Adakveo

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

2 

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 
 

Adakveo 10 mg/ml concentrate for solution for infusion 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each ml of concentrate for solution for infusion contains 10 mg crizanlizumab. 

 

One vial of 10 ml contains 100 mg crizanlizumab. 

 

Crizanlizumab is a monoclonal antibody produced in Chinese Hamster Ovary (CHO) cells by 

recombinant DNA technology. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Concentrate for solution for infusion (sterile concentrate) 

 

Colourless to slightly brownish-yellow liquid at pH 6 and with an osmolality of 300 mOsm/kg. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Adakveo is indicated for the prevention of recurrent vaso-occlusive crises (VOCs) in sickle cell 

disease patients aged 16 years and older. It can be given as an add-on therapy to 

hydroxyurea/hydroxycarbamide (HU/HC) or as monotherapy in patients for whom HU/HC is 

inappropriate or inadequate. 
 

4.2 Posology and method of administration 
 

Treatment should be initiated by physicians experienced in the management of sickle cell disease. 

 

Posology 

 

The recommended dose of crizanlizumab is 5 mg/kg administered over a period of 30 minutes by 

intravenous infusion at week 0, week 2, and every 4 weeks thereafter. 

 

Crizanlizumab can be given alone or with HU/HC. 

 

If a dose is missed, the treatment should be administered as soon as possible. 

- If crizanlizumab is administered within 2 weeks after the missed dose, dosing should be 
continued according to the patient’s original schedule. 

- If crizanlizumab is administered more than 2 weeks after the missed dose, dosing should be 
continued every 4 weeks thereafter. 

 



 

3 

Special populations 

Elderly 

Crizanlizumab has not been studied in elderly patients. No dose adjustment is required as the 

pharmacokinetics of crizanlizumab in adults are not affected by age. 

 

Renal impairment 

Based on the population pharmacokinetic (PK) results, no dose adjustment is required in patients with 

mild or moderate renal impairment (see section 5.2). Data from patients with severe renal impairment 

are too limited to draw conclusions on this population. 

 

Hepatic impairment 

The safety and efficacy of crizanlizumab in patients with hepatic impairment have not been 

established. Crizanlizumab is a monoclonal antibody and is cleared via catabolism (i.e. breakdown 

into peptides and amino acids), and a change in dose is not expected to be required for patients with 

hepatic impairment (see section 5.2). 

 

Paediatric population 

The safety and efficacy of crizanlizumab in paediatric patients from 6 months to 16 years have not 

been established. No data are available. 

 

There is no relevant use of crizanlizumab in infants aged less than 6 months for the indication of 

prevention of recurrent vaso-occlusive crises. 

 

Method of administration 

 

Adakveo should be diluted with sodium chloride 9 mg/ml (0.9%) solution for injection or dextrose 5% 

before administration. 

 

The diluted solution must be administered through a sterile, non-pyrogenic 0.2 micron in-line filter by 

intravenous infusion over a period of 30 minutes. It must not be administered by intravenous push or 

bolus. 

 

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. 

Hypersensitivity to Chinese Hamster Ovary (CHO) cell products. 

 

4.4 Special warnings and precautions for use 
 

Traceability 
 

In order to improve the traceability of biological medicinal products, the name and the batch number 

of the administered product should be clearly recorded. 

 

Infusion-related reactions 

 

In clinical studies, infusion-related reactions (defined as occurring within 24 hours) were observed in 

2 patients (1.8%) treated with crizanlizumab 5 mg/kg. Patients should be monitored for signs and 

symptoms of infusion-related reactions, which may include fever, chills, nausea, vomiting, fatigue, 

dizziness, pruritus, urticaria, sweating, shortness of breath or wheezing. In the event of a severe 

reaction, crizanlizumab should be discontinued and appropriate therapy should be instituted. 

 



 

4 

Laboratory test interference: automated platelet counts 

 

Interference with automated platelet counts (platelet clumping) has been observed in patients treated 

with crizanlizumab in clinical studies, in particular when tubes containing EDTA 

(ethylenediaminetetraacetic acid) were used. This may lead to unevaluable or falsely decreased platelet 

counts. There is no evidence that crizanlizumab causes a reduction in circulating platelets or has a 

pro-aggregant effect in vivo. 

 

To mitigate the potential for laboratory test interference, it is recommended to run the test as soon as 

possible (within 4 hours of blood collection) or use citrate tubes. When needed, platelet counts can be 

estimated via a peripheral blood smear. 

 

Excipients with known effect 

 

This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 

“sodium-free”. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Interactions between crizanlizumab and other medicinal products have not been investigated in 

dedicated studies. 

 

Monoclonal antibodies are not metabolised by cytochrome P450 (CYP450) enzymes. Therefore, 

medicinal products that are substrates, inhibitors or inducers of CYP450 are not expected to affect the 

pharmacokinetics of crizanlizumab. In clinical studies, HU/HC had no effect on crizanlizumab 

pharmacokinetics in patients. 

 

No effect on exposure of co-administered medicinal products is expected based on the metabolic 

pathways of monoclonal antibodies. 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

There is a limited amount of data from the use of Adakveo in pregnant women. Based on data from 

animal studies, crizanlizumab has the potential to cause foetal losses when administered to a pregnant 

woman (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Adakveo 

during pregnancy and in woman of childbearing potential not using contraception. 

 

To help determine the effects in pregnant women, healthcare professionals are encouraged to report all 

pregnancy cases and complications during pregnancy (from 105 days prior to the last menstrual period 

onward) to the local representative of the marketing authorisation holder (see package leaflet), in order 

to allow monitoring of these patients through the PRegnancy outcomes Intensive Monitoring 

programme (PRIM). In addition, all adverse pregnancy events should be reported via the national 

reporting system listed in Appendix V. 

 

Breast-feeding 

 

It is unknown whether crizanlizumab is excreted in human milk after administration of Adakveo. 

There are no data on the effects of crizanlizumab on the breast-fed newborn/infant or on milk 

production. 

 

Because many medicinal products, including antibodies, can be excreted in human milk, a risk to the 

newborn/infant cannot be excluded. 

 

A decision must be made whether to discontinue breast-feeding or to discontinue Adakveo therapy, 

taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. 

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5 

 

Fertility 

 

There are no data on the effect of Adakveo on human fertility. Available non-clinical data do not 

suggest an effect on fertility under crizanlizumab treatment (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

Adakveo may have a minor influence on the ability to drive and use machines. Dizziness, fatigue and 

somnolence may occur following administration of crizanlizumab. 

 

4.8 Undesirable effects 
 

Summary of the safety profile 

 

The most frequently reported adverse drug reactions (≥10% of patients) in the Adakveo 5 mg/kg group 

were arthralgia, nausea, back pain, pyrexia and abdominal pain. Severe events were observed for 

pyrexia and arthralgia (each 0.9%). 

 

Tabulated list of adverse reactions 

 

Table 1 lists adverse reactions based on pooled data from two studies: the pivotal study, SUSTAIN, 

and a single-arm, open-label pharmacokinetics/pharmacodynamics and safety study. Use of 

crizanlizumab in combination with HU/HC did not result in any meaningful differences in the safety 

profile. 

 

Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent 

reactions first. Within each frequency grouping, adverse reactions are presented in order of decreasing 

seriousness. In addition, the corresponding frequency category for each adverse reaction is based on 

the following convention: 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). 

 

Table 1 Adverse reactions in clinical studies 
 

System organ class Frequency Adverse reaction 

Respiratory, thoracic and mediastinal 

disorders 

Common Oropharyngeal pain 

Gastrointestinal disorders Very common Nausea, abdominal pain* 

Common Diarrhoea, vomiting 

Skin and subcutaneous tissue 

disorders 

Common Pruritus* 

Musculoskeletal and connective 

tissue disorders 

Very common Arthralgia, back pain 

Common Myalgia, musculoskeletal chest pain 

General disorders and administration 

site conditions 

Very common Pyrexia 

Common Infusion site reaction* 

Injury, poisoning and procedural 

complications 

Common Infusion-related reaction 

*The following groupings contain the following MedDRA preferred terms: 

- Abdominal pain: abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort, 
and abdominal tenderness 

- Pruritus: pruritus and vulvovaginal pruritus 

- Infusion site reaction: infusion site extravasation, infusion site pain, and infusion site swelling 
 



 

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Description of selected adverse reactions 

 

Immunogenicity 

In clinical studies, treatment-induced anti-crizanlizumab antibodies were transiently detected in 

1 patient (0.9%) among the 111 patients who received Adakveo 5 mg/kg. 

 

There was no evidence of altered pharmacokinetics or of an altered safety profile with 

anti-crizanlizumab antibody development. 

 

Paediatric population 

 

Frequency, type and severity of adverse reactions in patients aged 16 and 17 years are expected to be 

the same as in adults. The safety of crizanlizumab was evaluated in 3 patients aged <18 years. 

 

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 
 

No cases of overdose have been reported in clinical studies. 

 

General supportive measures and symptomatic treatment should be initiated in cases of suspected 

overdose. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Other haematological agents, ATC code: B06AX01 

 

Mechanism of action 

 

Crizanlizumab is a selective IgG2 kappa humanised monoclonal antibody (mAb) that binds to 

P-selectin with high affinity and blocks the interaction with its ligands, including P-selectin 

glycoprotein ligand 1. Crizanlizumab can also dissociate preformed P-selectin/PSGL-1 complex. 

P-selectin is an adhesion molecule expressed on activated endothelial cells and platelets. It plays an 

essential role in the initial recruitment of leukocytes and the aggregation of platelets to the site of 

vascular injury during inflammation. In the chronic pro-inflammatory state associated with sickle cell 

disease, P-selectin is over-expressed and circulating blood cells and the endothelium are activated and 

become hyperadhesive. P-selectin-mediated multi-cellular adhesion is a key factor in the pathogenesis 

of vaso-occlusion and vaso-occlusive crises (VOC). Elevated levels of P-selectin are found in patients 

with sickle cell disease. 

 

Binding P-selectin on the surface of the activated endothelium and platelets has been shown to 

effectively block interactions between endothelial cells, platelets, red blood cells and leukocytes, 

thereby preventing vaso-occlusion. 

 

Pharmacodynamic effects 

 

Throughout clinical studies, treatment with crizanlizumab 5 mg/kg resulted in dose-dependent, 

immediate and sustained P-selectin inhibition (as measured ex vivo) in patients with sickle cell disease. 

 

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Clinical efficacy and safety 

 

The efficacy of crizanlizumab, with or without HU/HC, was evaluated in the pivotal study SUSTAIN, 

a 52-week, randomised, placebo-controlled, double-blind, multicentre clinical study in sickle cell 

disease patients with a history of vaso-occlusive crises (VOCs). 

 

In this study, VOCs were defined as those leading to a healthcare visit, which captured all acute 

episodes of pain with no other cause than a vaso-occlusive event that required a healthcare visit and 

treatment with oral or parenteral opioids or parenteral non-steroidal anti-inflammatory drugs 

(NSAIDs). Acute chest syndrome, hepatic sequestration, splenic sequestration and priapism (requiring 

a healthcare visit), by definition, were also considered VOCs. 

 

A total of 198 sickle cell disease patients aged 16 to 63 years (inclusive; mean age 30.1±10.3 years), 

with any sickle cell disease genotype (including HbSS [71.2%], HbSC [16.2%], 

HbSbeta0-thalassaemia [6.1%], HbSbeta+-thalassaemia [5.1%], and others [1.5%]) and a history of 

between 2 and 10 VOCs in the previous 12 months (62.6% and 37.4% of the patients had 2-4 or 

5-10 VOCs, respectively), were randomised 1:1:1 to Adakveo 5 mg/kg, Adakveo 2.5 mg/kg or 

placebo. The majority of patients were Black or African American (91.9%). Patients received 

Adakveo with (62.1%) or without (37.9%) HU/HC. Randomisation was stratified by patients already 

receiving HU/HC (Y/N) and by number of VOCs in the previous 12 months (2 to 4, 5 to 10). Patients 

were allowed to take medicinal products to relieve pain (i.e. paracetamol, NSAIDs and opioids) and to 

receive occasional transfusions on an “as needed” basis. Patients participating in a chronic transfusion 

programme (pre-planned series of transfusions for prophylactic purposes) were excluded from the 

study. 

 

Treatment with Adakveo 5 mg/kg resulted in a 45.3% lower median annual rate of VOCs compared to 

placebo (Hodges-Lehmann, median absolute difference of -1.01 compared with placebo, 95% CI 

[-2.00, 0.00]), which was statistically significant (p=0.010). The median annual rates of uncomplicated 

VOCs (any VOCs as defined above, excluding acute chest syndrome, hepatic sequestration, splenic 

sequestration or priapism) and days hospitalised were 62.9% and 41.8% lower in the Adakveo 

5 mg/kg than in the placebo group, respectively. The VOCs occurring during the study were assessed 

by an independent review committee. 

 

Main efficacy outcomes of the pivotal SUSTAIN study are summarised in Tables 2 and 3. 

 

Table 2 Results from SUSTAIN clinical study in sickle cell disease 
 

Event Adakveo 5 mg/kg 

(N=67) 
(standard median) 

Placebo 

(N=65) 
(standard 

median) 

Change 

vs 

placebo 

Hodges-Lehmann 

median 

difference 
(95% CI) 

p-value 
(Wilcoxon 

rank sum) 

Primary 

endpoint 
Annual rate of 

VOCs 

1.63 2.98 -45.3% -1.01 

(-2.00, 0.00) 

0.010 

Secondary endpoints  

Annual rate of 

days hospitalised 

4.00 6.87 -41.8% 0.00 

(-4.36, 0.00) 

0.450 

Annual rate of 

uncomplicated 

VOCs 

1.08 2.91 -62.9% -1.00 

(-1.98, 0.00) 

- 

The primary (annual rate of VOC leading to healthcare visit) and key secondary (annual rate of days 

hospitalised) endpoints were the only ones formally tested for statistical significance according to protocol. 

 



 

8 

The clinical effect demonstrated in the primary efficacy analysis was supported by multiple 

supplementary analyses including a negative binomial regression on investigator assessments with a 

conservative method to handle missing data due to early discontinuation of treatment based on 

outcomes in the placebo group (RR=0.74, 95% CI=0.52, 1.06). 

 

In the Adakveo 5 mg/kg group, clinically significant reductions in the annual rate of VOCs were 

observed across important subgroups (HU/HC use, 2-4 or 5-10 VOCs in the previous 12 months, and 

HbSS or non-HbSS genotypes; see Table 3). 

 

Table 3 Annual rate of VOCs in patients - subgroup analyses 
 

Subgroup   Adakveo 

5 mg/kg 

(N=67) 
(standard 

median) 

Placebo 

(N=65) 
(standard 

median) 

Change vs 

placebo 

Hodges-Lehmann 

median difference 

(95% CI) 

HU/HC use 

Yes 
n=42 

2.43 

n= 40 

3.58 

-32.1% -1.01 

(-2.44, 0.00) 

No 
n=25 

1.00 

n=25 

2.00 

-50.0% -1.02 

(-2.00, 0.00) 

Number of VOCs 

in previous 

12 months 

2-4 VOCs 
n=42 

1.14 

n=41 

2.00 

-43.0% -0.05 

(-1.56, 0.01) 

5-10 VOCs 
n=25 

1.97 

n=24 

5.32 

-63.0% -2.74 

(-5.00, -0.83) 

Sickle cell 

disease 

genotypes, 

including HbSC 

HbSS 
n=47 

1.97 

n=47 

3.01 

-34.6% -1.01 

(-2.18, 0.00) 

Non-HbSS 
n=20 

0.99 

n=18 

2.00 

-50.5% -1.01 

(-2.01, 0.00) 

 

A greater than two-fold increase in the proportion of patients with no VOC and who completed the 

study was observed in the Adakveo 5 mg/kg group compared to placebo (22% vs 8%; odds ratio [95% 

CI]: 3.57 [1.20, 10.63]). A similar difference was also observed across important subgroups (HU/HC 

use, genotype). 

 

Treatment with Adakveo 5 mg/kg was also associated with a three-fold longer Kaplan-Meier 

estimated median time to first VOC compared with placebo (4.07 vs 1.38 months; HR=0.495, 95% CI: 

0.331, 0.741) (Figure 1) and a two-fold longer median time from randomisation to second VOC 

compared to placebo (10.32 vs 5.09 months; HR=0.534, 95% CI: 0.329, 0.866). 

 



 

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Figure 1 Kaplan-Meier curve of time to first VOC 
 

                                 
 

 

 

 

 

 

Paediatric population 

 

The efficacy of crizanlizumab in patients aged 16 and 17 years is expected to be the same as in adults. 

Three patients (2.7%) aged less than 18 years were treated with crizanlizumab 5 mg/kg in clinical 

studies. 

 

The European Medicines Agency has deferred the obligation to submit the results of studies with 

Adakveo in one or more subsets of the paediatric population in the treatment of sickle cell disease (see 

section 4.2 for information on paediatric use). 

 

Conditional approval 

 

This medicinal product has been authorised under a so-called “conditional approval” scheme. This 

means that further evidence on this medicinal product is awaited. 

 

The European Medicines Agency will review new information on this medicinal product at least every 

year and this SmPC will be updated as necessary. 

 

5.2 Pharmacokinetic properties 
 

Absorption 

 

The median time to reach maximum serum concentration of crizanlizumab (Tmax) was 1.92 hours at 

steady state following intravenous administration of 5 mg/kg over a period of 30 minutes in sickle cell 

disease patients. 

 

Distribution 

 

Crizanlizumab distribution is typical of endogenous human antibodies within the vascular and 

extracellular spaces. The volume of distribution (Vz) was 4.26 litres after a single 5 mg/kg intravenous 

infusion of crizanlizumab in healthy volunteers. 

 

Biotransformation 

 

Antibodies are primarily eliminated via proteolysis by lysosomal enzymes in the liver to small 

peptides and amino acids. 

Adakveo 5 mg/kg  

Placebo 

Number of patients at risk 

P
ro

b
a
b
ili

ty
 o

f 
b
e
in

g
 f
re

e
 f

ro
m

 f
ir
s
t 

V
O

C
 (

%
) 

67 49 41 35 30 26 24 20 18 17 16 15 7 

65 37 23 21 17 13 12 9 8 6 5 4 1 

0 

0 

Time (months) 

100 

90 

80 

70 

60 

50 

40 

30 

20 

10 

0 

0 1 2 3 4 5 6 7 8 9 10 11 12 13 

Adakveo 5 mg/kg  

Placebo 



 

10 

 

Elimination 

 

In healthy volunteers, the mean terminal elimination half-life (T½) was 10.6 days and the mean 

clearance was 11.7 ml/h at crizanlizumab dose level 5 mg/kg. In patients with sickle cell disease, the 

mean elimination T½ during the dosing interval was 7.5 days. 

 

Linearity/non-linearity 

 

The exposure to crizanlizumab (mean Cmax, AUClast, or AUCinf) increased in non-linear manner over 

the dose range of 0.2 to 8 mg/kg in healthy volunteers. 

 

Special populations 

 

Renal impairment 

In a population PK analysis in patients with eGFR ranging from 35 to 202 ml/min/1.73 m2, no 

clinically important differences in the pharmacokinetics of crizanlizumab were found between patients 

with mild or moderate renal impairment and patients with normal renal function. Data from patients 

with severe renal impairment are too limited to draw conclusions on this population (see section 4.2). 

 

Hepatic impairment 

The safety and efficacy of crizanlizumab in patients with hepatic impairment have not been 

established. Crizanlizumab is a monoclonal antibody and is cleared via catabolism (i.e. breakdown 

into peptides and amino acids), and a change in dose is not expected to be required for patients with 

hepatic impairment. 

 

Paediatric population 

Pharmacokinetics in paediatric patients below the age of 16 years have not been investigated. 

 

5.3 Preclinical safety data 
 

Non-clinical data revealed no special hazard for humans based on conventional studies of safety 

pharmacology, tissue cross-reactivity and repeated dose toxicity. 

 

In the 26-week repeated dose toxicity study, administration of crizanlizumab in cynomolgus monkeys 

at dose levels up to 50 mg/kg/dose once every 4 weeks (at least 13.5 times the human clinical 

exposure based on AUC in patients with sickle cell disease at 5 mg/kg once every four weeks) was 

generally well tolerated. There were no primary crizanlizumab-related findings on any endpoint 

evaluated. At 50 mg/kg, minimal to moderate inflammation of the vessels in multiple tissues 

considered to be an antigen-antibody complex reaction (primate antihuman antibody) was observed in 

2 of 10 animals. There was one death attributed to aspiration of gastric contents following a 

peri-infusional reaction mediated by anti-drug-antibody-dependent hypersensitivity. 

 

Pharmacological effects of crizanlizumab on haemodynamic and electrocardiographic parameters in 

the cynomolgus monkey were evaluated in the 26-week repeated dose toxicology study. Respiratory 

rate and neurological parameters were also assessed. There were no crizanlizumab-related effects on 

arterial blood pressure or on heart rate, PR, RR, QRS, QT, and heart rate corrected QT (QTc) intervals 

on the electrocardiograms (ECG). No rhythm abnormalities or qualitative changes were observed 

during the qualitative ECG assessment. There were no crizanlizumab-related effects on respiration rate 

or any neurological parameter evaluated. 

 

Formal carcinogenicity, genotoxicity and juvenile toxicity studies have not been conducted with 

crizanlizumab. 

 



 

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In a 26-week repeated dose toxicity study, cynomolgus monkeys were administered crizanlizumab 

once every 4 weeks at doses up to 50 mg/kg (at least 13.5 times the human clinical exposure based on 

AUC in patients with sickle cell disease at 5 mg/kg once every four weeks). There were no adverse 

effects of crizanlizumab on male and female reproductive organs. 

 

In an enhanced pre- and postnatal development study in cynomolgus monkeys, pregnant animals 

received intravenous crizanlizumab once every two weeks during the period of organogenesis, at doses 

of 10 and 50 mg/kg (approximately 2.8 and 16 times the human clinical exposure based on AUC in 

patients with sickle cell disease at 5 mg/kg/dose once every four weeks, respectively). No maternal 

toxicity was observed. There was an increase in foetal loss (abortions or stillbirths) at both doses and 

this was higher in the third trimester. The cause of the foetal losses in monkeys is unknown but may be 

due to the development of anti-drug antibodies against crizanlizumab. There were no effects on infant 

growth and development during the 6 months postpartum that were attributable to crizanlizumab. 

 

Measurable crizanlizumab serum concentrations were observed in the infant monkeys at postnatal 

day 28, confirming that crizanlizumab, like other IgG antibodies, crosses the placental barrier. 

 

 

6. PHARMACEUTICAL PARTICULARS 
 

6.1 List of excipients 
 

Sucrose 

Sodium citrate (E331) 

Citric acid (E330) 

Polysorbate 80 (E433) 

Water for injections 

 

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 

 

18 months 

 

Diluted solution 

 

Chemical and physical in-use stability, from the start of preparation of the diluted solution for infusion 

until end of infusion, has been demonstrated for up to 8 hours at room temperature (up to 25°C) and at 

2°C to 8°C for up to 24 hours overall. 

 

From a microbiological point of view, the diluted solution for infusion 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°C to 8°C, including 4.5 hours at room 

temperature (up to 25°C) from the start of preparation to completion of the infusion, unless dilution 

has taken place in controlled and validated aseptic conditions. 

 

  



 

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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. 

 

6.5 Nature and contents of container 
 

10 ml concentrate for solution for infusion in a type I glass vial with a coated chlorobutyl rubber 

stopper sealed with an aluminium cap with a plastic flip-off disk containing 100 mg crizanlizumab. 

 

Pack of 1 vial. 

 

6.6 Special precautions for disposal and other handling 
 

Adakveo vials are for single use only. 

 

Preparing the infusion 

 

The diluted solution for infusion should be prepared by a healthcare professional using aseptic 

techniques. 

 

The total dose and required volume of Adakveo depend on the patient’s body weight; 5 mg of 

crizanlizumab is administered per kg body weight. 

 

The volume to be used for the preparation of the infusion is calculated according to the following 

equation: 

 

Volume (ml) = 
Patient’s body weight (kg) x prescribed dose [5 mg/kg] 

Concentration of Adakveo [10 mg/ml] 

 

1. Obtain the number of vials required to deliver the prescribed dose and bring them to room 

temperature (for a maximum of 4 hours). One vial is needed for every 10 ml of Adakveo (see 

below table). 

 

Body weight 

(kg) 

Dose (mg) Volume (ml) Vials (n) 

40 200 20 2 

60 300 30 3 

80 400 40 4 

100 500 50 5 

120 600 60 6 

 

2. Visually inspect the vials. 

- The solution in the vials should be clear to opalescent. Do not use if particles are present 
in the solution. 

- The solution should be colourless or may have a slight brownish-yellow tint. 
 

3. Withdraw a volume equal to the required volume of Adakveo from a 100 ml infusion bag 

containing either sodium chloride 9 mg/ml (0.9%) solution for injection or dextrose 5% and 

discard. 

- No incompatibilities between the diluted Adakveo solution and infusion bags composed 

of polyvinylchloride (PVC), polyethylene (PE) and polypropylene (PP) have been 

observed. 

 



 

13 

4. Withdraw the necessary volume of Adakveo from the vials and inject slowly into the previously 

prepared infusion bag. 

- The solution must not be mixed or co-administered with other medicinal products through 

the same intravenous line. 

- Keep the volume of Adakveo added to the infusion bag in the range of 10 ml to 96 ml to 

obtain a final concentration in the infusion bag within 1 mg/ml to 9.6 mg/ml. 

 

5. Mix the diluted solution by gently inverting the infusion bag. DO NOT SHAKE. 

 

Administration 

 

Adakveo diluted solution must be administered through a sterile, non-pyrogenic 0.2 micron in-line 

filter by intravenous infusion over a period of 30 minutes. No incompatibilities have been observed 

between Adakveo and infusion sets composed of PVC, PE-lined PVC, polyurethane, and in-line filter 

membranes composed of polyethersulfone (PES), polyamide (PA) or polysulphone (PSU). 

 

After administration of Adakveo, flush the line with at least 25 ml sodium chloride 9 mg/ml (0.9%) 

solution for injection or dextrose 5%. 

 

Disposal 

 

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

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 
 

EU/1/20/1476/001 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

 

10. DATE OF REVISION OF THE TEXT 
 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

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

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


 

14 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 

SUBSTANCE(S) AND 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 

 

E. SPECIFIC OBLIGATION TO COMPLETE POST-

AUTHORISATION MEASURES FOR THE CONDITIONAL 

MARKETING AUTHORISATION 



 

15 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 

MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturer(s) of the biological active substance(s) 

 

Novartis Pharma AG 

Lichtstrasse 35 

4056 Basel 

Switzerland 

 

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

 

Novartis Pharma GmbH 

Roonstrasse 25 

90429 Nuremberg 

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 (PSURs) 
 

The requirements for submission of PSURs 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 (MAH) shall submit the first PSUR 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 marketing authorisation holder (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. 

 

 



 

16 

E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 

FOR THE CONDITIONAL MARKETING AUTHORISATION 

 

This being a conditional marketing authorisation and pursuant to Article 14a(4) of Regulation (EC) No 

726/2004, the MAH shall complete, within the stated timeframe, the following measures: 

 

Description Due date 

In order to further investigate the efficacy and safety of crizanlizumab, the MAH 

should submit the results of the primary analysis of a phase III CSEG101A2301 

study of crizanlizumab with or without hydroxyurea/hydroxycarbamide in 

adolescent and adult sickle cell disease patients with vaso-occlusive crises 

Clinical study 

report primary 

analysis: 

December 2025 

In order to further investigate the pharmacokinetics, pharmacodynamics and 

safety of crizanlizumab, the MAH should submit the final results of the phase II 

CSEG101A2202 study of crizanlizumab with or without 

hydroxyurea/hydroxycarbamide in sickle cell disease patients with vaso-occlusive 

crisis 

Clinical study 

report: 

December 2025 

  



 

17 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



 

18 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
  



 

19 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Adakveo 10 mg/ml concentrate for solution for infusion 

crizanlizumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each 10 ml vial contains 100 mg crizanlizumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: sucrose, sodium citrate (E331), citric acid (E330), polysorbate 80 (E433), water for 

injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Concentrate for solution for infusion 

 

1 vial 

100 mg/10 ml 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For intravenous use after dilution. 

Single use. 

Read the package leaflet before 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 

 

 



 

20 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/20/1476/001 

 

 

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 

  



 

21 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL 

 

 

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

 

Adakveo 10 mg/ml sterile concentrate 

crizanlizumab 

IV 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

100 mg/10 ml 

 

 

6. OTHER 

  



 

22 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



 

23 

Package leaflet: Information for the patient 
 

Adakveo 10 mg/ml concentrate for solution for infusion 
crizanlizumab 

 

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 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 or nurse. 
- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 

 

What is in this leaflet 
1. What Adakveo is and what it is used for 

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

3. How Adakveo is given 

4. Possible side effects 

5. How to store Adakveo 

6. Contents of the pack and other information 

 

 

1. What Adakveo is and what it is used for 
 

What Adakveo is 
Adakveo contains the active substance crizanlizumab, which belongs to a group of medicines called 

monoclonal antibodies (mAbs). 

 

What Adakveo is used for 
Adakveo is used to prevent recurrent painful crises occurring in patients aged 16 years and over with 

sickle cell disease. Adakveo can be given in combination with hydroxyurea/hydroxycarbamide, 

although it may also be used alone. 

 

Sickle cell disease is an inherited blood disorder. It causes affected red blood cells to become 

sickle-shaped and have difficulty passing through small blood vessels. Additionally in sickle cell 

disease the blood vessels are damaged and sticky due to ongoing chronic inflammation. This leads to 

blood cells sticking to the blood vessels, causing acute episodes of pain and organ damage. 

 

How Adakveo works 
Patients with sickle cell disease have higher levels of a protein called P-selectin. Adakveo binds 

P-selectin. This should stop blood cells sticking to the vessel walls and help prevent painful crises. 

 

If you have any questions about how Adakveo works or why this medicine has been prescribed for 

you, ask your doctor or nurse. 

 

 

  



 

24 

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

You must not be given Adakveo: 
- if you are allergic to crizanlizumab or any of the other ingredients of this medicine (listed in 

section 6). 

 

Warnings and precautions 
 

Infusion reactions 
Medicines of this type (called monoclonal antibodies) are administered into a vein (intravenously) as 

an infusion. They can cause unwanted reactions (side effects) when they are infused into your body. 

Such reactions may happen within 24 hours of receiving an infusion. 

 

Tell your doctor or nurse immediately if you experience any of the following, which may be signs 

of an infusion reaction: 

- Fever, chills, shivering, nausea, vomiting, tiredness, dizziness, pain where the infusion needle is 
inserted, blisters, itching, shortness of breath or wheezing. See also section 4, “Possible side 

effects”. 

Your doctor or nurse may monitor you for signs and symptoms of such infusion reactions. 

 

Blood tests during Adakveo treatment 
If you need to have any blood tests, tell the doctor or nurse that you are on treatment with Adakveo. 

This is important because this treatment may interfere with a laboratory test used to measure the 

number of platelets in your blood. 

 

Children and adolescents 
Adakveo should not be used in children or adolescents below 16 years of age. 

 

Other medicines and Adakveo 
Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines. 

 

Pregnancy and breast-feeding 
Adakveo has not been tested in pregnant women therefore there is limited information about its safety 

in pregnant women. 

 

If you are pregnant, or are a woman who could become pregnant and is not using contraception, it is 

not recommended to use Adakveo. 

 

It is not known whether Adakveo or its individual ingredients pass into breast milk. 

 

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 receiving this medicine. Your doctor will discuss with you the potential 

risk(s) of Adakveo during pregnancy or breast-feeding. 

 

Driving and using machines 
Adakveo could have a minor effect on your ability to drive and use machines. If you experience 

tiredness, drowsiness or dizziness, do not drive or use machines until you feel better. 

 

Adakveo contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 

“sodium-free”. 

 

 



 

25 

3. How Adakveo is given 
 

Adakveo will be given to you by a doctor or nurse. 

 

If you have any questions about how Adakveo is given, ask the doctor or nurse who is giving you the 

infusion. 

 

Your doctor will tell you when you will have your infusions and follow-up appointments. 

 

How much Adakveo you will be given 
The recommended dose is 5 mg per kilogram of body weight. You will be given the first infusion at 

Week 0 and the second infusion two weeks later (Week 2). After that you will be given an infusion 

every 4 weeks. 

 

How the infusion is given 
Adakveo is administered into a vein (intravenously) as an infusion lasting 30 minutes. 

 

Adakveo can be given alone or with hydroxyurea/hydroxycarbamide. 

 

How long Adakveo treatment lasts 
You should discuss with your doctor how long you will need to receive treatment. Your doctor will 

regularly monitor your condition to check that the treatment is having the desired effect. 

 

If you forget a Adakveo infusion 
It is very important that you receive all your infusions. If you miss an appointment for an infusion, 

contact your doctor as soon as possible to reschedule. 

 

If you stop Adakveo treatment 
Do not stop Adakveo treatment unless your doctor tells you that you can. 

 

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

 

 

4. Possible side effects 
 

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

 

Some side effects could be serious 
Tell the doctor or nurse giving you the infusion immediately if you develop any of the following: 

- Fever, chills, shivering, nausea, vomiting, tiredness, dizziness, pain where the infusion needle is 
inserted, blisters, itching, shortness of breath or wheezing. 

These symptoms can be signs of infusion reaction, which is a common side effect (this means it may 

affect up to 1 in every 10 people). 

 

Other possible side effects 
Other possible side effects include those listed below. If these side effects become severe, tell your 

doctor or nurse. 

 

Very common (may affect more than 1 in 10 people) 
- pain in the joints (arthralgia) 
- nausea 
- back pain 
- fever 
- pain in the lower or upper abdomen, feeling of tenderness in the abdomen and abdominal 

discomfort 

 



 

26 

Common (may affect up to 1 in every 10 people) 
- diarrhoea 
- itching (including vulvovaginal itching) 
- vomiting 
- muscle pain (myalgia) 
- pain in the muscles or bones of the chest (musculoskeletal chest pain) 
- sore throat (oropharyngeal pain) 
- redness or swelling and pain at the site of the infusion 

 

Reporting of side effects 

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 

listed in this leaflet. You can also report side effects directly via the national reporting system listed in 

Appendix V. By reporting side effects you can help provide more information on the safety of this 

medicine. 

 
 

5. How to store Adakveo 
 

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 outer carton and the label after 

“EXP”. The expiry date refers to the last day of that month. 

 

Keep the vial in the outer carton in order to protect from light. Store in a refrigerator (2°C – 8°C). Do 

not freeze. 

 

Infusion solutions should be used immediately after dilution. 

 

 

6. Contents of the pack and other information 
 

What Adakveo contains 
- The active substance is crizanlizumab. Each 10 ml vial contains 100 mg of crizanlizumab. 
- The other ingredients are sucrose, sodium citrate (E331), citric acid (E330), polysorbate 80 

(E433) and water for injections. 

 

What Adakveo looks like and contents of the pack 
Adakveo concentrate for solution for infusion is a colourless to slightly brownish-yellow liquid. 

 

Adakveo is available in packs containing 1 vial. 

 

Marketing Authorisation Holder 
Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 
Novartis Pharma GmbH 

Roonstrasse 25 

90429 Nuremberg 

Germany 

 

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


 

27 

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

Authorisation Holder: 

 

België/Belgique/Belgien 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 

SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел: +359 2 489 98 28 

 

Luxembourg/Luxemburg 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 

Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 88 04 52 555 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 

Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 

Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 



 

28 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 
 

This medicine has been given “conditional approval”. This means that there is more evidence to come 

about this medicine. 

The European Medicines Agency will review new information on this medicine at least every year and 

this leaflet will be updated as necessary. 

 

Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 



 

29 

The following information is intended for healthcare professionals only: 
 

Adakveo vials are for single use only. 

 

Preparing the infusion 

 

The diluted solution for infusion  should be prepared by a healthcare professional using aseptic 

techniques. 

 

The total dose and required volume of Adakveo depend on the patient’s body weight; 5 mg of 

crizanlizumab is administered per kg body weight. 

 

The volume to be used for the preparation of the infusion is calculated according to the following 

equation: 

 

Volume (ml) = 
Patient’s body weight (kg) x prescribed dose [5 mg/kg] 

Concentration of Adakveo [10 mg/ml] 

 

1. Obtain the number of vials required to deliver the prescribed dose and bring them to room 

temperature (for a maximum of 4 hours). One vial is needed for every 10 ml of Adakveo (see 

below table). 

 

Body weight 

(kg) 

Dose (mg) Volume (ml) Vials (n) 

40 200 20 2 

60 300 30 3 

80 400 40 4 

100 500 50 5 

120 600 60 6 

 

2. Visually inspect the vials. 

- The solution in the vials should be clear to opalescent. Do not use if particles are present 
in the solution. 

- The solution should be colourless or may have a slight brownish-yellow tint. 
 

3. Withdraw a volume equal to the required volume of Adakveo from a 100 ml infusion bag 

containing either sodium chloride 9 mg/ml (0.9%) solution for injection or dextrose 5% and 

discard. 

- No incompatibilities between the diluted Adakveo solution and infusion bags composed 

of polyvinylchloride (PVC), polyethylene (PE) and polypropylene (PP) have been 

observed. 

 
4. Withdraw the necessary volume of Adakveo from the vials and inject slowly into the previously 

prepared infusion bag. 

- The solution must not be mixed or co-administered with other medicinal products through 

the same intravenous line. 

- Keep the volume of Adakveo added to the infusion bag in the range of 10 ml to 96 ml to 

obtain a final concentration in the infusion bag within 1 mg/ml to 9.6 mg/ml. 
 

5. Mix the diluted solution by gently inverting the infusion bag. DO NOT SHAKE. 

 

  



 

30 

Storage of the diluted solution 

 

Chemical and physical in-use stability, from the start of preparation of the diluted solution for infusion 

until end of infusion, has been demonstrated for up to 8 hours at room temperature (up to 25°C) and at 

2°C to 8°C for up to 24 hours overall. 

 

From a microbiological point of view, the diluted solution for infusion 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°C to 8°C, including 4.5 hours at room 

temperature (up to 25°C) from the start of preparation to completion of the infusion, unless dilution 

has taken place in controlled and validated aseptic conditions. 

 

Administration 

 

Adakveo diluted solution must be administered through a sterile, non-pyrogenic 0.2 micron in-line 

filter by intravenous infusion over a period of 30 minutes. No incompatibilities have been observed 

between Adakveo and infusion sets composed of PVC, PE-lined PVC, polyurethane, and in-line filter 

membranes composed of polyethersulfone (PES), polyamide (PA) or polysulphone (PSU). 

 

After administration of Adakveo, flush the line with at least 25 ml sodium chloride 9 mg/ml (0.9%) 

solution for injection or dextrose 5%. 

 

Disposal 

 

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

  



 

31 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX IV 

 

CONCLUSIONS ON THE GRANTING OF THE CONDITIONAL MARKETING 

AUTHORISATION PRESENTED BY THE EUROPEAN MEDICINES AGENCY 



 

32 

Conclusions presented by the European Medicines Agency on: 

 

 Conditional marketing authorisation 
 

The CHMP having considered the application is of the opinion that the risk-benefit balance is 

favourable to recommend the granting of the conditional marketing authorisation as further explained 

in the European Public Assessment Report. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 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
	E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES FOR THE CONDITIONAL MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET
	CONCLUSIONS ON THE GRANTING OF THE CONDITIONAL MARKETING AUTHORISATION PRESENTED BY THE EUROPEAN MEDICINES AGENCY