Strensiq

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Strensiq 40 mg/ml solution for injection 
Strensiq 100 mg/ml solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Strensiq 40 mg/ml solution for injection 
 
Each ml of solution contains 40 mg of asfotase alfa*. 
 
Each vial contains 0.3 ml solution and 12 mg of asfotase alfa (40 mg/ml). 
Each vial contains 0.45 ml solution and 18 mg of asfotase alfa (40 mg/ml). 
Each vial contains 0.7 ml solution and 28 mg of asfotase alfa (40 mg/ml). 
Each vial contains 1.0 ml solution and 40 mg of asfotase alfa (40 mg/ml). 
 
Strensiq 100 mg/ml solution for injection 
 
Each ml of solution contains 100 mg of asfotase alfa*. 
 
Each vial contains 0.8 ml solution and 80 mg of asfotase alfa (100 mg/ml). 
 
* produced by recombinant DNA technology using mammalian Chinese Hamster Ovary (CHO) cell 
culture. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection).  
Clear, colourless to slightly yellow, aqueous solution; pH 7.4. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Strensiq is indicated for long-term enzyme replacement therapy in patients with paediatric-onset 
hypophosphatasia to treat the bone manifestations of the disease (see section 5.1). 
 
4.2 Posology and method of administration 
 
Treatment should be initiated by a physician experienced in the management of patients with 
metabolic or bone disorders. 
 



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Posology 
 
Recommended dosage regimen of asfotase alfa is 2 mg/kg of body weight administered 
subcutaneously three times per week, or a dosage regimen of 1 mg/kg of body weight administered 
subcutaneously six times per week. 
Maximum recommended dose of asfotase alfa is 6 mg/kg/week (see Section 5.1).  
 
Refer to the dosing chart below for more details. 
 

 

 
 
Missed dose 
If a dose of asfotase alfa is missed, a double dose should not be injected to make up for the missed 
dose.  

Body 
Weight 

(kg) 

If injecting 3x per week If injecting 6 x per week 

Dose to be 
injected 

Volume 
to be 

injected 

Vial type 
used for 
injection 

Dose to 
be 

injected 

Volume 
to be 

injected 

Vial type 
used for 
injection 

3 6 mg 0.15 ml 0.3 ml 

  
4 8 mg 0.20 ml 0.3 ml 
5 10 mg 0.25 ml 0.3 ml 
6 12 mg 0.30 ml 0.3 ml 6 mg 0.15 ml 0.3 ml 
7 14 mg 0.35 ml 0.45 ml 7 mg 0.18 ml 0.3 ml 
8 16 mg 0.40 ml 0.45 ml 8 mg 0.20 ml 0.3 ml 
9 18 mg 0.45 ml 0.45 ml 9 mg 0.23 ml 0.3 ml 
10 20 mg 0.50 ml 0.7 ml 10 mg 0.25 ml 0.3 ml 
11 22 mg 0.55 ml 0.7 ml 11 mg 0.28 ml 0.3 ml 
12 24 mg 0.60 ml 0.7 ml 12 mg 0.30 ml 0.3 ml 
13 26 mg 0.65 ml 0.7 ml 13 mg 0.33 ml 0.45 ml 
14 28 mg 0.70 ml 0.7 ml 14 mg 0.35 ml 0.45 ml 
15 30 mg 0.75 ml 1 ml 15 mg 0.38 ml 0.45 ml 
16 32 mg 0.80 ml 1 ml 16 mg 0.40 ml 0.45 ml 
17 34 mg 0.85 ml 1 ml 17 mg 0.43 ml 0.45 ml 
18 36 mg 0.90 ml 1 ml 18 mg 0.45 ml 0.45 ml 
19 38 mg 0.95 ml 1 ml 19 mg 0.48 ml 0.7 ml 
20 40 mg 1.00 ml 1 ml 20 mg 0.50 ml 0.7 ml 
25 50 mg 0.50 ml 0.8 ml 25 mg 0.63 ml 0.7 ml 
30 60 mg 0.60 ml 0.8 ml 30 mg 0.75 ml 1 ml 
35 70 mg 0.70 ml 0.8 ml 35 mg 0.88 ml 1 ml 
40 80 mg 0.80 ml 0.8 ml 40 mg 1.00 ml 1 ml 
50 

  

50 mg 0.50 ml 0.8 ml 
60 60 mg 0.60 ml 0.8 ml 
70 70 mg 0.70 ml 0.8 ml 
80 80 mg 0.80 ml 0.8 ml 
90 90 mg 0.90 ml 0.8 ml (x2) 

100 100 mg 1.00 ml 0.8 ml (x2) 



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Special population 
 
Adult patients 
The pharmacokinetics, pharmacodynamics, and safety of asfotase alfa have been studied in patients 
with hypophosphatasia > 18 years old. Dose adjustment is not needed in adult patients with paediatric-
onset hypophosphatasia (HPP) (see Sections 5.1 and 5.2). 
 
Elderly 
The safety and efficacy of asfotase alfa in elderly patients have not been established and no specific 
dose regimen can be recommended for these patients. 
 
Renal impairment 
The safety and efficacy of asfotase alfa in patients with renal impairment have not been evaluated and 
no specific dose regimen can be recommended for these patients. 
 
Hepatic impairment 
The safety and efficacy of asfotase alfa in patients with hepatic impairment have not been evaluated 
and no specific dose regimen can be recommended for these patients. 
 
Method of administration 
 
Strensiq is for subcutaneous use only. It is not intended for intravenous or intramuscular injection. 
The maximum volume of medicinal product per injection should not exceed 1 ml. If more than 1 ml is 
required, multiple injections may be administered at the same time. 
Strensiq should be administered using sterile disposable syringes and injection needles. The syringes 
should be of small enough volume that the prescribed dose can be withdrawn from the vial with 
reasonable accuracy. 
 
Injections sites should be rotated and carefully monitored for signs of potential reactions (see section 
4.4). 
 
Patients can self-inject only if they have properly been trained on administration procedures. 
For handling of the medicinal product before administration, see section 6.6. 
 
4.3 Contraindications 
 
Severe or life-threatening hypersensitivity to the active substance or to any of the excipients if 
hypersensitivity is not controllable (see section 4.4).   
 
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. 
 
Hypersensitivity 
 
Hypersensitivity reactions including signs and symptoms consistent with anaphylaxis have been 
reported in patients treated with asfotase alfa (see section 4.8). These symptoms included difficulty 
breathing, choking sensation, periorbital edema, and dizziness. The reactions have occurred within 
minutes after subcutaneous administration of asfotase alfa and can occur in patients on treatment for 
more than 1 year. Other hypersensitivity reactions included vomiting, nausea, fever, headache, 
flushing, irritability, chills, skin erythema, rash, pruritus, and oral hypoaesthesia. If these reactions 
occur, immediate discontinuation of treatment is recommended and appropriate medical treatment 
should be initiated. The current medical standards for emergency treatment should be observed. 



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Consider the risks and benefits of re-administering asfotase alfa to individual patients following a 
severe reaction, taking other factors into account that may contribute to the risk of a hypersensitivity 
reaction, such as concurrent infection and/ or use of antibiotics. If the decision is made to re-
administer the product, the re-challenge should be made under medical supervision and consideration 
may be given to use of appropriate pre-medication. Patients should be monitored for recurrence of 
signs and symptoms of a severe hypersensitivity reaction.    
 
The need for supervision for subsequent administrations and need for emergency treatment for home 
care should be at the discretion of the treating physician. 
 
Severe or potentially life-threatening hypersensitivity is a contraindication to re-challenge, if 
hypersensitivity is not controllable (see section 4.3). 
 
Injection reaction 
 
Administration of asfotase alfa may result in local injection site reactions (including, but not limited 
to, erythema, rash, discoloration, pruritus, pain, papule, nodule, atrophy) defined as any related 
adverse event occurring during the injection or until the end of the injection day (see section 4.8). 
Rotation of injection sites may help to minimize these reactions.   
Strensiq administration should be interrupted in any patient experiencing severe injection reactions 
and appropriate medical therapy administered. 
 
Lipodystrophy  
 
Localized lipodystrophy, including lipoatrophy and lipohypertrophy, has been reported at injection 
sites after several months in patients treated with asfotase alfa in clinical trials (see section 4.8). 
Patients are advised to follow proper injection technique and to rotate injection sites (see section 4.2). 
 
Craniosynostosis 
 
In asfotase alfa clinical studies adverse events of craniosynostosis (associated with increased 
intracranial pressure), including worsening of pre-existing craniosynostosis and occurrence of Arnold-
Chiari malformation, have been reported in hypophosphatasia patients < 5 years of age. There are 
insufficient data to establish a causal relationship between exposure to Strensiq and progression of 
craniosynostosis. Craniosynostosis as a manifestation of hypophosphatasia is documented in published 
literature and occurred in 61.3% of patients between birth and 5 years of age in a natural history study 
of untreated infantile-onset hypophosphatasia patients. Craniosynostosis can lead to increased 
intracranial pressure. Periodic monitoring (including fundoscopy for signs of papilloedema) and 
prompt intervention for increased intracranial pressure is recommended in hypophosphatasia patients 
below 5 years of age. 
 
Ectopic calcification 
 
In asfotase alfa clinical studies ophthalmic (conjunctival and corneal) calcification and 
nephrocalcinosis have been reported in patients with hypophosphatasia. There are insufficient data to 
establish a causal relationship between exposure to asfotase alfa and ectopic calcification. Ophthalmic 
(conjunctival and corneal) calcification and nephrocalcinosis as manifestations of hypophosphatasia 
are documented in published literature. Nephrocalcinosis occurred in 51.6% of patients between birth 
and 5 years of age in a natural history study of untreated infantile-onset hypophosphatasia patients. 
Ophthalmology examination and renal ultrasounds are recommended at baseline and periodically in 
hypophosphatasia patients. 
 
Serum Parathyroid Hormone and Calcium 
 
Serum parathyroid hormone concentration may increase in hypophosphatasia patients administered 
asfotase alfa, most notably during the first 12 weeks of treatment. It is recommended that serum 



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parathyroid hormone and calcium be monitored in patients treated with asfotase alfa. Supplements of 
calcium and oral vitamin D may be required. See section 5.1. 
 
Disproportionate weight gain 
 
Patients may display disproportionate weight increase. Dietary supervision is recommended. 
 
Excipients 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. the product is 
essentially ‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed with asfotase alfa. Based on its structure and 
pharmacokinetics, asfotase alfa is unlikely to affect Cytochrome P-450 related metabolism. 
 
Asfotase alfa contains a catalytic domain of tissue non-specific alkaline phosphatase. Administration 
of asfotase alfa will interfere with routine measurement of serum alkaline phosphatase by hospital 
laboratories resulting in serum alkaline phosphatase activity measurements of several thousand units 
per litre. Asfotase alfa activity results must not be interpreted as the same measure as serum alkaline 
phosphatase activity owing to differences in enzyme characteristics. 
 
Alkaline Phosphatase (ALP) is used as the detection reagent in many routine laboratory assays. If 
asfotase alfa is present in clinical laboratory samples, aberrant values could be reported. 
 
The treating physician should inform the testing lab that the patient is treated with medication 
affecting the ALP levels. Alternative assays (i.e. not utilizing an ALP-conjugated reporter system) 
may be considered in patients treated with Strensiq. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are insufficient data from the use of asfotase alfa in pregnant women. 
Following repeated subcutaneous administration to pregnant mice in the therapeutic dose range 
(>0.5 mg/kg), asfotase alfa levels were quantifiable in fetuses at all doses tested, suggesting 
cross-placental transport of asfotase alfa. Animal studies are insufficient with respect to reproductive 
toxicity (see section 5.3). Asfotase alfa is not recommended during pregnancy and in women of 
childbearing potential not using contraception. 
 
Breast-feeding 
 
There is insufficient information on the excretion of asfotase alfa in human milk. A risk to the 
newborns/infants cannot be excluded. 
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from asfotase 
alfa therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy 
for the woman. 
 
Fertility 
 
Preclinical fertility studies were conducted and showed no evidence of effect on fertility and 
embryo-fetal development (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Strensiq has no or negligible influence on the ability to drive and use machines. 



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4.8 Undesirable effects 
 
Summary of the safety profile 
 
Supportive safety data reflect exposure in 112 patients with perinatal/infantile (n=89), juvenile-onset 
(n = 22), adult onset (n = 1) HPP (age at enrollment from 1 day to 66.5 years) treated with asfotase 
alfa, with a treatment duration range from 1 day to 391.9 weeks [7.5 years]). The most common 
adverse reactions observed were injection site reactions (74%). A few case reports of 
anaphylactoid/hypersensitivity reaction have been received 
 
Tabulated list of adverse reactions  
 
Adverse reactions with asfotase alfa are listed by system organ class and preferred term using 
MedDRA frequency 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) and not known (cannot be 
estimated from the available data). Within each frequency grouping, adverse reactions are presented in 
order of decreasing seriousness. 
 
Table 1: Adverse Reactions Reported in clinical trials in hypophosphatasia patients 

System Organ Class Frequency 
category 

Adverse reaction 

Infections and infestations Common Injection site cellulitis 
Blood and lymphatic system 
disorders 

Common Increased tendency to bruise 

Immune system disorders Common 
 

Anaphylactoid reactions  
Hypersensitivity2  

Metabolism and nutrition 
disorders 

Common Hypocalcaemia 

Nervous system disorders Very common Headache 
Vascular disorders Common Hot flush 
Gastrointestinal disorders Common Hypoaesthesia oral 

Nausea 
Skin and subcutaneous 
tissue disorders 

Very common Erythema 
Common Skin discolouration  

Skin disorder (stretched skin) 

Musculoskeletal and 
connective tissue disorders 

Very common Pain in extremity 

Common Myalgia 

Renal and urinary disorders Common Nephrolithiasis 

General disorders and 
administration site 
conditions 

Very common Injection site reactions1 
Pyrexia 
Irritability 

Common Chills 
Injury, poisoning and 
procedural complications 

Very common Contusion 

Common Scar 
1- Preferred terms considered as injection site reactions are presented in section below 
2- Preferred terms considered as hypersensitivity are presented in the section below 

 



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Description of selected adverse reactions 
 
Injection site reactions 
 
Injection site reactions (including injection site atrophy, abscess, erythema, discolouration, pain, 
pruritus, macule, swelling, contusion, bruising, lipodystrophy (lipoatrophy or lipohypertrophy), 
induration, reaction, nodule, rash, papule, haematoma, inflammation, urticarial, calcification, warmth, 
haemorrhage, cellulitis, scar, mass, extravasation, exfoliation and vesicles) are the most common 
adverse reactions observed in about 74% of the patients in clinical studies. Most injection site 
reactions were mild and self-limiting, and the majority (> 99%) were reported as non-serious. In the 
clinical trial setting, the majority of patients who experienced an injection site reaction had the first 
occurrence within the first 12 weeks of treatment with asfotase alfa, and some patients continued to 
experience injection site reactions until 1 or more years after initiating asfotase alfa dosing.  
One patient withdrew from the trial due to injection site hypersensitivity. 
 
Hypersensitivity 
 
Hypersensitivity reactions include erythema/redness, pyrexia/fever, rash, pruritis, irritability, nausea, 
vomiting, pain, rigor/chills, hypoaesthesia oral, headache, flushing, tachycardia, cough, and signs and 
symptoms consistent with anaphylaxis (see section 4.4). A few case reports of 
anaphylactoid/hypersensitivity reaction have also been received and were associated with signs and 
symptoms of difficulty breathing, choking sensation, periorbital edema and dizziness. 
 
Immunogenicity 
 
There is potential for immunogenicity. Among 109 hypophosphatasia patients enrolled in the clinical 
studies and who have post baseline antibody data available, 97/109 (89.0%) tested positive for anti-
drug antibodies at some time point after starting Strensiq treatment. Among those 97 patients, 55 
(56.7%) also showed the presence of neutralizing antibodies at some time point post-baseline. The 
antibody response (with or without presence of neutralizing antibodies) was time variant in nature. In 
clinical trials, the development of antibodies has not been shown to affect clinical efficacy or safety 
(see section 5.2). Data from post-marketing cases suggests that the development of antibodies may 
affect clinical efficacy. 
 
No trends in adverse events based on antibody status were observed in clinical trials. Some patients 
confirmed positive for antidrug antibodies experienced injection site reactions (ISRs) and/or 
hypersensitivity, however there was no consistent trend in the frequency of these reactions over time 
noted between ADA ever positive and ADA always negative patients. 
 
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 limited experience with overdose of asfotase alfa. The maximum dose of asfotase alfa used in 
clinical studies is 28 mg/kg/week. No dose-related toxicity or change in the safety profile has been 
observed in clinical studies. Therefore, no overdose level has been determined. For management of 
adverse reactions, see sections 4.4 and 4.8. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 

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


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Pharmacotherapeutic group: Other alimentary tract and metabolism products, enzymes, ATC code: 
A16AB13 
 
Asfotase alfa is a human recombinant tissue-nonspecific alkaline phosphatase-Fc-deca-aspartate 
fusion protein that is expressed in an engineered Chinese hamster ovary cell line. Asfotase alfa is a 
soluble glycoprotein comprised of two identical polypeptide chains, each with a length of 726 amino 
acids made from (i) the catalytic domain of human tissue-nonspecific alkaline phosphatase, (ii) the 
human immunoglobulin G1 Fc domain and (iii) a deca-aspartate peptide domain. 
 
Hypophosphatasia  
 
Hypophosphatasia is a rare, severe, and potentially fatal, genetic disorder caused by loss-of-function 
mutation(s) in the gene encoding tissue non-specific alkaline phosphatase. Hypophosphatasia is 
associated with multiple bone manifestations including rickets / osteomalacia, altered calcium and 
phosphate metabolism, impaired growth and mobility, respiratory compromise that may require 
ventilation, and vitamin B6-responsive seizures. 
 
Mechanism of action  
 
Asfotase alfa, a human recombinant tissue-nonspecific alkaline phosphatase-Fc-deca-aspartate fusion 
protein with enzymatic activity, promotes mineralisation of the skeleton in patients with 
hypophosphatasia. 
 
Clinical efficacy and safety 
 
Study ENB-006-09/ENB-008-10 
 
Study ENB-006-09/ENB-008-10 was an open-label, randomised study. Thirteen patients were 
enrolled, 12 completed, and 1 discontinued (discontinuation early in the study due to a previously 
planned elective scoliosis surgery).  At study completion patients had received a median of over 
76 months (6.3 years) of treatment (1 to 79 months). Five patients presented with symptoms of 
hypophosphatasia before 6 months age and 8 patients presented after 6 months age. Age at inclusion in 
the study was between 6 and 12 years old and was between 10 and 18 years old at completion, with 
9 patients who became between 13 and 17 years old during the study. 
The study employed historical controls from the same centres as patients who received asfotase alfa 
and who had been subject to a similar protocol of clinical management. 
 
The effects of asfotase alfa on x-ray appearance 
Trained radiologists evaluated pre- and post-baseline x-rays of wrists and knees of patients for the 
following signs: apparent physeal widening, metaphyseal flaring, irregularity of provisional zone of 
calcification, metaphyseal radiolucencies, metadiaphyseal sclerosis, osteopenia, ‘popcorn’ 
calcification in metadiaphysis, demineralization of distal metaphysis, transverse subphyseal band of 
lucency and tongues of radiolucency. X-ray changes from baseline were then rated using the 
Radiographic Global Impression of Change rating scale as follows: -3=severe worsening, -2=moderate 
worsening, -1=minimal worsening, 0=no change, +1=minimal healing, +2=substantial healing, +3= 
near-complete or complete healing. The majority of the patients who received asfotase alfa moved to 
scores of +2 and +3 over the first 6 months of exposure and this was sustained with on-going 
treatment. Historical controls did not show change over time. 
 
Bone biopsy 
Tetracycline for bone-labelling was administered in two 3-day courses (separated by a 14-day interval) 
prior to acquisition of the bone biopsy. Trans-iliac crest bone biopsies were obtained by standard 
procedure. Histological analysis of biopsies used Osteomeasure software (Osteometrics, USA). 
Nomenclature, symbols and units followed recommendations of the American Society for Bone and 
Mineral Research. For 10 patients in the per-protocol set (excludes those patients who received oral 
vitamin D between baseline and week 24) who underwent biopsy of the trans-iliac bone crest before 
and after receiving asfotase alfa: 



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- Mean (SD) osteoid thickness was 12.8 (3.5) µm at baseline and 9.5 (5.1) µm at week 24 
- Mean (SD) osteoid volume / bone volume was 11.8 (5.9)% at baseline and 8.6 (7.2)% at week 

24 
- Mean (SD) mineralisation lag-time was 93 (70) days at baseline and 119 (225) days at week 24 
 
Growth 
Height, weight and head circumference were plotted on growth charts (series of percentile curves that 
illustrate distribution) available from the Centers for Disease Control and Prevention, USA. These 
reference data were drawn from a representative sample of healthy children and are not specific for 
children with special health care needs: they have been used in the absence of growth charts for 
children with hypophosphatasia. 
For those patients who received asfotase alfa: 11/13 patients displayed persistent apparent catch-up 
height-gain as shown by movement over time to a higher percentile on CDC growth charts. 
1/13 patients did not display apparent catch-up height-gain and 1 patient did not have enough data to 
permit judgement. Progress through Tanner stages appeared appropriate. 
For the time period of observation of historical controls: 1/16 patients displayed apparent catch-up 
height-gain, 12/16 patients did not display apparent catch-up height-gain and data were inconclusive in 
3/16 patients. 
Some patients required oral vitamin D supplements during the study (see sections 4.4 and 4.8). 
 
Study ENB-002-08/ENB-003-08  
 
Study ENB-002-08/ENB-003-08 was an open-label, non-randomised, non-controlled study. 
11 patients were enrolled in the initial study and 10 patients entered the extension study, with 
9 patients completing the extension study. At study completion, patients had received a median of over 
79 months (6.6 years) of treatment (1 to >84 months). Onset of hypophosphatasia was under 6 months 
in all patients. Age at treatment initiation in the study was between 0.5 to 35 months. 
7/11 patients in the full analysis set achieved Radiographic Global Impression of Change scores of +2 
at Week 24 compared to baseline radiographs. The improvement in rickets severity was maintained for 
at least 72 months of follow-up treatment (including at least 84 months in 4 patients), as measured by 
the RGI C. 
5/11 subjects displayed apparent catch-up height-gain. At last assessment (n = 10, 9 of whom had at 
least 72 months of treatment), median Z-score improvements from baseline were 1.93 for 
length/height and 2.43 for weight. Fluctuation in height-gain was apparent and may reflect the more 
severe disease and higher rate of morbidity in these younger patients. 
 
Study ENB-010-10 
 
Study ENB-010-10 was a controlled open-label study in 69 patients, aged 1 day to 72 months, with 
perinatal/infantile-onset HPP. The mean age at sign/symptom onset was 1.49 months. Patients 
received STRENSIQ at 6 mg/kg per week for the first 4 weeks. All patients began the study on a dose 
of asfotase alfa 6 mg/kg per week. The dose of asfotase alfa was increased for 11 patients during the 
study. Of these 11 patients, 9 patients had their doses increased specifically to improve clinical 
response. Thirty-eight patients were treated for at least 2 years (24 months) and 6 patients have been 
treated for at least 5 years (60 months).  
At Week 48, 50/69 patients (72.5%) in the full analysis set achieved Radiographic Global Impression 
of Change scores ≥ 2, and were considered responders. Improvements in median RGI-C were 
maintained over the course of treatment, which ranged from 0.9 to 302.3 weeks, even if fewer patients 
were followed after Week 96 (a total of 29 patients were followed after Week 96 and ≤8 patients after 
Week 192). 
Height, weight and head circumference were plotted on growth charts (series of percentile curves that 
illustrate distribution) available from the Centers for Disease Control and Prevention (CDC), USA. A 
total of 24/69 (35%) patients displayed apparent catch-up height-gain and 32/69 (46%) patients 
displayed apparent catch-up weight-gain, as shown by movement over time to a higher percentile on 
CDC growth charts. 40/69 patients and 32/69 patients did not show apparent catch-up gain in height 
and in weight, respectively. 4 patients did not have enough data to permit judgement and 1 patient 
could not be determined with certainty. 



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Study ENB-009-10 
 
Study ENB-009-10 was an open-label, randomised study. The patients were randomly assigned to 
treatment group for the primary treatment period. Nineteen patients were enrolled, 14 completed, and 
5 discontinued.  At study completion patients had received a median of over 60 months of treatment 
(24 to 68 months). The onset of hypophosphatasia was under 6 months in 4 patients, between 6 
months and 17 years in 14 patients, and over 18 years in one patient.  Age at inclusion was from 13 to 
66 years and was between 17 and 72 years at study completion. 
 
The adolescent (and adult) patients in this study did not display apparent height-gain. 
Patients underwent biopsy of the trans-iliac bone crest either as part of a control group or before and 
after exposure to asfotase alfa: 
- Control group, standard of care (5 evaluable patients): mean (SD) mineralisation lag-time was 

226 (248) days at baseline and 304 (211) days at week 24 
- 0.3 mg/kg/day asfotase alfa group (4 evaluable patients): mean (SD) mineralisation lag-time 

was 1236 (1468) days at baseline and 328 (200) days at week 48 
- 0.5 mg/kg/day asfotase alfa group (5 evaluable patients): mean (SD) mineralisation lag-time 

was 257 (146) days at baseline and 130 (142) days at week 48 
After approximately 48 weeks all patients were adjusted to the recommended dose 1.0 mg/kg/day. 
 
Ventilation support 
In studies ENB-002-08/ENB-003-08 (11 patients) and ENB-010-10 (69 patients), both open-label, 
non-randomised, non-controlled studies of patients aged 0.1 to 312 weeks at baseline. 69 patients 
completed the studies, and 11 discontinued. Patients received a median duration of treatment of 
27.6 month (range from 1 day to 90 months). 29 of 80 patients required ventilation support at baseline: 

∙ 16 patients required invasive ventilation support (intubation or tracheostomy) at baseline 
(one had a brief period of non-invasive ventilation at baseline before transfer). 

- 7 patients were weaned off invasive ventilation (time on ventilation from 12 to 
168 weeks), 4 patients were off any ventilation support, and 3 patients were on non-
invasive ventilation support. Five out of 7 patients achieved an RGI-C score ≥2 
- 5 patients continued with invasive ventilation support, 4 of them with RGI-C score 
<2 
- 3 patients died whilst on ventilation support 
- 1 patient withdrew consent 

∙ 13 patients required non-invasive ventilation support at baseline. 
- 10 patients were weaned off any ventilation support (time on ventilation from 3 to 
216 weeks). 9 out of 10 patients achieved a RGI-C score ≥2, only 1 with RGI-C <2.  
- 2 patients required invasive ventilation support and 1 patient continued with non-
invasive ventilation support, all 3 patients died and with RGI-C score <2  

The natural history of untreated infant hypophosphatasia patients suggests high mortality if ventilation 
is required. 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Strensiq in one or more subsets of the paediatric population in hypophosphatasia (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. 
 



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5.2 Pharmacokinetic properties 
 
Pharmacokinetics of asfotase alfa were evaluated in a 1-month, multicenter, open-label, dose-
escalating, study in adults with hypophosphatasia. Cohort 1 (n=3) of the study received asfotase alfa 
3 mg/kg intravenously the first week followed by 3 doses at 1 mg/kg subcutaneous at weekly intervals 
from weeks 2 to 4. Cohort 2 (n=3) received asfotase alfa 3 mg/kg intravenously the first week 
followed by 3 doses at 2 mg/kg subcutaneous at weekly intervals from weeks 2 to 4. After the 3 mg/kg 
for 1.08 hours intravenous infusion, the median time (Tmax) ranged between 1.25 to 1.50 hours, and the 
mean (SD) Cmax ranged between 42694 (8443) and 46890 (6635) U/L over the studied cohorts. The 
absolute bioavailability after the first and third subcutaneous administration ranged from 45.8 to 
98.4%, with median Tmax ranging between 24.2 to 48.1 hours. After the 1 mg/kg weekly subcutaneous 
administration in Cohort 1 the mean (SD) AUC over the dosing interval (AUCτ) was 66034 (19241) 
and 40444 (N=1) U*h/L following the first and the third dose, respectively. After the 2 mg/kg weekly 
subcutaneous administration in Cohort 2 the mean (SD) AUCτ was 138595 (6958) and 136109 
(41875) following the first and the third dose, respectively. 
 
Pharmacokinetic data from all asfotase alfa clinical trials were analysed using population 
pharmacokinetic methods. The pharmacokinetic variables characterized by population 
pharmacokinetic analysis represent the overall hypophosphatasia patient population with age range 
from 1 day to 66 years, subcutaneous doses of up to 28 mg/kg/week and a range of disease onset 
cohorts. Twenty five percent (15 out of 60) of the overall patient population was adult (>18 years) at 
baseline. The absolute bioavailability and absorption rate following subcutaneous administration were 
estimated to be 0.602 (95% CI: 0.567, 0.638) or 60.2% and 0.572 (95%CI: 0.338, 0.967)/day or 
57.2%, respectively. The central and peripheral volumes of distribution estimates for a patient with 
body weight of 70 kg (and 95% CI) were 5.66 (2.76, 11.6) L and 44.8 (33.2, 60.5) L, respectively. The 
central and peripheral clearance estimates for a patient with body weight of 70 kg (and 95% CI) were 
15.8 (13.2, 18.9) L/day and 51.9 (44.0, 61.2) L/day, respectively. The extrinsic factors affecting 
asfotase alfa pharmacokinetic exposures were formulation specific activity and total sialic acid 
content. The average ± SD elimination half-life following subcutaneous administration was 2.28 ± 
0.58 days. 
In adult patients with pediatric-onset HPP, the pharmacokinetics of asfotase alfa at doses of 0.5, 2 and 
3 mg/kg administered three times per week was consistent with those observed in pediatric patients 
with pediatric-onset HPP, and thus supported the approved dose of 6 mg/kg per week in treating adult 
patients with pediatric-onset HPP. 
 
Linearity/non-linearity 
 
Based on the results of population pharmacokinetic analysis it was concluded that asfotase alfa 
exhibits linear pharmacokinetic up to subcutaneous doses of 28 mg/kg/week. The model identified 
body weight to affect asfotase alfa clearance and volume of distribution parameters. It is expected that 
pharmacokinetic exposures will increase with body weight. The impact of immunogenicity on asfotase 
alfa pharmacokinetic varied over time due to the time varying nature of immunogenicity and overall 
was estimated to decrease pharmacokinetic exposures by less than 20%. 
 
5.3 Preclinical safety data 
 
In nonclinical safety testing in rats, no body system-specific adverse effects were noted at any dose or 
route of administration. 
 
Dose - and time-dependent acute injection reactions that were transient and self-limiting were noted in 
rats at intravenous use doses of 1 to 180 mg/kg. 
 
Ectopic calcifications and injection site reactions were observed in monkeys when asfotase alfa was 
administered subcutaneously at daily doses up to 10 mg/kg through 26 weeks. These effects were 
restricted to injection sites and were partially or completely reversible. 
There was no evidence of ectopic calcification observed in any other tissues examined. 
 



13 

 

Preclinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity or toxicity to reproduction and development. However, in 
pregnant rabbits administered intravenous doses of up to 50 mg/kg/day asfotase alfa, anti-drug 
antibodies were detected in up to 75% of animals which could affect the detection of reproductive 
toxicity. 
 
No animal studies have been conducted to evaluate the genotoxic and carcinogenic potential of 
asfotase alfa. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium chloride 
Sodium phosphate dibasic heptahydrate 
Sodium phosphate monobasic monohydrate 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
2 years 
 
Chemical and physical in-use stability has been demonstrated for up to 3 hours at a temperature 
between 23°C to 27°C. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C). 
Do not freeze. 
Store in the original package in order to protect from light. 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Type I glass vial with a stopper (butyl rubber) and a seal (aluminium) with a flip-off cap 
(polypropylene). 
 
Strensiq 40 mg/ml solution for injection 
 
Filled volumes of the vials are: 0.3 ml, 0.45 ml, 0.7 ml and 1.0 ml 
 
Strensiq 100 mg/ml solution for injection 
 
Filled volumes of the vials are: 0.8 ml 
 
Pack sizes of 1 or 12 vials 
Not all pack sizes may be marketed. 
 



14 

 

6.6 Special precautions for disposal and other handling 
 
Each vial is intended for single use only and should only be punctured once. Any unused solution in 
the vial should be discarded. 
 
Strensiq should be administered using sterile disposable syringes and injection needles. The syringes 
should be of small enough volume that the prescribed dose can be withdrawn from the vial with 
reasonable accuracy. An aseptic technique should be used. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Alexion Europe SAS 
103-105 rue Anatole France 
92300 Levallois-Perret 
France 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
Strensiq 40 mg/ml solution for injection 
 
EU/1/15/1015/001 
EU/1/15/1015/002 
EU/1/15/1015/005 
EU/1/15/1015/006 
EU/1/15/1015/007 
EU/1/15/1015/008 
EU/1/15/1015/009 
EU/1/15/1015/010 
 
Strensiq 100 mg/ml solution for injection 
 
EU/1/15/1015/003 
EU/1/15/1015/004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
28/08/2015 
 
 
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.  
 
 

  



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 
 
Lonza Biologics 
101 International Drive 
Pease International Tradeport 
03801 Portsmouth 
United States 
 
Name and address of the manufacturer responsible for batch release 
 
Alexion Pharma International Operations Unlimited Company 
College Business and Technology Park, Blanchardstown 
Dublin 15 
Ireland 
 
 
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. 
 
 
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.  

 
• Additional risk minimisation measures 
 
Prior to launch of Strensiq in each Member State the Marketing Authorisation Holder (MAH) must 
agree about the content and format of the educational programme, including communication media, 



17 

 

distribution modalities, and any other aspects of the programme, with the National Competent 
Authority.  
The educational programme is aimed to provide instruction to patients and carers for proper 
administration techniques to address the risks of medication errors and injection site and injection 
associated reactions, including hypersensitivity. 
The MAH shall ensure that in each Member State where Strensiq is marketed all patients/parents or 
caregivers who are expected to use Strensiq are provided with the following educational package: 

• Self-injection guide for patients 
• Injection guide for parents or caregivers with infant patients 

 
Educational materials for patients and caregivers shall contain the following key messages: 

• Warning and precautions on the potential risk of medication errors and injection site 
reactions associated with the use of Strensiq 

• Hypersensitivity reactions have been observed in patients treated with Strensiq, including a 
description of sign and symptoms 

• Instructions on the correct dose to be administered 
• Instruction on how the injection site is chosen and how the injection is carried out and 

recorded 
• Detailed description on how Strensiq is injected using aseptic techniques  
• Information on cold chain management for Strensiq during storage and travel 
• Information on reporting side effect 

 
 

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

 
This being a marketing authorisation under exceptional circumstances and pursuant to Article 14(8) of 
Regulation (EC) No 726/2004, the MAH shall complete, within the stated timeframe, the following 
measures: 
 
Description Due date 
The MAH should set up an observational, longitudinal, prospective, long-term registry of 
patients with HPP to collect information on the epidemiology of the disease, including 
clinical outcomes and quality of life, and to evaluate safety and effectiveness data in 
patients treated with Strensiq. 

Annually within 
annual 

reassessment 

  



18 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX III 

 
LABELLING AND PACKAGE LEAFLET 

  



19 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



20 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 40 mg/ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Strensiq 40 mg/ml solution for injection  
asfotase alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of solution contains 40 mg of asfotase alfa. 
Each vial contains 12 mg of asfotase alfa (12 mg/0.3 ml). 
Each vial contains 18 mg of asfotase alfa (18 mg/0.45 ml). 
Each vial contains 28 mg of asfotase alfa (28 mg/0.7 ml). 
Each vial contains 40 mg of asfotase alfa (40 mg/1 ml). 
 
 
3. LIST OF EXCIPIENTS 
 
List of excipients: Sodium chloride, sodium phosphate dibasic heptahydrate, sodium phosphate 
monobasic monohydrate, water for injections. 
 
See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 vial of 0.3[0.45; 0.7; 1] ml 
12 vials of 0.3[0.45; 0.7; 1] ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous 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 
 
 



21 

 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
Do not freeze.  
Store in the original pack 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 
 
Any unused solution should be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Alexion Europe SAS 
103-105 rue Anatole France 
92300 Levallois-Perret 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1015/001  
EU/1/15/1015/002  
EU/1/15/1015/005  
EU/1/15/1015/006  
EU/1/15/1015/007  
EU/1/15/1015/008 
EU/1/15/1015/009 
EU/1/15/1015/010  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 



22 

 

16. INFORMATION IN BRAILLE 
 
STRENSIQ 40 mg/ml 
12 mg/0.3 ml 
18 mg/0.45 ml 
28 mg/0.7 ml 
40 mg/1 ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC {number}  
SN {number}  
NN {number}  
  



23 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 40 mg/ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Strensiq 40 mg/ml injection  
Strensiq 40 mg/ml injection  
Strensiq 40 mg/ml injection  
Strensiq 40 mg/ml injection  
asfotase alfa 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 
12 mg/0.3 ml 
18 mg/0.45 ml 
28 mg/0.7 ml 
40 mg/1 ml 
 
 
  



24 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 100 mg/ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Strensiq 100 mg/ml solution for injection  
asfotase alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of solution contains 100 mg of asfotase alfa. 
Each vial contains 80 mg of asfotase alfa (80 mg/0.8 ml) 
 
 
3. LIST OF EXCIPIENTS 
 
List of excipients: Sodium chloride, sodium phosphate dibasic heptahydrate, sodium phosphate 
monobasic monohydrate, water for injections 
 
See package leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection. 
1 vial of 0.8 mL 
12 vials of 0.8 mL 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous 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 
 
 



25 

 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
Do not freeze.  
Store in the original pack 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 
 
Any unused solution should be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Alexion Europe SAS 
103-105 rue Anatole France 
92300 Levallois-Perret 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1015/003 
EU/1/15/1015/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
STRENSIQ 100 mg/ml 
80 mg/0.8 ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC {number}  
SN {number}  



26 

 

NN {number}  
  



27 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 100 mg/ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Strensiq 100 mg/ml injection  
asfotase alfa 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 
80 mg/0.8 ml 
 
 
  



28 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



29 

 

Package leaflet: Information for the user 
 

Strensiq 40 mg/ml solution for injection 
(12 mg/0.3 ml 18 mg/0.45 ml 28 mg/0.7 ml 40 mg/1 ml) 

asfotase 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, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Strensiq is and what it is used for  
2. What you need to know before you use Strensiq  
3. How to use Strensiq  
4. Possible side effects  
5. How to store Strensiq  
6. Contents of the pack and other information 
 
 
1. What Strensiq is and what it is used for 
 
What is Strensiq 
Strensiq is a medicine used to treat the inherited disease hypophosphatasia that started in childhood. It 
contains the active substance asfotase alfa. 
 
What is hypophosphatasia 
Patients with hypophosphatasia have low levels of an enzyme called alkaline phosphatase that is 
important for various body functions, including the proper hardening of bones and teeth. Patients have 
problems with bone growth and strength, which can lead to broken bones, bone pain, and difficulty 
walking, as well as difficulties with breathing and a risk of seizures (fits). 
 
What is Strensiq used for 
The active substance in Strensiq can replace the missing enzyme (alkaline phosphatase) in 
hypophosphatasia. It is used for long-term enzyme replacement treatment to manage symptoms. 
 
What benefits of Strensiq have been shown in clinical studies 
Strensiq has shown benefits for patients’ mineralization of the skeleton and growth. 
 
 
2. What you need to know before you use Strensiq  
 
Do not use Strensiq 
If you are severely allergic to asfotase alfa (see section ‘Warnings and precautions’ below) or any of 
the other ingredients of this medicine (listed in section 6).  
 



30 

 

Warnings and precautions  
Talk to your doctor before using Strensiq. 
• Patients receiving asfotase alfa have had allergic reactions including life threatening allergic 

reactions requiring medical treatment similar to anaphylaxis. Patients who experienced 
anaphylaxis-like symptoms had difficulty breathing, choking sensation, nausea, swelling around 
the eyes, and dizziness. The reactions occurred within minutes after taking asfotase alfa, and can 
occur in patients who were taking asfotase alfa for more than one year. If you experience any of 
these symptoms, discontinue Strensiq and seek medical help immediately. 
Should you experience anaphylactic reaction, or an event with similar symptoms, your doctor 
will discuss with you the next steps and the possibility to restart Strensiq under medical 
supervision. Always follow the instructions provided by your doctor.    

• The development of blood proteins against Strensiq, also called anti-drug antibodies, may occur 
during the treatment. Talk to your doctor if you experience decreased efficacy with Strensiq. 

• Fatty lumps or decreased fatty tissue on the surface of the skin (localized lipodystrophy) have 
been reported at injection sites after several months in patients using Strensiq. Read section 3 
carefully to know the injection recommendations. This is important to rotate the injection from 
among the following sites to reduce the risk of lipodystrophy: abdominal area, thigh, or deltoid. 

• In studies, some eye-related side-effects (e.g. calcium build-up on the eye [conjunctival and 
corneal calcification]) have been reported both in patients using Strensiq and those who were 
not, probably associated with hypophosphatasia. Talk to your doctor in case of problems with 
your vision. 

• Early fusion of the bones of the head (craniosynostosis) in children below 5 years of age has 
been reported in clinical studies of infants with hypophosphatasia, with and without use of 
Strensiq. Talk to your doctor if you notice any change in the shape of your infant’s head. 

• If you are treated with Strensiq, you may experience a reaction at the injection site (pain, 
nodule, rash, discoloration) during the injection of the medicine or during the hours following 
the injection. If you experience any severe reaction at the injection site, tell your doctor 
immediately. 

• Increase of parathyroid hormone concentration and low calcium levels have been reported in 
studies. As a consequence, your doctor may ask you to take supplements of calcium and oral 
vitamin D if needed.  

• Weight gain may occur during your treatment with Strensiq. Your doctor will provide dietary 
advice as necessary. 

 
Other medicines and Strensiq 
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. 
 
If you need to undergo laboratory tests (giving blood for testing), tell your doctor that you are treated 
with Strensiq. Strensiq may cause some tests to show wrongly higher or lower results. Therefore, 
another type of test may need to be used if you are treated with Strensiq.   
 
Pregnancy  
Strensiq should not be used during pregnancy. The use of effective birth control during treatment 
should be considered in women who are able to get pregnant.  
 
Breast-feeding  
It is not known whether Strensiq can pass into breast milk. Tell your doctor if you are breast-feeding 
or plan to do so. Your doctor will then help you decide whether to stop breast-feeding, or whether to 
stop taking Strensiq, considering the benefit of breast-feeding to the baby and the benefit of Strensiq to 
the mother. 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Driving and using machines 
This medicine is not expected to have any effect on the ability to drive or use machines. 



31 

 

 
Important information about some of the ingredients of Strensiq 
This medicine contains less than 1 mmol sodium (23 mg) per vial, which means it is essentially 
‘sodium-free’. 
 
 
3. How to use Strensiq 
 
Always use this medicine exactly as described in this leaflet or as your doctor, or pharmacist or nurse 
has told you. Check with your doctor, pharmacist or nurse if you are not sure. 
How to use Strensiq will be explained to you by a doctor who is experienced in the management of 
patients with metabolic or bone related diseases. After being trained by the doctor or specialized nurse, 
you can inject Strensiq yourself at home. 
 
Dose 
• The dose you receive is based on your body weight. 
• The correct dose will be calculated by your doctor and consists of a total of 6 mg of asfotase 

alfa per kg of body weight every week, given either as an injection of 1 mg/kg asfotase alfa 6 
times per week or as 2 mg/kg asfotase alfa 3 times per week depending on the recommendation 
of your doctor. Each dose will be administered by injection under the skin (subcutaneous), (see 
the dosing chart below for detailed information on the volume to be injected, and the type of 
vials to be used, based on your weight).  

• Doses will need to be adjusted regularly by your doctor as the body weight changes. 
• The maximum volume per injection should not exceed 1 ml. If more than 1 ml is required, you 

need to do multiple injections immediately one after the other. 
 
 



32 

 

If injecting 3 x per week 
 

Body 
Weight 
(kg) 

Volume 
to be 

injected 

Color code 
of the vial 
to be used 

3 0.15 ml Dark blue  
4 0.20 ml Dark blue  
5 0.25 ml Dark blue  
6 0.30 ml Dark blue  
7 0.35 ml Orange 
8 0.40 ml Orange 
9 0.45 ml Orange 
10 0.50 ml Light blue 
11 0.55 ml Light blue 
12 0.60 ml Light blue 
13 0.65 ml Light blue 
14 0.70 ml Light blue 
15 0.75 ml Pink 
16 0.80 ml Pink 
17 0.85 ml Pink 
18 0.90 ml Pink 
19 0.95 ml Pink 
20 1 ml Pink 
25 0.50 ml Green 
30 0.60 ml Green 
35 0.70 ml Green 
40 0.80 ml Green 

If injecting 6 x per week 
 

Body 
Weight 
(kg) 

Volume 
to be 

injected 

Color code 
of the vial 
to be used 

6 0.15 ml Dark blue 
7 0.18 ml Dark blue  
8 0.20 ml Dark blue  
9 0.23 ml Dark blue  
10 0.25 ml Dark blue  
11 0.28 ml Dark blue  
12 0.30 ml Dark blue  
13 0.33 ml Orange 
14 0.35 ml Orange 
15 0.38 ml Orange 
16 0.40 ml Orange 
17 0.43 ml Orange 
18 0.45 ml Orange 
19 0.48 ml Light blue 
20 0.50 ml Light blue 
25 0.63 ml Light blue 
30 0.75 ml Pink 
35 0.88 ml Pink 
40 1 ml Pink 
50 0.50 ml Green 
60 0.60 ml Green 
70 0.70 ml Green 
80 0.80 ml Green 
90 0.90 ml Green (x2) 

100 1 ml Green (x2) 
 
 
Injection recommendations 
• You may experience a reaction at the injection site. Read section 4 carefully to know what side 

effects can occur before using this medicine 
• When injecting regularly, the injection site should be changed between different areas of the 

body to help reduce potential pain and irritation 
• Areas with a good amount of fat below the skin (thighs, arms (deltoids), abdomen, and buttocks) 

are the most suitable areas to inject. Please discuss with you doctor or nurse the best sites for 
you.  

 
Before injecting Strensiq, please read the following instructions carefully 
• Each vial is for single use and should only be punctured once. Only clear and colourless to 

slightly yellow aqueous solution without visible signs of deterioration should be used. Any 
unused medicinal product or waste material should be disposed of immediately. 



33 

 

• If you are injecting this medicine yourself, you will be shown how to prepare and inject the 
medicine by your doctor, pharmacist or nurse. Do not inject this medicine yourself unless you 
have received training and you understand the procedure. 

 
How to inject Strensiq 
 
Step 1: Preparing the Strensiq dose 
 

1. Wash your hands thoroughly with soap and water. 
2. Take the unopened Strensiq vial(s) out of the refrigerator 15 to 30 minutes before injecting to 

allow the liquid to reach room temperature. Do not warm Strensiq in any other way (for 
example, do not warm it in a microwave or in hot water). Upon Removal of the vial(s) from 
refrigeration, Strensiq should be used within 3 hours maximum (see section 5. How to store 
Strensiq). 

3. Remove the protective cap from the Strensiq vial. Remove the protective plastic from the 
syringe to be used.  

4. Always use a new syringe contained in a protective plastic. 
5. Place a larger bore needle (e.g. 25G) on the empty syringe and with the protective cap on, 

push down and turn clockwise the needle onto the syringe until it is tight. 
6. Remove the plastic cap covering the syringe needle. Pay attention not to hurt yourself with the 

needle.  
7. Pull the plunger back to draw air into the syringe equal to your dose. 

 
Step 2: Withdrawing Strensiq solution from the vial 
 
 

 
 
 

 
 
 
 

 
 
 
 
 
 
 
 
 

1. Holding the syringe and vial, insert the 
needle through the sterile rubber seal 
and into the vial. 

 
2. Push the plunger in completely to 

inject air into the vial. 
 
 
 
 

3. Invert the vial and syringe. With the 
needle in the solution, pull the plunger 
to withdraw the correct dose into the 
syringe. 

 
 
 
 
 

4. Before removing the needle from the 
vial, check the syringe for air bubbles. 
In the event that bubbles appear in the 
syringe, hold the syringe with the 
needle pointing upwards and gently 
tap the side of the syringe until the 
bubbles rise to the top. 
 

5. Once all the bubbles are at the top of 
the syringe, gently push on the plunger 
to force the bubbles out of the syringe 
and back into the vial. 



34 

 

  
6. After removing the bubbles, check the dose of medication in the syringe to be sure you have 

drawn up the correct amount. You may need to use several vials to withdraw the complete 
amount needed to reach the correct dose. 

 
Step 3: Placing the needle for injection on the syringe 
 

1. Remove the needle from the vial and place back the protective cap over the needle. 
2. Remove the larger bore needle pushing down and turning counterclockwise. Dispose the 

needle with the protective cap in your sharps container. 
3. Place a smaller bore needle (e.g. 27 or 29G) on the filled syringe and with the protective cap 

on, push down and turn clockwise the needle onto the syringe until it is tight. Pull the cap 
straight off the needle. 

4. Hold the syringe with the needle pointing up and tap the barrel of the syringe with your finger 
to remove any air bubbles. 

Control visually that the volume contained into the syringe is correct. 
The volume per injection should not exceed 1 ml. If it is the case, multiple injections should be done at 
different sites. 
You are now ready to inject the correct dose. 
 
Step 4: Injecting Strensiq 
 

 
 
 

1. Choose an injection site (thighs, 
abdomen, arms (deltoids), buttocks). 
Most suitable areas for injection are 
marked grey in the picture. Your doctor 
will advise you on the possible injection 
sites 

 
NOTE: do not use any areas in which you feel 
lumps, firm knots, or pain; talk to your doctor 
about anything you find. 

 

2. Gently pinch the skin of the chosen 
injection area between your thumb and 
index finger.

 
 

 

3. Holding the syringe like a pencil or a 
dart, insert the needle into the raised skin 
so it is at an angle of between 45º and 90º 
to the skin surface.  

 
For patients who have little fat under the skin or 
thin skin, a 45º angle may be preferable.

 
 



35 

 

 
 
 
 
 

 
4. While continuing to hold the skin, push 

the syringe plunger to inject the medicine 
slowly, and steadily all the way in. 

 
5. Remove the needle, release the skin fold 

and gently place a piece of cotton wool 
or gauze over the injection site for a few 
seconds. 

This will help seal the punctured tissue and 
prevent any leakage. Do not rub the injection site 
after injection.  

If you need a second injection for your prescribed dose, get another Strensiq vial and repeat steps 1 
through 4. 
 
Step 5: Disposing of supplies 
 
Please collect your syringes, vials and needle in a sharps container. Your doctor, pharmacist or nurse 
will advise you on how you can obtain a sharps container. 

 
If you use more Strensiq than you should 
If you suspect that you have been accidently administered a higher dose of Strensiq than prescribed, 
please contact your doctor for advice. 
 
If you forget to use Strensiq 
Do not inject a double dose to make up for a forgotten dose and contact your doctor for advice. 
 
For more information, please consult: 
 

  
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
If you are not sure what the side effects below are, ask your doctor to explain them to you. 
 
The most serious side effects seen in patients receiving asfotase alfa have been allergic reactions 
including life threatening allergic reactions requiring medical treatment similar to anaphylaxis. This 
side effect is common [may affect up to 1 in 10 people]). Patients who experienced these serious 
allergic reactions had difficulty breathing, choking sensation, nausea, swelling around the eyes, and 
dizziness. The reactions occurred within minutes after using asfotase alfa and can occur in patients 
who were using asfotase alfa for more than one year. If you experience any of these symptoms, 
discontinue Strensiq and seek medical help immediately.  
 
Additionally, other allergic reactions (hypersensitivity) which may appear as redness (erythema), fever 
(pyrexia), rash, itchiness (pruritis), irritability, feeling sick (nausea), throwing up (vomiting), pain, 
chills (rigor), numbness of the mouth (hypoaesthesia oral), headache, blushing (flushing), fast beating 



 

36 

 

of the heart (tachycardia), and cough may occur commonly . If you experience any of these 
symptoms, discontinue Strensiq and seek medical help immediately. 
 
 
Very common: may affect more than 1 in 10 people 
Reactions at the injection site during the injection of the medicine or during the hours following the 
injection (which can lead to redness, discolorations, itching, pain, fatty lumps or decreased fatty tissue 
on the surface of the skin, skin hypopigmentation, and/or swelling) 
Fever (pyrexia) 
Irritability 
Skin redness (erythema) 
Pain in hands and feet (pain in extremity) 
Bruise (contusion) 
Headache 
 
Common: may affect up to 1 in 10 people 
Stretched skin, skin discolouration  
Feeling sick (nausea) 
Numbness of the mouth (hypoaesthesia oral) 
Aching muscles (myalgia) 
Scar 
Increased tendency to bruise  
Hot flush 
Infection of skin at injection site (injection site cellulitis) 
Reduced levels of calcium in the blood (hypocalcaemia) 
Kidney stones (nephrolithiasis) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist 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 Strensiq 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and the vial label after 
EXP. The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C-8°C). 
Do not freeze. 
Store in the original package in order to protect from light.  
After opening the vial, the product should be used immediately (within 3 hours maximum at room 
temperature, between 23°C and 27°C). 
 
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 Strensiq contains  
The active substance is asfotase alfa. Each ml of solution contains 40 mg of asfotase alfa. 
Each vial of 0.3 ml solution (40 mg/ml) contains 12 mg of asfotase alfa. 
Each vial of 0.45 ml solution (40 mg/ml) contains 18 mg of asfotase alfa. 

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


 

37 

 

Each vial of 0.7 ml solution (40 mg/ml) contains 28 mg of asfotase alfa. 
Each vial of 1 ml solution (40 mg/ml) contains 40 mg of asfotase alfa. 

 
The other ingredients are sodium chloride, sodium phosphate monobasic monohydrate, sodium 
phosphate dibasic heptahydrate and water for injections. 
 
What Strensiq looks like and contents of the pack 
Strensiq is presented as a clear colourless to slightly yellow aqueous solution for injection in vials 
containing 0.3 ml, 0.45 ml, 0.7 ml and 1 ml of solution. 
 
Pack sizes of 1 or 12 vials.  
Not all pack sizes may be marketed in your country. 
 
Marketing Authorisation Holder 
Alexion Europe SAS 
103-105 rue Anatole France 
92300 Levallois-Perret 
France 
 
Manufacturer 
Alexion Pharma International Operations Unlimited Company 
College Business and Technology Park, Blanchardstown 
Dublin 15 
Ireland 
 
This leaflet was last revised in 
 
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.  
 
 

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


 

38 

 

Package leaflet: Information for the user 
 

Strensiq 100 mg/ml solution for injection 
(80 mg/0.8 ml) 

asfotase 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, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Strensiq is and what it is used for  
2. What you need to know before you use Strensiq  
3. How to use Strensiq  
4. Possible side effects  
5. How to store Strensiq  
6. Contents of the pack and other information 
 
 
1. What Strensiq is and what it is used for 
 
What is Strensiq 
Strensiq is a medicine used to treat the inherited disease hypophosphatasia that started in childhood. It 
contains the active substance asfotase alfa. 
 
What is hypophosphatasia 
Patients with hypophosphatasia have low levels of an enzyme called alkaline phosphatase that is 
important for various body functions, including the proper hardening of bones and teeth. Patients have 
problems with bone growth and strength, which can lead to broken bones, bone pain, and difficulty 
walking, as well as difficulties with breathing and a risk of seizures (fits). 
 
What is Strensiq used for 
The active substance in Strensiq can replace the missing enzyme (alkaline phosphatase) in 
hypophosphatasia. It is used for long-term enzyme replacement treatment to manage symptoms. 
 
What benefits of Strensiq have been shown in clinical studies 
Strensiq has shown benefits for patients’ mineralization of the skeleton and growth. 
 
 
2. What you need to know before you use Strensiq  
 
Do not use Strensiq 
If you are severely allergic to asfotase alfa (see section ‘Warnings and precautions’ below) or any of 
the other ingredients of this medicine (listed in section 6).  
 
 
 



 

39 

 

Warnings and precautions  
Talk to your doctor before using Strensiq. 
• Patients receiving asfotase alfa have had allergic reactions including life threatening allergic 

reactions requiring medical treatment similar to anaphylaxis. Patients who experienced 
anaphylaxis-like symptoms had difficulty breathing, choking sensation, nausea, swelling around 
the eyes, and dizziness. The reactions occurred within minutes after taking asfotase alfa, and can 
occur in patients who were taking asfotase alfa for more than one year. If you experience any of 
these symptoms, discontinue Strensiq and seek medical help immediately.  
Should you experience anaphylactic reaction, or an event with similar symptoms, your doctor 
will discuss with you the next steps and the possibility to restart Strensiq under medical 
supervision. Always follow the instructions provided by your doctor. 

• The development of blood proteins against Strensiq, also called anti-drug antibodies, may occur 
during the treatment. Talk to your doctor if you experience decreased efficacy with Strensiq. 

• Fatty lumps or decreased fatty tissue on the surface of the skin (localized lipodystrophy) have 
been reported at injection sites after several months in patients using Strensiq. Read section 3 
carefully to know the injection recommendations. This is important to rotate the injection from 
among the following sites to reduce the risk of lipodystrophy: abdominal area, thigh, or deltoid. 

• In studies, some eye-related side-effects (e.g. calcium buildup on the eye [conjunctival and 
corneal calcification]) have been reported both in patients using Strensiq and those who were 
not, probably associated with hypophosphatasia. Talk to your doctor in case of problems with 
your vision. 

• Early fusion of the bones of the head (craniosynostosis) in children below 5 years of age has 
been reported in clinical studies of infants with hypophosphatasia, with and without use of 
Strensiq. Talk to your doctor if you notice any change in the shape of your infant’s head. 

• If you are treated with Strensiq, you may experience a reaction at the injection site (pain, 
nodule, rash, discoloration) during the injection of the medicine or during the hours following 
the injection. If you experience any severe reaction at the injection site, tell your doctor 
immediately. 

• Increase of parathyroid hormone concentration and low calcium levels have been reported in 
studies. As a consequence, your doctor may ask you to take supplements of calcium and oral 
vitamin D if needed.  

• Weight gain may occur during your treatment with Strensiq. Your doctor will provide dietary 
advice as necessary. 

 
Other medicines and Strensiq 
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. 
 
If you need to undergo laboratory tests (giving blood for testing), tell your doctor that you are treated 
with Strensiq. Strensiq may cause some tests to show wrongly higher or lower results. 
Therefore another type of test may need to be used if you are treated with Strensiq. 
 
Pregnancy 
Strensiq should not be used during pregnancy. The use of effective birth control during treatment 
should be considered in women who are able to get pregnant.  
 
Breast-feeding 
It is not known whether Strensiq can pass into breast milk. Tell your doctor if you are breast-feeding 
or plan to do so. Your doctor will then help you decide whether to stop breast-feeding, or whether to 
stop taking Strensiq, considering the benefit of breast-feeding to the baby and the benefit of Strensiq to 
the mother. 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Driving and using machines 
This medicine is not expected to have any effect on the ability to drive or use machines. 



 

40 

 

 
Important information about some of the ingredients of Strensiq 
This medicine contains less than 1 mmol sodium (23 mg) per vial, which means it is essentially 
‘sodium-free’. 
 
 
3. How to use Strensiq 
 
Always use this medicine exactly as described in this leaflet or as your doctor, or pharmacist or nurse 
has told you. Check with your doctor, pharmacist or nurse if you are not sure. 
How to use Strensiq will be explained to you by a doctor who is experienced in the management of 
patients with metabolic or bone related diseases. After being trained by the doctor or specialized nurse, 
you can inject Strensiq yourself at home. 
 
Dose 
• The dose you receive is based on your body weight. 
• The correct dose will be calculated by your doctor and consists of a total of 6 mg of asfotase 

alfa per kg of body weight every week, given either as an injection of 1 mg/kg asfotase alfa 6 
times per week or as 2 mg/kg asfotase alfa 3 times per week depending on the recommendation 
of your doctor. Each dose will be administered by injection under the skin (subcutaneous), (see 
the dosing chart below for detailed information on the volume to be injected, and the type of 
vials to be used, based on your weight). 

• Doses will need to be adjusted regularly by your doctor as the body weight changes. 
• The maximum volume per injection should not exceed 1 ml. If more than 1 ml is required, you 

need to do multiple injections immediately one after the other.  



 

41 

 

If injecting 3x per week 
 

Body 
Weight 
(kg) 

Volume 
to be 

injected 

Color code 
of the vial 
to be used 

3 0.15 ml Dark blue 
4 0.20 ml Dark blue 
5 0.25 ml Dark blue 
6 0.30 ml Dark blue 
7 0.35 ml Orange 
8 0.40 ml Orange 
9 0.45 ml Orange 
10 0.50 ml Light blue 
11 0.55 ml Light blue 
12 0.60 ml Light blue 
13 0.65 ml Light blue 
14 0.70 ml Light blue 
15 0.75 ml Pink 
16 0.80 ml Pink 
17 0.85 ml Pink 
18 0.90 ml Pink 
19 0.95 ml Pink 
20 1 ml Pink 
25 0.50 ml Green 
30 0.60 ml Green 
35 0.70 ml Green 
40 0.80 ml Green 

If injecting 6 x per week 
 

Body 
Weight 
(kg) 

Volume 
to be 

injected 

Color code 
of the vial 
to be used 

6 0.15 ml Dark blue 
7 0.18 ml Dark blue 
8 0.20 ml Dark blue 
9 0.23 ml Dark blue 
10 0.25 ml Dark blue 
11 0.28 ml Dark blue 
12 0.30 ml Dark blue 
13 0.33 ml Orange 
14 0.35 ml Orange 
15 0.38 ml Orange 
16 0.40 ml Orange 
17 0.43 ml Orange 
18 0.45 ml Orange 
19 0.48 ml Light blue 
20 0.50 ml Light blue 
25 0.63 ml Light blue 
30 0.75 ml Pink 
35 0.88 ml Pink 
40 1 ml Pink 
50 0.50 ml Green 
60 0.60 ml Green 
70 0.70 ml Green 
80 0.80 ml Green  
90 0.90 ml Green (x2) 

100 1 ml Green (x2) 
 
 
Injection recommendations 
• You may experience a reaction at the injection site. Read section 4 carefully to know what side 

effects can occur before using this medicine 
• When injecting regularly, the injection site should be changed between different areas of the 

body to help reduce potential pain and irritation 
• Areas with a good amount of fat below the skin (thighs, arms (deltoids), abdomen, and buttocks) 

are the most suitable areas to inject. Please discuss with you doctor or nurse the best sites for 
you.  

 
Before injecting Strensiq, please read the following instructions carefully 
• Each vial is for single use and should only be punctured once. Only clear and colourless to 

slightly yellow aqueous solution without visible signs of deterioration should be used. Any 
unused medicinal product or waste material should be disposed of immediately. 



 

42 

 

• If you are injecting this medicine yourself, you will be shown how to prepare and inject the 
medicine by your doctor, pharmacist or nurse. Do not inject this medicine yourself unless you 
have received training and you understand the procedure. 

 
How to inject Strensiq: 
 
Step 1: Preparing the Strensiq dose 
 

1. Wash your hands thoroughly with soap and water. 
2. Take the unopened Strensiq vial(s) out of the refrigerator 15 to 30 minutes before injecting to 

allow the liquid to reach room temperature. Do not warm Strensiq in any other way (for 
example, do not warm it in a microwave or in hot water). Upon removal of the vial(s) from 
refrigeration, Strensiq should be used within 3 hours maximum (see section 5. How to store 
Strensiq). 

3. Remove the protective cap from the Strensiq vial. Remove the protective plastic from the 
syringe to be used.  

4. Always use a new syringe contained in a protective plastic. 
5. Place a larger bore needle (e.g. 25G) on the empty syringe and with the protective cap on, 

push down and turn clockwise the needle onto the syringe until it is tight.  
6. Remove the plastic cap covering the syringe needle. Pay attention not to hurt yourself with the 

needle.  
7. Pull the plunger back to draw air into the syringe equal to your dose. 

 
Step 2: Withdrawing Strensiq solution from the vial 
 
 

 
 
 

 
 
 
 

 
 
 
 
 
 
 
 
 

1. Holding the syringe and vial, insert the 
needle through the sterile rubber seal 
and into the vial. 

 
2. Push the plunger in completely to 

inject air into the vial. 
 
 
 
 

3. Invert the vial and syringe. With the 
needle in the solution, pull the plunger 
to withdraw the correct dose into the 
syringe. 

 
 
 
 
 

4. Before removing the needle from the 
vial, check the syringe for air bubbles. 
In the event that bubbles appear in the 
syringe, hold the syringe with the 
needle pointing upwards and gently 
tap the side of the syringe until the 
bubbles rise to the top. 
 

5. Once all the bubbles are at the top of 
the syringe, gently push on the plunger 
to force the bubbles out of the syringe 
and back into the vial. 



 

43 

 

  
6. After removing the bubbles, check the dose of medication in the syringe to be sure you have 

drawn up the correct amount. You may need to use several vials to withdraw the complete 
amount needed to reach the correct dose. 

 
Step 3: Placing the needle for injection on the syringe 
 

1. Remove the needle from the vial and place back the protective cap over the needle. 
2. Remove the larger bore needle pushing down and turning counterclockwise. Dispose the 

needle with the protective cap in your sharps container. 
3. Place a smaller bore needle (e.g. 27 or 29G) on the filled syringe and with the protective cap 

on, push down and turn clockwise the needle onto the syringe until it is tight. Pull the cap 
straight off the needle. 

4. Hold the syringe with the needle pointing up and tap the barrel of the syringe with your finger 
to remove any air bubbles. 

Control visually that the volume contained into the syringe is correct. 
The volume per injection should not exceed 1 ml. If it is the case, multiple injections should be done at 
different sites. 
You are now ready to inject the correct dose. 
 
Step 4: Injecting Strensiq 
 
 

 
 
 

1. Choose an injection site (thighs, 
abdomen, arms (deltoids), buttocks). 
Most suitable areas for injection are 
marked grey in the picture. Your doctor 
will advise you on the possible injection 
sites. 

 
NOTE: do not use any areas in which you feel 
lumps, firm knots, or pain; talk to your doctor 
about anything you find. 

 

2. Gently pinch the skin of the chosen 
injection area between your thumb and 
index finger.

 
 

 

3. Holding the syringe like a pencil or a 
dart, insert the needle into the raised skin 
so it is at an angle of between 45º and 90º 
to the skin surface.  

 
For patients who have little fat under the skin or 
thin skin, a 45º angle may be preferable.

 



 

44 

 

 

 
 
 

4. While continuing to hold the skin, push 
the syringe plunger to inject the medicine 
slowly, and steadily all the way in. 

 
5. Remove the needle, release the skin fold 

and gently place a piece of cotton wool 
or gauze over the injection site for a few 
seconds. 

This will help seal the punctured tissue and 
prevent any leakage. Do not rub the injection site 
after injection.  

 
If you need a second injection for your prescribed dose, get another Strensiq vial and repeat steps 1 
through 4. 
 
Step 5: Disposing of supplies 
 
Please collect your syringes, vials and needle in a sharps container. Your doctor, pharmacist or nurse 
will advise you on how you can obtain a sharps container. 
 
If you use more Strensiq than you should 
If you suspect that you have been accidently administered a higher dose of Strensiq than prescribed, 
please contact your doctor for advice. 
 
If you forget to use Strensiq 
Do not inject a double dose to make up for a forgotten dose and contact your doctor for advice. 
 
For more information, please consult: 
 

 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
If you are not sure what the side effects below are, ask your doctor to explain them to you. 
 
The most serious side effects seen in patients receiving asfotase alfa have been allergic reactions 
including life threatening allergic reactions requiring medical treatment similar to anaphylaxis. This 
side effect is common [may affect up to 1 in 10 people]). Patients who experienced these serious 
allergic reactions had difficulty breathing, choking sensation, nausea, swelling around the eyes, and 
dizziness. The reactions occurred within minutes after using asfotase alfa and can occur in patients 
who were using asfotase alfa for more than one year. If you experience any of these symptoms, 
discontinue Strensiq and seek medical help immediately.  
 
Additionally, other allergic reactions (hypersensitivity) which may appear as redness (erythema), fever 
(pyrexia), rash, itchiness (pruritis), irritability, feeling sick (nausea), throwing up (vomiting), pain, 
chills (rigor), numbness of the mouth (hypoaesthesia oral), headache, blushing (flushing), fast beating 



 

45 

 

of the heart (tachycardia), and cough may occur commonly. If you experience any of these 
symptoms, discontinue Strensiq and seek medical help immediately. 
 
 
Very common: may affect more than 1 in 10 people 
Reactions at the injection site during the injection of the medicine or during the hours following the 
injection (which can lead to redness, discolorations, itching, pain, fatty lumps or decreased fatty tissue 
on the surface of the skin, skin hypopigmentation, and/or swelling) 
Fever (pyrexia) 
Irritability 
Skin redness (erythema) 
Pain in hands and feet (pain in extremity) 
Bruise (contusion) 
Headache 
 
Common: may affect up to 1 in 10 people 
Stretched skin, skin discolouration  
Feeling sick (nausea) 
Numbness of the mouth (hypoaesthesia oral) 
Aching muscles (myalgia) 
Scar 
Increased tendency to bruise  
Hot flush 
Infection of skin at injection site (injection site cellulitis) 
Reduced levels of calcium in the blood (hypocalcaemia) 
Kidney stones (nephrolithiasis) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist 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 Strensiq 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and the vial label after 
EXP. The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C-8°C). 
Do not freeze. 
Store in the original package in order to protect from light.  
After opening the vial, the product should be used immediately (within 3 hours maximum at room 
temperature, between 23°C and 27°C). 
 
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 Strensiq contains  
The active substance is asfotase alfa. Each ml of solution contains 100 mg of asfotase alfa. 
Each vial of 0.8 ml solution (100 mg/ml) contains 80 mg of asfotase alfa. 

 

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


 

46 

 

The other ingredients are sodium chloride, sodium phosphate monobasic monohydrate, sodium 
phosphate dibasic heptahydrate and water for injections. 
 
What Strensiq looks like and contents of the pack 
Strensiq is presented as a clear colourless to slightly yellow aqueous solution for injection in vials 
containing 0.8 ml of solution. 
 
Pack sizes of 1 or 12 vials.  
Not all pack sizes may be marketed in your country. 
 
Marketing Authorisation Holder 
Alexion Europe SAS 
103-105 rue Anatole France 
92300 Levallois-Perret 
France 
 
Manufacturer 
Alexion Pharma International Operations Unlimited Company 
College Business and Technology Park, Blanchardstown 
Dublin 15 
Ireland 
 
This leaflet was last revised in 
 
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.  

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

	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