Lamzede

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

Lamzede 10 mg powder for solution for infusion

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One vial contains 10 mg of velmanase alfa*. 
After reconstitution, one mL of the solution contains 2 mg of velmanase alfa (10 mg / 5 mL). 

For the full list of excipients, see section 6.1.

*Velmanase alfa is produced in mammalian Chinese Hamster Ovary (CHO) cells using recombinant 
DNA technology.

3. PHARMACEUTICAL FORM

Powder for solution for infusion.
White to off-white powder.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Enzyme replacement therapy for the treatment of non-neurological manifestations in patients with 
mild to moderate alpha-mannosidosis. See sections  4.4 and 5.1.

4.2 Posology and method of administration

The treatment should be supervised by a physician experienced in the management of patients with 
alpha-mannosidosis or in the administration of other enzyme replacement therapies (ERT) for 
lysosomal storage disorder. Administration of Lamzede should be carried out by a healthcare 
professional with the ability to manage ERT and medical emergencies.

Posology

The recommended dose regimen is 1 mg/kg of body weight administered once every week by 
intravenous infusion at a controlled speed. For infusion rate see section “Method of administration”.

Special populations
Renal or hepatic impairment
No dose adjustment is necessary for patients with renal or hepatic impairment. 

Elderly
No data are available and no relevant use in elderly patients is described. 

Paediatric population 
No dose adjustment is necessary for the paediatric population.



3

Method of administration 

For intravenous infusion use only.

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

The reconstituted solution of Lamzede should be administered using an infusion set equipped with a 
pump and an in-line low protein-binding 0.22 µm filter. The infusion duration should be calculated 
individually considering a maximum infusion rate of 25 mL/hour to control the protein load. The 
infusion duration should be a minimum of 50 minutes. A slower infusion rate may be prescribed when 
clinically appropriate according to the physician’s judgment, for example at the beginning of the 
treatment or in case of previous infusion-related reactions (IRRs).
For the calculation of the infusion rate and the infusion time based on body weight see the table in 
section 6.6.

The patient should be observed for IRRs for at least one hour after the infusion according to clinical 
conditions and the physician’s judgment. For further instructions, see section 4.4. 

4.3 Contraindications

Severe allergic reaction to the active substance or to any of the excipients listed in section 6.1. 

4.4 Special warnings and precautions for use

The effects of treatment with velmanase alfa should be periodically evaluated and discontinuation of 
treatment considered in cases where no clear benefits could be observed.

As the accumulation of end organ damage progresses over time, it is more difficult for the treatment to 
reverse the damage or to show improvements. As with other enzyme replacement therapies, velmanase 
alfa does not cross the blood-brain-barrier. It should be considered by the treating physician that the 
administration of velmanase alfa does not affect the irreversible complications (i.e. skeletal 
deformities, disostosis multiplex, neurological manifestations and impaired cognitive function). 

Hypersensitivity

Hypersensitivity reactions have been reported in patients in clinical studies. Appropriate medical 
support should be readily available when velmanase alfa is administered. If severe allergic or 
anaphylactic-type reactions occur, immediate discontinuation of velmanase alfa is recommended and 
current medical standards for emergency treatment are to be followed.

Infusion-related reaction 

Administration of velmanase alfa may result in an IRR, including anaphylactoid reaction (see 
section 4.8). The IRRs observed in clinical studies of velmanase alfa were characterised by a rapid 
onset of symptoms and were of mild to moderate severity. 

The management of IRRs should be based on the severity of the reaction and includes slowing the 
infusion rate, treatment with medicinal products such as antihistamines, antipyretics and/or 
corticosteroids, and/or stopping and resuming treatment with increased infusion time. Pre-treatment 
with antihistamines and/or corticosteroids may prevent subsequent reactions in those cases where 
symptomatic treatment was required. Patients were not routinely pre-medicated prior to infusion of 
velmanase alfa during clinical studies.

In case symptoms such as angioedema (tongue or throat swelling), upper airway obstruction or 
hypotension occur during or immediately after infusion, anaphylaxis or an anaphylactoid reaction 
should be suspected. In such a case, treatment with an antihistamine and corticosteroids should be 



4

considered as being appropriate. In the most severe cases, the current medical standards for emergency 
treatment are to be observed. 

The patient should be kept under observation for IRRs for one hour or longer after the infusion, 
according to the treating physician’s judgement.

Immunogenicity

Antibodies may play a role in treatment-related reactions observed with the use of velmanase alfa. To 
further evaluate the relationship, in instances of development of severe IRRs or lack or loss of 
treatment effect, patients should be tested for the presence of anti-velmanase alfa antibodies. In case 
the patient’s condition deteriorates during ERT, cessation of treatment should be considered.

There is a potential for immunogenicity. In the clinical studies at any time under treatment, 8 patients 
out of 33 (24%) developed IgG-class antibodies to velmanase alfa. No clear correlation was found 
between antibody titres (velmanase alfa IgG antibody level) and reduction in efficacy or occurrence of 
anaphylaxis or other hypersensitivity reactions. 
The development of antibodies has not been shown to affect clinical efficacy or safety.

Sodium content

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 
‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed. 

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no data from the use of velmanase alfa in pregnant women. Animal studies do not indicate 
direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition 
or postnatal development (see section 5.3). As velmanase alfa aims at normalizing alpha-mannosidase 
in alpha-mannosidosis patients, Lamzede should be used during pregnancy only when strictly needed.

Breast-feeding

It is unknown whether velmanase alfa or its metabolites are excreted in human milk. Nevertheless, the 
absorption of any ingested milk-containing velmanase alfa in the breastfed child is considered to be 
minimal and no untoward effects are therefore anticipated. Lamzede can be used during breastfeeding.

Fertility

There are no clinical data on the effects of velmanase alfa on fertility. Animal studies do not show 
evidence of impaired fertility.

4.7 Effects on ability to drive and use machines

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



5

4.8 Undesirable effects

Summary of the safety profile

The most common adverse reactions observed were weight increase (18%), IRRs (9%), diarrhoea 
(12%), headache (9%), arthralgia (9%), increased appetite (6%) and pain in extremity (6%). 
All of these adverse reactions were non-serious. IRRs include hypersensitivity in 3 patients and 
anaphylactoid reaction in 1 patient. These reactions were non-serious and mild to moderate in 
intensity. 
A total of 2 serious adverse reactions (loss of consciousness in 1 patient and acute renal failure in 
1 patient) were observed. In both cases the patients recovered without sequelae.

Tabulated list of adverse reactions

The adverse reactions reflecting exposure of 33 patients treated with velmanase alfa in clinical studies 
are listed in the table 1 below. Adverse reactions are classified by system organ class and preferred 
term according to the MedDRA frequency convention. Frequency is defined as 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) or not known (cannot be estimated from the available data). 

Table 1: Adverse reactions reported in clinical studies in patients with alpha-mannosidosis 
treated with velmanase alfa

System organ class Adverse reaction Frequency
Hypersensitivity(1) CommonImmune system disorders
Anaphylactoid reaction(1) Common

Metabolism and nutrition disorders Increased appetite Common
Psychotic behaviour CommonPsychiatric disorders
Initial insomnia Common
Confusional state Common
Loss of consciousness(2) Common
Syncope Common
Tremor Common
Dizziness Common

Nervous system disorders

Headache Common
Eye irritation Common
Eyelid oedema Common

Eye disorders

Ocular hyperaemia Common
Cardiac disorders Bradycardia Common
Respiratory, thoracic and 
mediastinal disorders

Epistaxis Common

Diarrhoea Very common
Abdominal pain Common
Abdominal pain upper Common
Nausea(1) Common
Vomiting(1) Common

Gastrointestinal disorders 

Reflux gastritis Common
Urticaria(1) CommonSkin and subcutaneous tissue 

disorders Hyperhidrosis(1) Common
Arthralgia Common
Back pain Common
Joint stiffness Common
Myalgia Common

Musculoskeletal and connective 
tissue disorders

Pain in extremity Common



6

System organ class Adverse reaction Frequency
Renal and urinary disorders Renal failure acute(2) Common

Pyrexia(1) Very common
Catheter site pain Common
Chills(1) Common
Feeling hot(1) Common
Fatigue Common

General disorder and 
administration site conditions

Malaise(1) Common
Investigations Weight increase Very common 
Injury, poisoning and procedural 
complications

Procedural headache Common

(1) Preferred terms considered as IRR as described in the section below 
(2) Selected adverse reaction as described in the section below

Description of selected adverse reactions

Infusion-related reaction
IRRs (including hypersensitivity, nausea, vomiting, pyrexia, chills, feeling hot, malaise, urticaria, 
anaphylactoid reaction and hyperhidrosis) were reported in 9% of the patients (3 out of 33 patients) in 
clinical studies. All were mild or moderate in severity and none were reported as a serious adverse 
event. All patients who experienced IRRs recovered.

Acute renal failure
In the clinical studies, one patient experienced acute renal failure considered possibly related to the 
study treatment. Acute renal failure was of moderate severity leading to temporary discontinuation of 
the study treatment and fully resolved within 3 months. Concomitant long-term treatment with high 
doses of ibuprofen was noted as a potentially causative contributor to the occurrence of the event.

Loss of consciousness
In one patient, loss of consciousness considered related to the study treatment with recovery after a 
few seconds was reported. The patient received saline infusion in a hospital setting and was then 
discharged after 6-hour observation. 
The patient later experienced epileptic seizures that were considered not related. 

Paediatric population

The safety profile of velmanase alfa in clinical studies involving children and adolescents was similar 
to that observed in adult patients. Overall, 58% of patients (19 out of 33) with alpha-mannosidosis 
receiving velmanase alfa in clinical studies were aged 6 to 17 years at the start of the study.

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 with overdose of velmanase alfa. The maximum dose of velmanase alfa in 
clinical studies was a single administration of 100 units/kg (approximately corresponding to 
3.2 mg/kg). During the infusion with this higher dose, fever of mild intensity and short duration 
(5 hours) was observed in one patient. No treatment was administered. 

For the management of adverse reactions, see sections 4.4 and 4.8. 



7

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other alimentary tract and metabolism products, enzymes.
ATC code: A16AB15.

Mechanism of action

Velmanase alfa, the active substance of Lamzede, is a recombinant form of human alpha-mannosidase. 
The amino acid sequence of the monomeric protein is identical to the naturally occurring human 
enzyme, alpha-mannosidase.
Velmanase alfa is intended to supplement or replace natural alpha-mannosidase, an enzyme that 
catalyses the sequential degradation of hybrid and complex high-mannose oligosaccharides in the 
lysosome, reducing the amount of accumulated mannose-rich oligosaccharides. 

Clinical efficacy and safety

A total of 33 patients (20 males and 13 females, ranging in age from 6 to 35 years) were exposed to 
velmanase alfa in five clinical studies. Patients were diagnosed based on alpha-mannosidase activity 
<10% of normal activity in blood leukocytes. Patients with the most severe rapidly progressing 
phenotype (with a deterioration within one year and central nervous system involvement) were 
excluded. Based on this criteria mild to moderate patients, presenting heterogeneous severity with 
ability to perform endurance tests, large variability of clinical manifestations and age of onset were 
enrolled. 

Overall effects of treatment were evaluated in the domains of pharmacodynamics (reduction of serum 
oligosaccharides), functional (three-minute stair climbing test (3MSCT), six-minute walking test 
(6MWT), and forced vital capacity (FVC) % predicted) and quality of life (childhood health 
assessment questionnaire (CHAQ) disability index (DI) and CHAQ VAS pain (visual analogue 
scale)).

In the phase 3 pivotal multi-centre, double-blind, randomised, placebo-controlled, parallel group study 
rhLAMAN-05, the efficacy and safety of repeated administrations of velmanase alfa over 52 weeks at 
a dose of 1 mg/kg given weekly as intravenous infusion were investigated. A total of 25 patients were 
enrolled, including 12 paediatric subjects (age range: 6 to 17 years; mean: 10.9 years) and 13 adult 
subjects (age range: 18 to 35 years; mean: 24.6). All but one patient were naïve to the treatment with 
velmanase alfa. In total 15 patients (7 paediatrics and 8 adults) received active treatment and 
10 patients received placebo (5 paediatrics and 5 adults). The results (serum oligosaccharide 
concentration, 3MSCT, 6MWT and FVC%) are presented in table 2. A pharmacodynamic effect with 
statistically significant decrease of serum oligosaccharides in comparison to placebo was 
demonstrated. The results observed in patients below 18 years of age showed an improvement. In 
patients over 18 years old a stabilisation has been demonstrated. The numerical improvement of most 
clinical endpoints over placebo (2 to 8 %) observed in the year of observation could be suggestive of 
the ability of velmanase alfa to slow down the existing disease progression.



8

Table 2: Results from placebo-controlled clinical study rhLAMAN-05 (source data: 
rhLAMAN-05)

Treatment with 
velmanase alfa for 12 months

(n=15)

Treatment with 
placebo for 12 months

(n=10)

Velmanase alfa 
vs. placebo

Patients Baseline
actual value
Mean (SD)

Absolute 
change from 

baseline
Mean 

Baseline
actual value
Mean (SD)

Absolute 
change from 

baseline
Mean 

Adjusted mean 
difference 

Serum oligosaccharide concentration (μmol/l)
Overall(1)

[95% CI]
p-value

6.8 (1.2) -5.11

[-5.66; -4.56]

6.6 (1.9) -1.61 

[-2.28; -0.94]

-3.50

[-4.37; -2.62] 
p<0.001

<18 years(2) 7.3 (1.1) -5.2 (1.5) 6.0 (2.4) -0.8 (1.7)

≥18 years(2) 6.3 (1.1) -5.1 (1.0) 7.2 (1.0) -2.4 (1.4)

-

3MSCT (steps/min)
Overall(1)

[95% CI]
p-value

52.9 (11.2) 0.46 

[-3.58; 4.50]

55.5 (16.0) -2.16 

[-7.12; 2.80]

2.62 

[-3.81; 9.05]
p=0.406

<18 years(2) 56.2 (12.5) 3.5 (10.0) 57.8 (12.6) -2.3 (5.4)

≥18 years(2) 50.0 (9.8) -1.9 (6.7) 53.2 (20.1) -2.5 (6.2)

-

6MWT (metres)
Overall(1)

[95% CI]
p-value

459.6 (72.26) 3.74 

[-20.32; 27.80]

465.7 (140.5) -3.61 

[-33.10; 25.87]

7.35 

[-30.76; 45.46]
p=0.692

<18 years(2) 452.4 (63.9) 12.3 (43.2) 468.8 (79.5) 3.6 (43.0)

≥18 years(2) 465.9 (82.7) -2.5 (50.4) 462.6 (195.1) -12.8 (41.6)

-

FVC (% of predicted)
Overall(1)

[95% CI]
p-value

81.67 (20.66) 8.20 

[1.79; 14.63]

90.44 (10.39) 2.30 

[-6.19; 10.79]

5.91 

[-4.78; 16.60]
p=0.278

<18 years(2) 69.7 (16.8) 14.2 (8.7) 88.0 (10.9) 8.0 (4.2)

≥18 years(2) 93.7 (17.7) 2.2 (7.2) 92.4 (10.8) -2.8 (15.5)

-

(1) For overall: adjusted mean change and adjusted mean difference estimated by ANCOVA model are 
presented
(2) By age: unadjusted mean and SD are presented.

The long-term efficacy and safety of velmanase alfa was investigated in the uncontrolled, open label, 
phase 3 clinical study rhLAMAN-10 in 33 subjects (19 paediatrics and 14 adults, from 6 to 35 years at 
treatment initiation) who previously participated in velmanase alfa studies. An integrated database was 
created by pooling cumulative databases from all studies with velmanase alfa. Statistically significant 
improvements were detected in serum oligosaccharide levels, 3MSCT, pulmonary function, serum IgG 



9

and EQ-5D-5L (euro quality of life-5 dimensions) over time, up to the last observation (table 3). The 
effects of velmanase alfa were more evident in patients younger than 18 years. 

Table 3: Change of clinical endpoints from baseline to the last observation in rhLAMAN-10 
study (source data: rhLAMAN-10)

Parameter Patients 
n=33

Baseline
actual value

Mean
(SD)

Last 
observation

% change from 
baseline

(SD)

p-value
[95% CI]

Serum oligosaccharide 
concentration (µmol/L)

Overall 6.90
(2.30)

-62.8
(33.61)

<0.001
[-74.7; -50.8]

3MSCT (steps/min) Overall 53.60
(12.53)

13.77
(25.83)

0.004
[4.609; 22.92]

6MWT (metres) Overall 466.6
(90.1)

7.1
(22.0)

0.071
[-0.7; 14.9]

FVC (% of predicted) Overall 84.9
(18.6)

10.5
(20.9)

0.011
[2.6; 18.5]

Data suggest that the beneficial effects of the treatment with velmanase alfa diminish with the increase 
of disease burden and disease-related respiratory infections.

A post-hoc multiparametric responders analysis supports the benefit of longer treatment with 
velmanase alfa in 87.9% of responders in at least 2 domains at last observation (table 4).

Table 4: Multiparametric responder analysis: MCID(1) Responders Rates by Endpoints and 
Domains (source data: rhLAMAN-05; rhLAMAN-10)

Responders Rates
rhLAMAN-05 study

n=25
rhLAMAN-10 study

n=33Domain Criterion
Placebo

12 months
Lamzede 

12 months
Lamzede 

Last Observation
Pharmacodynamic Oligosaccharides 20.0% 100% 91.0%
Pharmacodynamic Domain 
Response Oligosaccharides 20.0% 100% 91.0%

3MSCT 10.0% 20.0% 48.5%
6MWT 10.0% 20.0% 48.5%

Functional

FVC (%) 20.0% 33.3% 39.4%
Functional Domain Response Combined 30.0% 60.0% 72.7%

CHAQ-DI 20.0% 20.0% 42.2%Quality of Life
CHAQ-VAS 33.3% 40.0% 45.5%

QoL Domain Combined 40.0% 40.0% 66.7%
Three domains 0 13.3% 45.5%
Two domains 30.0% 73.3% 42.4%
One domain 30.0% 13.3% 9.1%

Overall response

No domains 40.0% 0 3.0%
(1) MCID: minimal clinically important difference

Paediatric population

Use of velmanase alfa in the age group 6 to 17 years is supported by evidence from clinical studies in 
paediatric (19 out of 33 patients) and adult patients. No clinical data are available in children below 
the age of 6 years. 



10

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

This medicinal product has been authorised under ‘exceptional circumstances’. This means that due to 
the rarity of the disease, it has not been possible to obtain complete information on this medicinal 
product.
The European Medicines Agency will review any new information which may become available every 
year and this SmPC will be updated as necessary.

5.2 Pharmacokinetic properties

There were no apparent pharmacokinetic gender differences in patients with alpha-mannosidosis 
disease. 

Absorption 

Lamzede is administered through intravenous infusion. At steady-state after weekly infusion 
administration of 1 mg/kg of velmanase alfa, the mean maximum plasma concentration was about 
8 µg/mL and was reached at 1.8 hours after the start of administration corresponding to the mean 
infusion duration time. 

Distribution

As expected for a protein of this size, the steady-state volume of distribution was low (0.27 L/kg), 
indicating distribution confined to plasma. The clearance of velmanase alfa from plasma (mean 
6.7 mL/h/kg) is consistent with a rapid cellular uptake of velmanase alfa via mannose receptors.

Biotransformation

The metabolic pathway of velmanase alfa is predicted to be similar to other natural occurring proteins 
that degrade into small peptides and finally into amino acids. 

Elimination

After the end of the infusion, velmanase alfa plasma concentrations fell in a biphasic fashion with a 
mean terminal elimination half-life of about 30 hours. 

Linearity/(Non)linearity

Velmanase alfa exhibited a linear (i.e. first-order) pharmacokinetic profile, and Cmax and AUC 
increased proportionally to the dose with doses ranging from 0.8 to 3.2 mg/kg (corresponding to 25 
and 100 units/kg).

Special populations

Velmanase alfa is a protein and is predicted to be metabolically degraded into amino acids. Proteins 
larger than 50,000 Da, such as velmanase alfa, are not eliminated renally. Consequently hepatic and 
renal impairment are not expected to affect the pharmacokinetic of velmanase alfa. As no patients 
older than 41 years have been identified across Europe, no relevant use in elderly patients is expected. 

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, juvenile toxicity and toxicity to reproduction and development. 



11

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Disodium phosphate dihydrate
Sodium dihydrogen phosphate dihydrate
Mannitol
Glycine

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products.

6.3 Shelf life

3 years.

Reconstituted solution for infusion

Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C - 8°C.
From a microbiological point of view, the medicinal product 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. 

6.4 Special precautions for storage

Store and transport refrigerated (2°C - 8°C).
Store in the original package in order to protect from light.
For storage conditions after reconstitution of the medicinal product, see section 6.3.

6.5 Nature and contents of container

10 mL vial (Type I glass) with a bromobutyl rubber stopper, an aluminium seal and a polypropylene 
flip off cap. 
Each vial contains 10 mg of velmanase alfa. 

Pack sizes of 1, 5 or 10 vials per carton.
Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Lamzede requires reconstitution and is intended for intravenous infusion only. 
Each vial is for single use only. 

Instructions for reconstitution and administration 

Lamzede should be reconstituted and administrated by a healthcare professional.
Aseptic technique is to be used during preparation. Filter needles must not be used during preparation.

a) The number of vials to be used should be calculated based on the individual patient’s weight. 
The recommended dose of 1 mg/kg is determined using the following calculation: 
- Patient’s weight (kg) × dose (mg/kg) = Patient dose (in mg)
- Patient dose (in mg) divided by 10 mg/vial (content of one vial) = number of vials to 

reconstitute. If the number of calculated vials includes a fraction, it should be rounded up 
to the next whole number. 



12

- Approximately 30 minutes prior to reconstitution, the required number of vials should be 
removed from the refrigerator. The vials should reach ambient temperature (between 
15°C and 25°C) prior to reconstitution.

Each vial is reconstituted by slowly injecting 5 mL of water for injections to the inside of the 
wall of each vial. Each mL of reconstituted solution contains 2 mg of velmanase alfa. Only the 
volume corresponding to the recommended dose should be administered.
Example: 
- Patient’s weight (44 kg) × dose (1 mg/kg) = Patient dose (44 mg)
- 44 mg divided by 10 mg/vial = 4.4 vials, therefore, 5 vials should be reconstituted.
- From the total reconstituted volume, only 22 mL (corresponding to 44 mg) should be 

administered.

b) The powder should be reconstituted in the vial by a slow drop-wise addition of the water for 
injections down the inside of the vial and not directly onto the lyophilised powder. Forcefully 
ejecting the water for injections from the syringe onto the powder should be avoided to 
minimise foaming. The reconstituted vials should stand on the table for about 5-10 minutes. 
Thereafter each vial should be tilted and rolled gently for 15-20 seconds to enhance the 
dissolution process. The vial should not be inverted, swirled, or shaken.

c) An immediate visual inspection of the solution for particulate matter and discoloration should 
be performed after reconstitution. The solution should be clear and not used if opaque 
particles are observed or if the solution is discoloured. Due to the nature of the medicinal 
product, the reconstituted solution may occasionally contain some proteinaceous particles in 
form of thin white strands or translucent fibers which will be removed by the in-line filter 
during infusion (see point e). 

d) The reconstituted solution is to be slowly withdrawn from each vial with caution to avoid 
foaming in the syringe. If the volume of the solution exceeds one syringe capacity, the required 
number of syringes should be prepared in order to replace the syringe quickly during the 
infusion. 

e) The reconstituted solution should be administered using an infusion set equipped with a pump 
and an in-line low protein-binding 0.22 μm filter. 
The total volume of infusion is determined by the patient’s weight and should be administrated 
over a minimum of 50 minutes. For patients weighing less than 18 kg, and receiving less than 
9 mL reconstituted solution, the infusion rate should be calculated so that the infusion time is 
≥50 minutes. The maximum infusion rate is 25 mL/hour (see section 4.2). The infusion time can 
be calculated from the following table:

Patient 
weight 
(kg)

Dose 
(mL)

Maximum 
infusion 
rate 
(mL/h)

Minimum 
infusion 
time (min)

Patient 
weight 
(kg)

Dose 
(mL)

Maximum 
infusion 
rate 
(mL/h)

Minimum 
infusion 
time (min)

5 2.5 3 50 53 26.5 25 64
6 3 3.6 50 54 27 25 65
7 3.5 4.2 50 55 27.5 25 67
8 4 4.8 50 56 28 25 67
9 4.5 5.4 50 57 28.5 25 68
10 5 6 50 58 29 25 70
11 5.5 6.6 50 59 29.5 25 71
12 6 7.2 50 60 30 25 72
13 6.5 7.8 50 61 30.5 25 73
14 7 8.4 50 62 31 25 74
15 7.5 9 50 63 31.5 25 76
16 8 9.6 50 64 32 25 77



13

Patient 
weight 
(kg)

Dose 
(mL)

Maximum 
infusion 
rate 
(mL/h)

Minimum 
infusion 
time (min)

Patient 
weight 
(kg)

Dose 
(mL)

Maximum 
infusion 
rate 
(mL/h)

Minimum 
infusion 
time (min)

17 8.5 10.2 50 65 32.5 25 78
18 9 10.8 50 66 33 25 79
19 9.5 11.4 50 67 33.5 25 80
20 10 12 50 68 34 25 82
21 10.5 12.6 50 69 34.5 25 83
22 11 13.2 50 70 35 25 84
23 11.5 13.8 50 71 35.5 25 85
24 12 14.4 50 72 36 25 86
25 12.5 15 50 73 36.5 25 88
26 13 15.6 50 74 37 25 89
27 13.5 16.2 50 75 37.5 25 90
28 14 16.8 50 76 38 25 91
29 14.5 17.4 50 77 38.5 25 92
30 15 18 50 78 39 25 94
31 15.5 18.6 50 79 39.5 25 95
32 16 19.2 50 80 40 25 96
33 16.5 19.8 50 81 40.5 25 97
34 17 20.4 50 82 41 25 98
35 17.5 21 50 83 41.5 25 100
36 18 21.6 50 84 42 25 101
37 18.5 22.2 50 85 42.5 25 102
38 19 22.8 50 86 43 25 103
39 19.5 23.4 50 87 43.5 25 104
40 20 24 50 88 44 25 106
41 20.5 24.6 50 89 44.5 25 107
42 21 25 50 90 45 25 108
43 21.5 25 52 91 45.5 25 109
44 22 25 53 92 46 25 110
45 22.5 25 54 93 46.5 25 112
46 23 25 55 94 47 25 113
47 23.5 25 56 95 47.5 25 114
48 24 25 58 96 48 25 115
49 24.5 25 59 97 48.5 25 116
50 25 25 60 98 49 25 118
51 25.5 25 61 99 49.5 25 119
52 26 25 62

f) When the last syringe is empty, the dosage syringe is replaced with a 20 mL syringe filled with 
sodium chloride 9 mg/mL (0.9%) solution for injection. A volume of 10 mL sodium chloride 
solution should be administered through the infusion system to infuse the remaining fraction of 
Lamzede in the line to the patient.

Disposal

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



14

7. MARKETING AUTHORISATION HOLDER

Chiesi Farmaceutici S.p.A.
Via Palermo 26/A
43122 Parma
Italy

8. MARKETING AUTHORISATION NUMBER

EU/1/17/1258/001
EU/1/17/1258/002
EU/1/17/1258/003

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 23/03/2018

10. DATE OF REVISION OF THE TEXT

{MM/YYYY}

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



15

ANNEX II

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR 
BATCH RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION

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

E. SPECIFIC OBLIGATION TO COMPLETE POST-
AUTHORISATION MEASURES FOR THE MARKETING 
AUTHORISATION UNDER EXCEPTIONAL 
CIRCUMSTANCES



16

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer of the biological active substance

Rentschler Biopharma SE
Erwin-Rentschler-Strasse 21
88471 Laupheim
Germany

Name and address of the manufacturer responsible for batch release

Chiesi Farmaceutici S.p.A.
Via San Leonardo, 96
43122 Parma 
Italy

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

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

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic Safety Update Reports

The 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.



17

E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 
FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL 
CIRCUMSTANCES

This being an approval under exceptional circumstances and pursuant to Article 14(8) of Regulation 
(EC) No 726/2004, the MAH shall conduct, within the stated timeframe, the following measures:

Description Due date
In order to obtain long-term data on effectiveness and safety of treatment with 
Lamzede and to characterize the entire alpha-mannosidosis population, including 
variability of clinical manifestation, progression and natural history, the MAH is 
requested to submit the results of a study based on adequate source of data 
deriving from a registry of patients with alpha-mannosidosis.

Annual reports 
to be submitted 
as part of the 
annual re-
assessment

Paediatric Study rhLAMAN-08. A 24 month multi-center, open label phase II 
trial investigating the safety and efficacy of repeated velmanase alfa (recombinant 
human alpha-mannosidase) treatment in paediatric patients <6 years of age with 
alpha-mannosidosis.

Final Study 
report: 
February 2021



18

ANNEX III

LABELLING AND PACKAGE LEAFLET



19

A. LABELLING



20

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Lamzede 10 mg powder for solution for infusion 
velmanase alfa 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

One vial contains 10 mg of velmanase alfa.
After reconstitution, one mL of the solution contains 2 mg of velmanase alfa (10 mg / 5 mL).

3. LIST OF EXCIPIENTS

Disodium phosphate dihydrate
Sodium dihydrogen phosphate dihydrate
Mannitol
Glycine

4. PHARMACEUTICAL FORM AND CONTENTS

Powder for solution for infusion
1 vial
5 vials
10 vials

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Intravenous 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



21

9. SPECIAL STORAGE CONDITIONS

Store and transport refrigerated.
Store in the original package in order to protect from light.
After reconstitution, the medicinal product should be used immediately. If not used immediately, the 
reconstituted solution should be stored in a refrigerator for no longer than 24 hours.

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

Chiesi Farmaceutici S.p.A. 
Via Palermo 26/A 
43122 Parma 
Italy

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/17/1258/001
EU/1/17/1258/002
EU/1/17/1258/003

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: {number}
SN: {number}
NN: {number}



22

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

VIAL LABEL

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

Lamzede 10 mg powder for solution for infusion 
velmanase alfa 
Intravenous use

2. METHOD OF ADMINISTRATION

Read the package leaflet before use

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

10 mg velmanase alfa

6. OTHER



23

B. PACKAGE LEAFLET



24

Package leaflet: Information for the patient

Lamzede 10 mg powder for solution for infusion
velmanase alfa

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.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor. This includes any possible side effects not listed 

in this leaflet. See section 4.

What is in this leaflet

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

1. What Lamzede is and what it is used for

Lamzede contains the active substance velmanase alfa which belongs to a group of medicines known 
as enzyme replacement therapies. It is used to treat patients with mild to moderate alpha-mannosidosis 
disease. It is given for the treatment of non-neurological symptoms of the disease.

Alpha-mannosidosis disease is a rare genetic disorder caused by a lack of an enzyme named 
alpha-mannosidase, which is needed to break down certain sugar compounds (called ‘mannose-rich 
oligosaccharides’) in the body. When this enzyme is missing or does not work properly, these sugar 
compounds build up inside cells and cause the signs and symptoms of the disease. The typical 
manifestations of the disease include distinctive facial features, mental retardation, difficulty in 
controlling movements, difficulties in hearing and speaking, frequent infections, skeletal problems, 
muscle pain and weakness.

Velmanase alfa is designed to replace the missing enzyme in patients with alpha-mannosidosis 
disease. This may improve the symptoms of the disease.

2. What you need to know before Lamzede is used

Lamzede must not be used:
- if you are allergic to velmanase alfa or any of the other ingredients of this medicine (listed in 

section 6).

Warnings and precautions 
Talk to your doctor before Lamzede is used.



25

If you are treated with Lamzede, you may experience a side effect during or immediately following 
the drip (infusion) used to give the medicine (see section 4). This is known as an infusion-related 
reaction and can sometimes be severe.
- Infusion-related reactions include dizziness, headache, nausea, low blood pressure, tiredness and 

fever. If you experience an infusion-related reaction, you must tell your doctor immediately.
- If you have an infusion-related reaction you may be given additional medicines to treat or help 

prevent future reactions. These medicines may include medicines used to treat allergies 
(antihistamines), medicines used to treat fever (antipyretics) and medicines to control 
inflammation (corticosteroids).

- If the infusion-related reaction is severe, your doctor will stop the infusion immediately and 
start giving you appropriate medical treatment.

- If the infusion-related reactions are severe and/or there is a loss of effect from this medicine, 
your doctor will perform a blood test to check for antibodies that might affect the outcome of 
your treatment.

- Most of the time you can still be given Lamzede even if you experience an infusion-related 
reaction.

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

Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before this medicine is used.

Lamzede should be used during pregnancy only when medically necessary. It is not known whether 
velmanase alfa passes into breast milk. Lamzede can be used during breast-feeding.

Driving and using machines
Lamzede has no or negligible influence on the ability to drive and use machines.

Lamzede contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially 
‘sodium-free’.

3. How Lamzede is used

This medicine is only to be used under the supervision of a doctor experienced in the treatment of 
alpha-mannosidosis or other similar diseases and should only be given by a healthcare professional. 

Dosage
The recommended dose of Lamzede is 1 mg/kg of body weight given once every week. 

Use in children and adolescents
Lamzede may be given to children and adolescents at the same dose and frequency as in adults. There 
is no experience with patients younger than 6 years of age.

Administration
Lamzede is supplied in a vial as a powder for infusion which will be made up with water for injections 
before being given.
Once it has been made up, the medicine will be given by infusion pump (drip) into a vein over a 
period of at least 50 minutes under your doctor’s supervision. 

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



26

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side 
effects occur during the infusion or shortly after (“infusion-related reaction”, see section 2 Warnings 
and precautions).

While under treatment with Lamzede, you may experience some of the following reactions:

Serious side effects

Common side effects (may affect up to 1 in 10 people)
- loss of consciousness (fainting, which may be preceded by feeling dizzy, lightheaded or 

confused)
- acute renal insufficiency (kidney problems which can be recognised from fluid retention, 

swelling in legs, ankles or feet, drowsiness, shortness of breath or fatigue)
- hypersensitivity and serious allergic reaction (symptoms including localised or diffuse skin 

itching, dizziness, difficulty breathing, chest pain, gastrointestinal symptoms such as nausea, 
vomiting, diarrhea or intestinal pain, swelling of the throat, face, lips or tongue)

If you experience any side effect like these, please tell your doctor immediately.

Other side effects

Very common side effects (may affect more than 1 in 10 people)
- diarrhoea
- weight increase
- fever/increased body temperature 

Common side effects (may affect up to 1 in 10 people)
- low heart beat (bradycardia)
- psychotic behaviour (mental illness with hallucinations, difficulty in thinking clearly and 

understanding reality, anxiety), initial difficulty in sleeping
- confused state, fainting, tremor, dizziness, headache
- intestinal (abdominal) pain, irritation of the stomach caused by digestive acids (reflux gastritis), 

nausea, vomiting
- pain at the site the infusion is given, chills, feeling hot, malaise, tiredness (fatigue)
- skin rashes (urticaria), increased sweating (hyperhidrosis) 
- nosebleed
- joint pain, back pain, joint stiffness, muscle pain, pain in extremity (hands, feet)
- eye irritation, eyelid swelling (eyelid oedema), eye redness
- increased appetite

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

5. How Lamzede is stored

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 the carton after ‘EXP’. 
The expiry date refers to the last day of that month.

Store and transport refrigerated (2°C - 8°C).
Store in the original package in order to protect from light.



27

After reconstitution, the medicine should be used immediately. If not used immediately, the 
reconstituted solution may be stored up to 24 hours at 2°C to 8°C.
This medicine must not be used if the reconstituted solution contains opaque particles or is 
discoloured.

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

6. Contents of the pack and other information

What Lamzede contains 
- The active substance is velmanase alfa.

One vial contains 10 mg of velmanase alfa. 
After reconstitution, one mL of the solution contains 2 mg of velmanase alfa (10 mg / 5 mL). 

- The other ingredients are: disodium phosphate dihydrate, sodium dihydrogen phosphate 
dihydrate, mannitol and glycine.

What Lamzede looks like and contents of the pack
Lamzede is a white to off-white powder for solution for infusion, supplied in a glass vial. 
Each carton contains 1, 5 or 10 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder 
Chiesi Farmaceutici S.p.A.
Via Palermo 26/A 
43122 Parma 
Italy

Manufacturer
Chiesi Farmaceutici S.p.A.
Via San Leonardo, 96
43122 Parma 
Italy

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

België/Belgique/Belgien
Chiesi sa/nv 
Tél/Tel: + 32 (0)2 788 42 00 

Lietuva
Chiesi Pharmaceuticals GmbH 
Tel: + 43 1 4073919 

България
Chiesi Bulgaria EOOD 
Teл.: + 359 29201205

Luxembourg/Luxemburg
Chiesi sa/nv 
Tél/Tel: + 32 (0)2 788 42 00

Česká republika
Chiesi CZ s.r.o. 
Tel: + 420 261221745 

Magyarország
Chiesi Hungary Kft. 
Tel.: + 36-1-429 1060 

Danmark
Chiesi Pharma AB 
Tlf: + 46 8 753 35 20 

Malta
Chiesi Farmaceutici S.p.A. 
Tel: + 39 0521 2791 



28

Deutschland
Chiesi GmbH 
Tel: + 49 40 89724-0 

Nederland
Chiesi Pharmaceuticals B.V. 
Tel: + 31 88 501 64 00

Eesti
Chiesi Pharmaceuticals GmbH 
Tel: + 43 1 4073919

Norge
Chiesi Pharma AB 
Tlf: + 46 8 753 35 20

Ελλάδα
Chiesi Hellas AEBE 
Τηλ: + 30 210 6179763 

Österreich
Chiesi Pharmaceuticals GmbH 
Tel: + 43 1 4073919

España
Chiesi España, S.A.U. 
Tel: + 34 93 494 8000

Polska
Chiesi Poland Sp. z.o.o. 
Tel.: + 48 22 620 1421 

France
Chiesi S.A.S. 
Tél: + 33 1 47688899 

Portugal
Chiesi Farmaceutici S.p.A. 
Tel: + 39 0521 2791 

Hrvatska
Chiesi Pharmaceuticals GmbH 
Tel: + 43 1 4073919

România
Chiesi Romania S.R.L. 
Tel: + 40 212023642

Ireland
Chiesi Farmaceutici S.p.A.
Tel: + 39 0521 2791

Slovenija
Chiesi Slovenija d.o.o. 
Tel: + 386-1-43 00 901 

Ísland
Chiesi Pharma AB 
Sími: +46 8 753 35 20 

Slovenská republika
Chiesi Slovakia s.r.o. 
Tel: + 421 259300060 

Italia
Chiesi Farmaceutici S.p.A. 
Tel: + 39 0521 2791

Suomi/Finland
Chiesi Pharma AB 
Puh/Tel: +46 8 753 35 20

Κύπρος
Chiesi Farmaceutici S.p.A. 
Τηλ: + 39 0521 2791 

Sverige
Chiesi Pharma AB 
Tel: +46 8 753 35 20

Latvija
Chiesi Pharmaceuticals GmbH 
Tel: + 43 1 4073919

United Kingdom
Chiesi Ltd 
Tel: + 44 (0)161 488 5555

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

This medicine has been authorised under ‘exceptional circumstances’. This means that because of the 
rarity of this disease it has been impossible to get complete information on this medicine.
The European Medicines Agency will review any new information on this medicine 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. There are also links to other websites about rare diseases and treatments.



29

---------------------------------------------------------------------------------------------------------------------------
The following information is intended for healthcare professionals only.

Lamzede requires reconstitution and is intended for intravenous infusion only. 
Each vial is for single use only.

Instructions for reconstitution and administration 

Lamzede should be reconstituted and administrated by a healthcare professional.
Aseptic technique is to be used during preparation. Filter needles must not be used during preparation.

a) The number of vials to be used should be calculated based on the individual patient’s weight. 
The recommended dose of 1 mg/kg is determined using the following calculation: 
- Patient’s weight (kg) × dose (mg/kg) = Patient dose (in mg)
- Patient dose (in mg) divided by 10 mg/vial (content of one vial) = number of vials to 

reconstitute. If the number of calculated vials includes a fraction, it should be rounded up 
to the next whole number. 

- Approximately 30 minutes prior to reconstitution, the required number of vials should be 
removed from the refrigerator. The vials should reach ambient temperature (between 
15°C and 25°C) prior to reconstitution.

Each vial is reconstituted by slowly injecting 5 mL of water for injections to the inside of the 
wall of each vial. Each mL of reconstituted solution contains 2 mg of velmanase alfa. Only the 
volume corresponding to the recommended dose should be administered.
Example: 
- Patient’s weight (44 kg) × dose (1 mg/kg) = Patient dose (44 mg)
- 44 mg divided by 10 mg/vial = 4.4 vials, therefore, 5 vials should be reconstituted.
- From the total reconstituted volume, only 22 mL (corresponding to 44 mg) should be 

administered.

b) The powder should be reconstituted in the vial by a slow drop-wise addition of the water for 
injections down the inside of the vial and not directly onto the lyophilised powder. Forcefully 
ejecting the water for injections from the syringe onto the powder should be avoided to 
minimise foaming. The reconstituted vials should stand on the table for about 5-10 minutes. 
Thereafter each vial should be tilted and rolled gently for 15-20 seconds to enhance the 
dissolution process. The vial should not be inverted, swirled, or shaken.

c) An immediate visual inspection of the solution for particulate matter and discoloration should 
be performed after reconstitution. The solution should be clear and not used if opaque 
particles are observed or if the solution is discoloured. Due to the nature of the medicinal 
product, the reconstituted solution may occasionally contain some proteinaceous particles in 
form of thin white strands or translucent fibers which will be removed by the in-line filter 
during infusion (see point e). 

d) The reconstituted solution is to be slowly withdrawn from each vial with caution to avoid 
foaming in the syringe. If the volume of the solution exceeds one syringe capacity, the required 
number of syringes should be prepared in order to replace the syringe quickly during the 
infusion. 

e) The reconstituted solution should be administered using an infusion set equipped with a pump 
and an in-line low protein-binding 0.22 μm filter. 
The total volume of infusion is determined by the patient’s weight and should be administrated 
over a minimum of 50 minutes. For patients weighing less than 18 kg, and receiving less than 
9 mL reconstituted solution, the infusion rate should be calculated so that the infusion time is 
≥50 minutes. The maximum infusion rate is 25 mL/hour. The infusion time can be calculated 
from the following table:



30

Patient 
weight 
(kg)

Dose 
(mL)

Maximum 
infusion 
rate 
(mL/h)

Minimum 
infusion 
time (min)

Patient 
weight 
(kg)

Dose 
(mL)

Maximum 
infusion 
rate 
(mL/h)

Minimum 
infusion 
time (min)

5 2.5 3 50 53 26.5 25 64
6 3 3.6 50 54 27 25 65
7 3.5 4.2 50 55 27.5 25 67
8 4 4.8 50 56 28 25 67
9 4.5 5.4 50 57 28.5 25 68
10 5 6 50 58 29 25 70
11 5.5 6.6 50 59 29.5 25 71
12 6 7.2 50 60 30 25 72
13 6.5 7.8 50 61 30.5 25 73
14 7 8.4 50 62 31 25 74
15 7.5 9 50 63 31.5 25 76
16 8 9.6 50 64 32 25 77
17 8.5 10.2 50 65 32.5 25 78
18 9 10.8 50 66 33 25 79
19 9.5 11.4 50 67 33.5 25 80
20 10 12 50 68 34 25 82
21 10.5 12.6 50 69 34.5 25 83
22 11 13.2 50 70 35 25 84
23 11.5 13.8 50 71 35.5 25 85
24 12 14.4 50 72 36 25 86
25 12.5 15 50 73 36.5 25 88
26 13 15.6 50 74 37 25 89
27 13.5 16.2 50 75 37.5 25 90
28 14 16.8 50 76 38 25 91
29 14.5 17.4 50 77 38.5 25 92
30 15 18 50 78 39 25 94
31 15.5 18.6 50 79 39.5 25 95
32 16 19.2 50 80 40 25 96
33 16.5 19.8 50 81 40.5 25 97
34 17 20.4 50 82 41 25 98
35 17.5 21 50 83 41.5 25 100
36 18 21.6 50 84 42 25 101
37 18.5 22.2 50 85 42.5 25 102
38 19 22.8 50 86 43 25 103
39 19.5 23.4 50 87 43.5 25 104
40 20 24 50 88 44 25 106
41 20.5 24.6 50 89 44.5 25 107
42 21 25 50 90 45 25 108
43 21.5 25 52 91 45.5 25 109
44 22 25 53 92 46 25 110
45 22.5 25 54 93 46.5 25 112
46 23 25 55 94 47 25 113
47 23.5 25 56 95 47.5 25 114
48 24 25 58 96 48 25 115
49 24.5 25 59 97 48.5 25 116
50 25 25 60 98 49 25 118



31

Patient 
weight 
(kg)

Dose 
(mL)

Maximum 
infusion 
rate 
(mL/h)

Minimum 
infusion 
time (min)

Patient 
weight 
(kg)

Dose 
(mL)

Maximum 
infusion 
rate 
(mL/h)

Minimum 
infusion 
time (min)

51 25.5 25 61 99 49.5 25 119
52 26 25 62

f) When the last syringe is empty, the dosage syringe is replaced with a 20 mL syringe filled with 
sodium chloride 9 mg/mL (0.9%) solution for injection. A volume of 10 mL sodium chloride 
solution should be administered through the infusion system to infuse the remaining fraction of 
Lamzede in the line to the patient.

Disposal

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


	SUMMARY OF PRODUCT CHARACTERISTICS
	A.	MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B.	CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C.	OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D.	CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	E.	SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL CIRCUMSTANCES
	A. LABELLING
	B. PACKAGE LEAFLET