Alpivab

1 

ANNEX I 

SUMMARY OF PRODUCT CHARACTERISTICS 

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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 

1. NAME OF THE MEDICINAL PRODUCT

Alpivab 200 mg concentrate for solution for infusion 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 20 mL vial of concentrate contains 200 mg peramivir. 
1 mL concentrate for solution for infusion contains 10 mg peramivir (anhydrous base). 

Excipients with known effect 

Each mL of concentrate contains 0.154 millimole (mmol) sodium, which is 3.54 mg of sodium. 

For the full list of excipients, see section 6.1. 

3. PHARMACEUTICAL FORM

Concentrate for solution for infusion. 
Clear, colourless, solution. 

4. CLINICAL PARTICULARS

4.1 Therapeutic indications 

Alpivab is indicated for the treatment of uncomplicated influenza in adults and children from the age 
of 2 years (see sections 4.4 and 5.1). 

4.2 Posology and method of administration 

Posology 

Alpivab should be administered as a single intravenous dose within 48 hours of the onset of symptoms 
of influenza. 

The recommended single intravenous dose of peramivir depends on age and body weight as shown in 
Table 1. 

Table 1: Peramivir dose based on age and body weight 

Age and body weight Recommended single dose 

Children aged from 2 years and <50 kg 12 mg/kg 

Children aged from 2 years and ≥50 kg body weight 600 mg 

Adults and adolescents (13 years and older) 600 mg 

Elderly 
No dose adjustment is required based on age (see sections 4.4 and 5.2). 

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Renal impairment 
The dose should be reduced for adults and adolescents (13 years and older) with absolute glomerular 
filtration rate (GFR) below 50 mL/min as shown in Table 2 (see sections 4.4 and 5.2).  
 
Table 2: Peramivir dose for adults and adolescents (from 13 years and 50 kg) based on absolute 

GFR 
Absolute Glomerular Filtration Rate 

(GFR)* Recommended single dose 

≥50 600 mg 
30 to 49 300 mg 
10 to 29 200 mg 

*Absolute GFR not adjusted for body surface area 
 
In adults and adolescents (from 13 years and 50 kg) with chronic renal impairment maintained on 
haemodialysis, peramivir should be administered after dialysis at a dose adjusted for renal function 
(Table 2). 
 
There are insufficient clinical data available in children and adolescents aged less than 13 years or 
with body weight less than 50 kg with renal impairment to be able to make any dosing 
recommendation. 
 
Hepatic impairment 
No dose adjustment is required in patients with hepatic impairment (see section 5.2). 
 
Paediatric population 
The safety and efficacy of peramivir in children aged under 2 years has not yet been established. No 
data are available. 
 
Method of administration 
  
Alpivab is administered via intravenous infusion for 15 to 30 minutes.  
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. 
 
4.4 Special warnings and precautions for use 
 
Serious hypersensitivity reactions 
 
Anaphylactic reactions and serious skin reactions (including erythema multiforme, toxic epidermal 
necrolysis and Stevens-Johnson syndrome) have been reported with peramivir (see section 4.8). If any 
hypersensitivity reaction occurs during infusion of peramivir, the infusion must be stopped 
immediately and appropriate management should be instituted. 
 
Neuropsychiatric events 
 
Delirium, hallucinations and abnormal behaviour have been reported in patients with influenza who 
were receiving peramivir. These events were reported primarily among paediatric patients and often 
had an abrupt onset and rapid resolution. The contribution of peramivir to these events has not been 
established. Patients with influenza should be closely monitored for signs of abnormal behaviour.  
 
Reduced renal function 
 

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Acute renal failure, renal failure, pre-renal failure, renal disorder, anuria, nephritis, and increased 
blood creatinine have been reported in patients with influenza who were receiving peramivir. Most of 
the cases occurred in elderly patients with comorbidities and multiple concomitant medicinal products. 
The contribution of peramivir to these events has not been established. Patients with influenza and 
already existing diseases should be closely monitored for renal function. 

Limitations of the clinical data 

The efficacy of peramivir as a single dose treatment for uncomplicated influenza was demonstrated in a 
single placebo-controlled study conducted in 300 adult patients in Japan during the 2007/2008 influenza 
season. The recommended 600 mg single intravenous dose resulted in shortening of the median time to 
alleviation of symptoms by 21 hours (see section 5.1). 

Available data do not support a conclusion that peramivir is effective in patients with influenza B or in 
patients with complicated influenza. 

Resistance to peramivir 

Influenza A/H1N1 viruses that contain the H275Y mutation have reduced susceptibility to peramivir 
and oseltamivir. In a clinical trial, no statistically significant clinical benefit could be demonstrated for 
peramivir over placebo in patients infected with the A/H1N1 virus containing the H275Y mutation. 
Available information on influenza drug susceptibility should be taken into account when deciding 
whether to use peramivir (see section 5.1).  

Risk of bacterial infections 

There is no evidence for efficacy of peramivir in any illness caused by agents other than influenza 
viruses. Serious bacterial infections may begin with influenza-like symptoms or may coexist with or 
occur as complications during the course of influenza. Peramivir has not been shown to prevent such 
complications.  

Excipients 

This medicinal product contains 212.4 mg sodium per 3 vials, equivalent to 10.6% of the World 
Health Organization (WHO) recommended maximum daily intake of 2 g sodium for an adult. 

4.5 Interaction with other medicinal products and other forms of interaction 

The potential for interactions of peramivir with other medicines is low, based on the known 
elimination pathway of peramivir.  

Live attenuated influenza vaccines are not recommended to be used until 48 hours following Alpivab 
administration due to a theoretical risk that peramivir could reduce the immunogenicity of the vaccine. 

4.6 Fertility, pregnancy and lactation 

Pregnancy 

There are no or limited amount of data (less than 300 pregnancies outcomes) from the use of peramivir 
in pregnant women.  

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity 
(see section 5.3).  

As a precautionary measure, it is preferable to avoid the use of peramivir during pregnancy. 

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Breast-feeding 

Available pharmacodynamic/toxicological data in animals have shown excretion of peramivir in milk 
(see section 5.3). 

A risk to the newborns/infants cannot be excluded. 

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

Fertility 

No human data on the effect of peramivir on fertility are available. Peramivir had no effects on mating 
or fertility in animal studies (see section 5.3).  

4.7 Effects on ability to drive and use machines 

Peramivir has no or negligible influence on the ability to drive and use machines. 

4.8 Undesirable effects 

Summary of the safety profile 

The most important serious adverse reactions associated with peramivir in patients are anaphylaxis and 
skin reactions, including erythema multiforme and Stevens-Johnson Syndrome.  
Among 467 adult subjects with uncomplicated influenza who received a single intravenous dose of 
peramivir 600 mg in clinical trials, the most commonly observed adverse reactions were neutrophil 
count decreased (3.2 %) and nausea (2.4 %).  

Tabulated list of adverse reactions 

Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to 
<1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000). 

Table 3: Adverse reactions in studies investigating peramivir for treatment of uncomplicated 
influenza in adults  

System Organ Class 
(SOC) 

Adverse Reaction According to Frequency* 

Common Uncommon Rare Unknown
Blood and 
lymphatic system 
disorders 

neutrophil count 
decreased 

Immune system 
disorders 

anaphylactic 
reaction*, 
anaphylactic 
shock* 

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System Organ Class 
(SOC) 

Adverse Reaction According to Frequency* 

Common Uncommon Rare Unknown 

Metabolism and 
nutrition disorders 

blood lactate 
dehydrogenase 
increased 

decreased appetite, blood 
albumin decreased, blood 
chloride increased, blood 
glucose decreased, blood 
lactate dehydrogenase 
decreased, blood potassium 
increased, blood sodium 
increased, blood uric acid 
increased, protein total 
increased 

    

Psychiatric 
disorders   insomnia   

abnormal 
behaviour*, 
delirium* 

Nervous system 
disorders   hypoaesthesia, paraesthesia     

Eye disorders   vision blurred     

Cardiac disorders   electrocardiogram QT prolonged     

Gastrointestinal 
disorders nausea, vomiting 

abdominal pain upper, 
abdominal discomfort, 
gastritis 

    

Hepatobiliary 
disorders   

increased gamma-
glutamyltransferase   

liver disorder*, 
alanine 
aminotransferase 
increased*, 
aspartate 
aminotransferase 
increased*  

Skin and 
subcutaneous tissue 
disorders 

  dermatitis, drug eruption, eczema, urticaria 
erythema 
multiforme 

dermatitis 
exfoliative*, 
Stevens-Johnson 
syndrome* 

Musculoskeletal and 
connective tissue 
disorders 

  arthralgia, blood creatine phosphokinase increased     

Renal and urinary 
disorders   

blood urea increased, blood 
present in urine, urobilin 
present in urine, blood 
creatinine increased, urine 
ketone body increased 

  
acute kidney 
injury*, renal 
impairment* 

General disorders 
and administration 
site conditions 

  chest discomfort, fatigue     

*These events reported from post-authorization use occurred with different dosage and dosing 
schedule to that described in the SmPC. 

 
Paediatrics 

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In paediatric subjects (age 2 to 17 years) with uncomplicated influenza enrolled in a clinical trial, the 
safety profile of peramivir was similar to that reported in adults. Common adverse reactions not 
reported in adults were injection site rash, pyrexia, tympanic membrane hyperaemia, psychomotor 
hyperactivity, and pruritus.  
 
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 
 
There is no experience of acute overdose with peramivir in humans. Treatment of an overdose should 
consist of general supportive measures including monitoring of vital signs and observation of the 
clinical status of the patient.  
 
Peramivir is cleared by renal excretion and can be cleared by haemodialysis. There is no specific 
antidote to treat an overdose of this medicine. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antivirals for systemic use, neuraminidase inhibitors ATC code:  
J05AH03 
 
Mechanism of action 
 
Peramivir is an inhibitor of influenza virus neuraminidase, an enzyme that releases viral particles from 
the plasma membrane of infected cells and is also important for viral entry into uninfected cells, which 
causes further spread of infectious virus in the body. 
 
In-vitro activity  
 
Neuraminidase inhibition occurred at very low peramivir concentrations in-vitro, with median 
inhibitory concentration 50% (IC50) values of 0.13 nanomolar (nM) to 0.99 nM against influenza A 
and B strains. 
 
Resistance 
In a clinical trial in which 245 subjects were infected at baseline with influenza A/H1N1 containing 
the H275Y mutation, the median baseline IC50 values for peramivir, oseltamivir and zanamivir were 
51.0 nM, 487.6 nM and 0.95 nM, respectively.  
 
In clinical trials, H275Y was the only resistance-associated treatment-emergent mutation in the 
neuraminidase gene that occurred in virus obtained from more than one peramivir-treated subject (in 9 
of 481[1.9 %] infected with the A/H1N1 influenza virus).  
 
Cross resistance 
The H275Y substitution is associated with reduced susceptibility to peramivir and oseltamivir. Cross-
resistance between peramivir and each of oseltamivir and zanamivir may also occur.  
 
Clinical studies 
 
Uncomplicated influenza in adults 

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A randomised, multicentre, double-blind trial conducted in Japan evaluated a single intravenous 
administration of peramivir 300 mg or 600 mg, or placebo administered over 30 minutes in subjects 20 
to 64 years of age with uncomplicated influenza. Subjects were eligible if they had fever greater than 
38 °C and a positive rapid antigen test for influenza virus, accompanied by at least two of the 
following symptoms: cough, nasal symptoms, sore throat, myalgia, chills/sweats, malaise, fatigue or 
headache.  

Study treatment was started within 48 hours of onset of symptoms. Subjects participating in the trial 
were required to self-assess their influenza symptoms as “none’, ‘mild’, ‘moderate’ or ‘severe’ twice 
daily. The primary endpoint, time to alleviation of symptoms, was defined as the number of hours 
from initiation of study drug until the start of the 24 hour period in which all seven symptoms of 
influenza (cough, sore throat, nasal congestion, headache, feverishness, myalgia and fatigue) were 
either absent or present at a level no greater than mild for at least 21.5 hours. 

The intent to treat influenza population (ITTI) included 296 subjects with influenza confirmed by 
polymerase chain reaction (PCR). Among the 97 subjects enrolled in the peramivir 600 mg dose 
group, 99 % were infected with influenza A virus (subtypes H1 and H3; 71 % and 26 %, respectively) 
and 1 % with influenza B virus. At enrollment 85 % of the 296 subjects had a composite influenza 
symptom score <15. The mean temperature at enrolment was 38.6 °C (axillary). Key efficacy results 
are presented in Table 4. 

Table 4: Key efficacy results from study 0722T0621 (ITTI Population)  
Peramivir 600 mg  

n=97 
Placebo  
n=100 

Time to alleviation of symptoms 
median (hours) 
(95 % CI) 

59.9 
(54.4, 68.1) 

81.8 
(68.0, 101.5) 

Time to recovery of normal temperature 
median (hours) 
(95 % CI) 

30.2 
(25.9, 31.9) 

42.4 
(32.9, 46.5) 

CI = Confidence Interval 

Uncomplicated influenza in paediatric subjects aged 2-17 years 
The safety of peramivir was evaluated in a randomised, active-controlled study of 110 subjects with 
uncomplicated influenza who received open label treatment with a single dose of peramivir (600 mg 
for subjects 13 to 17 years of age and 12 mg/kg up to a maximum dose of 600 mg in subjects 2 to 
12 years of age) or oral oseltamivir administered twice daily for 5 days. The ITTI population included 
84 subjects with influenza confirmed by PCR. Among the 93 subjects enrolled in the peramivir dose 
group, 43% were infected with influenza A virus (subtypes H1 and H3; 54 % and 46 %, respectively) 
and 27% with influenza B virus. Randomisation was 4:1 for peramivir and oseltamivir. Treatment was 
given or commenced within 48 hours of onset of symptoms of influenza. Efficacy (time to resolution 
of fever; time to resolution of influenza symptoms, viral shedding, virus susceptibility) was a 
secondary endpoint. 

Subjects receiving peramivir experienced a median time to alleviation of their combined influenza 
symptoms of 79.0 hours and the median time to recovery to normal temperature (less than 37 °C) was 
approximately 40.0 hours. 

Elderly patients 
Clinical trials in which single intravenous doses of peramivir were administered to patients with 
uncomplicated influenza included few subjects aged 65 and over (n=10). 

The European Medicines Agency has deferred the obligation to submit the results of studies with 
Alpivab in one or more subsets of the paediatric population for the treatment of influenza (see 
section 4.2 for information on paediatric use). 

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5.2 Pharmacokinetic properties 
 
Absorption 
 
The pharmacokinetic parameters following intravenous (IV) administration of peramivir (0.17 to 
2 times the recommended dose) showed a linear relationship between dose and exposure parameters 
(maximum serum concentration [Cmax] and area under the curve [AUC]). Following intravenous 
administration of a single dose of peramivir 600 mg over 30 minutes, Cmax was reached at the end of 
infusion.  
 
Distribution 
 
In-vitro binding of peramivir to human plasma proteins is less than 30 %.  
Based on a population pharmacokinetic analysis, the central volume of distribution was 12.56 L. 
 
Biotransformation 
 
Peramivir is not significantly metabolised in humans. 
 
Elimination 
 
The elimination half-life of peramivir following IV administration to healthy subjects of 600 mg as a 
single dose is approximately 20 hours. The major route of elimination of peramivir is via the kidney. 
Renal clearance of unchanged peramivir accounts for approximately 90 % of total clearance. 
 
Special populations 
 
Race 
In simulations of a single dose of 600 mg, the predicted AUC in Asians (AUC0-24 88,800 ng•h/mL) 
was slightly higher as compared to Non-Asians (AUC0-24 77,200 ng•h/mL).   
 
Gender 
The pharmacokinetics of peramivir following a 600 mg intramuscular (IM) injection was similar in 
males and females with AUC0-∞ of 76,600 ng•hr/mL and 101,000 ng•hr/mL, respectively, and Cmax of 
27,760 ng/mL and 34,710 ng/mL, respectively. 
 
Paediatrics 
The pharmacokinetics of peramivir has been evaluated in a study in paediatric subjects 2 to 17 years of 
age with uncomplicated influenza. Pharmacokinetic sampling in this study was limited to 
approximately 3 hours after administration of peramivir. Pharmacokinetics of peramivir in subjects 2 
to 17 years of age (administered 12 mg/kg or 600 mg according to age and body weight) and in 
healthy adults (administered 600 mg) was similar (Table 5).  
 
Table 5: Pharmacokinetic parameters in paediatric subjects  

Age Group  N Cmax (ng/mL) AUClast (ng•h/mL) 

2 years - <7 years 
Mean (SD) 28 53,600 (26,200) 74,000 (30,000) 

Geometric Mean  47,400 68,100 
%CV  48.9 40.6 

7 years - <13 years 
Mean (SD) 39 66,800 (35,400) 87,000 (40,800) 

Geometric Mean  61200 81,000 
%CV  53.0 46.8 

13 years - <18 Mean (SD) 20 54,300 (17,900) 72,400 (20,000) 

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Geometric Mean 51,500 69,500 
%CV 33.0 27.6

2 years - <18 years 
Mean (SD) 87 59,700 (29,700) 79,500 (34,000) 

Geometric Mean 54,200 74,000 
%CV 49.8 42.7

SD = Standard Deviation; CV = Coefficient of Variation 

Elderly 
The pharmacokinetics of peramivir was evaluated in 20 elderly subjects (>65 years of age) following a 
single 4 mg/kg IV dose of peramivir. The elderly subjects enrolled were aged 65 to 79 years, with a 
mean age of 70.1 years, with creatinine clearance (Cockcroft-Gault calculation) CrClcg ranging from 
82.8 mL/min to 197.9 mL/min. The pharmacokinetics in elderly subjects was similar to non-elderly 
subjects. Mean peak concentrations of peramivir were approximately 10 % higher in elderly subjects 
following administration of a single dose when compared to young adults (22,647 vs. 20,490 ng/mL, 
respectively). Exposure (AUC0-12) to peramivir following a single dose was approximately 33 % 
higher in elderly subjects compared to young adults (61,334 vs. 46,200 ng•hr/mL, respectively). 

Renal impairment 
In a study in subjects with various degrees of renal impairment and subjects with normal renal 
function, a single 2 mg/kg IV dose of peramivir was administered. Serum creatinine measurements 
were used to calculate creatinine clearance (Cockcroft-Gault equation). The mean AUC0- was 
increased by 28 %, 302 % and 412 % in subjects with creatinine clearance of 50-79, 30-49 and 10-29 
mL/min, respectively. Haemodialysis initiated at 2 hours after dosing reduced systemic exposure of 
peramivir by 73 to 81 %. 

Hepatic impairment 
The pharmacokinetics of peramivir in subjects with hepatic impairment has not been studied. No 
clinically relevant alterations to peramivir pharmacokinetics are expected in patients with hepatic 
impairment based on the route of peramivir elimination. 

5.3 Preclinical safety data 

Peramivir was not teratogenic in embryo-fetal development studies in rats and rabbits and had no 
effects on mating or fertility in rats up to 600 mg/kg/day, at which exposures were approximately 
8-fold of those in humans at the clinically recommended dose. However, in an embryo-foetal
development study in rats, in which dams received continuous infusions of peramivir from day 6-17 of
gestation at doses of 50, 400 or 1000 mg/kg/day, dose related increases in the incidences of reduction
of the renal papillae and dilatation of the ureters were observed. The teratological importance of these
findings is unclear.

Carcinogenicity studies by intravenous injection of peramivir were not performed.  

Peramivir was not mutagenic or clastogenic in a battery of in-vitro and in-vivo assays. 

Acute renal necrosis was found in rabbits at doses ≥ 200 mg/kg with a clear no observed adverse effect 
level (NOAEL) established in multiple studies at 100 mg/kg/day.  

Two-week oral toxicity studies were conducted in juvenile rats and rabbits, and a four-week IV 
toxicity study was conducted in juvenile rats. In general, nephrotoxicity was observed in rabbits, no 
unexpected toxicity was observed, and no other target organ toxicity was identified in juvenile 
animals. 

6. PHARMACEUTICAL PARTICULARS

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6.1 List of excipients 
 
Sodium chloride 
Water for injections 
Sodium hydroxide (for pH adjustment) 
Hydrochloric acid (for pH adjustment) 
 
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 
 
Unopened vial 
 
5 years 
 
After dilution 
 
Chemical and physical in-use stability has been demonstrated for 72 hours at 5 ºC and 25 ºC. 
From a microbiological point of view, the product, once diluted, should be used 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 ºC to 8 ºC, unless dilution has taken place in 
controlled and validated aseptic conditions. 
 
6.4 Special precautions for storage 
 
Do not refrigerate or freeze. 
For storage conditions after dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Clear glass vial (Type I) with a coated bromobutyl-rubber stopper, aluminium overseal and flip-off 
cap.  
 
Pack size of 3 single-use vials. 
 
6.6 Special precautions for disposal and other handling 
 
Aseptic technique should be used during the preparation of Alpivab to prevent inadvertent microbial 
contamination.  
 
The following steps should be followed to prepare a diluted solution of peramivir: 
 Check the seal of each vial. Do not use if seal opening is broken or missing. 
 Visually inspect the peramivir concentrate 10 mg/mL. It must be colourless and without 

particulate matter.  
 If a patient receives 600 mg peramivir the required volume of peramivir concentrate is 60 mL 

(3 vials with 20 mL each). In the case of a 300 mg peramivir dose, 30 mL (1½ vials) of peramivir 
concentrate is needed and for a 200 mg dose, only 20 mL (1 vial). Fractions of a vial may be 
needed for appropriate dose adjustments in children with a bodyweight of less than 50 kg. 

 Add the measured volume of peramivir concentrate into the infusion container. 
 Dilute the required dose of peramivir concentrate in sodium chloride 9 mg/mL (0.9 %) or 

4.5 mg/mL (0.45 %) solution for infusion, 5 % dextrose or Ringer lactate solution to a volume of 
100 mL. 

 Administer the diluted solution via intravenous infusion for 15 to 30 minutes. 

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 Once a diluted peramivir solution has been prepared, administer immediately or store in a
refrigerator (2 °C to 8 °C) for up to 24 hours. If refrigerated, allow the diluted peramivir solution
to reach room temperature, then administer immediately.

 Discard any unused diluted solution of peramivir after 24 hours.

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

7. MARKETING AUTHORISATION HOLDER

BioCryst Ireland Limited 
Atlantic Avenue 
Westpark Business Campus 
Shannon 
V14 YX01 
Ireland  
Tel: +353 1223 3541 
E-mail: safety@biocryst.com

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/18/1269/001 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

13/04/2018 

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.  

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ANNEX II 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH
RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE
MARKETING AUTHORISATION

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

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A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

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

Seqirus Vaccines Ltd 
Gaskill Road 
Speke 
Liverpool 
L24 9GR 
UNITED KINGDOM 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription. 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING
AUTHORISATION

 Periodic Safety Update Reports

The requirements for submission of periodic safety update reports for this medicinal product are 
set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 
Directive 2001/83/EC and any subsequent updates published on the European medicines web-
portal. 

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

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

 Risk Management Plan (RMP)

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

An updated RMP should be submitted: 
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information

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

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ANNEX III 

LABELLING AND PACKAGE LEAFLET 

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A. LABELLING

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

CARTON 

1. NAME OF THE MEDICINAL PRODUCT

Alpivab 200 mg concentrate for solution for infusion 
peramivir 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 mL concentrate contains 10 mg peramivir (anhydrous basis). 
Each 20 mL vial contains 200 mg peramivir. 

3. LIST OF EXCIPIENTS

Sodium chloride  
Water for injections 
Sodium hydroxide (for pH adjustment) 
Hydrochloric acid (for pH adjustment) 

4. PHARMACEUTICAL FORM AND CONTENTS

Concentrate for solution for infusion 
3 vials 

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use. 
Intravenous use after dilution 

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

Do not refrigerate or freeze. 

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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

BioCryst Ireland Limited 
Atlantic Avenue 
Westpark Business Campus 
Shannon 
V14 YX01 
Ireland  

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/18/1269/001  

13. BATCH NUMBER

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted. 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: 
SN:  
NN: 

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PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
VIAL LABEL 

1. NAME OF THE MEDICINAL PRODUCT

Alpivab 200 mg concentrate for solution for infusion 
peramivir 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 mL concentrate contains 10 mg peramivir (anhydrous base). 
Each 20 mL vial contains 200 mg peramivir. 

3. LIST OF EXCIPIENTS

Sodium chloride  
Water for injections 
Sodium hydroxide (for pH adjustment) 
Hydrochloric acid (for pH adjustment) 

4. PHARMACEUTICAL FORM AND CONTENTS

Concentrate for solution for infusion 

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use. 
Intravenous use after dilution 

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

Do not refrigerate or freeze. 

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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

BioCryst Ireland Limited 
Atlantic Avenue 
Westpark Business Campus 
Shannon 
V14 YX01 
Ireland  

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/18/1269/001  

13. BATCH NUMBER

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY

-- 

15. INSTRUCTIONS ON USE

-- 

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted. 

17. UNIQUE IDENTIFIER – 2D BARCODE

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

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21 

B. PACKAGE LEAFLET

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Package leaflet: Information for the patient 
 

Alpivab 200 mg concentrate for solution for infusion 
peramivir 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
 Keep this leaflet. You may need to read it again.  
 If you have any further questions, ask your doctor or pharmacist. 
 If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Alpivab is and what it is used for  
2. What you need to know before you are given Alpivab  
3. How Alpivab is given 
4. Possible side effects  
5. How to store Alpivab  
6. Contents of the pack and other information 
 
 
1. What Alpivab is and what it is used for 
 
Alpivab contains the active substance peramivir which belongs to a group of medicines called 
neuraminidase inhibitors. These medicines prevent the influenza virus from spreading inside the body.  
 
Alpivab is used to treat adults and children aged from 2 years with influenza that is not severe enough 
to require hospitalisation.  
 
 
2. What you need to know before you are given Alpivab  
 
You must not receive Alpivab 
 
 if you are allergic to peramivir or any of the other ingredients of this medicine (listed in section 

6) 
 
Warnings and precautions 
 
Talk to your doctor or pharmacist before you are given Alpivab if you have reduced kidney function. 
Your doctor may have to adjust your dose. 
 
Tell your doctor immediately if you experience serious skin or allergic reactions after Alpivab is 
given. Symptoms may include skin or throat swelling, difficulty breathing, blistering rash or peeling 
skin. See section 4. 
 
Tell your doctor immediately if you experience abnormal behaviour after Alpivab is given. Symptoms 
may include confusion, difficulty thinking or hallucinations. See section 4. 
 

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Children and adolescents 
 
Alpivab is not recommended in children aged under 2 years. 
 
Other medicines and Alpivab 
 
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. 
 
Live attenuated influenza vaccines should not be given until 48 hours after treatment with Alpivab. 
This is because Alpivab may prevent these vaccines from working well enough. 
 
Pregnancy and breast-feeding 
 
Tell your doctor if you are pregnant or breast-feeding. Your doctor will advise on whether you can be 
given Alpivab during pregnancy, or whether you are to stop breast-feeding for a short period after 
getting Alpivab. 
 
Driving and using machines 
 
Alpivab is not likely to change your ability to drive and use machines. 
 
Alpivab contains sodium 
 
This medicine contains 212.4 mg sodium (main component of cooking/table salt) in each dose 
consisting of 3 vials. This is equivalent to 10.6 % of the recommended maximum daily dietary intake 
of sodium for an adult.  
 
 
3. How Alpivab is given 
 
Alpivab is given by a healthcare profesional as a single dose within 2 days of the start of influenza 
symptoms. It is first diluted and then given into a vein  by infusion (drip), over 15 to 30 minutes.   
 
 Adults and adolescents (13 years and older) receive 600 mg (3 Alpivab vials). 
 Children aged from 2 years weighing 50 kg or more receive 600 mg (3 Alpivab vials). 
 Children aged from 2 years weighing less than 50 kg receive 12 mg per kg body weight. 
 Patients with reduced kidney function may require a reduced dose. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Contact your doctor immediately if any of the following side effects occur: 

Rare, may affect up to 1 in 1,000 people 
 severe skin rash with or without blisters and fever 
 
Not known, frequency cannot be estimated from the available data  
 very severe skin reactions, including Steven-Johnson syndrome and dermatitis exfoliative  

These skin reactions are life-threatening rashes with fever and blisters and can effect the lining 
of the mouth and genitals. 

 severe allergic reactions, including severe allergic shock reaction with features such as itchy 
rash, swelling of the throat and tongue, breathing difficulty, lightheadedness and vomiting 

 

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Other side effects occur with the following frequencies: 

Common, may affect up to 1 in 10 people 
 low levels of a white blood cell type called neutrophils 
 blood tests showing increased levels of lactate dehydrogenase 
 nausea (feeling sick), vomiting 

 
Uncommon, may affect up to 1 in 100 people 
 decreased appetite 
 blood tests showing decreased levels of albumin, glucose, lactate dehydrogenase 
 blood tests showing increased levels of chloride, potassium, sodium, uric acid, protein total, 

gamma-glutamyltransferase, creatine phosphokinase, urea, creatinine 
 sleeplessness 
 reduced sense of touch or sensation 
 abnormal sensation such as prickling, tingling and itchiness 
 blurred vision 
 prolonged time of the heart ventricle activity, measured in the ECG 
 upper abdominal pain, abdominal discomfort 
 inflammation of stomach lining 
 skin inflammation, eczema, rash, nettle-rash 
 joint pain 
 urobilin presented in the urine 
 increased level of urine ketone body 
 chest discomfort, fatigue 

 
Not known, frequency cannot be estimated from the available data 
 abnormal behaviour, delirium 
 liver disorder 
 blood test showing increased levels of alanine aminotransferase, aspartate aminotransferase 
 acute kidney injury, reduced kidney function 
 
Children and Adolescents from 2 years 
Side effects were similar to adults but also included the following: 
Common, may affect up to 1 in 10 people 
 rash on the injection site 
 fever 
 red ear drum 
 restlessness 
 itching 

 
Reporting of side effects 
 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Alpivab 
 
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. 
 
Do not refrigerate or freeze. 

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25 

 
Once diluted, administer the prepared Alpivab solution immediately; otherwise, store in a refrigerator 
(2 °C – 8 °C) for up to 24 hours.  
 
 
6. Contents of the pack and other information 
 
What Alpivab contains 
 
 The active substance is peramivir. 

Each 20 mL vial contains 200 mg peramivir. 1 mL concentrate for solution for infusion contains 
10 mg peramivir (anhydrous base). 

 The other ingredients are sodium chloride, water for injections, hydrochloric acid (for pH 
adjustment), sodium hydroxide (for pH adjustment). 

 
What Alpivab looks like and contents of the pack 
 
Alpivab is a clear, colourless, sterile concentrate for solution for infusion. It is provided in a clear glass 
vial with a coated rubber stopper, aluminium overseal and flip-off cap.  
 
Each carton contains 3 vials. 
 
Marketing Authorisation Holder  
BioCryst Ireland Limited 
Atlantic Avenue 
Westpark Business Campus 
Shannon 
V14 YX01 
Ireland  
Tel: +353 1223 3541 
E-mail: safety@biocryst.com 
 
Manufacturer 
Seqirus Vaccines Limited 
Gaskill Road, Speke 
Liverpool 
L24 9GR 
UK 
 
This leaflet was last revised in {MM/YYYY}. 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
------------------------------------------------------------------------------------------------------------------------ 
 
The following information is intended for healthcare professionals only: 
 
Use aseptic technique during the preparation of Alpivab to prevent microbial contamination. There is 
no preservative or antibacterial agent in the solution. Do not mix or co-infuse Alpivab with other 
medicines administered into a vein. 
 
Follow the steps below in the provided order to prepare a diluted solution of Alpivab: 
1. Check the seal of each vial. Do not use if the seal opening is broken or missing. 
2. Inspect the Alpivab concentrate. It must be colourless and without particulate matter.  
3. If a patient receives 600 mg peramivir the required volume of Alpivab concentrate is 60 mL (3 vials 

of 20 mL each). In the case of a 300 mg peramivir dose, 30 mL (1½ vials) of Alpivab concentrate 

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26 

is needed and for a 200 mg dose, only 20 mL (1 vial). Fractions of a vial may be needed for 
appropriate dose adjustments in children with a bodyweight of less than 50 kg. 

4. Add the measured volume of Alpivab concentrate into the infusion container. 
5. Dilute the required dose of Alpivab concentrate in sodium chloride 9 mg/mL (0.9 %) or 4.5 mg/mL 

(0.45 %) solution for infusion, 5 % dextrose or Ringer lactate solution to a volume of 100 mL. 
6. Administer the diluted solution via intravenous infusion over 15 to 30 minutes. 
7. Once a diluted Alpivab solution has been prepared, administer immediately or store in a refrigerator 

(2 °C to 8 °C) for up to 24 hours. If refrigerated, allow the diluted Alpivab solution to reach room 
temperature, then administer immediately. 

8. Discard any unused diluted solution of Alpivab after 24 hours. 
 
No special requirements for disposal. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 

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	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