
hallucination, 
depression, paranoia, 
irritability, 
depression 
aggravated, 
nervousness, affect 
lability, mental status 
changes, anxiety 
aggravated, 
confusion aggravated 

delirium, psychotic 
disorder, suicidal 
ideation, suicide 
attempt, thought 
blocking, abnormal 
dreams, 
aggressiveness 



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System Organ 
Class 

Very common Common Uncommon Not Known 

Nervous system 
disorders 

dizziness, 
nystagmus, 
memory 
impairment, 
headache, 
somnolence 

dysarthria, amnesia, 
dysgeusia, tremor, 
balance impaired, 
ataxia, aphasia, 
burning sensation, 
sedation, 
paraesthesia, 
hypoaesthesia, 
disturbance in attenti
on, speech disorder, 
areflexia, 
coordination abnorm
al, dizziness postural, 
cognitive disorder, 
hyperaesthesia, 
hyporeflexia, 
ageusia, depressed 
level of 
consciousness, 
dysaesthesia, 
parosmia, mental 
impairment 

incoherence, loss of 
consciousness, 
coma, stupor, 
convulsions, 
cerebrovascular 
accident, 
encephalopathy 

Eye disorders vision blurred diplopia, 
visual disturbance, 
photophobia 

Ear and 
labyrinth 
disorders 

vertigo, tinnitus 

Cardiac 
disorders 

atrial fibrillation 

Vascular 
disorders 

orthostatic hypotensi
on, hypotension 

Respiratory, 
thoracic and 
mediastinal 
disorders 

dyspnoea respiratory distress  

Gastrointestinal 
disorders 

nausea, 
vomiting 

diarrhoea, dry mouth, 
constipation, nausea 
aggravated, upper 
abdominal pain 

dyspepsia 

Skin and 
subcutaneous 
tissue disorders 

pruritus, sweating 
increased 

rash 

Musculoskeletal 
and connective 
tissue disorders 

pain in limb, 
myalgia, muscle 
spasms, muscle 
cramp, muscle 
weakness, arthralgia, 
peripheral swelling 

rhabdomyolysis, 
myositis, back pain, 
muscle twitching, 
neck pain 



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System Organ 
Class 

Very common Common Uncommon Not Known 

Renal and 
urinary 
disorders 

urinary retention, 
urinary hesitation, 
dysuria, urinary 
incontinence 

acute renal failure  

General 
disorders and 
administration 
site conditions 

gait abnormal, 
asthenia 

fatigue, pyrexia, 
lethargy, 
oedema peripheral, 
rigors, fall, 
chest pain, feeling 
cold, pain, feeling 
jittery, pain 
exacerbated 

difficulty in 
walking 

Investigations blood 
creatine phosphokina
se increased, weight 
decreased 

electrocardiogram 
abnormal, aspartate 
aminotransferase 
increased, blood 
creatine 
phosphokinase MM 
increased, body 
temperature 
increased 

a. From spontaneous reporting 

Description of selected adverse reactions 

Meningitis 

Administration of medicinal products by the intrathecal route carries the risk of potential serious 
infections, such as meningitis, which may be life threatening. Patients and physicians must be vigilant 
for typical symptoms and signs of meningitis (see section 4.4). 

Elevations of creatine phosphokinase 

Elevations in creatine phosphokinase were usually asymptomatic. Monitoring of creatine 
phosphokinase is recommended.  Discontinuation of ziconotide should be considered in the event of 
progressive or significant elevation of creatine phosphokinase in association with clinical features of 
myopathy or rhabdomyolysis (see section 4.4). 

CNS adverse reactions 

Cognitive and neuropsychiatric adverse reactions are common in patients treated with ziconotide. 
Cognitive impairment typically appears after several weeks of treatment. Episodes of acute psychiatric 
disturbances, such as hallucinations, paranoid reactions, hostility, aggressiveness, delirium, psychosis 
and manic reactions have been reported in patients treated with ziconotide. The ziconotide dose should 
be reduced or discontinued if signs or symptoms of cognitive impairment or neuropsychiatric adverse 
reactions develop, but other contributing causes should also be considered. The cognitive effects of 
ziconotide are typically reversible within 1 - 4 weeks after discontinuation of the medicinal product, 
but may persist in some cases.  It is recommended that patients undergo a neuropsychiatric evaluation 
before and after starting intrathecal ziconotide (see section 4.4).

Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 



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professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 

4.9 Overdose 

In intravenous infusion studies, healthy male volunteers received ziconotide at doses of up 
to70,000 μg/day or 3,200 times the maximum recommended daily intrathecal infusion dose.  Postural 
hypotension was observed in almost all subjects who received high intravenous doses of ziconotide. 

The maximum recommended intrathecal dose is 21.6 μg/day.  The maximum intended intrathecal dose 
of ziconotide in clinical trials was 912 μg/day following upward titration over 7 days. 

Symptoms 
In one clinical study a male cancer patient received an accidental IT ziconotide overdose of 744 μg 
over a 24-hour period (31 μg/hour) and resumed treatment at the intended dose after experiencing a 
reduction in Visual Analog Scale of Pain Intensity (VASPI) from 82 to 2.5 mm.  In some patients who 
received intrathecal doses greater than the maximum recommended dose, exaggerated 
pharmacological effects, e.g., ataxia, nystagmus, dizziness, stupor, depressed level of consciousness, 
muscle spasms, confusional state, sedation, hypotension, aphasia, speech disorder, nausea and 
vomiting were observed.  There was no indication of respiratory depression.  Most patients under 
observation recovered within 24 hours of withdrawal of the medicinal product. 

Management 
General medical supportive measures should be administered to patients who receive an overdose until 
the exaggerated pharmacological effects of the medicinal product have resolved. 

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group:  Analgesics, other analgesics and antipyretics,   ATC code:  N02BG08 

Mechanism of action 
Ziconotide is a synthetic analogue of a ω-conopeptide, MVIIA, found in the venom of the Conus 
magus marine snail.  It is an N-type calcium channel blocker (NCCB).  NCCs regulate 
neurotransmitter release in specific neuronal populations responsible for the spinal processing of pain.  
In binding to these neuronal NCCs ziconotide inhibits the voltage sensitive calcium current into 
primary nociceptive afferents terminating in the superficial layers of the dorsal horn of the spinal cord.  
In turn, this inhibits their release of neurotransmitters (including Substance P) and therefore, the spinal 
signalling of pain. 

Pharmacodynamic effects 
Though statistically significant relationships and reasonable correlation between cerebrospinal fluid 
(CSF) exposure (AUC, Cmax) and clinical response measures have been observed following 1 hour IT 
administration, no well-defined dose-concentration-response relationships have yet been identified.  
Many responsive patients obtain near-maximal analgesia within a few hours of delivery of an 
appropriate dose.  However, maximal effects may be delayed for approximately 24 hours in some 
patients.  Given the occurrence of analgesia and adverse reactions at similar doses, the recommended 
interval between dose increases is 48 hours or more.  If necessary the dose can be decreased by any 
amount (including stopping the infusion) for the management of adverse reactions. 

Nervous system adverse reactions, particularly dizziness, nausea and abnormal gait appear to be 
correlated with CSF exposure, though a definitive relationship has not been established. 

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


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Low plasma exposure occurs during IT infusion due to the low recommended IT infusion rates and 
relatively rapid plasma clearance (see section 5.2).  Therefore, pharmacological effects related to 
systemic exposure should be minimal. 

The median dose at response is approximately 6.0 μg/day and approximately 75% of responsive 
patients require ≤ 9.6 μg/day.  To limit the occurrence of serious adverse reactions, a maximum dose 
of 21.6 μg/day is recommended.  However, in clinical trials it has been observed that patients who 
tolerate doses of 21.6 μg/day following slow titration over a 3 to 4-week period, generally tolerate 
higher doses up to 48.0 μg/day. 

There is no evidence of the development of pharmacological tolerance to ziconotide in patients.  
However, in view of limited data, the development of tolerance cannot be excluded.  Examination of 
the patency of the intrathecal catheter should be considered if the required ziconotide dose continually 
increases and there is no benefit or increase in adverse reactions. 

Alternative dosing regimens including initiation of dosing with lower doses of ziconotide and bolus 
administration have been explored in a limited number of studies available in the literature. 

The use of lower doses through continuous administration was demonstrated to achieve efficacy with 
fewer adverse reactions. 

Bolus administration studies suggest that bolus dosing may be useful in identifying patients who may 
benefit from long term use of ziconotide, however, may result in more adverse reactions than 
administration by continuous infusion. 

These studies suggest that these alternative methods of administration of ziconotide may be possible 
however, due to the limited numbers of patients, these results are inconclusive and there is currently 
insufficient evidence available to make definitive recommendations for such alternative dosing 
regimens. 

Clinical efficacy and safety 
There were three placebo-controlled clinical trials of IT ziconotide. 

Two short-term studies, 95-001 (malignant pain) and 96-002 (non malignant pain), involving 
366 patients, demonstrated the efficacy of IT ziconotide in severe chronic pain using the percent 
change in Visual Analog Scale of Pain Intensity (VASPI) as the primary efficacy measure.  These 
studies were of short duration, 5 and 6 days respectively, and used a more rapid dose escalation and 
higher doses than recommended in Section 4.2. 



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Efficacy results from study 95-001 

Initial treatment assignment 
Parameter Ziconotide (n = 71) Placebo (n = 40) p-value 

Mean VASPI score at 
baseline in mm (SD) 

74.1 (± 13.82) 77.9 (± 13.60) _ 

Mean VASPI score at end of 
initial titration in mm (SD) 

35.7 (± 33.27) 61.0 (± 22.91) _ 

% improvement in VASPI 
score at end of initial titration
(SD) 

51.4 (± 43.63) 18.1 (± 28.28) < 0.001 

Respondera n (%) 34 (47.9%) 7 (17.5%) 0.001 
Dose at end of titration 
(μg/hr) 

Mean 
Median 

Range

0.91 
0.60 

0.074 - 9.36 
aResponders were defined as those patients who 1) experienced a ≥ 30% drop in VASPI score 
compared to baseline; 2) had stable or decreased concomitant opioid analgesics; and 3) had opiate type 
unchanged from preinfusion if receiving opiates. 
SD – Standard Deviation. 

Efficacy results from study 96-002 

Initial treatment assignment 
Parameter Ziconotide (n = 169)b Placebo (n = 86) p-value 

Mean VASPI score at 
baseline in mm (SD) 

80.1 (± 15.10) 76.9 (± 14.58) _ 

Mean VASPI score at end of 
initial titration in mm (SD) 

54.4 (± 29.30) 71.9 (± 30.93) _ 

% improvement in VASPI 
score at end of initial titration
(SD) 

31.2 (± 38.69) 6.0 (± 42.84) < 0.001 

Respondera n (%) 57 (33.7%) 11 (12.8%) < 0.001 
Dose at end of titration 
(μg/hr) 

Mean 
Median 

Range

1.02 
0.50 

0.019 - 9.60 
aResponders were defined as those patients who 1) experienced a ≥ 30% drop in VASPI score 
compared to baseline; 2) had stable or decreased concomitant opioid analgesics; and 3) had opiate type 
unchanged from preinfusion if receiving opiates. 
b164 patients provided VASPI scores for ziconotide at the end of titration. 
SD – Standard Deviation. 

The aetiologies of pain in studies 95-001 (malignant pain) and 96-002 (non-malignant pain) were 
varied and included bone pain (n = 38) mostly due to bone metastases (n = 34), myelopathy (n = 38), 
half of whom had spinal cord injury with paralysis (n = 19), neuropathy (n = 79), radiculopathy 
(n = 24), spinal pain (n = 91) mostly due to failed back surgery (n = 82), and other aetiologies (n = 82).  
Some patients had more than one cause of pain.  The efficacy of IT ziconotide was apparent in all 
groups. 

Study 301 (n = 220) was of longer duration (21 days), involved more cautious up-titration and lower 
doses of IT ziconotide, and enrolled the most refractory population of patients studied in the three 
studies.  All patients in the 301 study had failed IT therapy with combinations of analgesics and their 
physicians considered that 97% of the patients were refractory to currently available treatments.  The 
majority had spinal pain (n = 134), especially failed back surgery (n = 110); a lower proportion had 



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neuropathy (n = 36).  Only five had malignant pain.  The primary endpoint was the percent change in 
VASPI score.  The efficacy of IT ziconotide in study 301 was lower than in the previous two, 
short-term studies.  The frequency and severity of adverse reactions were also lower. 

Efficacy results from study 301

Initial treatment assignment 
Parameter Ziconotide (n = 112) Placebo (n = 108) p-value 

Mean VASPI score at baseline 
in mm (SD) 

80.7 (± 14.98) 80.7 (± 14.91) - 

Mean VASPI score at end of 
initial titration in mm (SD) 

67.9 (± 22.89) 74.1 (± 21.28) _ 

% improvement in VASPI score 
at end of initial titration (SD) 

14.7 (± 27.71) 7.2 (± 24.98) 0.0360 

Respondera n (%) 18 (16.1%) 13 (12.0%) 0.390 
Dose at end of titration (μg/hr) 

Mean 
Median 

Range

0.29 
0.25 

0.0 - 0.80 
aResponders were defined as those who experienced a ≥ 30% drop in VASPI score compared to 
baseline. 
SD – Standard Deviation. 

Combination studies with IT Morphine 
Clinical studies 201 and 202 indicate that the combination of IT ziconotide and IT morphine may 
effectively reduce pain and decrease systemic opioid use over a sustained period of time for patients 
whose pain was inadequately controlled with their maximum tolerated dose of IT ziconotide (median 
8.7 μg/day, mean 25.7 μg/day – study 201) or with IT morphine (study 202) alone.  When adding IT 
ziconotide to stable doses of IT morphine, as with the initiation of IT ziconotide monotherapy, the 
appearance of psychotic adverse reactions. (e.g., hallucinations, paranoid reactions) or discontinuation 
due to increased adverse reactions may occur. (see section 4.5). 

5.2 Pharmacokinetic properties

The CSF pharmacokinetics of ziconotide have been studied following one-hour IT infusions of 
1 - 10 μg of ziconotide in patients with chronic pain.  The plasma pharmacokinetics following 
intravenous doses (0.3 – 10 μg/kg/24 hr) were also studied.  IT and intravenous pharmacokinetics data 
are summarised below. 

CSF and Plasma Pharmacokinetics of Ziconotide [mean ± SD (median)] 

Route of 
administration 

Fluid 
matrix 

Number 
of 

patients  

CL (ml/min) Vd (ml) t½ (hr) 

Intrathecal CSF 23 0.38 ± 0.56 
(0.26) 

155 ± 263 
(99) 

4.6 ± 0.9 
(4.5) 

Intravenous Plasma 21 270 ± 44 
(260) 

30,460 ± 6,366 
(29,320) 

1.3 ± 0.3 
(1.3) 

CL = clearance; Vd = distribution volume; t½ = half life 

Absorption 
Following one-hour IT administration (1 – 10 μg), both cumulative exposure (AUC; range:  83.6 –
608 ng/h/ml) and peak exposure (Cmax; range:  16.4 – 132 ng/ml) values were variable and 
dose-dependent, but appeared only approximately dose-proportional.  Plasma concentrations following 
continuous (≥ 48 h) IT infusion (≤ 21.6 μg/day) appear to be relatively low and typically undetectable 
(i.e., about 80% of plasma samples collected from pain patients contain no quantifiable medicinal 



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product; < 0.04 ng/ml).  No accumulation of ziconotide in plasma following long-term IT 
administration (up to 9 months) has been observed. 

Distribution
Median ziconotide CSF volume of distribution (Vd:  99 ml) is between the spinal cord CSF volume 
(approximately 75 ml) and total CSF volume (approximately 130 ml).  Ziconotide appears to distribute 
mainly within the CSF until transferred to the systemic circulation.  Upon reaching the systemic 
circulation, ziconotide appears to be more extensively distributed, based on a plasma distribution 
volume of approximately 30 l and is only about 53% bound (non-specifically) to human plasma 
proteins. 

Biotransformation 
Ziconotide is a peptide consisting of 25 naturally-occurring amino acids of the L-configuration, and 
does not appear to be appreciably metabolised in the CSF.  Following passage into the systemic 
circulation, ziconotide is expected to be primarily susceptible to proteolytic cleavage by various 
ubiquitous peptidases/proteases present in most organs (e.g., kidney, liver, lung, muscle, etc.), and thus 
degraded to peptide fragments and its individual constituent free amino acids.  The generated free 
amino acids are expected to be taken up by cellular carrier systems and either subjected to normal 
intermediary metabolism or used as substrates for constitutive biosynthetic processes.  Due to the wide 
distribution of these peptidases it is not expected that hepatic or renal impairment would affect the 
systemic clearance of ziconotide.  The biological activity of the various expected proteolytic 
degradation products has not been assessed.  It is unlikely that the degradation products of ziconotide 
will have significant biological activity, as peptides consisting of the individual peptide loop structures 
have been found to have binding affinities for N-type voltage sensitive calcium channels that are 
several orders of magnitude lower than that of the parent (ziconotide) compound. 

Elimination 
Mean ziconotide CL (0.38 ml/min) approximates adult human CSF turnover rate (0.3 - 0.4 ml/min).  
Hence, ziconotide appears to be mainly eliminated from the CSF (mean t½ = 4.6 hr) by bulk flow of 
CSF out of the CNS through the arachnoid villi with subsequent transfer into the systemic circulation.  
Very low circulating plasma concentrations of ziconotide may be observed following IT 
administration due to both the low IT infusion rate and relatively rapid plasma clearance.  The mean 
plasma elimination half-life (t½) is 1.3 hr.  Ziconotide is a relatively small molecular weight peptide 
(MW = 2,639) and is filtered by the kidney glomerulus, but only minimal amounts of ziconotide 
(< 1%) are recovered in human urine following intravenous infusion.  This is because almost all of the 
filtered active substance is rapidly endocytosed and ultimately transported back to the systemic 
circulation. 

Renal and hepatic impairment 
No formal studies assessing the impact of renal or hepatic dysfunction have been conducted; however, 
given that peptidases are present in various body organs, it is not anticipated that renal or hepatic 
dysfunction will significantly impact systemic exposure of ziconotide. 

Other special populations
Although only limited data are available, there is no obvious effect of race, height, weight, gender or 
age on CSF ziconotide exposure after IT administration.   

5.3 Preclinical safety data 

Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the 
maximum human exposure indicating little relevance to clinical use. 

In subchronic continuous intrathecal infusion studies in rats and dogs, behavioural effects were seen at 
doses ≥ 8-fold the maximum recommended clinical intrathecal infusion dose of 21.6 μg/day (on a 
mg/kg basis).  These effects were defined by exaggerated pharmacological actions of ziconotide and 
not by neurotoxic lesions or target organ toxicity.  Observations included transient and reversible 
neurological effects consisting of tremors, uncoordinated movements and hyper- and hypoactivity. 



14 

The long-term consequences to neuronal function of continuous N-type calcium-channel block have 
not been demonstrated in experimental animals.  Changes in neurological signalling have not been 
studied in experimental animals.  Ziconotide did not induce bacterial gene mutation and was not 
genotoxic.  Chronic animal studies have not been performed to assess the carcinogenic potential of 
ziconotide.  However, ziconotide did not induce cell transformation in the in vitro Syrian hamster 
embryo (SHE) assay and did not increase cell proliferation (pre-neoplastic lesion formation) or 
apoptosis after subchronic intrathecal exposure in dogs. 

In rat fertility studies, there were no effects in males while reductions in corpora lutea; implantation 
sites and number of live embryos were observed in females.  No adverse effects on female 
reproduction and post-natal development in rats were seen at systemic exposures up to 2,300 times 
human exposures at the maximum recommended intrathecal dose. 

Ziconotide was not teratogenic in rats and rabbits at exposures < 100 times human plasma levels. 

These results do not indicate a significant risk to humans due to the relatively high systemic exposures 
needed to elicit these effects in rats and rabbits. 

6. PHARMACEUTICAL PARTICULARS 

6.1 List of excipients 

Methionine 
Sodium chloride 
Water for injections 
Hydrochloric acid (pH adjuster) 
Sodium hydroxide (pH adjuster) 

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 

6.3 Shelf life

4 years 

In-use shelf-life (diluted product) 
Chemical and physical in use stability has been demonstrated for 60 days at 37°C. 

From a microbiological point of view, if the product is diluted it should be transferred to the infusion 
pump immediately.  If not used immediately, in-use storage times and conditions prior to use are the 
responsibility of the user and would normally not be longer than 24 hours at 2°C – 8°C, unless dilution 
has taken place in controlled and validated aseptic conditions. 

6.4 Special precautions for storage

Store in a refrigerator (2°C - 8°C).  Do not freeze.  Keep the vial in the outer carton in order to protect 
from light. 

For storage conditions after dilution of the medicinal product, see section 6.3. 



15 

6.5 Nature and contents of container 

Type I glass vials with butyl rubber stoppers coated with fluorinated polymer. 

Each vial contains 20 ml solution for infusion. 

One vial per carton. 

6.6 Special precautions for disposal and other handling

If dilution is required, Prialt must be diluted aseptically with preservative-free sodium chloride 
9 mg/ml (0.9%) solution for injection before use.  The concentration of the solution used in the 
infusion pump must be no lower than 5 μg/ml ziconotide in an external pump and 25 μg/ml in an 
internal pump. 

Strict aseptic procedures must be used during the preparation and handling of the solution for infusion 
and refilling of the pump.  The patient and health-care providers must be familiar with the handling of 
the external or internal infusion system and be aware of the need to guard against infection. 

Specific instructions for using the pumps must be obtained from the manufacturer.   

Prialt has been shown to be chemically and physically compatible with the implantable Synchromed 
pump and the external CADD-Micro pump at the concentration levels indicated above.  Chemical and 
physical in-use stability has been demonstrated for 14 days at 37ºC in the Synchromed pump when the 
pump has not previously been exposed to the medicinal product.  The initial fill must therefore be 
replaced after 14 days. 

Prialt was stable for 60 days at 37°C in the Synchromed pump previously exposed to the medicinal 
product.  Stability has been demonstrated for 21 days at room temperature in the CADD-Micro pump. 

The technical data are given only for information and should not limit health-care providers’ choice.
CE marked pumps equivalent to the Synchromed and CADD-Micro pump should be used to deliver 
Prialt.   

Pumps previously used to deliver other medicinal products must be washed out three times with 
sodium chloride 9 mg/ml (0.9%) solution for injection (preservative-free) before being filled with 
Prialt.  The introduction of air into the pump reservoir or cartridge should be minimized, as oxygen can 
degrade ziconotide. 

Prior to initiation of therapy, an internal pump must be rinsed three times with 2 ml of Prialt at 
25 μg/ml.  The concentration of Prialt in a naïve pump may be reduced due to adsorption onto the 
surfaces of the device, and/or dilution by the residual space of the device.  Because of this, after the 
first use of Prialt, the reservoir should be emptied and refilled after 14 days.  Subsequently the pump 
should be emptied and refilled every 60 days. 

Prialt should be inspected visually for particulate matter and discolouration prior to administration.  
The solution should not be used if discoloured or cloudy or if particulate matter is observed. 

For single use only.  Any unused medicinal product or waste material should be disposed of in 
accordance with local requirements.  



16 

7. MARKETING AUTHORISATION HOLDER

RIEMSER Pharma GmbH 
An der Wiek 7  
17493 Greifswald-Insel Riems  
Germany 

8. MARKETING AUTHORISATION NUMBER(S) 

EU/1/04/302/004 – 20 ml solution for infusion 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 21 February 2005 
Date of latest renewal: 18 September 2014 

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 



17 

1. NAME OF THE MEDICINAL PRODUCT

Prialt 100 micrograms/ml solution for infusion 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One ml solution contains 100 μg ziconotide (as acetate). 

Each 1 ml vial contains 100 μg ziconotide (as acetate). 

Each 2 ml vial contains 200 μg ziconotide (as acetate). 

Each 5 ml vial contains 500 μg ziconotide (as acetate). 

For the full list of excipients, see section 6.1. 

3. PHARMACEUTICAL FORM

Solution for infusion (infusion). 

Clear, colourless solution. 

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Ziconotide is indicated for the treatment of severe, chronic pain in adults who require intrathecal (IT) 
analgesia. 

4.2 Posology and method of administration 

Treatment with ziconotide should only be undertaken by physicians experienced in intrathecal (IT) 
administration of medicinal products.   

Posology 

Adults (including the elderly ≥ 65 years of age) 

Dosing of ziconotide should be initiated at 2.4 μg/day and titrated on an individual patient basis 
according to the patient’s analgesic response and adverse reactions.  Patients should be titrated in dose 
increments of ≤ 2.4 μg/day, up to a maximum dose of 21.6 μg/day.  The minimal interval between 
dose increases is 24 hours; the recommended interval, for safety reasons, is 48 hours or more.  If 
necessary the dose can be decreased by any amount (including stopping the infusion) for the 
management of adverse reactions.  Approximately 75% of patients who respond satisfactorily to 
treatment require a dose of ≤ 9.6 μg/day. 

Renal impairment 

Studies have not been conducted in patients with impaired renal function.  Caution should be exercised 
when ziconotide is administered to patients with impaired renal function. 

Hepatic impairment 



18 

Studies have not been conducted in patients with impaired hepatic function.  Caution should be 
exercised when ziconotide is administered to patients with impaired hepatic function. 

Paediatric population 

The safety and efficacy of ziconotide in children aged 0 to 18 years have not been established. 

No data are available. 

Method of administration 

Intrathecal use. 

Ziconotide must be administered as a continuous infusion via an intrathecal catheter, using an external 
or internally implanted mechanical infusion pump capable of delivering an accurate infusion volume.  
As the risk of meningitis secondary to prolonged catheterisation of the intrathecal space is greater with 
an external catheter infusion system, internal systems are recommended to administer ziconotide for 
prolonged periods (see section 4.4).  An external catheter system should only be used when an internal 
system cannot be implanted. 

When low doses of ziconotide are required, for example when initiating titration, ziconotide must be 
diluted before use with preservative-free sodium chloride 9 mg/ml (0.9%) solution for injection. 

For instructions on dilution of the medicinal product 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. 

Combination with IT chemotherapy (see section 4.5). 

4.4 Special warnings and precautions for use

Long-term use 
Although ziconotide has been studied in long-term, open label efficacy and safety clinical trials, 
controlled studies of longer than 3 weeks duration have not been conducted (see section 5.1).  Possible 
long-term local toxic effects on the spinal cord have not been excluded and preclinical data in this 
respect are limited (see section 5.3).  Therefore, caution is needed during long-term treatment. 

Risk of infection 
The administration of medicinal products by the intrathecal (IT) route carries the risk of potentially 
serious infections, such as meningitis, which may be life threatening.  Meningitis due to the entrance 
of organisms along the catheter track or inadvertent contamination of the infusion system is a known 
complication of intrathecal medicinal product administration, especially with external systems. 

Patients and physicians must be vigilant for typical symptoms and signs of meningitis. 

The optimal intrathecal placement of the catheter tip has not been established.  Lower catheter tip 
placement, e.g. at the lumbar level, may reduce the incidence of ziconotide-related neurological 
adverse reactions.  Therefore, catheter tip placement should be carefully considered to allow adequate 
access to spinal nociceptive segments whilst minimising medicinal product concentrations at cerebral 
levels. 

Only a small number of patients have received systemic chemotherapy and IT ziconotide.  Caution 
should be exercised when ziconotide is administered to patients who are receiving systemic 
chemotherapy (see section 4.5). 



19 

Elevations in creatine kinase 
Elevations in creatine kinase, which are usually asymptomatic, are common amongst patients on 
intrathecal ziconotide.  Progressive elevation of the creatine kinase is uncommon.  However 
monitoring of creatine kinase is recommended.  In the event of progressive elevation, or clinically 
significant elevation in association with clinical features of myopathy or rhabdomyolysis, 
discontinuation of ziconotide should be considered. 

Hypersensitivity reactions 
Hypersensitivity reactions, including anaphylaxis, have not been observed during clinical trials and the 
immunogenicity of ziconotide administered by the IT route appears to be low.  However, the potential 
for severe allergic reactions cannot be excluded and spontaneous reports of anaphylactic reactions 
have been received. 

Cognitive and neuropsychiatric adverse reactions 
Cognitive and neuropsychiatric adverse reactions, particularly confusion, are common in patients 
treated with ziconotide.  Cognitive impairment typically appears after several weeks of treatment.  
Episodes of acute psychiatric disturbances, such as hallucinations, paranoid reactions, hostility, 
aggressiveness, delirium, psychosis and manic reactions have been reported in patients treated with 
ziconotide.  The ziconotide dose should be reduced or discontinued if signs or symptoms of cognitive 
impairment or neuropsychiatric adverse reactions develop, but other contributing causes should also be 
considered.  The cognitive effects of ziconotide are typically reversible within 1 - 4 weeks after 
discontinuation of the medicinal product, but may persist in some cases.  It is recommended that patients 
undergo a neuropsychiatric evaluation before and after starting intrathecal ziconotide. 

In patients with severe chronic pain there is a higher incidence of suicide and suicide attempts than in 
the general population.  Ziconotide may cause or worsen depression with the risk of suicide in 
susceptible patients. 

Depression of Central Nervous System (CNS) 
Patients have experienced depressed levels of consciousness while receiving ziconotide.  The patient 
usually remains conscious and breathing is not depressed.  The event may be self limited, but 
ziconotide should be discontinued until the event resolves.  The re-introduction of ziconotide is not 
recommended in these patients.  Withdrawal of concomitant CNS depressant medicinal products 
should also be considered as they may contribute to the reduced level of arousal. 

4.5 Interaction with other medicinal products and other forms of interaction

Specific clinical medicinal product interaction studies have not been conducted with ziconotide.  
However, low plasma ziconotide concentrations, metabolism by ubiquitous peptidases and relatively 
low plasma protein binding (see section 5.2) make metabolic-based interactions or plasma protein 
displacement type interactions between ziconotide and other medicinal products unlikely. 

No clinical data are available on the interaction between IT chemotherapy and IT ziconotide.  
Ziconotide is contraindicated in combination with IT chemotherapy (see section 4.3). 

Only a small number of patients have received systemic chemotherapy and IT ziconotide.  Caution 
should be exercised when ziconotide is administered to patients who are receiving systemic 
chemotherapy (see section 4.4). 

Medicinal products that affect specific peptidases/proteases would not be expected to impact upon 
ziconotide plasma exposure.  Based on very limited clinical investigations, both angiotensin 
converting enzyme inhibitors (e.g., benazepril, lisinopril and moexipril) and HIV protease inhibitors 
(e.g., ritonavir, saquinavir, indinavir), have no readily apparent effect on plasma ziconotide exposure. 

Ziconotide does not interact with opiate receptors. If discontinuing opiates when initiating ziconotide 
therapy, opiate withdrawal should be gradual. For patients being withdrawn from IT opiates, the IT 



20 

opiate infusion dose should be gradually tapered over a few weeks and replaced with a 
pharmacologically equivalent dose of oral opiates.  Adding IT ziconotide to stable doses of IT 
morphine (see section 5.1), is possible but requires special attention, as a high rate of neuropsychiatric 
adverse reactions (confusion/thinking abnormal, paranoid reactions and hallucinations, and abnormal 
gait), some of them serious, was observed in Study 202 despite a low dose of ziconotide. Vomiting and 
anorexia, and peripheral oedema were also observed when IT ziconotide was added to IT morphine.  
The addition of IT morphine to stable doses of IT ziconotide is better tolerated (pruritis has been 
reported) (see section 5.1). 

An increased incidence of somnolence has been observed when ziconotide is administered 
concomitantly with systemic baclofen, clonidine, bupivacaine or propofol thus for the time being their 
simultaneous use is discouraged. 

No data are available regarding the concomitant use of partial opioid agonists (e.g. buprenorphine) 
with ziconotide. 

4.6 Fertility, pregnancy and lactation 

Pregnancy  

There are no or limited amount of data from the use of ziconotide in pregnant women.   

Studies in animals have shown reproductive toxicity (see section 5.3 

Ziconotide is not recommended during pregnancy and in women of childbearing potential not using 
contraception.  

Breast-feeding 

It is unknown whether ziconotide/metabolites are excreted in human milk. 

A risk to newborns/infants cannot be excluded.  

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from 
ziconotide therapy taking into account the benefit of breast-feeding for the child and the benefit of 
therapy for the woman. 

Fertility 

No specific studies with ziconotide in humans have been conducted to evaluate effects on fertility. In a 
study on male and female fertility in rats no effects in males while reductions in corpora lutea; 
implantation sites and number of live embryos were observed in females (see section 5.3). 

4.7 Effects on ability to drive and use machines

Ziconotide has moderate influence on the ability to drive and use machines. 

Ziconotide may cause confusion, somnolence and other neurological adverse reactions, therefore 
patients must be advised not to drive or operate machines if affected. 

4.8 Undesirable effects 

Summary of the safety profile 
The safety of ziconotide administered as a continuous intrathecal infusion has been evaluated in more 
than 1,400 patients participating in acute and chronic pain clinical trials.  The duration of treatment has 
ranged from one-hour bolus infusion to continuous use for more than 6 years.  The median exposure 



21 

time was 43 days.  The infusion dose rate ranged from 0.03 - 912 μg/day, with a median final dose rate 
of 7.2 μg/day. 

In clinical trials, 88% of patients experienced adverse reactions.  The most common adverse reactions 
reported in long-term clinical trials were dizziness (42%), nausea (30%), nystagmus (23%), 
confusional state (25%), gait abnormal (16%), memory impairment (13%), vision blurred (14%), 
headache (12%), asthenia (13%), vomiting (11%), and somnolence (10%).  Most adverse reactions 
were mild to moderate in severity and resolved over time. 

Tabulated list of adverse reactions 
Unless otherwise noted shows the incidence rates of adverse reactions reported in the intrathecal 
clinical trials with ziconotide (short- and long-term exposure). Within each frequency grouping 
undesirable effects are presented in order of decreasing frequency. 

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) 

System Organ 
Class 

Very common Common Uncommon Not Known 

Infections and 
infestations 

sepsis, meningitis  

Immune system 
disorders 

Anaphylactic 
reactiona

Metabolism and 
nutrition 
disorders 

appetite 
decreased, 
anorexia 

Psychiatric 
disorders 

confusional 
state 

anxiety, 
auditory 
hallucination, 
insomnia, 
agitation, 
disorientation, 
hallucination, 
visual 
hallucination, 
depression, 
paranoia, 
irritability, 
depression 
aggravated, 
nervousness, 
affect lability, 
mental status 
changes, anxiety 
aggravated, 
confusion 
aggravated 

delirium, psychotic 
disorder, suicidal 
ideation, suicide 
attempt, thought 
blocking, abnormal 
dreams, 
aggressiveness 



22 

System Organ 
Class 

Very common Common Uncommon Not Known 

Nervous system 
disorders 

dizziness, 
nystagmus, 
memory 
impairment, 
headache, 
somnolence 

dysarthria, 
amnesia, 
dysgeusia, 
tremor, balance 
impaired, ataxia, 
aphasia, burning 
sensation, 
sedation, 
paraesthesia, 
hypoaesthesia, 
disturbance in at
tention, speech 
disorder, 
areflexia, 
coordination abn
ormal, dizziness 
postural, 
cognitive 
disorder, 
hyperaesthesia, 
hyporeflexia, 
ageusia, 
depressed level 
of 
consciousness, 
dysaesthesia, 
parosmia, 
mental 
impairment 

incoherence, loss of 
consciousness, 
coma, stupor, 
convulsions, 
cerebrovascular 
accident, 
encephalopathy 

Eye disorders vision blurred diplopia, 
visual disturban
ce, photophobia 

Ear and 
labyrinth 
disorders 

vertigo, tinnitus  

Cardiac 
disorders 

atrial fibrillation 

Vascular 
disorders 

orthostatic hypot
ension, 
hypotension 

Respiratory, 
thoracic and 
mediastinal 
disorders 

dyspnoea respiratory distress  

Gastrointestinal 
disorders 

nausea, 
vomiting 

diarrhoea, 
dry mouth, 
constipation, 
nausea 
aggravated, 
upper 
abdominal pain 

dyspepsia 

Skin and 
subcutaneous 

pruritus, 
sweating 

rash 



23 

System Organ 
Class 

Very common Common Uncommon Not Known 

tissue disorders increased 
Musculoskeletal 
and connective 
tissue disorders 

pain in limb, 
myalgia, muscle 
spasms, muscle 
cramp, muscle 
weakness, 
arthralgia, 
peripheral 
swelling 

rhabdomyolysis, 
myositis, back pain, 
muscle twitching, 
neck pain 

Renal and 
urinary 
disorders 

urinary retention
, urinary 
hesitation, 
dysuria, urinary 
incontinence 

acute renal failure  

General 
disorders and 
administration 
site conditions 

gait abnormal, 
asthenia 

fatigue, pyrexia, 
lethargy, 
oedema peripher
al, rigors, fall, 
chest pain, 
feeling cold, 
pain, feeling 
jittery, pain 
exacerbated 

difficulty in 
walking 

Investigations blood 
creatine phosph
okinase increase
d, weight 
decreased 

electrocardiogram 
abnormal, aspartate 
aminotransferase 
increased, blood 
creatine 
phosphokinase MM 
increased, body 
temperature 
increased 

a. From spontaneous reporting 

Description of selected adverse reactions 

Meningitis 

Administration of medicinal products by the intrathecal route carries the risk of potential serious 
infections, such as meningitis, which may be life threatening. Patients and physicians must be vigilant 
for typical symptoms and signs of meningitis (see section 4.4). 

Elevations of creatine phosphokinase 

Elevations in creatine phosphokinase were usually asymptomatic. Monitoring of creatine 
phosphokinase is recommended.  Discontinuation of ziconotide should be considered in the event of 
progressive or significant elevation of creatine phosphokinase in association with clinical features of 
myopathy or rhabdomyolysis (see section 4.4). 

CNS adverse reactions 



24 

Cognitive and neuropsychiatric adverse reactions are common in patients treated with ziconotide. 
Cognitive impairment typically appears after several weeks of treatment. Episodes of acute psychiatric 
disturbances, such as hallucinations, paranoid reactions, hostility, aggressiveness, delirium, psychosis 
and manic reactions have been reported in patients treated with ziconotide. The ziconotide dose should 
be reduced or discontinued if signs or symptoms of cognitive impairment or neuropsychiatric adverse 
reactions develop, but other contributing causes should also be considered. The cognitive effects of 
ziconotide are typically reversible within 1 - 4 weeks after discontinuation of the medicinal product, 
but may persist in some cases.  It is recommended that patients undergo a neuropsychiatric evaluation 
before and after starting intrathecal ziconotide (see section 4.4). 

Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 

4.9 Overdose 

In intravenous infusion studies, healthy male volunteers received ziconotide at doses of up to 
70,000 μg/day or 3,200 times the maximum recommended daily intrathecal infusion dose.  Postural 
hypotension was observed in almost all subjects who received high intravenous doses of ziconotide. 

The maximum recommended intrathecal dose is 21.6 μg/day.  The maximum intended intrathecal dose 
of ziconotide in clinical trials was 912 μg/day following upward titration over 7 days. 

Symptoms 
In one clinical study a male cancer patient received an accidental IT ziconotide overdose of 744 μg 
over a 24-hour period (31 μg/hour) and resumed treatment at the intended dose after experiencing a 
reduction in Visual Analog Scale of Pain Intensity (VASPI) from 82 to 2.5 mm.  In some patients who 
received intrathecal doses greater than the maximum recommended dose, exaggerated 
pharmacological effects, e.g., ataxia, nystagmus, dizziness, stupor, depressed level of consciousness, 
muscle spasms, confusional state, sedation, hypotension, aphasia, speech disorder, nausea and 
vomiting were observed.  There was no indication of respiratory depression.  Most patients under 
observation recovered within 24 hours of withdrawal of the medicinal product. 

Management 
General medical supportive measures should be administered to patients who receive an overdose until 
the exaggerated pharmacological effects of the medicinal product have resolved. 

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group:  Analgesics, other analgesics and antipyretics, ATC code:  N02BG08 

Mechanism of action 
Ziconotide is a synthetic analogue of a ω-conopeptide, MVIIA, found in the venom of the Conus 
magus marine snail.  It is an N-type calcium channel blocker (NCCB).  NCCs regulate 
neurotransmitter release in specific neuronal populations responsible for the spinal processing of pain.  
In binding to these neuronal NCCs ziconotide inhibits the voltage sensitive calcium current into 
primary nociceptive afferents terminating in the superficial layers of the dorsal horn of the spinal cord.  
In turn, this inhibits their release of neurotransmitters (including Substance P) and therefore, the spinal 
signalling of pain. 

Pharmacodynamic effects 

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


25 

Though statistically significant relationships and reasonable correlation between cerebrospinal fluid 
(CSF) exposure (AUC, Cmax) and clinical response measures have been observed following 1 hour IT 
administration, no well-defined dose-concentration-response relationships have yet been identified.  
Many responsive patients obtain near-maximal analgesia within a few hours of delivery of an 
appropriate dose.  However, maximal effects may be delayed for approximately 24 hours in some 
patients.  Given the occurrence of analgesia and adverse reactions at similar doses, the recommended 
interval between dose increases is 48 hours or more.  If necessary the dose can be decreased by any 
amount (including stopping the infusion) for the management of adverse reactions. 

Nervous system adverse reactions, particularly dizziness, nausea and abnormal gait appear to be 
correlated with CSF exposure, though a definitive relationship has not been established. 

Low plasma exposure occurs during IT infusion due to the low recommended IT infusion rates and 
relatively rapid plasma clearance (see section 5.2).  Therefore, pharmacological effects related to 
systemic exposure should be minimal. 

The median dose at response is approximately 6.0 μg/day and approximately 75% of responsive 
patients require ≤ 9.6 μg/day.  To limit the occurrence of serious adverse reactions, a maximum dose 
of 21.6 μg/day is recommended.  However, in clinical trials it has been observed that patients who 
tolerate doses of 21.6 μg/day following slow titration over a 3 to 4-week period, generally tolerate 
higher doses up to 48.0 μg/day. 

There is no evidence of the development of pharmacological tolerance to ziconotide in patients.  
However, in view of limited data, the development of tolerance cannot be excluded.  Examination of 
the patency of the intrathecal catheter should be considered if the required ziconotide dose continually 
increases and there is no benefit or increase in adverse reactions. 

Alternative dosing regimens including initiation of dosing with lower doses of ziconotide and bolus 
administration have been explored in a limited number of studies available in the literature. 

The use of lower doses through continuous administration was demonstrated to achieve efficacy with 
fewer adverse reactions. 

Bolus administration studies suggest that bolus dosing may be useful in identifying patients who may 
benefit from long term use of ziconotide, however, may result in more adverse reactions than 
administration by continuous infusion. 

These studies suggest that these alternative methods of administration of ziconotide may be possible 
however, due to the limited numbers of patients, these results are inconclusive and there is currently 
insufficient evidence available to make definitive recommendations for such alternative dosing 
regimens. 

Clinical efficacy and safety 

There were three placebo-controlled clinical trials of IT ziconotide. 

Two short-term studies, 95-001 (malignant pain) and 96-002 (non malignant pain), involving 
366 patients, demonstrated the efficacy of IT ziconotide in severe chronic pain using the percent 
change in Visual Analog Scale of Pain Intensity (VASPI) as the primary efficacy measure.  These 
studies were of short duration, 5 and 6 days respectively, and used a more rapid dose escalation and 
higher doses than recommended in Section 4.2. 

Efficacy results from study 95-001 

Initial treatment assignment 
Parameter Ziconotide (n = 71) Placebo (n = 40) p-value 

Mean VASPI score at 74.1 (± 13.82) 77.9 (± 13.60) _ 



26 

baseline in mm (SD) 
Mean VASPI score at end of 
initial titration in mm (SD) 

35.7 (± 33.27) 61.0 (± 22.91) _ 

% improvement in VASPI 
score at end of initial titration
(SD) 

51.4 (± 43.63) 18.1 (± 28.28) < 0.001 

Respondera n (%) 34 (47.9%) 7 (17.5%) 0.001 
Dose at end of titration 
(μg/hr) 

Mean 
Median 

Range

0.91 
0.60 

0.074 - 9.36 
aResponders were defined as those patients who 1) experienced a ≥ 30% drop in VASPI score 
compared to baseline; 2) had stable or decreased concomitant opioid analgesics; and 3) had opiate type 
unchanged from preinfusion if receiving opiates. 
SD – Standard Deviation. 

Efficacy results from study 96-002 

Initial treatment assignment 
Parameter Ziconotide (n = 169)b Placebo (n = 86) p-value 

Mean VASPI score at 
baseline in mm (SD) 

80.1 (± 15.10) 76.9 (± 14.58) _ 

Mean VASPI score at end of 
initial titration in mm (SD) 

54.4 (± 29.30) 71.9 (± 30.93) _ 

% improvement in VASPI 
score at end of initial titration
(SD) 

31.2 (± 38.69) 6.0 (± 42.84) < 0.001 

Respondera n (%) 57 (33.7%) 11 (12.8%) < 0.001 
Dose at end of titration 
(μg/hr) 

Mean 
Median 

Range

1.02 
0.50 

0.019 - 9.60 
aResponders were defined as those patients who 1) experienced a ≥ 30% drop in VASPI score 
compared to baseline; 2) had stable or decreased concomitant opioid analgesics; and 3) had opiate type 
unchanged from preinfusion if receiving opiates. 
b164 patients provided VASPI scores for ziconotide at the end of titration. 
SD – Standard Deviation. 

The aetiologies of pain in studies 95-001 (malignant pain) and 96-002 (non-malignant pain) were 
varied and included bone pain (n = 38) mostly due to bone metastases (n = 34), myelopathy (n = 38), 
half of whom had spinal cord injury with paralysis (n = 19), neuropathy (n = 79), radiculopathy 
(n = 24), spinal pain (n = 91) mostly due to failed back surgery (n = 82), and other aetiologies (n = 82).  
Some patients had more than one cause of pain.  The efficacy of IT ziconotide was apparent in all 
groups. 

Study 301 (n = 220) was of longer duration (21 days), involved more cautious up-titration and lower 
doses of IT ziconotide, and enrolled the most refractory population of patients studied in the three 
studies.  All patients in the 301 study had failed IT therapy with combinations of analgesics and their 
physicians considered that 97% of the patients were refractory to currently available treatments.  The 
majority had spinal pain (n = 134), especially failed back surgery (n = 110); a lower proportion had 
neuropathy (n = 36).  Only five had malignant pain.  The primary endpoint was the percent change in 
VASPI score.  The efficacy of IT ziconotide in study 301 was lower than in the previous two, 
short-term studies.  The frequency and severity of adverse reactions were also lower. 



27 

Efficacy results from study 301

Initial treatment assignment 
Parameter Ziconotide (n = 112) Placebo (n = 108) p-value 

Mean VASPI score at baseline 
in mm (SD) 

80.7 (± 14.98) 80.7 (± 14.91) - 

Mean VASPI score at end of 
initial titration in mm (SD) 

67.9 (± 22.89) 74.1 (± 21.28) _ 

% improvement in VASPI score 
at end of initial titration (SD) 

14.7 (± 27.71) 7.2 (± 24.98) 0.0360 

Respondera n (%) 18 (16.1%) 13 (12.0%) 0.390 
Dose at end of titration (μg/hr) 

Mean 
Median 

Range

0.29 
0.25 

0.0 - 0.80 
aResponders were defined as those who experienced a ≥ 30% drop in VASPI score compared to 
baseline. 
SD – Standard Deviation. 

Combination studies with IT Morphine 
Clinical studies 201 and 202 indicate that the combination of IT ziconotide and IT morphine may 
effectively reduce pain and decrease systemic opioid use over a sustained period of time for patients 
whose pain was inadequately controlled with their maximum tolerated dose of IT ziconotide (median 
8.7 μg/day, mean 25.7 μg/day – study 201) or with IT morphine (study 202) alone.  When adding IT 
ziconotide to stable doses of IT morphine, as with the initiation of IT ziconotide monotherapy, the 
appearance of psychotic adverse reactions (e.g., hallucinations, paranoid reactions) or discontinuation 
due to increased adverse reactions may occur. (see section 4.5). 

5.2 Pharmacokinetic properties

The CSF pharmacokinetics of ziconotide have been studied following one-hour IT infusions of 
1 - 10 μg of ziconotide in patients with chronic pain.  The plasma pharmacokinetics following 
intravenous doses (0.3 – 10 μg/kg/24 hr) were also studied.  IT and intravenous pharmacokinetics data 
are summarised below. 

CSF and Plasma Pharmacokinetics of Ziconotide [mean ± SD (median)] 

Route of 
administration 

Fluid 
matrix 

Number 
of 

patients  

CL (ml/min) Vd (ml) t½ (hr) 

Intrathecal CSF 23 0.38 ± 0.56 
(0.26) 

155 ± 263 
(99) 

4.6 ± 0.9 
(4.5) 

Intravenous Plasma 21 270 ± 44 
(260) 

30,460 ± 6,366 
(29,320) 

1.3 ± 0.3 
(1.3) 

CL = clearance; Vd = distribution volume; t½ = half life 

Absorption   
Following one-hour IT administration (1 – 10 μg), both cumulative exposure (AUC; range:  83.6 –
608 ng/h/ml) and peak exposure (Cmax; range:  16.4 – 132 ng/ml) values were variable and 
dose-dependent, but appeared only approximately dose-proportional.  Plasma concentrations following 
continuous (≥ 48 h) IT infusion (≤ 21.6 μg/day) appear to be relatively low and typically undetectable 
(i.e., about 80% of plasma samples collected from pain patients contain no quantifiable medicinal 
product; < 0.04 ng/ml).  No accumulation of ziconotide in plasma following long-term IT 
administration (up to 9 months) has been observed. 



28 

Distribution   
Median ziconotide CSF volume of distribution (Vd:  99 ml) is between the spinal cord CSF volume 
(approximately 75 ml) and total CSF volume (approximately 130 ml).  Ziconotide appears to distribute 
mainly within the CSF until transferred to the systemic circulation.  Upon reaching the systemic 
circulation, ziconotide appears to be more extensively distributed, based on a plasma distribution 
volume of approximately 30 l and is only about 53% bound (non-specifically) to human plasma 
proteins. 

Biotransformation   
Ziconotide is a peptide consisting of 25 naturally-occurring amino acids of the L-configuration, and 
does not appear to be appreciably metabolised in the CSF.  Following passage into the systemic 
circulation, ziconotide is expected to be primarily susceptible to proteolytic cleavage by various 
ubiquitous peptidases/proteases present in most organs (e.g., kidney, liver, lung, muscle, etc.), and thus 
degraded to peptide fragments and its individual constituent free amino acids.  The generated free 
amino acids are expected to be taken up by cellular carrier systems and either subjected to normal 
intermediary metabolism or used as substrates for constitutive biosynthetic processes.  Due to the wide 
distribution of these peptidases it is not expected that hepatic or renal impairment would affect the 
systemic clearance of ziconotide.  The biological activity of the various expected proteolytic 
degradation products has not been assessed.  It is unlikely that the degradation products of ziconotide 
will have significant biological activity, as peptides consisting of the individual peptide loop structures 
have been found to have binding affinities for N-type voltage sensitive calcium channels that are 
several orders of magnitude lower than that of the parent (ziconotide) compound. 

Elimination   
Mean ziconotide CL (0.38 ml/min) approximates adult human CSF turnover rate (0.3 - 0.4 ml/min).  
Hence, ziconotide appears to be mainly eliminated from the CSF (mean t½ = 4.6 hr) by bulk flow of 
CSF out of the CNS through the arachnoid villi with subsequent transfer into the systemic circulation.  
Very low circulating plasma concentrations of ziconotide may be observed following IT 
administration due to both the low IT infusion rate and relatively rapid plasma clearance.  The mean 
plasma elimination half-life (t½) is 1.3 hr.  Ziconotide is a relatively small molecular weight peptide 
(MW = 2,639) and is filtered by the kidney glomerulus, but only minimal amounts of ziconotide 
(< 1%) are recovered in human urine following intravenous infusion.  This is because almost all of the 
filtered active substance is rapidly endocytosed and ultimately transported back to the systemic 
circulation. 

Renal and hepatic impairment 
No formal studies assessing the impact of renal or hepatic dysfunction have been conducted; however, 
given that peptidases are present in various body organs, it is not anticipated that renal or hepatic 
dysfunction will significantly impact systemic exposure of ziconotide. 

Other special populations   
Although only limited data are available, there is no obvious effect of race, height, weight, gender or 
age on CSF ziconotide exposure after IT administration.   

5.3 Preclinical safety data 

Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the 
maximum human exposure indicating little relevance to clinical use. 

In subchronic continuous intrathecal infusion studies in rats and dogs, behavioural effects were seen at 
doses ≥ 8-fold the maximum recommended clinical intrathecal infusion dose of 21.6 μg/day (on a 
mg/kg basis).  These effects were defined by exaggerated pharmacological actions of ziconotide and 
not by neurotoxic lesions or target organ toxicity.  Observations included transient and reversible 
neurological effects consisting of tremors, uncoordinated movements and hyper- and hypoactivity. 

The long-term consequences to neuronal function of continuous N-type calcium-channel block have 
not been demonstrated in experimental animals.  Changes in neurological signalling have not been 



29 

studied in experimental animals.  Ziconotide did not induce bacterial gene mutation and was not 
genotoxic.  Chronic animal studies have not been performed to assess the carcinogenic potential of 
ziconotide.  However, ziconotide did not induce cell transformation in the in vitro Syrian hamster 
embryo (SHE) assay and did not increase cell proliferation (pre-neoplastic lesion formation) or 
apoptosis after subchronic intrathecal exposure in dogs. 

In rat fertility studies, there were no effects in males while reductions in corpora lutea; implantation 
sites and number of live embryos were observed in females.  No adverse effects on female 
reproduction and post-natal development in rats were seen at systemic exposures up to 2,300 times 
human exposures at the maximum recommended intrathecal dose. 

Ziconotide was not teratogenic in rats and rabbits at exposures < 100 times human plasma levels. 

These results do not indicate a significant risk to humans due to the relatively high systemic exposures 
needed to elicit these effects in rats and rabbits. 

6. PHARMACEUTICAL PARTICULARS 

6.1 List of excipients 

Methionine 
Sodium chloride 
Water for injections 
Hydrochloric acid (pH adjuster) 
Sodium hydroxide (pH adjuster) 

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 

6.3 Shelf life

4 years 

In-use shelf life (diluted product) 
Chemical and physical in use stability has been demonstrated for 60 days at 37°C. 

From a microbiological point of view, if the product is diluted it should be transferred to the infusion 
pump immediately.  If not used immediately, in-use storage times and conditions prior to use are the 
responsibility of the user and would normally not be longer than 24 hours at 2°C – 8°C, unless dilution 
has taken place in controlled and validated aseptic conditions. 

6.4 Special precautions for storage

Store in a refrigerator (2°C - 8°C).  Do not freeze.  Keep the vial in the outer carton in order to protect 
from light. 

For storage conditions after dilution of the medicinal product, see section 6.3. 



30 

6.5 Nature and contents of container 

Type I glass vials with butyl rubber stoppers coated with fluorinated polymer. 

Each vial contains 1, 2 or 5 ml solution for infusion. 

One vial per carton. 

Not all pack sizes may be marketed. 

6.6 Special precautions for disposal and other handling

If dilution is required, Prialt must be diluted aseptically with preservative-free sodium chloride 
9 mg/ml (0.9%) solution for injection before use.  The concentration of the solution used in the 
infusion pump must be no lower than 5 μg/ml ziconotide in an external pump and 25 μg/ml in an 
internal pump. 

Strict aseptic procedures must be used during the preparation and handling of the solution for infusion 
and refilling of the pump.  The patient and health-care providers must be familiar with the handling of 
the external or internal infusion system and be aware of the need to guard against infection. 

Specific instructions for using the pumps must be obtained from the manufacturer.   

Prialt has been shown to be chemically and physically compatible with the implantable Synchromed 
pump and the external CADD-Micro pump at the concentration levels indicated above.  Chemical and 
physical in-use stability has been demonstrated for 14 days at 37ºC in the Synchromed pump when the 
pump has not previously been exposed to the medicinal product.  The initial fill must therefore be 
replaced after 14 days. 

Prialt was stable for 60 days at 37°C in the Synchromed pump previously exposed to the medicinal 
product.  Stability has been demonstrated for 21 days at room temperature in the CADD-Micro pump. 

The technical data are given only for information and should not limit health-care providers’ choice.
CE marked pumps equivalent to the Synchromed and CADD-Micro pump should be used to deliver 
Prialt.   

Pumps previously used to deliver other medicinal products must be washed out three times with 
sodium chloride 9 mg/ml (0.9%) solution for injection (preservative-free) before being filled with 
Prialt.  The introduction of air into the pump reservoir or cartridge should be minimized, as oxygen can 
degrade ziconotide. 

Prior to initiation of therapy, an internal pump must be rinsed three times with 2 ml of Prialt at 
25 μg/ml.  The concentration of Prialt in a naïve pump may be reduced due to adsorption onto the 
surfaces of the device, and/or dilution by the residual space of the device.  Because of this, after the 
first use of Prialt, the reservoir should be emptied and refilled after 14 days.  Subsequently the pump 
should be emptied and refilled every 60 days. 

Prialt should be inspected visually for particulate matter and discolouration prior to administration.  
The solution should not be used if discoloured or cloudy or if particulate matter is observed. 

For single use only.  Any unused medicinal product or waste material should be disposed of in 
accordance with local requirements.  



31 

7. MARKETING AUTHORISATION HOLDER

RIEMSER Pharma GmbH 
An der Wiek 7  
17493 Greifswald-Insel Riems  
Germany 

8. MARKETING AUTHORISATION NUMBER(S) 

EU/1/04/302/001 – 1 ml solution for infusion. 
EU/1/04/302/002 – 2 ml solution for infusion. 
EU/1/04/302/003 – 5 ml solution for infusion. 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 21 February 2005 
Date of latest renewal: 18 September 2014 

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 



32 

ANNEX II 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE 

C. OTHER CONDITIONS AND REQUIREMENTSOF THE 
MARKETING AUTHORISATION 

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



33 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturer(s) responsible for batch release 

RIEMSER Pharma GmbH 
Bahnhofstr. 44b 
17489 Greifswald  
Germany 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2.) 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 

• Periodic Safety Update Reports  

The marketing authorisation holder shall submit periodic safety update reports for this product 
in accordance with the requirements set out in the list of Union reference dates (EURD list) 
provided for under Article 107c(7) of Directive 2001/83/EC and  published on the European 
medicines web-portal. 

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

• Risk Management Plan (RMP) 

Not applicable. 



34 

ANNEX III 

LABELLING AND PACKAGE LEAFLET 



35 

A. LABELLING 



36 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

OUTER CARTON 

1. NAME OF THE MEDICINAL PRODUCT 

Prialt 25 micrograms/ml solution for infusion 
ziconotide 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each ml contains 25 micrograms ziconotide (as acetate) 
Each vial contains 500 micrograms ziconotide (as acetate). 

3. LIST OF EXCIPIENTS 

methionine, sodium chloride, water for injections, hydrochloric acid and sodium hydroxide. 

4. PHARMACEUTICAL FORM AND CONTENTS 

Solution for infusion. 

1 vial of 20 ml  
500 micrograms/20ml 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Read the package leaflet before use. 
Intrathecal use 

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

Keep out of the sight and reach of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

8. EXPIRY DATE 

EXP 

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator (2°C – 8°C).  Do not freeze.  Keep the vial in the outer carton in order to protect 
from light. 



37 

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 

RIEMSER Pharma GmbH 
An der Wiek 7  
17493 Greifswald-Insel Riems  
Germany 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/04/302/004 

13. BATCH NUMBER 

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY 

Medicinal product subject to medical prescription. 

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:  



38 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING  

VIAL LABEL 

1. NAME OF THE MEDICINAL PRODUCT 

Prialt 25 μg/ml solution for infusion 
ziconotide 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each ml contains 25 micrograms ziconotide (as acetate) 
Each vial contains 500 micrograms ziconotide (as acetate). 

3. LIST OF EXCIPIENTS 

methionine, sodium chloride, water for injections, hydrochloric acid and sodium hydroxide. 

4. PHARMACEUTICAL FORM AND CONTENTS 

Solution for infusion. 

1 vial of 20 ml  
500 micrograms/20ml 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Read the package leaflet before use. 
Intrathecal use 

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

Keep out of the sight and reach of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator (2°C – 8°C).  Do not freeze.  Keep the vial in the outer carton in order to protect 
from light. 



39 

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 

RIEMSER Pharma GmbH 
An der Wiek 7  
17493 Greifswald-Insel Riems  
Germany 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/04/302/004 

13. BATCH NUMBER

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted



40 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

OUTER CARTON 

1. NAME OF THE MEDICINAL PRODUCT 

Prialt 100 micrograms/ml solution for infusion 
ziconotide 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

1 ml: 
Each ml contains 100 micrograms ziconotide (as acetate). 
Each vial contains 100 micrograms ziconotide (as acetate). 

2 ml: 
Each ml contains 100 micrograms ziconotide (as acetate). 
Each vial contains 200 micrograms ziconotide (as acetate). 

5 ml: 
Each ml contains 100 micrograms ziconotide (as acetate) 
Each vial contains 500 micrograms ziconotide (as acetate). 

3. LIST OF EXCIPIENTS 

methionine, sodium chloride, water for injections, hydrochloric acid and sodium hydroxide. 

4. PHARMACEUTICAL FORM AND CONTENTS 

Solution for infusion. 

1 ml: 
1 vial of 1 ml  
1ml 
100 micrograms /1ml 

2 ml: 
1 vial of 2 ml  
2ml 
200 micrograms/2ml 

5 ml: 
1 vial of 5 ml  
5ml 
500 micrograms/5ml 



41 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Read the package leaflet before use. 
Intrathecal use 

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

Keep out of the sight and reach of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

8. EXPIRY DATE 

EXP 

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator (2°C – 8°C).  Do not freeze.  Keep the vial in the outer carton 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 

RIEMSER Pharma GmbH 
An der Wiek 7  
17493 Greifswald-Insel Riems  
Germany 

12. MARKETING AUTHORISATION NUMBER(S) 

1 ml: 
EU/1/04/302/001 

2 ml: 
EU/1/04/302/002 

5 ml: 
EU/1/04/302/003 

13. BATCH NUMBER 

Lot 



42 

14. GENERAL CLASSIFICATION FOR SUPPLY 

Medicinal product subject to medical prescription. 

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:  



43 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

VIAL LABEL 

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

Prialt 100 μg/ml infusion 
Ziconotide 
Intrathecal use  

2. METHOD OF ADMINISTRATION 

3. EXPIRY DATE 

EXP 

4. BATCH NUMBER 

Lot 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

1 ml: 
1 ml 
100 μg/1ml 

2 ml: 
2 ml 
200 μg/2ml 

5 ml: 
5 ml 
500 μg/5ml 

6. OTHER 



44 

B. PACKAGE LEAFLET 



45 

Package leaflet: Information for the patient

Prialt 25 micrograms/ml solution for infusion 
Ziconotide 

Read all of this leaflet carefully before you are given 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. 
- If you get any side effects, talk to your doctor.  This includes any possible side effects not listed 

in this leaflet.  See section 4. 

What is in this leaflet

1. What Prialt is and what it is used for 
2. What you need to know before you are given Prialt 
3. How to use Prialt 
4. Possible side effects 
5. How to store Prialt 
6. Contents of the pack and other information 

1. What Prialt is and what it is used for

Prialt contains the active substance ziconotide which belongs to a group of medicines, called 
analgesics or ‘painkillers’.  Prialt is used for the treatment of severe, long-term pain in adults who need 
a painkiller by intrathecal injection (injection into the space that surrounds the spinal cord and the 
brain). 

2. What you need to know before you are given Prialt

You should not be given Prialt 
- If you are allergic to ziconotide or any of the other ingredients of this medicine (listed in section 

6). 
- If you are receiving an anticancer medicine into the space around your spinal cord. 

Warnings and precautions 
Talk to your doctor before you are given Prialt 
- The effects of long-term treatment of Prialt are uncertain at this time and the possibility of toxic 

effects on the spinal cord have not yet been ruled out.  In case of a need for long term treatment, 
monitoring may be necessary (as decided by your doctor). 

- If you are receiving Prialt via a pump worn outside your body, it is important you check once 
daily for any signs of infection at the point where the tube enters your body. 

- If you observe any signs of infection around the tube, such as skin redness, swelling, pain or 
discharge, you must tell your doctor immediately and seek treatment for the infection. 

- If you develop any tenderness in the area around the tube without signs of infection, you should 
seek advice from your doctor as soon as possible as tenderness may be an early sign of 
infection. 

- If you are receiving Prialt via a pump worn outside your body and any part of the infusion 
tubing becomes disconnected, you must contact your doctor or nurse immediately. 

- If you have any of the following symptoms:  high temperature, headache, stiff neck, tiredness, 
confusion, feeling sick, vomiting or occasional fits, these may be signs of meningitis.  You must 
tell your doctor immediately if you experience any of the above symptoms. 

- If you notice any adverse change in your thinking, mood or memory, please tell your doctor. 
- If you are receiving chemotherapy please tell your doctor. 



46 

- You may have an increased level of an enzyme called creatine kinase in your blood and 
although this does not usually cause any symptoms or problems, your doctor is likely to monitor 
its level.  In addition, you may also occasionally experience muscular problems. If such is the 
case, you should immediately notify your doctor, as he/she may decide to halt your Prialt 
treatment. 

- You should tell your doctor immediately if you experience any of the following symptoms after 
receiving your treatment; sudden wheeziness, difficulty in breathing, pain in the chest, swelling 
of eyelids, face or lips, rash or itching (especially affecting the whole body). These may be signs 
of a severe allergic reaction. 

- In patients that suffer from severe long term pain, there is a higher likelihood of suicide and 
attempted suicide than in the general population. Prialt may also cause or worsen depression in 
people that are already susceptible. If you are experiencing depression or have a history of 
depression please inform your healthcare professional before you are commenced on Prialt. If 
after starting Prialt you experience a worsening of your depression or have any other symptoms 
affecting your mood, please inform your healthcare professional.

- You may experience drowsiness or may not be fully aware of your surroundings whilst 
receiving treatment.  If this happens, you should immediately notify your doctor, as he/she may 
decide to halt your Prialt treatment. 

Children and adolescents 
Prialt is not recommended for use in children and adolescents. 

Other medicines and Prialt 
Tell your doctor if you are taking, have recently taken or might take any other medicines (for example, 
baclofen used to treat muscle spasticity, clonidine used to treat high blood pressure, bupivacaine used 
for local anaesthesia, morphine used for pain, propofol used for general anaesthesia, or any medicine 
which is  administered by intrathecal injection (injection into the space that surrounds the spinal cord 
and the brain)).  You may feel drowsy if you are given Prialt with certain other medicines used to treat 
pain. 

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. 

Prialt is not recommended during pregnancy and in women of childbearing potential not using 
contraception.  

Driving and using machines 
The use of Prialt has been reported to cause confusion and drowsiness.  Ask your doctor for advice 
before you drive or operate machinery. 

This medicinal product contains less than 1 mmol sodium (23 mg) per maximum recommended 
intrathecal dose (21.6 μg/day), i.e. essentially ‘sodium- free’.

3. How to use Prialt

Your treatment with Prialt will be managed by a doctor who has experience of giving medicines into 
the space around the spinal cord, and in the use of internal and external infusion pumps. 

The recommended starting dose is no more than 2.4 micrograms per day.  Your doctor will adjust the 
dose of Prialt according to the severity of your pain by adding no more than 2.4 micrograms/day.  The 
maximum dose is 21.6 micrograms/day.  At the start of your treatment your doctor may increase your 
dose every 1 to 2 days or more.  If needed, the dose may be decreased or injection stopped if the side 
effects are too great. 



47 

Prialt is given as a very slow continuous injection into the space surrounding the spinal cord 
(intrathecal use).  The medicine will be administered continuously from a pump either implanted into 
your abdominal wall or placed externally in a belt pouch.  Your doctor will discuss with you the kind 
of pump that will be most suitable for you and when you need to have your pump refilled. 

If you feel that you are still in too much pain while receiving Prialt, or that the side effects are too 
great, talk to your doctor. 

Before giving you Prialt, your doctor might decide to slowly stop giving you opiates (other types of 
medicinal product which are used to treat pain) into your spinal cord and instead replace with 
alternative pain medicinal products. 

If you receive more Prialt than you should 
If you receive more Prialt than your doctor intended, you may feel unwell with signs such as 
confusion, problems with speech, word finding difficulties, excessive shaking, light-headedness, 
excessive sleepiness, feeling or being sick.  If this happens, consult your doctor or hospital 
immediately. 

If you have any further questions on the use of this medicine, ask your doctor. 

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

Serious side effects 

You must tell your doctor immediately if you notice these serious side effects as you may require 
urgent medical treatment. 

• Meningitis (may affect up to 1 in 100 people) – is inflammation of the coverings of the brain and 
spinal cord usually caused by an infection. Symptoms of meningitis are headache, stiff neck, 
dislike of bright lights, fever, vomiting, confusion and drowsiness.  

• Convulsions (may affect up to 1 in 100 people) – convulsions (fits) are when a person's body 
shakes rapidly and uncontrollably. During a convulsion, the person's muscles contract and relax 
repeatedly and the person may lose consciousness. 

• Suicidal thoughts or suicide attempt (may affect up to 1 in 100 people). 

• Rhabdomyolysis (may affect up to 1 in 100 people) – is breakdown of muscle fibres that can lead 
to kidney damage. Symptoms of rhabdomyolysis are abnormal urine colour (brown coloured), 
reduced urine production, muscle weakness, muscle aching and muscle tenderness. 

• Coma (may affect up to 1 in 100 people) – a state of unconsciousness with difficulty responding 
or waking up. 

• Anaphylactic reaction (it is not known how many people this affects) – is a severe allergic 
reaction, the signs of which are sudden wheeziness, difficulty in breathing, pain in the chest, 
swelling of eyelids, face or lips, rash or itching (especially affecting the whole body). 

Other side effects 

Very common (may affect more than 1 user in 10) 
Confusion, dizziness, blurred vision, headache, rapid back-and-forth movement of the eyes, loss or 
impairment of memory (forgetfulness), vomiting, nausea, general weakness and drowsiness. 



48 

Common (may affect 1 to 10 users in 100)
Decreased appetite, anxiety or worsened anxiety, hallucinations, inability to fall or stay asleep, 
agitation, disorientation, depression or worsened depression, nervousness, mood swings, mental status 
changes (thinking abnormal, confusion), paranoia, irritability, worsened confusion, difficulty with 
learning, memory or thinking, reflexes absent or impaired, problems expressing or understanding 
words, slurred speech, difficulty with speech or loss of ability to speak, sluggishness, balance or 
coordination impaired, burning sensation, increased abnormal sensation, reduced level of 
consciousness (unresponsive or almost unconscious), sedation, difficulty in concentrating, problems 
with the sense of smell, odd or no sense of taste, shaking, pins and needles, double vision, visual 
disturbance, intolerance to light, tinnitus (ringing in the ears), dizziness or spinning sensation, light-
headedness or dizziness when standing, low blood pressure, shortness of breath, dry mouth, abdominal 
pain, worsened nausea, diarrhoea, constipation, sweating, itching, muscle weakness, muscle spasms, 
muscle cramp, muscle or joint pain, difficult or painful urination, difficulty starting or controlling 
urination, feeling jittery, falling, pain or pain exacerbated, fatigue, feeling cold, swelling of the face, 
legs or feet, chest pain, blood chemistry changes, mental impairment and weight decreased. 

Uncommon (may affect 1 to 10 users in 1000) 
Infection of the blood stream, delirium (feeling of mental confusion), psychotic disorder (abnormal 
thinking and perceptions), thought disorders, abnormal dreams, incoherence (inability to make sense), 
loss of consciousness, stupor (unresponsive/difficult to arouse), stroke, encephalopathy (brain 
disorder), aggressiveness, abnormal heart rhythm, difficulty breathing, indigestion, rash,  muscle 
inflammation, back pain, muscle twitching, neck pain, acute kidney failure, abnormal heart trace 
measurements (ECG), raised body temperature, difficulty walking. 

Reporting of side effects 

If you get any side effects, talk to your doctor. 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 Prialt

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 label and carton after EXP.  The 
expiry date refers to the last day of that month. 

Store in a refrigerator (2°C – 8°C). 
Do not freeze. 
Keep the vial in the outer carton in order to protect from light. 

Chemical and physical in use stability has been demonstrated for 60 days at 37°C. 

From a microbiological point of view, if the product is diluted it should be transferred to the infusion 
pump immediately.  If not used immediately, in-use storage times and conditions prior to use are the 
responsibility of the user and would normally not be longer than 24 hours at 2°C – 8°C, unless dilution 
has taken place in controlled and validated aseptic conditions. 

Do not use this medicine if you notice any discolouration or cloudiness or if particulate matter is 
observed. 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 

6. Contents of the pack and other information 

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


49 

What Prialt contains 
- The active substance is ziconotide.   
- One ml solution contains 25 micrograms ziconotide (as acetate).   
- Each 20 ml vial contains 500 micrograms ziconotide (as acetate).
- The other ingredients are methionine, sodium chloride, water for injections, hydrochloric acid 

and sodium hydroxide.

What Prialt looks like and contents of the pack 
Prialt is a solution for infusion (infusion).  The solution is clear and colourless.  Prialt is supplied in 
packs containing a single vial of 20 ml. 

Marketing Authorisation Holder 
RIEMSER Pharma GmbH 
An der Wiek 7  
17493 Greifswald-Insel Riems  
Germany 

Manufacturer 
RIEMSER Pharma GmbH 
Bahnhofstr. 44b 
17489 Greifswald  
Germany 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 

België/Belgique/Belgien
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Duitsland/Allemagne/Deutschland) 

Lietuva 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Vokietija)

България 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Германия) 

Luxembourg/Luxemburg
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Allemagne/Deutschland)  

Česká republika 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Německo) 

Magyarország 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Németország)

Danmark 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Tyskland) 

Malta 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Il-Ġermanja/Germany) 



50 

Deutschland 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 

Nederland
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Duitsland) 

Eesti 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Saksamaa) 

Norge 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Tyskland) 

Ελλάδα 
RIEMSER Pharma GmbH 
Τηλ: +49 (0)30 338427-0 
info@RIEMSER.com 
(Γερμανία) 

Österreich 
AGEA Pharma GmbH 
Tel: +43 (0)1 336 01 41 
office@ageapharma.com 

España 
Riemser Iberia S.L. 
Tel.: +34 (0)91 794 22 39 
informacion@riemser.com 

Polska 
IMED POLAND Sp. z o.o. 
Tel: +48 (0)22 663 43 03 
imed@imed.com.pl 

France 
KEOCYT 
Tél: +33 (0)1 42 31 07 10 
contact@keocyt.com 

Portugal 
BCN Farma 
Tel: +34 (0)932 684 208 
info@bcnfarma.com  
(Spain) 

Hrvatska
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Njemačka) 

România  
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Germania) 

Ireland 
Intrapharm Laboratories Ltd 
Tel: + 44 (0)1628 771800 
medinfo@intrapharmlabs.com 
(United Kingdom) 

Slovenija 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Nemčija) 

Ísland 
RIEMSER Pharma GmbH 
Sími: +49 (0)30 338427-0 
info@RIEMSER.com 
(Þýskaland) 

Slovenská republika 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Nemecko) 

Italia 
Euromed S.R.L. 
Tel: +39 (0)081 241 5204 
moreinfo@euromed.it 

Suomi/Finland 
RIEMSER Pharma GmbH 
Puh/Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Saksa/Tyskland) 



51 

Κύπρος 
RIEMSER Pharma GmbH 
Τηλ: +49 (0)30 338427-0 
info@RIEMSER.com 
(Γερμανία) 

Sverige 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Tyskland) 

Latvija 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Vācija) 

United Kingdom 
Intrapharm Laboratories Ltd 
Tel: + 44 (0)1628 771800 
medinfo@intrapharmlabs.com 

This leaflet was last revised in {MM/YYYY}.

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency web site:  
http://www.ema.europa.eu.  There are also links to other websites about rare diseases and treatments. 

------------------------------------------------------------------------------------------------------------------------------ 

The following information is intended for healthcare professionals only: 

Instructions for use and handling 

Prialt is supplied as a clear, colourless solution in single use vials.  It should be inspected visually for 
particulate matter and discolouration prior to administration.  The solution should not be used if 
discoloured or cloudy or if particulate matter is observed. 

For single use only.  Any unused medicinal product or waste material should be disposed of in 
accordance with local requirements.  

If dilution is required, Prialt must be diluted aseptically with preservative-free sodium chloride 
9 mg/ml (0.9%) solution for injection before use.  The concentration of the solution used in the 
infusion pump must be no lower than 5 μg/ml ziconotide in an external pump and 25 μg/ml in an 
internal pump. 

Strict aseptic procedures must be used during the preparation and handling of the solution for infusion 
and refilling of the pump.  The patient and health-care providers must be familiar with the handling of 
the external or internal infusion system and be aware of the need to guard against infection. 

Specific instructions for using the pumps must be obtained from the manufacturer.   

Prialt has been shown to be chemically and physically compatible with the implantable Synchromed 
pump and the external CADD-Micro pump at the concentration levels indicated above.  Chemical and 
physical in-use stability has been demonstrated for 14 days at 37ºC in the Synchromed pump when the 
pump has not previously been exposed to the medicinal product.  The initial fill must therefore be 
replaced after 14 days. 

Prialt was stable for 60 days at 37°C in the Synchromed pump previously exposed to the medicinal 
product.  Stability has been demonstrated for 21 days at room temperature in the CADD-Micro pump. 

The technical data are given only for information and should not limit health-care providers’ choice. 
CE marked pumps equivalent to the Synchromed and CADD-Micro pump should be used to deliver 
ziconotide.   



52 

Pumps previously used to deliver other medicinal products must be washed out three times with 
sodium chloride 9 mg/ml (0.9%) solution for injection (preservative-free) before being filled with 
ziconotide.  The introduction of air into the pump reservoir or cartridge should be minimized, as 
oxygen can degrade ziconotide. 

Prior to initiation of therapy, an internal pump must be rinsed three times with 2 ml of the solution at 
25 μg/ml.  The concentration of Prialt in a naïve pump may be reduced due to adsorption onto the 
surfaces of the device, and/or dilution by the residual space of the device.  Because of this, after the 
first use of Prialt, the reservoir should be emptied and refilled after 14 days.  Subsequently the pump 
should be emptied and refilled every 60 days. 



53 

Package leaflet: Information for the patient

Prialt 100 micrograms/ml solution for infusion 
Ziconotide 

Read all of this leaflet carefully before you are given 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. 
- If you get any side effects, talk to your doctor.  This includes any possible side effects not listed 

in this leaflet.  See section 4. 

What is in this leaflet
1. What Prialt is and what it is used for 
2. What you need to know before you are given Prialt 
3. How to use Prialt 
4. Possible side effects 
5. How to store Prialt 
6. Contents of the pack and other information 

1. What Prialt is and what it is used for

Prialt contains the active substance ziconotide which belongs to a group of medicines, called 
analgesics or ‘painkillers’.  Prialt is used for the treatment of severe, long-term pain in adults who need 
a painkiller by intrathecal injection (injection into the space that surrounds the spinal cord and the 
brain). 

2. What you need to know before you are given Prialt

You should not be given Prialt 
- If you are allergic to ziconotide or any of the other ingredients of this medicine (listed in section 

6). 
- If you are receiving an anticancer medicine into the space around your spinal cord. 

Warnings and precautions 
Talk to your doctor before you are given Prialt 
- The effects of long-term treatment of Prialt are uncertain at this time and the possibility of toxic 

effects on the spinal cord have not yet been ruled out.  In case of a need for long term treatment, 
monitoring may be necessary (as decided by your doctor). 

- If you are receiving Prialt via a pump worn outside your body, it is important you check once 
daily for any signs of infection at the point where the tube enters your body. 

- If you observe any signs of infection around the tube, such as skin redness, swelling, pain or 
discharge, you must tell your doctor immediately and seek treatment for the infection. 

- If you develop any tenderness in the area around the tube without signs of infection, you should 
seek advice from your doctor as soon as possible as tenderness may be an early sign of 
infection. 

- If you are receiving Prialt via a pump worn outside your body and any part of the infusion 
tubing becomes disconnected, you must contact your doctor or nurse immediately. 

- If you have any of the following symptoms:  high temperature, headache, stiff neck, tiredness, 
confusion, feeling sick, vomiting or occasional fits, these may be signs of meningitis.  You must 
tell your doctor immediately if you experience any of the above symptoms. 

- If you notice any adverse change in your thinking, mood or memory, please tell your doctor. 
- If you are receiving chemotherapy please tell your doctor. 



54 

- You may have an increased level of an enzyme called creatine kinase in your blood and 
although this does not usually cause any symptoms or problems, your doctor is likely to monitor 
its level. In addition, you may also occasionally experience muscular problems. If such is the 
case, you should immediately notify your doctor, as he/she may decide to halt your Prialt 
treatment. 

- You should tell your doctor immediately if you experience any of the following symptoms after 
receiving your treatment; sudden wheeziness, difficulty in breathing, pain in the chest, swelling 
of eyelids, face or lips, rash or itching (especially affecting the whole body). These may be signs 
of a severe allergic reaction. 

- In patients that suffer from severe long term pain, there is a higher likelihood of suicide and 
attempted suicide than in the general population. Prialt may also cause or worsen depression in 
people that are already susceptible. If you are experiencing depression or have a history of 
depression please inform your healthcare professional before you are commenced on Prialt. If 
after starting Prialt you experience a worsening of your depression or have any other symptoms 
affecting your mood, please inform your healthcare professional. 

- You may experience drowsiness or may not be fully aware of your surroundings whilst 
receiving treatment.  If this happens, you should immediately notify your doctor, as he/she may 
decide to halt your Prialt treatment. 

Children and adolescents 
Prialt is not recommended for use in children and adolescents. 

Other medicines and Prialt 
Tell your doctor if you are taking, have recently taken or might take any other medicines (for example, 
baclofen used to treat muscle spasticity, clonidine used to treat high blood pressure, bupivacaine used 
for local anaesthesia, morphine used for pain, propofol used for general anaesthesia or any medicine 
which is administered by intrathecal injection (injection into the space that surrounds the spinal cord 
and the brain)).  You may feel drowsy if you are given Prialt with certain other medicines used to treat 
pain. 

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. 

Prialt is not recommended during pregnancy and in women of childbearing potential not using 
contraception.  

Driving and using machines 
The use of Prialt has been reported to cause confusion and drowsiness.  Ask your doctor for advice 
before you drive or operate machinery. 

This medicinal product contains less than 1 mmol sodium (23 mg) per maximum recommended 
intrathecal dose (21.6 μg/day), i.e. essentially ‘sodium- free’.

3. How to use Prialt

Your treatment with Prialt will be managed by a doctor who has experience of giving medicines into 
the space around the spinal cord, and in the use of internal and external infusion pumps. 

The recommended starting dose is no more than 2.4 micrograms per day.  Your doctor will adjust the 
dose of Prialt according to the severity of your pain by adding no more than 2.4 micrograms/day.  The 
maximum dose is 21.6 micrograms/day.  At the start of your treatment your doctor may increase your 
dose every 1 to 2 days or more.  If needed, the dose may be decreased or injection stopped if the side 
effects are too great. 



55 

Prialt is given as a very slow continuous injection into the space surrounding the spinal cord 
(intrathecal use).  The medicine will be administered continuously from a pump either implanted into 
your abdominal wall or placed externally in a belt pouch.  Your doctor will discuss with you the kind 
of pump that will be most suitable for you and when you need to have your pump refilled. 

If you feel that you are still in too much pain while receiving Prialt, or that the side effects are too 
great, talk to your doctor. 

Before giving you Prialt, your doctor might decide to slowly stop giving you opiates (other types of 
medicinal product which are used to treat pain) into your spinal cord and instead replace with 
alternative pain medicinal products. 

If you receive more Prialt than you should 
If you receive more Prialt than your doctor intended, you may feel unwell with signs such as 
confusion, problems with speech, word finding difficulties, excessive shaking, light-headedness, 
excessive sleepiness, feeling or being sick.  If this happens, consult your doctor or hospital 
immediately. 

If you have any further questions on the use of this medicine, ask your doctor. 

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

Serious side effects 

You must tell your doctor immediately if you notice these serious side effects as you may require 
urgent medical treatment. 

• Meningitis (may affect up to 1 in 100 people) – is inflammation of the coverings of the brain and 
spinal cord usually caused by an infection. Symptoms of meningitis are headache, stiff neck, 
dislike of bright lights, fever, vomiting, confusion and drowsiness.  

• Convulsions (may affect up to 1 in 100 people) – convulsions (fits) are when a person's body 
shakes rapidly and uncontrollably. During a convulsion, the person's muscles contract and relax 
repeatedly and the person may lose consciousness. 

• Suicidal thoughts or suicide attempt (may affect up to 1 in 100 people). 

• Rhabdomyolysis (may affect up to 1 in 100 people) – is breakdown of muscle fibres that can lead 
to kidney damage. Symptoms of rhabdomyolysis are abnormal urine colour (brown coloured), 
reduced urine production, muscle weakness, muscle aching and muscle tenderness. 

• Coma (may affect up to 1 in 100 people) – a state of unconsciousness with difficulty responding 
or waking up. 

• Anaphylactic reaction (it is not known how many people this affects) – is a severe allergic 
reaction, the signs of which are sudden wheeziness, difficulty in breathing, pain in the chest, 
swelling of eyelids, face or lips, rash or itching (especially affecting the whole body). 

Other side effects 

Very common (may affect more than 1 user in 10) 
Confusion, dizziness, blurred vision, headache, rapid back-and-forth movement of the eyes, loss or 
impairment of memory (forgetfulness), vomiting, nausea, general weakness and drowsiness. 



56 

Common (may affect 1 to 10 users in 100)
Decreased appetite, anxiety or worsened anxiety, hallucinations, inability to fall or stay asleep, 
agitation, disorientation, depression or worsened depression, nervousness, mood swings, mental status 
changes (thinking abnormal, confusion), paranoia, irritability, worsened confusion, difficulty with 
learning, memory or thinking, reflexes absent or impaired, problems expressing or understanding 
words, slurred speech, difficulty with speech or loss of ability to speak, sluggishness, balance or 
coordination impaired, burning sensation, increased abnormal sensation, reduced level of 
consciousness (unresponsive or almost unconscious), sedation, difficulty in concentrating, problems 
with the sense of smell, odd or no sense of taste, shaking, pins and needles, double vision, visual 
disturbance, intolerance to light, tinnitus (ringing in the ears), dizziness or spinning sensation, light-
headedness or dizziness when standing, low blood pressure, shortness of breath, dry mouth, abdominal 
pain, worsened nausea, diarrhoea, constipation, sweating, itching, muscle weakness, muscle spasms, 
muscle cramp, muscle or joint pain, difficult or painful urination, difficulty starting or controlling 
urination, feeling jittery, falling, pain or pain exacerbated, fatigue, feeling cold, swelling of the face, 
legs or feet, chest pain, blood chemistry changes, mental impairment and weight decreased. 

Uncommon (may affect 1 to 10 users in 1000) 
Infection of the blood stream, delirium (feeling of mental confusion), psychotic disorder (abnormal 
thinking and perceptions), thought disorders, abnormal dreams, incoherence (inability to make sense), 
loss of consciousness, stupor (unresponsive/difficult to arouse), stroke, encephalopathy (brain 
disorder), aggressiveness, abnormal heart rhythm, difficulty breathing, indigestion, rash,  muscle 
inflammation, back pain, muscle twitching, neck pain, acute kidney failure, abnormal heart trace 
measurements (ECG), raised body temperature, difficulty walking.. 

Reporting of side effects 

If you get any side effects, talk to your doctor. 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 Prialt

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 label and carton after EXP.  The 
expiry date refers to the last day of that month. 

Store in a refrigerator (2°C – 8°C). 
Do not freeze. 
Keep the vial in the outer carton in order to protect from light. 

Chemical and physical in use stability has been demonstrated for 60 days at 37°C. 

From a microbiological point of view, if the product is diluted it should be transferred to the infusion 
pump immediately.  If not used immediately, in-use storage times and conditions prior to use are the 
responsibility of the user and would normally not be longer than 24 hours at 2°C – 8°C, unless dilution 
has taken place in controlled and validated aseptic conditions. 

Do not use this medicine if you notice any discolouration or cloudiness or if particulate matter is 
observed. 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 

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


57 

6. Contents of the pack and other information 

What Prialt contains 
- The active substance is ziconotide. 
- One ml solution contains 100 micrograms ziconotide (as acetate). 
- Each 1 ml vial contains 100 micrograms; each 2 ml vial contains 200 micrograms; each 5 ml 

vial contains 500 micrograms. 
- The other ingredients (excipients) are methionine, sodium chloride, water for injections, 

hydrochloric acid and sodium hydroxide. 

What Prialt looks like and contents of the pack 
Prialt is a solution for infusion (infusion).  The solution is clear and colourless.  Prialt is supplied in 
packs containing a single vial of either 1 ml, 2 ml or 5 ml.  Not all pack sizes may be marketed. 

Marketing Authorisation Holder: 
RIEMSER Pharma GmbH 
An der Wiek 7  
17493 Greifswald-Insel Riems  
Germany 

Manufacturer: 
RIEMSER Pharma GmbH 
Bahnhofstr. 44b 
17489 Greifswald  
Germany 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 

België/Belgique/Belgien
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Duitsland/Allemagne/Deutschland) 

Lietuva 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Vokietija)

България 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Германия) 

Luxembourg/Luxemburg
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Allemagne/Deutschland)  

Česká republika 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Německo) 

Magyarország 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Németország)

Danmark 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Tyskland) 

Malta 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Il-Ġermanja/Germany) 



58 

Deutschland 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 

Nederland
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Duitsland) 

Eesti 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Saksamaa) 

Norge 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Tyskland) 

Ελλάδα 
RIEMSER Pharma GmbH 
Τηλ: +49 (0)30 338427-0 
info@RIEMSER.com 
(Γερμανία) 

Österreich 
AGEA Pharma GmbH 
Tel: +43 (0)1 336 01 41 
office@ageapharma.com 

España 
Riemser Iberia S.L. 
Tel.: +34 (0)91 794 22 39 
informacion@riemser.com 

Polska 
IMED POLAND Sp. z o.o. 
Tel: +48 (0)22 663 43 03 
imed@imed.com.pl 

France 
KEOCYT 
Tél: +33 (0)1 42 31 07 10 
contact@keocyt.com 

Portugal 
BCN Farma 
Tel: +34 (0)932 684 208 
info@bcnfarma.com 
(Spain) 

Hrvatska
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Njemačka) 

România  
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Germania) 

Ireland 
Intrapharm Laboratories Ltd 
Tel: + 44 (0)1628 771800 
medinfo@intrapharmlabs.com 
(United Kingdom) 

Slovenija 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Nemčija) 

Ísland 
RIEMSER Pharma GmbH 
Sími: +49 (0)30 338427-0 
info@RIEMSER.com 
(Þýskaland) 

Slovenská republika 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Nemecko) 

Italia 
Euromed S.R.L. 
Tel: +39 (0)081 241 5204 
moreinfo@euromed.it 

Suomi/Finland 
RIEMSER Pharma GmbH 
Puh/Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Saksa/Tyskland) 



59 

Κύπρος 
RIEMSER Pharma GmbH 
Τηλ: +49 (0)30 338427-0 
info@RIEMSER.com 
(Γερμανία) 

Sverige 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Tyskland) 

Latvija 
RIEMSER Pharma GmbH 
Tel: +49 (0)30 338427-0 
info@RIEMSER.com 
(Vācija) 

United Kingdom 
Intrapharm Laboratories Ltd 
Tel: + 44 (0)1628 771800 
medinfo@intrapharmlabs.com 

This leaflet was last revised in {MM/YYYY}.

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency web site:  
http://www.ema.europa.eu.  There are also links to other websites about rare diseases and treatments. 

------------------------------------------------------------------------------------------------------------------------------ 

The following information is intended for healthcare professionals only: 

Instructions for use and handling 

Prialt is supplied as a clear, colourless solution in single use vials.  It should be inspected visually for 
particulate matter and discolouration prior to administration.  The solution should not be used if 
discoloured or cloudy or if particulate matter is observed. 

For single use only.  Any unused medicinal product or waste material should be disposed of in 
accordance with local requirements.  

If dilution is required, Prialt must be diluted aseptically with preservative-free sodium chloride 
9 mg/ml (0.9%) solution for injection before use.  The concentration of the solution used in the 
infusion pump must be no lower than 5 μg/ml ziconotide in an external pump and 25 μg/ml in an 
internal pump. 

Strict aseptic procedures must be used during the preparation and handling of the solution for infusion 
and refilling of the pump.  The patient and health-care providers must be familiar with the handling of 
the external or internal infusion system and be aware of the need to guard against infection. 

Specific instructions for using the pumps must be obtained from the manufacturer.   

Prialt has been shown to be chemically and physically compatible with the implantable Synchromed 
pump and the external CADD-Micro pump at the concentration levels indicated above.  Chemical and 
physical in-use stability has been demonstrated for 14 days at 37ºC in the Synchromed pump when the 
pump has not previously been exposed to the medicinal product.  The initial fill must therefore be 
replaced after 14 days. 

Prialt was stable for 60 days at 37°C in the Synchromed pump previously exposed to the medicinal 
product.  Stability has been demonstrated for 21 days at room temperature in the CADD-Micro pump. 

The technical data are given only for information and should not limit health-care providers’ choice. 
CE marked pumps equivalent to the Synchromed and CADD-Micro pump should be used to deliver 
ziconotide.   



60 

Pumps previously used to deliver other medicinal products must be washed out three times with 
sodium chloride 9 mg/ml (0.9%) solution for injection (preservative-free) before being filled with 
ziconotide.  The introduction of air into the pump reservoir or cartridge should be minimized, as 
oxygen can degrade ziconotide. 

Prior to initiation of therapy, an internal pump must be rinsed three times with 2 ml of the solution at 
25 μg/ml.  The concentration of Prialt in a naïve pump may be reduced due to adsorption onto the 
surfaces of the device, and/or dilution by the residual space of the device.  Because of this, after the 
first use of Prialt, the reservoir should be emptied and refilled after 14 days.  Subsequently the pump 
should be emptied and refilled every 60 days. 


	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