Nplate

1

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Nplate 125 micrograms powder for solution for injection 
Nplate 250 micrograms powder for solution for injection 
Nplate 500 micrograms powder for solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Nplate 125 micrograms powder for solution for injection 
 
Each vial contains 125 mcg of romiplostim. After reconstitution, a deliverable volume of 0.25 mL 
solution contains 125 mcg of romiplostim (500 mcg/mL). An additional overfill is included in each 
vial to ensure that 125 mcg of romiplostim can be delivered. 
 
Nplate 250 micrograms powder for solution for injection 
 
Each vial contains 250 mcg of romiplostim. After reconstitution, a deliverable volume of 0.5 mL 
solution contains 250 mcg of romiplostim (500 mcg/mL). An additional overfill is included in each 
vial to ensure that 250 mcg of romiplostim can be delivered. 
 
Nplate 500 micrograms powder for solution for injection 
 
Each vial contains 500 mcg of romiplostim. After reconstitution, a deliverable volume of 1 mL 
solution contains 500 mcg of romiplostim (500 mcg/mL). An additional overfill is included in each 
vial to ensure that 500 mcg of romiplostim can be delivered. 
 
Romiplostim is produced by recombinant DNA technology in Escherichia coli (E. coli). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder for solution for injection (powder for injection). 
 
The powder is white. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Nplate is indicated for chronic immune (idiopathic) thrombocytopenic purpura (ITP) patients one year 
of age and older who are refractory to other treatments (e.g. corticosteroids, immunoglobulins) (see 
sections 4.2 and 5.1). 
 
4.2 Posology and method of administration 
 
Treatment should remain under the supervision of a physician who is experienced in the treatment of 
haematological diseases. 
 
Posology 
 
Nplate should be administered once weekly as a subcutaneous injection. 
 



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Initial dose 
 
The initial dose of romiplostim is 1 mcg/kg based on actual body weight. 
 
Dose calculation 
 
The volume of romiplostim to administer is calculated based on body weight, dose required, and 
concentration of product. 
 
Table 1. Guidelines for calculating individual patient dose and volume of romiplostim to 
administer 
 
Individual patient dose 
(mcg) 

Individual patient dose (mcg) = weight (kg) x dose in mcg/kg 
 
Actual body weight at initiation of treatment should always be used when 
calculating initial dose. 
 In adults, future dose adjustments are based on changes in platelet 

counts only. 
 In paediatric patients, future dose adjustments are based on changes 

in platelet counts and changes in body weight. Reassessment of 
body weight is recommended every 12 weeks. 
 

If individual patient 
dose is ≥ 23 mcg 

Reconstitute lyophilised product as described in section 6.6. The resulting 
concentration is 500 mcg/mL. 
 
Volume to administer (mL) = Individual patient dose (mcg) / 500 mcg/mL 
(Round volume to the nearest hundredth mL) 
 

If individual patient 
dose is < 23 mcg 

Dilution is required to ensure accurate dosing. Reconstitute lyophilised 
product and then dilute the product as described in section 6.6. The 
resulting concentration is 125 mcg/mL. 
 
Volume to administer (mL) = Individual patient dose (mcg) / 125 mcg/mL 
(Round volume to the nearest hundredth mL) 
 

Example 10 kg patient is initiated at 1 mcg/kg of romiplostim. 
 
Individual patient dose (mcg) = 10 kg x 1 mcg/kg = 10 mcg 
 
Because the dose is < 23 mcg, dilution is required to ensure accurate 
dosing. Reconstitute lyophilised product and then dilute the product as 
described in section 6.6. The resulting concentration is 125 mcg/mL. 
 
Volume to administer (mL) = 10 mcg / 125 mcg/mL = 0.08 mL 
 

 
Dose adjustments 
 
A subject’s actual body weight at initiation of therapy should be used to calculate dose. The once 
weekly dose of romiplostim should be increased by increments of 1 mcg/kg until the patient achieves a 
platelet count ≥ 50 x 109/L. Platelet counts should be assessed weekly until a stable platelet count 
(≥ 50 x 109/L for at least 4 weeks without dose adjustment) has been achieved. Platelet counts should 
be assessed monthly thereafter and appropriate dose adjustments made as per the dose adjustment 
table (table 2) in order to maintain platelet counts within the recommended range. See table 2 below 
for dose adjustment and monitoring. A maximum once weekly dose of 10 mcg/kg should not be 
exceeded. 
 



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Table 2. Dose adjustment guidance based on platelet count 
 

Platelet count 
(x 109/L) Action 

< 50 Increase once weekly dose by 1 mcg/kg  

> 150 for two 
consecutive weeks Decrease once weekly dose by 1 mcg/kg 

> 250 

Do not administer, continue to assess the platelet count weekly 
 
After the platelet count has fallen to < 150 x 109/L, resume dosing with once 
weekly dose reduced by 1 mcg/kg

 
Due to the interindividual variable platelet response, in some patients platelet count may abruptly fall 
below 50 x 109/L after dose reduction or treatment discontinuation. In these cases, if clinically 
appropriate, higher cut-off levels of platelet count for dose reduction (200 x 109/L) and treatment 
interruption (400 x 109/L) may be considered according to medical judgement. 
 
A loss of response or failure to maintain a platelet response with romiplostim within the recommended 
dosing range should prompt a search for causative factors (see section 4.4, loss of response to 
romiplostim). 
 
Treatment discontinuation 
 
Treatment with romiplostim should be discontinued if the platelet count does not increase to a level 
sufficient to avoid clinically important bleeding after four weeks of romiplostim therapy at the highest 
weekly dose of 10 mcg/kg. 
 
Patients should be clinically evaluated periodically and continuation of treatment should be decided on 
an individual basis by the treating physician, and in non-splenectomised patients this should include 
evaluation relative to splenectomy. The reoccurrence of thrombocytopenia is likely upon 
discontinuation of treatment (see section 4.4). 
 
Elderly patients (≥ 65 years) 
 
No overall differences in safety or efficacy have been observed in patients < 65 and ≥ 65 years of age 
(see section 5.1). Although based on these data no adjustment of the dosing regimen is required for 
older patients, care is advised considering the small number of elderly patients included in the clinical 
trials so far. 
 
Paediatric population 
 
The safety and efficacy of romiplostim in children under the age of one year has not been established. 
 
Patients with hepatic Impairment 
 
Romiplostim should not be used in patients with moderate to severe hepatic impairment (Child-Pugh 
score ≥ 7) unless the expected benefit outweighs the identified risk of portal venous thrombosis in 
patients with thrombocytopenia associated to hepatic insufficiency treated with thrombopoietin (TPO) 
agonists (see section 4.4). 
 
If the use of romiplostim is deemed necessary, platelet count should be closely monitored to minimise 
the risk of thromboembolic complications. 
 



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Patients with renal impairment 
 
No formal clinical trials have been conducted in these patient populations. Nplate should be used with 
caution in these populations. 
 
Method of administration 
 
For subcutaneous use. 
 
After reconstitution of the powder, Nplate solution for injection is administered subcutaneously. The 
injection volume may be very small. Caution should be used during preparation of Nplate in 
calculating the dose and reconstitution with the correct volume of sterile water for injection. If the 
calculated individual patient dose is less than 23 mcg, dilution with preservative-free, sterile, sodium 
chloride 9 mg/mL (0.9%) solution for injection is required to ensure accurate dosing (see section 6.6). 
Special care should be taken to ensure that the appropriate volume of Nplate is withdrawn from the 
vial for subcutaneous administration – a syringe with graduations of 0.01 mL should be used. 
 
Self-administration of Nplate is not allowed for paediatric patients. 
 
For instructions on reconstitution of the medicinal product before administration, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to E. coli 
derived proteins. 
 
4.4 Special warnings and precautions for use 
 
Reoccurrence of thrombocytopenia and bleeding after cessation of treatment 
 
Thrombocytopenia is likely to reoccur upon discontinuation of treatment with romiplostim. There is 
an increased risk of bleeding if romiplostim treatment is discontinued in the presence of anticoagulants 
or anti-platelet agents. Patients should be closely monitored for a decrease in platelet count and 
medically managed to avoid bleeding upon discontinuation of treatment with romiplostim. It is 
recommended that, if treatment with romiplostim is discontinued, ITP treatment be restarted according 
to current treatment guidelines. Additional medical management may include cessation of 
anticoagulant and/or antiplatelet therapy, reversal of anticoagulation, or platelet support. 
 
Increased bone marrow reticulin 
 
Increased bone marrow reticulin is believed to be a result of TPO receptor stimulation, leading to an 
increased number of megakaryocytes in the bone marrow, which may subsequently release cytokines. 
Increased reticulin may be suggested by morphological changes in the peripheral blood cells and can 
be detected through bone marrow biopsy. Therefore, examinations for cellular morphological 
abnormalities using peripheral blood smear and complete blood count (CBC) prior to and during 
treatment with romiplostim are recommended. See section 4.8 for information on the increases of 
reticulin observed in romiplostim clinical trials. 
 
If a loss of efficacy and abnormal peripheral blood smear is observed in patients, administration of 
romiplostim should be discontinued, a physical examination should be performed, and a bone marrow 
biopsy with appropriate staining for reticulin should be considered. If available, comparison to a prior 
bone marrow biopsy should be made. If efficacy is maintained and abnormal peripheral blood smear is 
observed in patients, the physician should follow appropriate clinical judgment, including 
consideration of a bone marrow biopsy, and the risk-benefit of romiplostim and alternative ITP 
treatment options should be re-assessed. 
 



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Thrombotic/thromboembolic complications 
 
Platelet counts above the normal range present a risk for thrombotic/thromboembolic complications. 
The incidence of thrombotic/thromboembolic events observed in clinical trials was 6.0% with 
romiplostim and 3.6% with placebo. Caution should be used when administering romiplostim to 
patients with known risk factors for thromboembolism including but not limited to inherited (e.g. 
Factor V Leiden) or acquired risk factors (e.g. ATIII deficiency, antiphospholipid syndrome), 
advanced age, patients with prolonged periods of immobilisation, malignancies, contraceptives and 
hormone replacement therapy, surgery/trauma, obesity and smoking. 
 
Cases of thromboembolic events (TEEs), including portal vein thrombosis, have been reported in 
patients with chronic liver disease receiving romiplostim. Romiplostim should be used with caution in 
these populations. Dose adjustment guidelines should be followed (see section 4.2). 
 
Medication errors 
 
Medication errors including overdose and underdose have been reported in patients receiving Nplate, 
dose calculation and dose adjustment guidelines should be followed. In some paediatric patients, 
accurate dosing relies on an additional dilution step after reconstitution which may increase the risk 
for medication errors (see section 4.2). 
 
Overdose may result in an excessive increase in platelet counts associated with 
thrombotic/thromboembolic complications. If the platelet counts are excessively increased, 
discontinue Nplate and monitor platelet counts. Reinitiate treatment with Nplate in accordance with 
dosing and administration recommendations. Underdose may result in lower than expected platelet 
counts and potential for bleeding. Platelet counts should be monitored in patients receiving Nplate (see 
sections 4.2, 4.4 and 4.9). 
 
Progression of existing Myelodysplastic Syndromes (MDS) 
 
A positive benefit/risk for romiplostim is only established for the treatment of thrombocytopenia 
associated with chronic ITP and romiplostim must not be used in other clinical conditions associated 
with thrombocytopenia. 
 
The diagnosis of ITP in adults and elderly patients should have been confirmed by the exclusion of 
other clinical entities presenting with thrombocytopenia, in particular the diagnosis of MDS must be 
excluded. A bone marrow aspirate and biopsy should normally have been done over the course of the 
disease and treatment, particularly in patients over 60 years of age, for those with systemic symptoms 
or abnormal signs such as increased peripheral blast cells. 
 
In adult clinical studies of treatment with romiplostim in patients with MDS, cases of transient 
increases in blast cell counts were observed and cases of MDS disease progression to AML were 
reported. In a randomised placebo-controlled trial in MDS subjects, treatment with romiplostim was 
prematurely stopped due to a numerical excess of disease progression to AML and an increase in 
circulating blasts greater than 10% in patients receiving romiplostim. Of the cases of MDS disease 
progression to AML that were observed, patients with RAEB-1 classification of MDS at baseline were 
more likely to have disease progression to AML compared to lower risk MDS. 
 
Romiplostim must not be used for the treatment of thrombocytopenia due to MDS or any other cause 
of thrombocytopenia other than ITP outside of clinical trials. 
 
Loss of response to romiplostim 
 
A loss of response or failure to maintain a platelet response with romiplostim treatment within the 
recommended dosing range should prompt a search for causative factors, including immunogenicity 
(see section 4.8) and increased bone marrow reticulin (see above). 
 



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Effects of romiplostim on red and white blood cells 
 
Alterations in red (decrease) and white (increase) blood cell parameters have been observed in 
non-clinical toxicology studies (rat and monkey) as well as in ITP patients. Concurrent anaemia and 
leucocytosis (within a 4-week window) may occur in patients regardless of splenectomy status, but 
have been seen more often in patients who have had a prior splenectomy. Monitoring of these 
parameters should be considered in patients treated with romiplostim. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. The potential interactions of romiplostim with 
co-administered medicinal products due to binding to plasma proteins remain unknown. 
 
Medicinal products used in the treatment of ITP in combination with romiplostim in clinical trials 
included corticosteroids, danazol, and/or azathioprine, intravenous immunoglobulin (IVIG), and 
anti-D immunoglobulin. Platelet counts should be monitored when combining romiplostim with other 
medicinal products for the treatment of ITP in order to avoid platelet counts outside of the 
recommended range (see section 4.2). 
 
Corticosteroids, danazol, and azathioprine use may be reduced or discontinued when given in 
combination with romiplostim (see section 5.1). Platelet counts should be monitored when reducing or 
discontinuing other ITP treatments in order to avoid platelet counts below the recommended range 
(see section 4.2). 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data from the use of romiplostim in pregnant women. 
 
Studies in animals have shown that romiplostim crossed the placenta and increased foetal platelet 
counts. Post implantation loss and a slight increase in peri-natal pup mortality also occurred in animal 
studies (see section 5.3). 
 
Romiplostim is not recommended during pregnancy and in women of childbearing potential not using 
contraception. 
 
Breast-feeding 
 
It is unknown whether romiplostim/metabolites are excreted 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 romiplostim therapy taking into account the benefit of breast feeding for 
the child and the benefit of therapy for the woman. 
 
Fertility 
 
There is no data available on fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Nplate has moderate influence on the ability to drive and use machines. In clinical trials, mild to 
moderate, transient bouts of dizziness were experienced by some patients. 
 



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4.8 Undesirable effects 
 
Summary of the safety profile 
 
Based on an analysis of all adult ITP patients receiving romiplostim in 4 controlled and 5 uncontrolled 
clinical trials, the overall subject incidence of all adverse reactions for romiplostim-treated subjects 
was 91.5% (248/271). The mean duration of exposure to romiplostim in this study population was 
50 weeks. 
 
The most serious adverse reactions that may occur during Nplate treatment include: reoccurrence of 
thrombocytopenia and bleeding after cessation of treatment, increased bone marrow reticulin, 
thrombotic/thromboembolic complications, medication errors and progression of existing MDS to 
AML. The most common adverse reactions observed include hypersensitivity reactions (including 
cases of rash, urticaria and angioedema) and headache. 
 
Tabulated list of adverse reactions 
 
Frequencies are 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) and not 
known (cannot be estimated from the available data). Within each MedDRA system organ class and 
frequency grouping, undesirable effects are presented in order of decreasing incidence. 
 
MedDRA system 
organ class 

Very common  Common  Uncommon 

Infections and 
infestations 

Upper respiratory tract 
infection 
Rhinitis*** 

Gastroenteritis 
Pharyngitis*** 
Conjunctivitis*** 
Ear infection*** 
Sinusitis***

Influenza 
Localised infection 
Nasopharyngitis 

Neoplasms benign, 
malignant and 
unspecified (including 
cysts and polyps) 

  Multiple myeloma 
Myelofibrosis 

Blood and lymphatic 
system disorders 

 Bone marrow 
disorder* 
Thrombocytopenia* 
Anaemia 

Aplastic anaemia 
Bone marrow failure 
Leucocytosis 
Splenomegaly 
Thrombocythaemia 
Platelet count 
increased 
Platelet count 
abnormal 

Immune system 
disorder 

Hypersensitivity** 
 

Angioedema  

Metabolism and 
nutrition disorders 

  Alcohol intolerance 
Anorexia 
Decreased appetite 
Dehydration 
Gout 

Psychiatric disorders  Insomnia Depression 
Abnormal dreams



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MedDRA system 
organ class 

Very common  Common  Uncommon 

Nervous system 
disorders 

Headache Dizziness 
Migraine 
Paraesthesia 

Clonus 
Dysgeusia 
Hypoaesthesia 
Hypogeusia 
Neuropathy peripheral 
Transverse sinus 
thrombosis 

Eye disorders   Conjunctival 
haemorrhage 
Accommodation 
disorder 
Blindness 
Eye disorder 
Eye pruritus 
Lacrimation increased 
Papilloedema 
Visual disturbances

Ear and labyrinth 
disorders 

  Vertigo 

Cardiac disorders  Palpitations Myocardial infarction 
Heart rate increased

Vascular disorders  Flushing Deep vein thrombosis 
Hypotension 
Peripheral embolism 
Peripheral ischaemia 
Phlebitis 
Thrombophlebitis 
superficial 
Thrombosis 
Erythromelalgia 

Respiratory, thoracic 
and mediastinal 
disorders 

Oropharyngeal 
pain*** 

Pulmonary embolism* Cough 
Rhinorrhoea 
Dry throat 
Dyspnoea 
Nasal congestion 
Painful respiration

Gastrointestinal 
disorders 

Upper abdominal 
pain*** 

Nausea 
Diarrhoea 
Abdominal pain 
Constipation 
Dyspepsia 

Vomiting 
Rectal haemorrhage 
Breath odour 
Dysphagia 
Gastro-oesophageal 
reflux disease 
Haematochezia 
Mouth haemorrhage 
Stomach discomfort 
Stomatitis 
Tooth discolouration

Hepatobiliary disorders   Portal vein thrombosis 
Increase in 
transaminase 



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MedDRA system 
organ class 

Very common  Common  Uncommon 

Skin and subcutaneous 
tissue disorders 

 Pruritus 
Ecchymosis 
Rash 

Alopecia 
Photosensitivity 
reaction 
Acne 
Dermatitis contact 
Dry skin 
Eczema 
Erythema 
Exfoliative rash 
Hair growth abnormal 
Prurigo 
Purpura 
Rash papular 
Rash pruritic 
Skin nodule 
Skin odour abnormal 
Urticaria 

Musculoskeletal and 
connective tissue 
disorders 

 Arthralgia 
Myalgia 
Muscle spasms 
Pain in extremity 
Back pain 
Bone pain

Muscle tightness 
Muscular weakness 
Shoulder pain 
Muscle twitching 

Renal and urinary 
disorders 

  Protein urine present 

Reproductive system 
and breast disorders 

  Vaginal haemorrhage 

General disorders and 
administration site 
conditions 

 Fatigue 
Oedema peripheral 
Influenza like illness 
Pain 
Asthenia 
Pyrexia 
Chills 
Injection site reaction 
Peripheral swelling***

Injection site 
haemorrhage 
Chest pain 
Irritability 
Malaise 
Face oedema 
Feeling hot 
Feeling jittery 

Investigations   Blood pressure 
increased 
Blood lactate 
dehydrogenase 
increased 
Body temperature 
increased 
Weight decreased 
Weight increased

Injury, poisoning and 
procedural 
complications 

 Contusion  

* see section 4.4 
** Hypersensitivity reactions including cases of rash, urticaria, and angioedema 
*** Additional adverse reactions observed in paediatric studies 
 



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Paediatric population 
 
In the paediatric studies, 282 paediatric ITP subjects were treated with romiplostim in 2 controlled and 
3 uncontrolled clinical trials. The median duration of exposure was 65.4 weeks. The overall safety 
profile was similar to that seen in adults. 
 
The paediatric adverse reactions are derived from each of the paediatric ITP randomised safety set 
(2 controlled clinical trials) and paediatric ITP safety set (2 controlled and 3 uncontrolled clinical 
trials) where the subject incidence was at least 5% higher in the romiplostim arm compared to placebo 
and at least a 5% subject incidence in romiplostim-treated subjects. 
 
The most common adverse reactions in paediatric ITP patients 1 year and older were upper respiratory 
tract infection, rhinitis, cough, oropharyngeal pain, upper abdominal pain, diarrhoea, rash, pyrexia, 
contusion (reported very commonly (≥ 1/10)), and pharyngitis, conjunctivitis, ear infection, 
gastroenteritis, sinusitis, purpura, urticaria and peripheral swelling (reported commonly (≥ 1/100 to 
< 1/10)). 
 
Oropharyngeal pain, upper abdominal pain, rhinitis, pharyngitis, conjunctivitis, ear infection, sinusitis 
and peripheral swelling were additional adverse reactions observed in paediatric studies compared to 
those seen in adult studies. 
 
Some of the adverse reactions seen in adults were reported more frequently in paediatric subjects such 
as cough, diarrhoea, rash, pyrexia and contusion reported very commonly (≥ 1/10) in paediatric 
subjects and purpura and urticaria were reported commonly (≥ 1/100 to < 1/10) in paediatric subjects. 
 
Description of selected adverse reactions 
 
In addition the reactions listed below have been deemed to be related to romiplostim treatment. 
 
Bleeding events 
 
Across the entire adult ITP clinical programme an inverse relationship between bleeding events and 
platelet counts was observed. All clinically significant (≥ grade 3) bleeding events occurred at platelet 
counts < 30 x 109/L. All bleeding events ≥ grade 2 occurred at platelet counts < 50 x 109/L. No 
statistically significant differences in the overall incidence of bleeding events were observed between 
Nplate and placebo treated patients. 
 
In the two adult placebo-controlled studies, 9 patients reported a bleeding event that was considered 
serious (5 [6.0%] romiplostim, 4 [9.8%] placebo; Odds Ratio [romiplostim/placebo] = 0.59; 95% 
CI = (0.15, 2.31)). Bleeding events that were grade 2 or higher were reported by 15% of patients 
treated with romiplostim and 34% of patients treated with placebo (Odds Ratio; 
[romiplostim/placebo] = 0.35; 95% CI = (0.14, 0.85)). 
 
In the Phase 3 paediatric study, the mean (SD) number of composite bleeding episodes (see 
section 5.1) was 1.9 (4.2) for the romiplostim arm and 4.0 (6.9) for the placebo arm. 
 
Thrombocytosis 
 
Based on an analysis of all adult ITP patients receiving romiplostim in 4 controlled and 5 uncontrolled 
clinical trials, 3 events of thrombocytosis were reported, n = 271. No clinical sequelae were reported 
in association with the elevated platelet counts in any of the 3 subjects. 
 
Thrombocytosis in paediatric subjects occurred uncommonly (≥ 1/1,000 to < 1/100), with a subject 
incidence of 1 (0.4%). Subject incidence was 1 (0.4%) for either grade ≥ 3 or serious thrombocytosis. 
 



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Thrombocytopenia after cessation of treatment 
 
Based on an analysis of all adult ITP patients receiving romiplostim in 4 controlled and 5 uncontrolled 
clinical trials, 4 events of thrombocytopenia after cessation of treatment were reported, n = 271 (see 
section 4.4). 
 
Progression of existing Myelodysplastic Syndromes (MDS) 
 
In a randomised placebo-controlled trial in MDS adult subjects treatment with romiplostim was 
prematurely stopped due to a numerical increase in cases of MDS disease progression to AML and 
transient increases in blast cell counts in patients treated with romiplostim compared to placebo. Of the 
cases of MDS disease progression to AML that were observed, patients with RAEB-1 classification of 
MDS at baseline were more likely to have disease progression to AML (see section 4.4). Overall 
survival was similar to placebo. 
 
Increased bone marrow reticulin 
 
In adult clinical trials, romiplostim treatment was discontinued in 4 of the 271 patients because of 
bone marrow reticulin deposition. In 6 additional patients reticulin was observed upon bone marrow 
biopsy (see section 4.4). 
 
In an ongoing paediatric clinical trial, of the subjects with an evaluable on-study bone marrow biopsy, 
5 out of 27 subjects (18.5%) developed increased reticulin in cohort 1 and 2 out of 4 subjects (50.0%) 
developed increased reticulin in cohort 2. However, no subject showed any bone marrow 
abnormalities that were inconsistent with an underlying diagnosis of ITP at baseline or on-treatment. 
 
Immunogenicity 
 
Clinical trials in adult ITP patients examined antibodies to romiplostim and TPO. While 5.7% 
(60/1,046) and 3.2% (33/1,046) of the subjects were positive for developing binding antibodies to 
romiplostim and TPO respectively, only 4 subjects were positive for neutralising antibodies to 
romiplostim but these antibodies did not cross react with endogenous TPO. Of the 4 subjects, 
2 subjects tested negative for neutralising antibodies to romiplostim at the subject’s last timepoint 
(transient positive) and 2 subjects remained positive at the subject’s last timepoint (persistent 
antibodies). The incidence of pre-existing antibodies to romiplostim and TPO was 3.3% (35/1,046) 
and 3.0% (31/1,046), respectively. 
 
In paediatric studies, the incidence of binding antibodies to romiplostim at any time was 9.6% 
(27/282). Of the 27 subjects, 2 subjects had pre-existing binding non-neutralising romiplostim 
antibodies at baseline. Additionally, 2.8% (8/282) developed neutralising antibodies to romiplostim. A 
total of 3.9% (11/282) subjects had binding antibodies to TPO at any time during romiplostim 
treatment. Of these 11 subjects, 2 subjects had pre-existing binding non-neutralising antibodies to 
TPO.  One subject (0.35%) had a weakly positive postbaseline result for neutralising antibodies 
against TPO while on study (consistently negative for anti-romiplostim antibodies) with a negative 
result at baseline. The subject showed a transient antibody response for neutralising antibodies against 
TPO, with a negative result at the subject’s last timepoint tested within the study period. 
 
In the post-marketing registry study, 19 confirmed paediatric patients were included. The incidence of 
binding antibody post treatment was 16% (3/19) to romiplostim, of which 5.3% (1/19) were positive 
for neutralising antibodies to romiplostim. There were no antibodies detected to TPO. A total of 
184 confirmed adult patients were included in this study; for these patients, the incidence of binding 
antibody post treatment was 3.8% (7/184) to romiplostim, of which 0.5% (1/184) was positive for 
neutralising antibodies to romiplostim. A total of 2.2% (4/184) adult patients developed binding, 
non-neutralising antibody against TPO. 
 



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As with all therapeutic proteins, there is a potential for immunogenicity. If formation of neutralising 
antibodies is suspected, contact the local representative of the Marketing Authorisation Holder (see 
section 6 of the Package Leaflet) for antibody testing. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
No adverse effects were seen in rats given a single dose of 1,000 mcg/kg or in monkeys after repeated 
administration of romiplostim at 500 mcg/kg (100 or 50 times the maximum clinical dose of 
10 mcg/kg, respectively). 
 
In the event of overdose, platelet counts may increase excessively and result in 
thrombotic/thromboembolic complications. If the platelet counts are excessively increased, 
discontinue Nplate and monitor platelet counts. Reinitiate treatment with Nplate in accordance with 
dosing and administration recommendations (see sections 4.2 and 4.4). 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antihaemorrhagics, other systemic haemostatics, ATC code: B02BX04 
 
Mechanism of action 
 
Romiplostim is an Fc-peptide fusion protein (peptibody) that signals and activates intracellular 
transcriptional pathways via the TPO receptor (also known as cMpl) to increase platelet production. 
The peptibody molecule is comprised of a human immunoglobulin IgG1 Fc domain, with each 
single-chain subunit covalently linked at the C-terminus to a peptide chain containing 2 TPO 
receptor-binding domains. 
 
Romiplostim has no amino acid sequence homology to endogenous TPO. In pre-clinical and clinical 
trials no anti-romiplostim antibodies cross reacted with endogenous TPO. 
 
Clinical efficacy and safety 
 
The safety and efficacy of romiplostim have been evaluated for up to 3 years of continuous treatment. 
In clinical trials, treatment with romiplostim resulted in dose-dependent increases in platelet count. 
Time to reach the maximum effect on platelet count is approximately 10-14 days, and is independent 
of the dose. After a single subcutaneous dose of 1 to 10 mcg/kg romiplostim in ITP patients, the peak 
platelet count was 1.3 to 14.9 times greater than the baseline platelet count over a 2 to 3 week period 
and the response was variable among patients. The platelet counts of ITP patients who received 
6 weekly doses of 1 or 3 mcg/kg of romiplostim were within the range of 50 to 450 x 109/L for most 
patients. Of the 271 patients who received romiplostim in ITP clinical trials, 55 (20%) were age 65 
and over, and 27 (10%) were 75 and over. No overall differences in safety or efficacy have been 
observed between older and younger patients in the placebo-controlled studies. 
 



 14

Results from pivotal placebo-controlled studies 
 
The safety and efficacy of romiplostim was evaluated in two placebo-controlled, double-blind studies 
in adults with ITP who had completed at least one treatment prior to study entry and are representative 
of the entire spectrum of such ITP patients. 
 
Study S1 (212) evaluated patients who were non-splenectomised and had an inadequate response or 
were intolerant to prior therapies. Patients had been diagnosed with ITP for approximately 2 years at 
the time of study entry. Patients had a median of 3 (range, 1 to 7) treatments for ITP prior to study 
entry. Prior treatments included corticosteroids (90% of all patients), immunoglobulins (76%), 
rituximab (29%), cytotoxic therapies (21%), danazol (11%), and azathioprine (5%). Patients had a 
median platelet count of 19 x 109/L at study entry. 
 
Study S2 (105) evaluated patients who were splenectomised and continued to have thrombocytopenia. 
Patients had been diagnosed with ITP for approximately 8 years at the time of study entry. In addition 
to a splenectomy, patients had a median of 6 (range, 3 to 10) treatments for ITP prior to study entry. 
Prior treatments included corticosteroids (98% of all patients), immunoglobulins (97%), rituximab 
(71%), danazol (37%), cytotoxic therapies (68%), and azathioprine (24%). Patients had a median 
platelet count of 14 x 109/L at study entry. 
 
Both studies were similarly designed. Patients (≥ 18 years) were randomised in a 2:1 ratio to receive a 
starting dose of romiplostim 1 mcg/kg or placebo. Patients received single subcutaneous weekly 
injections for 24 weeks. Doses were adjusted to maintain (50 to 200 x 109/L) platelet counts. In both 
studies, efficacy was determined by an increase in the proportion of patients who achieved a durable 
platelet response. The median average weekly dose for splenectomised patients was 3 mcg/kg and for 
non-splenectomised patients was 2 mcg/kg. 
 
A significantly higher proportion of patients receiving romiplostim achieved a durable platelet 
response compared to patients receiving placebo in both studies. Following the first 4-weeks of study 
romiplostim maintained platelet counts ≥ 50 x 109/L in between 50% to 70% of patients during the 
6 month treatment period in the placebo-controlled studies. In the placebo group, 0% to 7% of patients 
were able achieve a platelet count response during the 6 months of treatment. A summary of the key 
efficacy endpoints is presented below. 
 
Summary of key efficacy results from placebo-controlled studies 
 
 Study 1 

non-splenectomised 
patients 

Study 2 
splenectomised patients 

Combined  
studies 1 & 2  

romiplostim 
(n = 41)

Placebo 
(n = 21)

romiplostim 
(n = 42)

Placebo 
(n = 21)

romiplostim 
(n = 83) 

Placebo 
(n = 42)

No. (%) 
patients 
with 
durable 
platelet 
responsea  

25 (61%) 1 (5%) 16 (38%) 0 (0%) 41 (50%) 1 (2%) 

 (95% CI) (45%, 76%) (0%, 24%) (24%, 54%) (0%, 16%) (38%, 61%) (0%, 13%)
 p-value < 0.0001 0.0013 < 0.0001
No. (%) 
patients 
with 
overall 
platelet 
responseb 

36 (88%) 3 (14%) 33 (79%) 0 (0%) 69 (83%) 3 (7%) 

 (95% CI) (74%, 96%) (3%, 36%) (63%, 90%) (0%, 16%) (73%, 91%) (2%, 20%)
 p-value < 0.0001 < 0.0001 < 0.0001



 15

 Study 1 
non-splenectomised 

patients 

Study 2 
splenectomised patients 

Combined  
studies 1 & 2  

romiplostim 
(n = 41)

Placebo 
(n = 21)

romiplostim 
(n = 42)

Placebo 
(n = 21)

romiplostim 
(n = 83) 

Placebo 
(n = 42)

Mean no. 
weeks with 
platelet 
responsec 

15  1  12 0 14 1 

 (SD) 3.5 7.5 7.9 0.5 7.8 2.5
 p-value < 0.0001 < 0.0001 < 0.0001
No. (%) 
patients 
requiring 
rescue 
therapiesd  

8(20%) 13 (62%) 11 (26%) 12 (57%) 19 (23%) 25 (60%) 

 (95% CI) (9%, 35%) (38%, 82%) (14%, 42%) (34%, 78%) (14%, 33%) (43%, 74%)
 p-value 0.001 0.0175 < 0.0001
No. (%) 
patients 
with 
durable 
platelet 
response 
with stable 
dosee 

21 (51%) 0 (0%) 13 (31%) 0 (0%) 34 (41%) 0 (0%) 

 (95% CI) (35%, 67%) (0%, 16%) (18%, 47%) (0%, 16%) (30%, 52%) (0%, 8%)
 p-value 0.0001 0.0046 < 0.0001
a Durable platelet response was defined as weekly platelet count ≥ 50 x 109/L for 6 or more times for study 
weeks 18-25 in the absence of rescue therapies any time during the treatment period. 
b Overall platelet response is defined as achieving durable or transient platelet responses. Transient platelet 
response was defined as weekly platelet count ≥ 50 x 109/L for 4 or more times during study weeks 2-25 but 
without durable platelet response. Patient may not have a weekly response within 8 weeks after receiving any 
rescue medicinal products. 
c Number of weeks with platelet response is defined as number of weeks with platelet counts ≥ 50 x 109/L during 
study weeks 2-25. Patient may not have a weekly response within 8 weeks after receiving any rescue medicinal 
products. 
d Rescue therapies defined as any therapy administered to raise platelet counts. Patients requiring rescue 
medicinal products were not considered for durable platelet response. Rescue therapies allowed in the study were 
IVIG, platelet transfusions, anti-D immunoglobulin, and corticosteroids. 
e Stable dose defined as dose maintained within ± 1 mcg/kg during the last 8 weeks of treatment. 
 
Results of studies compared to standard of care (SOC) in non-splenectomised patients 
 
Study S3 (131) was an open-label randomised 52 week trial in adult subjects who received 
romiplostim or medical standard of care (SOC) treatment. This study evaluated non-splenectomised 
patients with ITP and platelet counts < 50 x 109/L. Romiplostim was administered to 157 subjects by 
subcutaneous (SC) injection once weekly starting at a dose of 3 mcg/kg, and adjusted throughout the 
study within a range of 1-10 mcg/kg in order to maintain platelet counts between 50 and 200 x 109/L, 
77 subjects received SOC treatment according to standard institutional practice or therapeutic 
guidelines. 
 
The overall subject incidence rate of splenectomy was 8.9% (14 of 157 subjects) in the romiplostim 
group compared with 36.4% (28 of 77 subjects) in the SOC group, with an odds ratio (romiplostim vs 
SOC) of 0.17 (95% CI: 0.08, 0.35). 
 



 16

The overall subject incidence of treatment failure was 11.5% (18 of 157 subjects) in the romiplostim 
group compared with 29.9% (23 of 77 subjects) in the SOC group, with an odds ratio (romiplostim vs 
SOC) of 0.31 (95% CI: 0.15, 0.61). 
 
Of the 157 subjects randomised to the romiplostim group, three subjects did not receive romiplostim. 
Among the 154 subjects who received romiplostim, the total median exposure to romiplostim was 
52.0 weeks and ranged from 2 to 53 weeks. The most frequently used weekly dose was between 
3-5 mcg/kg (25th-75th percentile respectively; median 3 mcg/kg). 
 
Of the 77 subjects randomised to the SOC group, two subjects did not receive any SOC. Among the 
75 subjects who received at least one dose of SOC, the total median exposure to SOC was 51 weeks 
and ranged from 0.4 to 52 weeks. 
 
Reduction in permitted concurrent ITP medical therapies 
 
In both adult placebo-controlled, double-blind studies, patients already receiving ITP medical 
therapies at a constant dosing schedule were allowed to continue receiving these medical treatments 
throughout the study (corticosteroids, danazol and/or azathioprine). Twenty-one non-splenectomised 
and 18 splenectomised patients received on-study ITP medical treatments (primarily corticosteroids) at 
the start of study. All (100%) splenectomised patients who were receiving romiplostim were able to 
reduce the dose by more than 25% or discontinue the concurrent ITP medical therapies by the end of 
the treatment period compared to 17% of placebo treated patients. Seventy-three percent of 
non-splenectomised patients receiving romiplostim were able to reduce the dose by more than 25% or 
discontinue concurrent ITP medical therapies by the end of the study compared to 50% of placebo 
treated patients (see section 4.5). 
 
Bleeding events 
 
Across the entire adult ITP clinical programme an inverse relationship between bleeding events and 
platelet counts was observed. All clinically significant (≥ grade 3) bleeding events occurred at platelet 
counts < 30 x 109/L. All bleeding events ≥ grade 2 occurred at platelet counts < 50 x 109/L. No 
statistically significant differences in the overall incidence of bleeding events were observed between 
Nplate and placebo treated patients. 
 
In the two adult placebo-controlled studies, 9 patients reported a bleeding event that was considered 
serious (5 [6.0%] romiplostim, 4 [9.8%] placebo; Odds Ratio [romiplostim/placebo] = 0.59; 95% 
CI = (0.15, 2.31)). Bleeding events that were grade 2 or higher were reported by 15% of patients 
treated with romiplostim and 34% of patients treated with placebo (Odds Ratio; 
[romiplostim/placebo] = 0.35; 95% CI = (0.14, 0.85)). 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit data for children < 1 year. 
 
The safety and efficacy of romiplostim was evaluated in two placebo-controlled, double-blind studies. 
Study S4 (279) was a phase 3 study with 24 weeks of romiplostim treatment and study S5 (195) was a 
phase 1/2 study with 12 weeks of romiplostim treatment (up to 16 weeks for eligible responders who 
enter a 4-week pharmacokinetic assessment period). 
 
Both studies enrolled paediatric subjects (≥ 1 year to < 18 years of age) with thrombocytopenia 
(defined by a mean of 2 platelet counts ≤ 30 x 109/L with neither count > 35 x 109/L in both studies) 
with ITP, regardless of splenectomy status. 
 
In study S4, 62 subjects were randomised in a 2:1 ratio to receive romiplostim (n = 42) or placebo 
(n = 20) and stratified into 1 of 3 age cohorts. The starting dose of romiplostim 1 mcg/kg and doses 
were adjusted to maintain (50 to 200 x 109/L) platelet counts. The most frequently used weekly dose 
was 3-10 mcg/kg and the maximum allowed dose on study was 10 mcg/kg. Patients received single 



 17

subcutaneous weekly injections for 24 weeks. Of those 62 subjects, 48 subjects had ITP > 12 months 
of duration (32 subjects received romiplostim and 16 subjects received placebo). 
 
The primary endpoint was the incidence of durable response, defined as achieving at least 6 weekly 
platelet counts of ≥ 50 x 109/L during weeks 18 through 25 of treatment. Overall, a significant greater 
proportion of subjects in the romiplostim arm achieved the primary endpoint compared with subjects 
in the placebo arm (p = 0.0018). A total of 22 subjects (52%) had durable platelet response in the 
romiplostim arm compared with 2 subjects (10%) in the placebo arm: ≥ 1 to < 6 years 38% versus 
25%; ≥ 6 to < 12 years 56% versus 11%; ≥ 12 to < 18 years 56% versus 0. 
 
In the subset of subjects with ITP > 12 months of duration, the incidence of durable response was also 
significantly greater in the romiplostim arm compared with the placebo arm (p = 0.0022). A total of 
17 subjects (53.1%) had durable platelet response in the romiplostim arm compared with 1 subject 
(6.3%) in the placebo arm: ≥ 1 to < 6 years 28.6% versus 25%; ≥ 6 to < 12 years 63.6% versus 0%; 
≥ 12 to < 18 years 57.1% versus 0%. 
 
The composite bleeding episode was defined as clinically significant bleeding events or the use of a 
rescue medication to prevent a clinical significant bleeding event during weeks 2 through 25 of the 
treatment period. A clinically significant bleeding event was defined as a Common Terminology 
Criteria for Adverse Events (CTCAE) version 3.0 grade ≥ 2 bleeding event. The mean (SD) number of 
composite bleeding episodes was 1.9 (4.2) for the romiplostim arm and 4.0 (6.9) for the placebo arm 
with a median (Q1, Q3) number of bleeding events of 0.0 (0, 2) for the romiplostim arm and 
0.5 (0, 4.5) in the placebo arm. In the subset of subjects with ITP > 12 months of duration, the mean 
(SD) number of composite bleeding episodes was 2.1 (4.7) for the romiplostim arm and 4.2 (7.5) for 
the placebo arm with a median (Q1, Q3) number of bleeding events of 0.0 (0, 2) for the romiplostim 
arm and 0.0 (0, 4) in the placebo arm. Because the statistical testing for the incidence of rescue 
medication use was not significant, no statistical test was done for the number of composite bleeding 
episodes endpoint. 
 
In study S5, 22 subjects were randomised in a 3:1 ratio to receive romiplostim (n = 17) or placebo 
(n = 5). Doses were increased in increments of 2 mcg/kg every 2 weeks and the target platelet count 
was ≥ 50 x 109/L. Treatment with romiplostim resulted in statistically significantly greater incidence 
of platelet response compared with placebo (p = 0.0008). Of those 22 subjects, 17 subjects had 
ITP > 12 months of duration (14 subjects received romiplostim and 3 subjects received placebo). 
Treatment with romiplostim resulted in statistically significantly greater incidence of platelet response 
compared with placebo (p = 0.0147). 
 
Paediatric subjects who had completed a prior romiplostim study (including study S4) were allowed to 
enroll in study S6 (340), an open-label extension study evaluating the safety and efficacy of long-term 
dosing of romiplostim in thrombocytopenic paediatric subjects with ITP. 
 
A total of 66 subjects were enrolled in this study, including 54 subjects (82%) who had completed 
study S4. Of these, 65 subjects (98.5%) received at least 1 dose of romiplostim. The median (Q1, Q3) 
duration of treatment was 135.0 weeks (95.0 weeks, 184.0 weeks). The median (Q1, Q3) average 
weekly dose was 4.82 mcg/kg (1.88 mcg/kg, 8.79 mcg/kg). The median (Q1, Q3) of most frequent 
dose received by subjects during the treatment period was 5.0 mcg/kg (1.0 mcg/kg, 10.0 mcg/kg). Of 
the 66 subjects enrolled in the study, 63 subjects had ITP > 12 months of duration. All the 63 subjects 
received at least 1 dose of romiplostim. The median (Q1, Q3) duration of treatment was 138.0 weeks 
(91.1 weeks, 186.0 weeks). The median (Q1, Q3) average weekly dose was 4.82 mcg/kg 
(1.88 mcg/kg, 8.79 mcg/kg). The median (Q1, Q3) of most frequent dose received by subjects during 
the treatment period was 5.0 mcg/kg (1.0 mcg/kg, 10.0 mcg/kg). 
 
Across the study, the overall subject incidence of platelet response (1 or more platelet count 
≥ 50 x 109/L in the absence of rescue medication) was 93.8% (n = 61) and was similar across age 
groups. Across all subjects, the median (Q1, Q3) number of months with platelet response was 
30.0 months (13.0 months, 43.0 months) and the median (Q1, Q3) time on study was 34.0 months 



 18

(24.0 months, 46.0 months). Across all subjects, the median (Q1, Q3) percentage of months with 
platelet response was 93.33% (67.57%, 100.00%) and was similar across age groups. 
 
In the subset of subjects with ITP > 12 months of duration, the overall subject incidence of platelet 
response was 93.7% (n = 59) and was similar across age groups. Across all subjects, the median (Q1, 
Q3) number of months with platelet response was 30.0 months (13.0 months, 43.0 months) and the 
median (Q1, Q3) time on study was 35.0 months (23.0 months, 47.0 months). Across all subjects, the 
median (Q1, Q3) percentage of months with platelet response was 93.33% (67.57%, 100.00%) and 
was similar across age groups. 
 
A total of 31 subjects (47.7%) used concurrent ITP therapy during the study including 23 subjects 
(35.4%) who used rescue medication and 5 subjects (7.7%) who used concurrent ITP medication at 
baseline. The subject prevalence of concurrent ITP medication use showed a trend towards a reduction 
over the course of the study: from 30.8% (weeks 1 to 12) to < 20.0% (weeks 13 to 240), and then 0% 
from week 240 to the end of the study. 
 
In the subset of subjects with ITP > 12 months of duration, 29 subjects (46.0%) used concurrent ITP 
therapy during the study including 21 subjects (33.3%) who used rescue medication and 5 subjects 
(7.9%) who used concurrent ITP medication at baseline. The subject prevalence of concurrent ITP 
medication use showed a trend towards a reduction over the course of the study: from 31.7% (weeks 1 
to 12) to < 20.0% (weeks 13 to 240), and then 0% from week 240 to the end of the study. 
 
The subject prevalence of rescue medication use showed a trend towards a reduction over the course 
of the study: from 24.6% (weeks 1 to 12) to < 13.0% (weeks 13 to 216), then 0% after week 216 until 
the end of the study. Similar reduction of the subject prevalence of rescue medication over the course 
of the study was seen in the subset of subjects with ITP > 12 months of duration: from 25.4% (weeks 1 
to 12) to ≤ 13.1% (weeks 13 to 216), then 0% after week 216 until the end of the study. 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of romiplostim involved target-mediated disposition, which is presumably 
mediated by TPO receptors on platelets and other cells of the thrombopoietic lineage such as 
megakaryocytes. 
 
Absorption 
 
After subcutaneous administration of 3 to 15 mcg/kg romiplostim, maximum romiplostim serum 
levels in ITP patients were obtained after 7-50 hours (median 14 hours). The serum concentrations 
varied among patients and did not correlate with the dose administered. Romiplostim serum levels 
appear inversely related to platelet counts. 
 
Distribution 
 
The volume of distribution of romiplostim following intravenous administration of romiplostim 
decreased nonlinearly from 122, 78.8, to 48.2 mL/kg for intravenous doses of 0.3, 1.0 and 10 mcg/kg, 
respectively in healthy subjects. This non-linear decrease in volume of distribution is in line with the 
(megakaryocyte and platelet) target-mediated binding of romiplostim, which may be saturated at the 
higher doses applied. 
 
Elimination 
 
Elimination half-life of romiplostim in ITP patients ranged from 1 to 34 days (median, 3.5 days). 
 
The elimination of serum romiplostim is in part dependent on the TPO receptor on platelets. As a 
result for a given dose, patients with high platelet counts are associated with low serum concentrations 
and vice versa. In another ITP clinical trial, no accumulation in serum concentrations was observed 
after 6 weekly doses of romiplostim (3 mcg/kg). 



 19

 
Special populations 
 
Pharmacokinetics of romiplostim in patients with renal and hepatic impairment has not been 
investigated. Romiplostim pharmacokinetics appear not affected by age, weight and gender to a 
clinically significant extent. 
 
Paediatric population 
 
Pharmacokinetic data of romiplostim were collected from two studies in 21 paediatric subjects with 
ITP. In study S5 (195), romiplostim concentrations were available from 17 subjects at doses ranging 
from 1 to 10 mcg/kg. In Study S6 (340), intensive romiplostim concentrations were available from 4 
subjects (2 at 7 mcg/kg and 2 at 9 mcg/kg). Serum concentrations of romiplostim in paediatrics with 
ITP were within the range observed in adult ITP subjects receiving the same dose range of 
romiplostim. Similar to adults with ITP, romiplostim pharmacokinetics are highly variable in 
paediatric subjects with ITP and are not reliable and predictive. However, the data are insufficient to 
draw any meaningful conclusion relating to the impact of dose and age on the pharmacokinetics of 
romiplostim. 
 
5.3 Preclinical safety data 
 
Multiple dose romiplostim toxicology studies were conducted in rats for 4 weeks and in monkeys for 
up to 6 months. In general, effects observed during these studies were related to the thrombopoietic 
activity of romiplostim and were similar regardless of study duration. Injection site reactions were also 
related to romiplostim administration. Myelofibrosis has been observed in the bone marrow of rats at 
all tested dose levels. In these studies, myelofibrosis was not observed in animals after a 4-week 
post-treatment recovery period, indicating reversibility. 
 
In 1-month rat and monkey toxicology studies, a mild decrease in red blood cell count, haematocrit 
and haemoglobin was observed. There was also a stimulatory effect on leukocyte production, as 
peripheral blood counts for neutrophils, lymphocytes, monocytes, and eosinophils were mildly 
increased. In the longer duration chronic monkey study, there was no effect on the erythroid and 
leukocytic lineages when romiplostim was administered for 6 months where the administration of 
romiplostim was decreased from thrice weekly to once weekly. Additionally, in the phase 3 pivotal 
studies, romiplostim did not affect the red blood cell and white blood cells lineages relative to placebo 
treated subjects. 
 
Due to the formation of neutralising antibodies pharmacodynamic effects of romiplostim in rats were 
often decreasing at prolonged duration of administration. Toxicokinetic studies showed no interaction 
of the antibodies with the measured concentrations. Although high doses were tested in the animal 
studies, due to differences between the laboratory species and humans with regard to the sensitivity for 
the pharmacodynamic effect of romiplostim and the effect of neutralising antibodies, safety margins 
cannot be reliably estimated. 
 
Carcinogenesis 
 
The carcinogenic potential of romiplostim has not been evaluated. Therefore, the risk of potential 
carcinogenicity of romiplostim in humans remains unknown. 
 
Reproductive toxicology 
 
In all developmental studies neutralising antibodies were formed, which may have inhibited 
romiplostim effects. In embryo-foetal development studies in mice and rats, reductions in maternal 
body weight were found only in mice. In mice there was evidence of increased post-implantation loss. 
In a prenatal and postnatal development study in rats an increase of the duration of gestation and a 
slight increase in the incidence of peri-natal pup mortality was found. Romiplostim is known to cross 



 20

the placental barrier in rats and may be transmitted from the mother to the developing foetus and 
stimulate foetal platelet production. Romiplostim had no observed effect on the fertility of rats. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol (E421) 
Sucrose 
L-histidine 
Hydrochloric acid (for pH adjustment) 
Polysorbate 20 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products, except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
5 years. 
 
After reconstitution: Chemical and physical in-use stability has been demonstrated for 24 hours at 
25ºC and for 24 hours at 2ºC – 8ºC, when protected from light and kept in the original vial. 
 
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 25ºC or 24 hours in a refrigerator (2ºC – 8ºC), protected 
from light. 
 
After dilution: Chemical and physical in-use stability has been demonstrated for 4 hours at 25ºC when 
the diluted product was held in a disposable syringe, or 4 hours in a refrigerator (2ºC – 8ºC) when the 
diluted product was held in the original vial. 
 
From a microbiological point of view, the diluted 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 4 hours at 25ºC in disposable syringes, or 4 hours in a 
refrigerator (2ºC – 8ºC) in the original vials, protected from light. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2ºC – 8ºC). 
Do not freeze. 
Store in the original carton in order to protect from light. 
May be removed from the refrigerator for a period of 30 days at room temperature (up to 25ºC) when 
stored in the original carton. 
 
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Single-dose vial (type 1 clear glass) with a stopper (chlorobutyl rubber), seal (aluminium) and a 
flip-off cap (polypropylene). The 125 mcg vial cap is beige, the 250 mcg vial cap is red and the 
500 mcg vial cap is blue. 
 
Carton containing 1 or 4 vials of romiplostim. 



 21

 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Reconstitution 
 
Nplate is a sterile but unpreserved medicinal product and is intended for single use only. Nplate should 
be reconstituted in accordance with good aseptic practice. 
 
Nplate 125 micrograms powder for solution for injection 
 
Nplate 125 micrograms powder for solution for injection should be reconstituted with 0.44 mL sterile 
water for injections, yielding a deliverable volume of 0.25 mL. An additional overfill is included in 
each vial to ensure that 125 mcg of romiplostim can be delivered (see vial content table below). 
 
Nplate 250 micrograms powder for solution for injection 
 
Nplate 250 micrograms powder for solution for injection should be reconstituted with 0.72 mL sterile 
water for injections, yielding a deliverable volume of 0.5 mL. An additional overfill is included in 
each vial to ensure that 250 mcg of romiplostim can be delivered (see vial content table below). 
 
Nplate 500 micrograms powder for solution for injection 
 
Nplate 500 micrograms powder for solution for injection should be reconstituted with 1.2 mL sterile 
water for injections, yielding a deliverable volume of 1 mL. An additional overfill is included in each 
vial to ensure that 500 mcg of romiplostim can be delivered (see vial content table below). 
 
Vial Content: 
 
Nplate single- 
use vial 

Total vial 
content of 
romiplostim  

 Volume of 
sterile water 
for injection  

 Deliverable 
product and 
volume 

Final 
concentration 

125 mcg 230 mcg + 0.44 mL = 125 mcg in 0.25 mL 500 mcg/mL
250 mcg 375 mcg + 0.72 mL = 250 mcg in 0.50 mL 500 mcg/mL
500 mcg 625 mcg + 1.20 mL = 500 mcg in 1.00 mL 500 mcg/mL
 
Sterile water for injections only should be used when reconstituting the medicinal product. Sodium 
chloride solutions or bacteriostatic water should not be used when reconstituting the medicinal 
product. 
 
Water for injections should be injected into the vial. The vial contents may be swirled gently and 
inverted during dissolution. The vial should not be shaken or vigorously agitated. Generally, 
dissolution of Nplate takes less than 2 minutes. Visually inspect the solution for particulate matter and 
discolouration before administration. The reconstituted solution should be clear and colourless and 
should not be administered if particulate matter and/or discolouration are observed. 
 
For the storage condition after reconstitution of the medicinal product see section 6.3. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 



 22

Dilution (required when the calculated individual patient dose is less than 23 mcg) 
 
Initial reconstitution of romiplostim with designated volumes of sterile water for injections results in a 
concentration of 500 mcg/mL in all vial sizes. If the calculated individual patient dose is less than 
23 mcg (see section 4.2), an additional dilution step to 125 mcg/mL with preservative-free, sterile, 
sodium chloride 9 mg/mL (0.9%) solution for injection is required to ensure accurate volume (see 
table below). 
 
Dilution Guidelines: 
 
Nplate single-use vial Add this volume of preservative-free, sterile, 

sodium chloride 9 mg/mL (0.9%) solution 
for injection to the reconstituted vial 

Concentration after dilution 

125 mcg 1.38 mL 125 mcg/mL 
250 mcg 2.25 mL 125 mcg/mL 
500 mcg 3.75 mL 125 mcg/mL 
 
Preservative-free, sterile, sodium chloride 9 mg/mL (0.9%) solution for injection only must be used 
for dilution. Dextrose (5%) in water or sterile water for injection should not be used for the dilution. 
No other diluents have been tested. 
 
For the storage condition after dilution of the reconstituted medicinal product see section 6.3. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/08/497/009 
EU/1/08/497/010 
EU/1/08/497/001 
EU/1/08/497/003 
EU/1/08/497/002 
EU/1/08/497/004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 4 February 2009 
Date of latest renewal: 20 December 2013 
 
 
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 



 23

1. NAME OF THE MEDICINAL PRODUCT 
 
Nplate 250 micrograms powder and solvent for solution for injection 
Nplate 500 micrograms powder and solvent for solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Nplate 250 micrograms powder and solvent for solution for injection 
 
Each vial contains 250 mcg of romiplostim. After reconstitution, a deliverable volume of 0.5 mL 
solution contains 250 mcg of romiplostim (500 mcg/mL). An additional overfill is included in each 
vial to ensure that 250 mcg of romiplostim can be delivered. 
 
Nplate 500 micrograms powder and solvent for solution for injection 
 
Each vial contains 500 mcg of romiplostim. After reconstitution, a deliverable volume of 1 mL 
solution contains 500 mcg of romiplostim (500 mcg/mL). An additional overfill is included in each 
vial to ensure that 500 mcg of romiplostim can be delivered. 
 
Romiplostim is produced by recombinant DNA technology in Escherichia coli (E. coli). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection (powder for injection). 
 
The powder is white. 
The solvent is a clear colourless liquid. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Nplate is indicated for adult chronic immune (idiopathic) thrombocytopenic purpura (ITP) patients 
who are refractory to other treatments (e.g. corticosteroids, immunoglobulins) (see sections 4.2 
and 5.1). 
 
4.2 Posology and method of administration 
 
Treatment should remain under the supervision of a physician who is experienced in the treatment of 
haematological diseases. 
 
Posology 
 
Nplate should be administered once weekly as a subcutaneous injection. 
 
Initial dose 
 
The initial dose of romiplostim is 1 mcg/kg based on actual body weight. 
 



 24

Dose calculation 
 
Initial or subsequent 
once weekly dose: 

Weight* in kg x Dose in mcg/kg = Individual patient dose in mcg 

Volume to administer: Dose in mcg x 1 mL = Amount to inject in mL 500 mcg
 

Example: 75 kg patient is initiated at 1 mcg/kg of romiplostim. 
The individual patient dose = 
75 kg x 1 mcg/kg = 75 mcg 
The corresponding amount of Nplate solution to inject = 

75 mcg x 1 mL = 0.15 mL 500 mcg
 

*Actual body weight at initiation of treatment should always be used when calculating dose of romiplostim. 
Future dose adjustments are based on changes in platelet counts only and made in 1 mcg/kg increments (see 
table below). 
 
Dose adjustments 
 
A subject’s actual body weight at initiation of therapy should be used to calculate dose. The once 
weekly dose of romiplostim should be increased by increments of 1 mcg/kg until the patient achieves a 
platelet count ≥ 50 x 109/L. Platelet counts should be assessed weekly until a stable platelet count 
(≥ 50 x 109/L for at least 4 weeks without dose adjustment) has been achieved. Platelet counts should 
be assessed monthly thereafter. A maximum once weekly dose of 10 mcg/kg should not be exceeded. 
 
Adjust the dose as follows: 
 

Platelet count 
(x 109/L) Action 

< 50 Increase once weekly dose by 1 mcg/kg  

> 150 for two 
consecutive weeks Decrease once weekly dose by 1 mcg/kg 

> 250 

Do not administer, continue to assess the platelet count weekly 
 
After the platelet count has fallen to < 150 x 109/L, resume dosing with once 
weekly dose reduced by 1 mcg/kg

 
Due to the interindividual variable platelet response, in some patients platelet count may abruptly fall 
below 50 x 109/L after dose reduction or treatment discontinuation. In these cases, if clinically 
appropriate, higher cut-off levels of platelet count for dose reduction (200 x 109/L) and treatment 
interruption (400 x 109/L) may be considered according to medical judgement. 
 
A loss of response or failure to maintain a platelet response with romiplostim within the recommended 
dosing range should prompt a search for causative factors (see section 4.4, loss of response to 
romiplostim). 
 
Treatment discontinuation 
 
Treatment with romiplostim should be discontinued if the platelet count does not increase to a level 
sufficient to avoid clinically important bleeding after four weeks of romiplostim therapy at the highest 
weekly dose of 10 mcg/kg. 
 
Patients should be clinically evaluated periodically and continuation of treatment should be decided on 
an individual basis by the treating physician, and in non-splenectomised patients this should include 
evaluation relative to splenectomy. The reoccurrence of thrombocytopenia is likely upon 
discontinuation of treatment (see section 4.4). 
 



 25

Elderly patients (≥ 65 years) 
 
No overall differences in safety or efficacy have been observed in patients < 65 and ≥ 65 years of age 
(see section 5.1). Although based on these data no adjustment of the dosing regimen is required for 
older patients, care is advised considering the small number of elderly patients included in the clinical 
trials so far. 
 
Paediatric population 
 
The safety and efficacy of romiplostim 250/500 mcg powder and solvent for solution for injection, 
also used for self-administration in eligible adult patients, have not been established in patients aged 
under 18 years. Self-administration of romiplostim is not allowed for paediatric patients. No data are 
available. Other pharmaceutical forms/strengths may be more appropriate for administration to this 
population. 
 
Patients with hepatic Impairment 
 
Romiplostim should not be used in patients with moderate to severe hepatic impairment (Child-Pugh 
score ≥ 7) unless the expected benefit outweighs the identified risk of portal venous thrombosis in 
patients with thrombocytopenia associated to hepatic insufficiency treated with thrombopoietin (TPO) 
agonists (see section 4.4). 
 
If the use of romiplostim is deemed necessary, platelet count should be closely monitored to minimise 
the risk of thromboembolic complications. 
 
Patients with renal impairment 
 
No formal clinical trials have been conducted in these patient populations. Nplate should be used with 
caution in these populations. 
 
Method of administration 
 
For subcutaneous use. 
 
After reconstitution of the powder, Nplate solution for injection is administered subcutaneously. The 
injection volume may be very small. Caution should be used during preparation of Nplate in 
calculating the dose and reconstitution with the correct volume of sterile water for injection. Special 
care should be taken to ensure that the appropriate volume of Nplate is withdrawn from the vial for 
subcutaneous administration – a syringe with graduations of 0.01 mL should be used. 
 
Patients who have a stable platelet count ≥ 50 x 109/L for at least 4 weeks without dose adjustment 
may, at the discretion of the supervising physician, self-administer Nplate solution for injection. 
Patients eligible for self-administration of Nplate should be trained in these procedures. 
 
After the first 4 weeks of self-administration, the patient should again be supervised while 
reconstituting and administering Nplate. Only patients who demonstrate the ability to reconstitute and 
self-administer Nplate are allowed to continue doing so. 
 
For instructions on reconstitution and administration of the medicinal product, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to E. coli 
derived proteins. 
 



 26

4.4 Special warnings and precautions for use 
 
Reoccurrence of thrombocytopenia and bleeding after cessation of treatment 
 
Thrombocytopenia is likely to reoccur upon discontinuation of treatment with romiplostim. There is an 
increased risk of bleeding if romiplostim treatment is discontinued in the presence of anticoagulants or 
anti-platelet agents. Patients should be closely monitored for a decrease in platelet count and medically 
managed to avoid bleeding upon discontinuation of treatment with romiplostim. It is recommended 
that, if treatment with romiplostim is discontinued, ITP treatment be restarted according to current 
treatment guidelines. Additional medical management may include cessation of anticoagulant and/or 
antiplatelet therapy, reversal of anticoagulation, or platelet support. 
 
Increased bone marrow reticulin 
 
Increased bone marrow reticulin is believed to be a result of TPO receptor stimulation, leading to an 
increased number of megakaryocytes in the bone marrow, which may subsequently release cytokines. 
Increased reticulin may be suggested by morphological changes in the peripheral blood cells and can 
be detected through bone marrow biopsy. Therefore, examinations for cellular morphological 
abnormalities using peripheral blood smear and complete blood count (CBC) prior to and during 
treatment with romiplostim are recommended. See section 4.8 for information on the increases of 
reticulin observed in romiplostim clinical trials. 
 
If a loss of efficacy and abnormal peripheral blood smear is observed in patients, administration of 
romiplostim should be discontinued, a physical examination should be performed, and a bone marrow 
biopsy with appropriate staining for reticulin should be considered. If available, comparison to a prior 
bone marrow biopsy should be made. If efficacy is maintained and abnormal peripheral blood smear is 
observed in patients, the physician should follow appropriate clinical judgment, including 
consideration of a bone marrow biopsy, and the risk-benefit of romiplostim and alternative ITP 
treatment options should be re-assessed. 
 
Thrombotic/thromboembolic complications 
 
Platelet counts above the normal range present a risk for thrombotic/thromboembolic complications. 
The incidence of thrombotic/thromboembolic events observed in clinical trials was 6.0% with 
romiplostim and 3.6% with placebo. Caution should be used when administering romiplostim to 
patients with known risk factors for thromboembolism including but not limited to inherited (e.g. 
Factor V Leiden) or acquired risk factors (e.g. ATIII deficiency, antiphospholipid syndrome), 
advanced age, patients with prolonged periods of immobilisation, malignancies, contraceptives and 
hormone replacement therapy, surgery/trauma, obesity and smoking. 
 
Cases of thromboembolic events (TEEs), including portal vein thrombosis, have been reported in 
patients with chronic liver disease receiving romiplostim. Romiplostim should be used with caution in 
these populations. Dose adjustment guidelines should be followed (see section 4.2). 
 
Medication Errors 
 
Medication errors including overdose and underdose have been reported in patients receiving Nplate, 
dose calculation and dose adjustment guidelines should be followed (see section 4.2). 
 
Overdose may result in an excessive increase in platelet counts associated with 
thrombotic/thromboembolic complications. If the platelet counts are excessively increased, 
discontinue Nplate and monitor platelet counts. Reinitiate treatment with Nplate in accordance with 
dosing and administration recommendations. Underdose may result in lower than expected platelet 
counts and potential for bleeding. Platelet counts should be monitored in patients receiving Nplate (see 
sections 4.2, 4.4 and 4.9). 
 



 27

Progression of existing Myelodysplastic Syndromes (MDS) 
 
A positive benefit/risk for romiplostim is only established for the treatment of thrombocytopenia 
associated with chronic ITP and romiplostim must not be used in other clinical conditions associated 
with thrombocytopenia. 
 
The diagnosis of ITP in adults and elderly patients should have been confirmed by the exclusion of 
other clinical entities presenting with thrombocytopenia, in particular the diagnosis of MDS must be 
excluded. A bone marrow aspirate and biopsy should normally have been done over the course of the 
disease and treatment, particularly in patients over 60 years of age, for those with systemic symptoms 
or abnormal signs such as increased peripheral blast cells. 
 
In clinical studies of treatment with romiplostim in patients with MDS, cases of transient increases in 
blast cell counts were observed and cases of MDS disease progression to AML were reported. In a 
randomised placebo-controlled trial in MDS subjects, treatment with romiplostim was prematurely 
stopped due to a numerical excess of disease progression to AML and an increase in circulating blasts 
greater than 10% in patients receiving romiplostim. Of the cases of MDS disease progression to AML 
that were observed, patients with RAEB-1 classification of MDS at baseline were more likely to have 
disease progression to AML compared to lower risk MDS. 
 
Romiplostim must not be used for the treatment of thrombocytopenia due to MDS or any other cause 
of thrombocytopenia other than ITP outside of clinical trials. 
 
Loss of response to romiplostim 
 
A loss of response or failure to maintain a platelet response with romiplostim treatment within the 
recommended dosing range should prompt a search for causative factors, including immunogenicity 
(see section 4.8) and increased bone marrow reticulin (see above). 
 
Effects of romiplostim on red and white blood cells 
 
Alterations in red (decrease) and white (increase) blood cell parameters have been observed in 
non-clinical toxicology studies (rat and monkey) as well as in ITP patients. Concurrent anaemia and 
leucocytosis (within a 4-week window) may occur in patients regardless of splenectomy status, but 
have been seen more often in patients who have had a prior splenectomy. Monitoring of these 
parameters should be considered in patients treated with romiplostim. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. The potential interactions of romiplostim with 
co-administered medicinal products due to binding to plasma proteins remain unknown. 
 
Medicinal products used in the treatment of ITP in combination with romiplostim in clinical trials 
included corticosteroids, danazol, and/or azathioprine, intravenous immunoglobulin (IVIG), and 
anti-D immunoglobulin. Platelet counts should be monitored when combining romiplostim with other 
medicinal products for the treatment of ITP in order to avoid platelet counts outside of the 
recommended range (see section 4.2). 
 
Corticosteroids, danazol, and azathioprine use may be reduced or discontinued when given in 
combination with romiplostim (see section 5.1). Platelet counts should be monitored when reducing or 
discontinuing other ITP treatments in order to avoid platelet counts below the recommended range 
(see section 4.2). 
 



 28

4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data from the use of romiplostim in pregnant women. 
 
Studies in animals have shown that romiplostim crossed the placenta and increased foetal platelet 
counts. Post implantation loss and a slight increase in peri-natal pup mortality also occurred in animal 
studies (see section 5.3). 
 
Romiplostim is not recommended during pregnancy and in women of childbearing potential not using 
contraception. 
 
Breast-feeding 
 
It is unknown whether romiplostim/metabolites are excreted 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 romiplostim therapy taking into account the benefit of breast feeding for 
the child and the benefit of therapy for the woman. 
 
Fertility 
 
There is no data available on fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Nplate has moderate influence on the ability to drive and use machines. In clinical trials, mild to 
moderate, transient bouts of dizziness were experienced by some patients. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Based on an analysis of all adult ITP patients receiving romiplostim in 4 controlled and 5 uncontrolled 
clinical trials, the overall subject incidence of all adverse reactions for romiplostim-treated subjects 
was 91.5% (248/271). The mean duration of exposure to romiplostim in this study population was 
50 weeks. 
 
The most serious adverse reactions that may occur during Nplate treatment include: reoccurrence of 
thrombocytopenia and bleeding after cessation of treatment, increased bone marrow reticulin, 
thrombotic/thromboembolic complications, medication errors and progression of existing MDS to 
AML. The most common adverse reactions observed include hypersensitivity reactions (including 
cases of rash, urticaria and angioedema) and headache. 
 
Tabulated list of adverse reactions 
 
Frequencies are 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) and not 
known (cannot be estimated from the available data). Within each MedDRA system organ class and 
frequency grouping, undesirable effects are presented in order of decreasing incidence. 
 



 29

MedDRA system 
organ class 

Very common  Common  Uncommon 

Infections and 
infestations 

Upper respiratory 
tract infection 

Gastroenteritis Influenza 
Localised infection 
Nasopharyngitis 

Neoplasms benign, 
malignant and 
unspecified (including 
cysts and polyps) 

  Multiple myeloma 
Myelofibrosis 

Blood and lymphatic 
system disorders 

 Bone marrow 
disorder* 
Thrombocytopenia* 
Anaemia 

Aplastic anaemia 
Bone marrow failure 
Leucocytosis 
Splenomegaly 
Thrombocythaemia 
Platelet count increased 
Platelet count abnormal 

Immune system 
disorder 

Hypersensitivity** Angioedema  

Metabolism and 
nutrition disorders 

  Alcohol intolerance 
Anorexia 
Decreased appetite 
Dehydration 
Gout

Psychiatric disorders  Insomnia Depression 
Abnormal dreams 

Nervous system 
disorders 

Headache Dizziness 
Migraine 
Paraesthesia 

Clonus 
Dysgeusia 
Hypoaesthesia 
Hypogeusia 
Neuropathy peripheral 
Transverse sinus thrombosis

Eye disorders   Conjunctival haemorrhage 
Accommodation disorder 
Blindness 
Eye disorder 
Eye pruritus 
Lacrimation increased 
Papilloedema 
Visual disturbances 

Ear and labyrinth 
disorders 

  Vertigo 

Cardiac disorders  Palpitations Myocardial infarction 
Heart rate increased 

Vascular disorders  Flushing Deep vein thrombosis 
Hypotension 
Peripheral embolism 
Peripheral ischaemia 
Phlebitis 
Thrombophlebitis superficial 
Thrombosis 
Erythromelalgia 

Respiratory, thoracic 
and mediastinal 
disorders 

 Pulmonary 
embolism* 

Cough 
Rhinorrhoea 
Dry throat 
Dyspnoea 
Nasal congestion 
Painful respiration 



 30

MedDRA system 
organ class 

Very common  Common  Uncommon 

Gastrointestinal 
disorders 

 Nausea 
Diarrhoea 
Abdominal pain 
Constipation 
Dyspepsia 

Vomiting 
Rectal haemorrhage 
Breath odour 
Dysphagia 
Gastro-oesophageal reflux 
disease 
Haematochezia 
Mouth haemorrhage 
Stomach discomfort 
Stomatitis 
Tooth discolouration 

Hepatobiliary 
disorders 

  Portal vein thrombosis 
Increase in transaminase

Skin and 
subcutaneous tissue 
disorders 

 Pruritus 
Ecchymosis 
Rash 

Alopecia 
Photosensitivity reaction 
Acne 
Dermatitis contact 
Dry skin 
Eczema 
Erythema 
Exfoliative rash 
Hair growth abnormal 
Prurigo 
Purpura 
Rash papular 
Rash pruritic 
Skin nodule 
Skin odour abnormal 
Urticaria 

Musculoskeletal and 
connective tissue 
disorders 

 Arthralgia 
Myalgia 
Muscle spasms 
Pain in extremity 
Back pain 
Bone pain

Muscle tightness 
Muscular weakness 
Shoulder pain 
Muscle twitching 

Renal and urinary 
disorders 

  Protein urine present 

Reproductive system 
and breast disorders 

  Vaginal haemorrhage 

General disorders and 
administration site 
conditions 

 Fatigue 
Oedema peripheral 
Influenza like illness 
Pain 
Asthenia 
Pyrexia 
Chills 
Injection site reaction

Injection site haemorrhage 
Chest pain 
Irritability 
Malaise 
Face oedema 
Feeling hot 
Feeling jittery 



 31

MedDRA system 
organ class 

Very common  Common  Uncommon 

Investigations   Blood pressure increased 
Blood lactate dehydrogenase 
increased 
Body temperature increased 
Weight decreased 
Weight increased 

Injury, poisoning and 
procedural 
complications 

 Contusion  

* see section 4.4 
** Hypersensitivity reactions including cases of rash, urticaria, and angioedema 
 
Description of selected adverse reactions 
 
In addition the reactions listed below have been deemed to be related to romiplostim treatment. 
 
Thrombocytosis 
 
Based on an analysis of all adult ITP patients receiving romiplostim in 4 controlled and 5 uncontrolled 
clinical trials, 3 events of thrombocytosis were reported, n = 271. No clinical sequelae were reported 
in association with the elevated platelet counts in any of the 3 subjects. 
 
Thrombocytopenia after cessation of treatment 
 
Based on an analysis of all adult ITP patients receiving romiplostim in 4 controlled and 5 uncontrolled 
clinical trials, 4 events of thrombocytopenia after cessation of treatment were reported, n = 271 (see 
section 4.4). 
 
Progression of existing Myelodysplastic Syndromes (MDS) 
 
In a randomised placebo-controlled trial in MDS subjects treatment with romiplostim was prematurely 
stopped due to a numerical increase in cases of MDS disease progression to AML and transient 
increases in blast cell counts in patients treated with romiplostim compared to placebo. Of the cases of 
MDS disease progression to AML that were observed, patients with RAEB-1 classification of MDS at 
baseline were more likely to have disease progression to AML (see section 4.4). Overall survival was 
similar to placebo. 
 
Increased bone marrow reticulin 
 
In clinical trials, romiplostim treatment was discontinued in 4 of the 271 patients because of bone 
marrow reticulin deposition. In 6 additional patients reticulin was observed upon bone marrow biopsy 
(see section 4.4). 
 
Immunogenicity 
 
Clinical trials in adult ITP patients examined antibodies to romiplostim and TPO. While 5.7% 
(60/1,046) and 3.2% (33/1,046) of the subjects were positive for developing binding antibodies to 
romiplostim and TPO respectively, only 4 subjects were positive for neutralising antibodies to 
romiplostim but these antibodies did not cross react with endogenous TPO. Of the 4 subjects, 
2 subjects tested negative for neutralising antibodies to romiplostim at the subject’s last timepoint 
(transient positive) and 2 subjects remained positive at the subject’s last timepoint (persistent 
antibodies). The incidence of pre-existing antibodies to romiplostim and TPO was 3.3% (35/1,046) 
and 3.0% (31/1,046), respectively. 
 



 32

As with all therapeutic proteins, there is a potential for immunogenicity. If formation of neutralising 
antibodies is suspected, contact the local representative of the Marketing Authorisation Holder (see 
section 6 of the Package Leaflet) for antibody testing. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
No adverse effects were seen in rats given a single dose of 1,000 mcg/kg or in monkeys after repeated 
administration of romiplostim at 500 mcg/kg (100 or 50 times the maximum clinical dose of 
10 mcg/kg, respectively). 
 
In the event of overdose, platelet counts may increase excessively and result in 
thrombotic/thromboembolic complications. If the platelet counts are excessively increased, 
discontinue Nplate and monitor platelet counts. Reinitiate treatment with Nplate in accordance with 
dosing and administration recommendations (see sections 4.2 and 4.4). 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antihaemorrhagics, other systemic haemostatics, ATC code: B02BX04 
 
Mechanism of action 
 
Romiplostim is an Fc-peptide fusion protein (peptibody) that signals and activates intracellular 
transcriptional pathways via the TPO receptor (also known as cMpl) to increase platelet production. 
The peptibody molecule is comprised of a human immunoglobulin IgG1 Fc domain, with each 
single-chain subunit covalently linked at the C-terminus to a peptide chain containing 2 TPO 
receptor-binding domains. 
 
Romiplostim has no amino acid sequence homology to endogenous TPO. In pre-clinical and clinical 
trials no anti-romiplostim antibodies cross reacted with endogenous TPO. 
 
Clinical efficacy and safety 
 
The safety and efficacy of romiplostim have been evaluated for up to 3 years of continuous treatment. 
In clinical trials, treatment with romiplostim resulted in dose-dependent increases in platelet count. 
Time to reach the maximum effect on platelet count is approximately 10-14 days, and is independent 
of the dose. After a single subcutaneous dose of 1 to 10 mcg/kg romiplostim in ITP patients, the peak 
platelet count was 1.3 to 14.9 times greater than the baseline platelet count over a 2 to 3 week period 
and the response was variable among patients. The platelet counts of ITP patients who received 
6 weekly doses of 1 or 3 mcg/kg of romiplostim were within the range of 50 to 450 x 109/L for most 
patients. Of the 271 patients who received romiplostim in ITP clinical trials, 55 (20%) were age 65 
and over, and 27 (10%) were 75 and over. No overall differences in safety or efficacy have been 
observed between older and younger patients in the placebo-controlled studies. 
 



 33

Results from pivotal placebo-controlled studies 
 
The safety and efficacy of romiplostim was evaluated in two placebo-controlled, double-blind studies 
in adults with ITP who had completed at least one treatment prior to study entry and are representative 
of the entire spectrum of such ITP patients. 
 
Study S1 (212) evaluated patients who were non-splenectomised and had an inadequate response or 
were intolerant to prior therapies. Patients had been diagnosed with ITP for approximately 2 years at 
the time of study entry. Patients had a median of 3 (range, 1 to 7) treatments for ITP prior to study 
entry. Prior treatments included corticosteroids (90% of all patients), immunoglobulins (76%), 
rituximab (29%), cytotoxic therapies (21%), danazol (11%), and azathioprine (5%). Patients had a 
median platelet count of 19 x 109/L at study entry. 
 
Study S2 (105) evaluated patients who were splenectomised and continued to have thrombocytopenia. 
Patients had been diagnosed with ITP for approximately 8 years at the time of study entry. In addition 
to a splenectomy, patients had a median of 6 (range, 3 to 10) treatments for ITP prior to study entry. 
Prior treatments included corticosteroids (98% of all patients), immunoglobulins (97%), rituximab 
(71%), danazol (37%), cytotoxic therapies (68%), and azathioprine (24%). Patients had a median 
platelet count of 14 x 109/L at study entry. 
 
Both studies were similarly designed. Patients (≥ 18 years) were randomised in a 2:1 ratio to receive a 
starting dose of romiplostim 1 mcg/kg or placebo. Patients received single subcutaneous weekly 
injections for 24 weeks. Doses were adjusted to maintain (50 to 200 x 109/L) platelet counts. In both 
studies, efficacy was determined by an increase in the proportion of patients who achieved a durable 
platelet response. The median average weekly dose for splenectomised patients was 3 mcg/kg and for 
non-splenectomised patients was 2 mcg/kg. 
 
A significantly higher proportion of patients receiving romiplostim achieved a durable platelet 
response compared to patients receiving placebo in both studies. Following the first 4-weeks of study 
romiplostim maintained platelet counts ≥ 50 x 109/L in between 50% to 70% of patients during the 
6 month treatment period in the placebo-controlled studies. In the placebo group, 0% to 7% of patients 
were able achieve a platelet count response during the 6 months of treatment. A summary of the key 
efficacy endpoints is presented below. 
 
Summary of key efficacy results from placebo-controlled studies 
 
 Study 1 

non-splenectomised 
patients 

Study 2 
splenectomised patients 

Combined  
studies 1 & 2  

romiplostim 
(n = 41)

Placebo 
(n = 21)

romiplostim 
(n = 42)

Placebo 
(n = 21)

romiplostim 
(n = 83) 

Placebo 
(n = 42)

No. (%) 
patients 
with 
durable 
platelet 
responsea  

25 (61%) 1 (5%) 16 (38%) 0 (0%) 41 (50%) 1 (2%) 

 (95% CI) (45%, 76%) (0%, 24%) (24%, 54%) (0%, 16%) (38%, 61%) (0%, 13%)
 p-value < 0.0001 0.0013 < 0.0001
No. (%) 
patients 
with 
overall 
platelet 
responseb  

36 (88%) 3 (14%) 33 (79%) 0 (0%) 69 (83%) 3 (7%) 

 (95% CI) (74%, 96%) (3%, 36%) (63%, 90%) (0%, 16%) (73%, 91%) (2%, 20%)
 p-value < 0.0001 < 0.0001 < 0.0001



 34

 Study 1 
non-splenectomised 

patients 

Study 2 
splenectomised patients 

Combined  
studies 1 & 2  

romiplostim 
(n = 41)

Placebo 
(n = 21)

romiplostim 
(n = 42)

Placebo 
(n = 21)

romiplostim 
(n = 83) 

Placebo 
(n = 42)

Mean no. 
weeks with 
platelet 
responsec 

15  1  12 0 14 1 

 (SD) 3.5 7.5 7.9 0.5 7.8 2.5
 p-value < 0.0001 < 0.0001 < 0.0001
No. (%) 
patients 
requiring 
rescue 
therapiesd  

8(20%) 13 (62%) 11 (26%) 12 (57%) 19 (23%) 25 (60%) 

 (95% CI) (9%, 35%) (38%, 82%) (14%, 42%) (34%, 78%) (14%, 33%) (43%, 74%)
 p-value 0.001 0.0175 < 0.0001
No. (%) 
patients 
with 
durable 
platelet 
response 
with stable 
dosee 

21 (51%) 0 (0%) 13 (31%) 0 (0%) 34 (41%) 0 (0%) 

 (95% CI) (35%, 67%) (0%, 16%) (18%, 47%) (0%, 16%) (30%, 52%) (0%, 8%)
 p-value 0.0001 0.0046 < 0.0001
a Durable platelet response was defined as weekly platelet count ≥ 50 x 109/L for 6 or more times for study 
weeks 18-25 in the absence of rescue therapies any time during the treatment period. 
b Overall platelet response is defined as achieving durable or transient platelet responses. Transient platelet 
response was defined as weekly platelet count ≥ 50 x 109/L for 4 or more times during study weeks 2-25 but 
without durable platelet response. Patient may not have a weekly response within 8 weeks after receiving any 
rescue medicinal products. 
c Number of weeks with platelet response is defined as number of weeks with platelet counts ≥ 50 x 109/L during 
study weeks 2-25. Patient may not have a weekly response within 8 weeks after receiving any rescue medicinal 
products. 
d Rescue therapies defined as any therapy administered to raise platelet counts. Patients requiring rescue 
medicinal products were not considered for durable platelet response. Rescue therapies allowed in the study were 
IVIG, platelet transfusions, anti-D immunoglobulin, and corticosteroids. 
e Stable dose defined as dose maintained within ± 1 mcg/kg during the last 8 weeks of treatment. 
 
Results of studies compared to standard of care (SOC) in non-splenectomised patients 
 
Study S3 (131) was an open-label randomised 52 week trial in subjects who received romiplostim or 
medical standard of care (SOC) treatment. This study evaluated non-splenectomised patients with ITP 
and platelet counts < 50 x 109/L. Romiplostim was administered to 157 subjects by subcutaneous (SC) 
injection once weekly starting at a dose of 3 mcg/kg, and adjusted throughout the study within a range 
of 1-10 mcg/kg in order to maintain platelet counts between 50 and 200 x 109/L, 77 subjects received 
SOC treatment according to standard institutional practice or therapeutic guidelines. 
 
The overall subject incidence rate of splenectomy was 8.9% (14 of 157 subjects) in the romiplostim 
group compared with 36.4% (28 of 77 subjects) in the SOC group, with an odds ratio (romiplostim vs 
SOC) of 0.17 (95% CI: 0.08, 0.35). 
 
The overall subject incidence of treatment failure was 11.5% (18 of 157 subjects) in the romiplostim 
group compared with 29.9% (23 of 77 subjects) in the SOC group, with an odds ratio (romiplostim vs 
SOC) of 0.31 (95% CI: 0.15, 0.61). 



 35

 
Of the 157 subjects randomised to the romiplostim group, three subjects did not receive romiplostim. 
Among the 154 subjects who received romiplostim, the total median exposure to romiplostim was 
52.0 weeks and ranged from 2 to 53 weeks. The most frequently used weekly dose was between 
3-5 mcg/kg (25th-75th percentile respectively; median 3 mcg/kg). 
 
Of the 77 subjects randomised to the SOC group, two subjects did not receive any SOC. Among the 
75 subjects who received at least one dose of SOC, the total median exposure to SOC was 51 weeks 
and ranged from 0.4 to 52 weeks. 
 
Reduction in permitted concurrent ITP medical therapies 
 
In both placebo-controlled, double-blind studies, patients already receiving ITP medical therapies at a 
constant dosing schedule were allowed to continue receiving these medical treatments throughout the 
study (corticosteroids, danazol and/or azathioprine). Twenty-one non-splenectomised and 
18 splenectomised patients received on-study ITP medical treatments (primarily corticosteroids) at the 
start of study. All (100%) splenectomised patients who were receiving romiplostim were able to 
reduce the dose by more than 25% or discontinue the concurrent ITP medical therapies by the end of 
the treatment period compared to 17% of placebo treated patients. Seventy-three percent of 
non-splenectomised patients receiving romiplostim were able to reduce the dose by more than 25% or 
discontinue concurrent ITP medical therapies by the end of the study compared to 50% of placebo 
treated patients (see section 4.5). 
 
Bleeding events 
 
Across the entire ITP clinical programme an inverse relationship between bleeding events and platelet 
counts was observed. All clinically significant (≥ grade 3) bleeding events occurred at platelet counts 
< 30 x 109/L. All bleeding events ≥ grade 2 occurred at platelet counts < 50 x 109/L. No statistically 
significant differences in the overall incidence of bleeding events were observed between Nplate and 
placebo treated patients. 
 
In the two placebo-controlled studies, 9 patients reported a bleeding event that was considered serious 
(5 [6.0%] romiplostim, 4 [9.8%] placebo; Odds Ratio [romiplostim/placebo] = 0.59; 95% CI = (0.15, 
2.31)). Bleeding events that were grade 2 or higher were reported by 15% of patients treated with 
romiplostim and 34% of patients treated with placebo (Odds Ratio; [romiplostim/placebo] = 0.35; 95% 
CI = (0.14, 0.85)). 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Nplate in one or more subsets of the paediatric population in the treatment of immune 
thrombocytopenia (idiopathic thrombocytopenic purpura) (see section 4.2 for information on 
paediatric use). 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of romiplostim involved target-mediated disposition, which is presumably 
mediated by TPO receptors on platelets and other cells of the thrombopoietic lineage such as 
megakaryocytes. 
 
Absorption 
 
After subcutaneous administration of 3 to 15 mcg/kg romiplostim, maximum romiplostim serum 
levels in ITP patients were obtained after 7-50 hours (median 14 hours). The serum concentrations 
varied among patients and did not correlate with the dose administered. Romiplostim serum levels 
appear inversely related to platelet counts. 
 



 36

Distribution 
 
The volume of distribution of romiplostim following intravenous administration of romiplostim 
decreased nonlinearly from 122, 78.8, to 48.2 mL/kg for intravenous doses of 0.3, 1.0 and 10 mcg/kg, 
respectively in healthy subjects. This non-linear decrease in volume of distribution is in line with the 
(megakaryocyte and platelet) target-mediated binding of romiplostim, which may be saturated at the 
higher doses applied. 
 
Elimination 
 
Elimination half-life of romiplostim in ITP patients ranged from 1 to 34 days (median, 3.5 days). 
The elimination of serum romiplostim is in part dependent on the TPO receptor on platelets. As a 
result for a given dose, patients with high platelet counts are associated with low serum concentrations 
and vice versa. In another ITP clinical trial, no accumulation in serum concentrations was observed 
after 6 weekly doses of romiplostim (3 mcg/kg). 
 
Special populations 
 
Pharmacokinetics of romiplostim in patients with renal and hepatic impairment has not been 
investigated. Romiplostim pharmacokinetics appear not affected by age, weight and gender to a 
clinically significant extent. 
 
5.3 Preclinical safety data 
 
Multiple dose romiplostim toxicology studies were conducted in rats for 4 weeks and in monkeys for 
up to 6 months. In general, effects observed during these studies were related to the thrombopoietic 
activity of romiplostim and were similar regardless of study duration. Injection site reactions were also 
related to romiplostim administration. Myelofibrosis has been observed in the bone marrow of rats at 
all tested dose levels. In these studies, myelofibrosis was not observed in animals after a 4-week 
post-treatment recovery period, indicating reversibility. 
 
In 1-month rat and monkey toxicology studies, a mild decrease in red blood cell count, haematocrit 
and haemoglobin was observed. There was also a stimulatory effect on leukocyte production, as 
peripheral blood counts for neutrophils, lymphocytes, monocytes, and eosinophils were mildly 
increased. In the longer duration chronic monkey study, there was no effect on the erythroid and 
leukocytic lineages when romiplostim was administered for 6 months where the administration of 
romiplostim was decreased from thrice weekly to once weekly. Additionally, in the phase 3 pivotal 
studies, romiplostim did not affect the red blood cell and white blood cells lineages relative to placebo 
treated subjects. 
 
Due to the formation of neutralising antibodies pharmacodynamic effects of romiplostim in rats were 
often decreasing at prolonged duration of administration. Toxicokinetic studies showed no interaction 
of the antibodies with the measured concentrations. Although high doses were tested in the animal 
studies, due to differences between the laboratory species and humans with regard to the sensitivity for 
the pharmacodynamic effect of romiplostim and the effect of neutralising antibodies, safety margins 
cannot be reliably estimated. 
 
Carcinogenesis 
 
The carcinogenic potential of romiplostim has not been evaluated. Therefore, the risk of potential 
carcinogenicity of romiplostim in humans remains unknown. 
 
Reproductive toxicology 
 
In all developmental studies neutralising antibodies were formed, which may have inhibited 
romiplostim effects. In embryo-foetal development studies in mice and rats, reductions in maternal 
body weight were found only in mice. In mice there was evidence of increased post-implantation loss. 



 37

In a prenatal and postnatal development study in rats an increase of the duration of gestation and a 
slight increase in the incidence of peri-natal pup mortality was found. Romiplostim is known to cross 
the placental barrier in rats and may be transmitted from the mother to the developing foetus and 
stimulate foetal platelet production. Romiplostim had no observed effect on the fertility of rats. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol (E421) 
Sucrose 
L-histidine 
Hydrochloric acid (for pH adjustment) 
Polysorbate 20 
 
Solvent: 
Water for injections 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products, except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
3 years. 
 
After reconstitution: Chemical and physical in-use stability has been demonstrated for 24 hours at 
25ºC and for 24 hours at 2ºC – 8ºC, when protected from light and kept in the original vial. 
 
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 25ºC or 24 hours in a refrigerator (2ºC – 8ºC), protected 
from light. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2ºC – 8ºC). 
Do not freeze. 
Store in the original carton in order to protect from light. 
May be removed from the refrigerator for a period of 30 days at room temperature (up to 25ºC) when 
stored in the original carton. 
 
For storage conditions after reconstitution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Powder: 
 
5 mL single-dose vial (type 1 clear glass) with a stopper (chlorobutyl rubber), seal (aluminium) and a 
flip-off cap (polypropylene). 
 
Solvent: 
 
Nplate 250 micrograms powder and solvent for solution for injection: Pre-filled syringe (type 1 clear 
glass with bromobutyl rubber plunger) containing 0.72 mL of water for injections for reconstitution. 



 38

 
Nplate 500 micrograms powder and solvent for solution for injection: Pre-filled syringe (type 1 clear 
glass with bromobutyl rubber plunger) containing 1.2 mL of water for injections for reconstitution. 
 
Pack size: 
 
Nplate 250 micrograms powder and solvent for solution for injection: 
Nplate is supplied as a 1 pack or multipack comprising 4 packs. Each pack contains: 
1 vial of 250 micrograms romiplostim. 
1 pre-filled syringe containing 0.72 mL of water for injections for reconstitution. 
1 plunger rod for the pre-filled syringe. 
1 sterile vial adapter. 
1 sterile 1 mL Luer lock syringe. 
1 sterile safety needle. 
4 alcohol swabs. 
 
Nplate 500 micrograms powder and solvent for solution for injection: 
Nplate is supplied as a 1 pack or multipack comprising 4 packs. Each pack contains: 
1 vial of 500 micrograms romiplostim. 
1 pre-filled syringe containing 1.2 mL of water for injections for reconstitution. 
1 plunger rod for the pre-filled syringe. 
1 sterile vial adapter. 
1 sterile 1 mL Luer lock syringe. 
1 sterile safety needle. 
4 alcohol swabs. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Nplate is a sterile but unpreserved medicinal product and is intended for single use only. Nplate should 
be reconstituted in accordance with good aseptic practice. 
 
Nplate 250 micrograms powder and solvent for solution for injection 
 
Nplate 250 micrograms powder for solution for injection should be reconstituted with 0.72 mL sterile 
water for injections, yielding a deliverable volume of 0.5 mL. An additional overfill is included in 
each vial to ensure that 250 mcg of romiplostim can be delivered (see vial content table below). 
 
Nplate 500 micrograms powder and solvent for solution for injection 
 
Nplate 500 micrograms powder for solution for injection should be reconstituted with 1.2 mL sterile 
water for injections, yielding a deliverable volume of 1 mL. An additional overfill is included in each 
vial to ensure that 500 mcg of romiplostim can be delivered (see vial content table below). 
 
Vial Content: 
 
Nplate single- 
use vial 

Total vial 
content of 
romiplostim  

 Volume of 
sterile water for 
injection  

 Deliverable 
product and 
volume 

Final 
concentration 

250 mcg 375 mcg + 0.72 mL = 250 mcg in 
0.50 mL

500 mcg/mL 

500 mcg 625 mcg + 1.20 mL = 500 mcg in 
1.00 mL

500 mcg/mL 

 



 39

From a microbiological point of view, the 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 25ºC or 24 hours in a refrigerator (2ºC – 8ºC), protected 
from light. 
 
1. Remove the plastic cap from Nplate powder vial and 

clean rubber stopper using the provided alcohol swab. 
 

 

2. Attach vial adapter to Nplate vial by peeling off paper 
backing from vial adapter, keeping the vial adapter in 
its packaging. Keeping the vial on the bench, push the 
vial adapter down onto the centre of the vial until it is 
firmly in place. 

 
Note: To prevent contamination of the product, do not 
touch the vial adapter spike or Luer lock. 

 

3. Remove and discard vial adapter packaging.  

4. Attach plunger rod to the pre-filled syringe of water 
for injections by twisting the plunger rod clockwise onto 
the syringe plunger, until you feel a slight resistance. 

 

 

5. Holding the pre-filled syringe of water for injections 
with one hand, bend the tip of the white plastic cover 
downward with your other hand. This will break the 
seal of the white plastic cover. Once the seal is broken, 
pull cover off to separate the grey rubber cap from 
the clear plastic tip on the syringe. 

 
6. Keeping the vial on the bench, attach the pre-filled 

syringe of water for injections to vial adapter: hold the 
outer edge of the vial adapter with one hand and twist the 
syringe tip clockwise onto the adapter with the other hand 
until you feel a slight resistance. 

 

7. Very slowly and gently expel all water into powder 
vial. Water should flow slowly onto powder. GENTLY 
swirl the vial until all of the powder has dissolved and the 
liquid in the vial is clear and colourless. 

 
Do not shake the vial 

 
Note: From a microbiological point of view, the 
product must be used immediately after 
reconstitution. If reconstituted product is not used 
immediately, the syringe should not be removed from 
the vial adapter to maintain microbiological integrity. 

 

 
Note: This may take up to 
2 minutes for the powder to 
completely dissolve. 
 

 



 40

Before continuing: 
 
Do visually inspect the reconstituted solution for particulate matter and/or discolouration. The 
reconstituted solution should be clear and colourless and should not be administered if particulate 
matter and/or discolouration are observed. 
 
Do make sure solution is fully dissolved before removing syringe. 
 
8. Remove the empty pre-filled syringe from the vial 

adapter. 
 

 

9. Remove 1 mL administration syringe from package. 
Attach the 1 mL syringe to vial adapter of reconstituted 
solution by twisting the syringe tip onto the vial adapter 
until you feel a slight resistance. 

 

 

10. Turn assembled syringe-vial unit upside down, so the 
vial of reconstituted product is above the syringe. 
Withdraw all of the medicinal product solution into the 
administration syringe. 
 
Do ensure that the plunger remains in the syringe. 

 

11. Ensure the correct amount of solution for the patient 
dose is in the administration syringe by injecting any 
excess solution back into the vial. 

 
Note: Remove all air bubbles from syringe to ensure 
precise solution amount is in syringe. 

 

 
12. Twist off administration syringe from vial adapter. 
 

Attach safety needle to the filled administration syringe 
by twisting needle clockwise into syringe Luer lock tip. 

 
 

 
 



 41

13. Prepare injection site with a new alcohol swab. Pull back 
on the pink safety cover toward the syringe and away 
from the needle. 

 
Remove clear needle shield from prepared needle by 
holding syringe in one hand and carefully pulling shield 
straight off with the other hand. 

  
14. Administer subcutaneous injection following local 

protocols and good aseptic technique. 
 

 

15. After injecting, activate the pink safety cover by 
pushing the cover forward using the same hand until you 
hear and/or feel it click/lock. 

 

16. Immediately discard syringe and needle into an 
approved Sharps Container. 

 

 
For the storage condition after reconstitution of the product see section 6.3. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/08/497/005 
EU/1/08/497/006 
EU/1/08/497/007 
EU/1/08/497/008 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 4 February 2009 
Date of latest renewal: 20 December 2013 
 
 



 42

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 



 43

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURERS 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 



 44

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

 
Name and address of the manufacturers of the biological active substance 
 
Amgen Inc 
One Amgen Center Drive 
Thousand Oaks, CA 91320 
USA 
 
Amgen Manufacturing Limited 
State Road 31, 
Km 24.6, 
Juncos, 
Puerto Rico 00777-4060 
USA 
 
Name and address of the manufacturers responsible for batch release 
 
Amgen Europe B.V. 
Minervum 7061 
NL-4817 ZK Breda 
The Netherlands 
 
Amgen Technology (Ireland) Unlimited Company 
Pottery Road 
Dun Laoghaire 
Co Dublin 
Ireland 
 
Amgen NV 
Telecomlaan 5-7 
1831 Diegem 
Belgium 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

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



 45

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. 

 
If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 
 
 Additional risk minimisation measures 
 
The MAH shall agree the details of the following educational tools with the National Competent 
Authorities and must implement such programme nationally. 
 
Dose calculator 
 
 Physicians involved in the prescribing of romiplostim are provided with a dosing calculator to 

simplify the calculation of the correct dose and as a guide to the correct reconstitution, dilution 
(if required) and administration procedures. 

 
Home Administration Training (HAT) pack 
 
 Physicians who express an interest in initiating self-administration for specific patients are 

provided with a HAT pack for those patients. The HAT pack includes materials for HCPs on 
how to select and train patients for self-administration of romiplostim; and for patients, in order 
to help them with the process of preparation and self-administration of the correct dose of 
romiplostim. 

 As self-administration of Nplate is not allowed for paediatric patients, the HAT pack is intended 
for use with adult patients and not with paediatric patients. 

 
 
 
 



 46

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX III 

 
LABELLING AND PACKAGE LEAFLET 



 47

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



 48

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nplate 125 micrograms powder for solution for injection 
romiplostim 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Vial containing 125 micrograms of romiplostim. After reconstitution, a deliverable volume of 0.25 mL 
solution contains 125 micrograms of romiplostim (500 micrograms/mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Mannitol (E421), sucrose, l-histidine, hydrochloric acid (for pH adjustment) and polysorbate 20. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for injection. 
1 vial. 
4 vials. 
 
 
5. METHOD AND ROUTE 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 
 
After reconstitution: 24 hours when stored at 25°C or in a refrigerator (2ºC – 8ºC) if kept in the 
original vial and protected from light. 
 
 



 49

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBERS 
 
EU/1/08/497/009 
EU/1/08/497/010 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Nplate 125 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



 50

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Nplate 125 µg powder for injection 
romiplostim 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
125 µg 
 
 
6. OTHER 
 
Amgen Europe B.V. 



 51

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nplate 250 micrograms powder for solution for injection 
romiplostim 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Vial containing 250 micrograms of romiplostim. After reconstitution, a deliverable volume of 0.5 mL 
solution contains 250 micrograms of romiplostim (500 micrograms/mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Mannitol (E421), sucrose, l-histidine, hydrochloric acid (for pH adjustment) and polysorbate 20. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for injection. 
1 vial. 
4 vials. 
 
 
5. METHOD AND ROUTE 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 
 
After reconstitution: 24 hours when stored at 25°C or in a refrigerator (2ºC – 8ºC) if kept in the 
original vial and protected from light. 
 
 



 52

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBERS 
 
EU/1/08/497/001 
EU/1/08/497/003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Nplate 250 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 53

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Nplate 250 µg powder for injection 
romiplostim 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
250 µg 
 
 
6. OTHER 
 
Amgen Europe B.V. 



 54

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nplate 500 micrograms powder for solution for injection 
romiplostim 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Vial containing 500 micrograms of romiplostim. After reconstitution, a deliverable volume of 1 mL 
solution contains 500 micrograms of romiplostim (500 micrograms/mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Mannitol (E421), sucrose, l-histidine, hydrochloric acid (for pH adjustment) and polysorbate 20. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for injection. 
1 vial. 
4 vials. 
 
 
5. METHOD AND ROUTE 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 
 
After reconstitution: 24 hours when stored at 25°C or in a refrigerator (2ºC – 8ºC) if kept in the 
original vial and protected from light. 
 
 



 55

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBERS 
 
EU/1/08/497/002 
EU/1/08/497/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Nplate 500 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 56

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Nplate 500 µg powder for injection 
romiplostim 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
500 µg 
 
 
6. OTHER 
 
Amgen Europe B.V. 
 



 57

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
RECONSTITUTION PACK INNER CARTON WITHOUT BLUE BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nplate 250 micrograms powder and solvent for solution for injection 
romiplostim 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Vial containing 250 micrograms of romiplostim. After reconstitution, a deliverable volume of 0.5 mL 
solution contains 250 micrograms of romiplostim (500 micrograms/mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Powder: Mannitol (E421), sucrose, l-histidine, hydrochloric acid (for pH adjustment) and 
polysorbate 20. 
Solvent: water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Component of a multipack, not to be sold separately. 
1 pack containing: 
1 vial of powder for solution for injection. 
1 pre-filled syringe containing 0.72 mL of solvent. 
1 plunger rod for pre-filled syringe. 
1 sterile vial adapter. 
1 sterile 1 mL Luer lock syringe. 
1 sterile safety needle. 
4 alcohol swabs. 
 
 
5. METHOD AND ROUTE 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 
 
 



 58

8. EXPIRY DATE 
 
EXP 
 
After reconstitution: 24 hours when stored at 25°C or in a refrigerator (2ºC – 8ºC) if kept in the 
original vial and protected from light. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBERS 
 
EU/1/08/497/006 – 1 pack 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Nplate 250 
 
 



 59

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 60

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
RECONSTITUTION PACK OUTER CARTON WITH BLUE BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nplate 250 micrograms powder and solvent for solution for injection 
romiplostim 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Vial containing 250 micrograms of romiplostim. After reconstitution, a deliverable volume of 0.5 mL 
solution contains 250 micrograms of romiplostim (500 micrograms/mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Powder: Mannitol (E421), sucrose, l-histidine, hydrochloric acid (for pH adjustment) and 
polysorbate 20. 
Solvent: water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
1 pack containing: 
Multipack: comprising 4 packs 
Each pack contains: 
1 vial of powder for solution for injection. 
1 pre-filled syringe containing 0.72 mL of solvent. 
1 plunger rod for pre-filled syringe. 
1 sterile vial adapter. 
1 sterile 1 mL Luer lock syringe. 
1 sterile safety needle. 
4 alcohol swabs. 
 
 
5. METHOD AND ROUTE 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 
 
 



 61

8. EXPIRY DATE 
 
EXP 
 
After reconstitution: 24 hours when stored at 25°C or in a refrigerator (2ºC – 8ºC) if kept in the 
original vial and protected from light. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBERS 
 
EU/1/08/497/005 – 1 pack 
EU/1/08/497/006 – 4 pack 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Nplate 250 
 
 



 62

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 63

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
WATER FOR INJECTIONS LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for Nplate 
Water for injections 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
0.72 ml 
 
 
6. OTHER 
 
For 250 µg kit 
 
 



 64

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
RECONSTITUTION PACK INNER CARTON WITHOUT BLUE BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nplate 500 micrograms powder and solvent for solution for injection 
romiplostim 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Vial containing 500 micrograms of romiplostim. After reconstitution, a deliverable volume of 1 mL 
solution contains 500 micrograms of romiplostim (500 micrograms/mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Powder: Mannitol (E421), sucrose, l-histidine, hydrochloric acid (for pH adjustment) and 
polysorbate 20. 
Solvent: water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Component of a multipack, not to be sold separately. 
1 pack containing: 
1 vial of powder for solution for injection. 
1 pre-filled syringe containing 1.2 mL of solvent. 
1 plunger rod for pre-filled syringe. 
1 sterile vial adapter. 
1 sterile 1 mL Luer lock syringe. 
1 sterile safety needle. 
4 alcohol swabs. 
 
 
5. METHOD AND ROUTE 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 
 
 



 65

8. EXPIRY DATE 
 
EXP 
 
After reconstitution: 24 hours when stored at 25°C or in a refrigerator (2ºC – 8ºC) if kept in the 
original vial and protected from light. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBERS 
 
EU/1/08/497/008 – 1 pack 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Nplate 500 
 
 



 66

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 67

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
RECONSTITUTION PACK OUTER CARTON WITH BLUE BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nplate 500 micrograms powder and solvent for solution for injection 
romiplostim 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Vial containing 500 micrograms of romiplostim. After reconstitution, a deliverable volume of 1 mL 
solution contains 500 micrograms of romiplostim (500 micrograms/mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Powder: Mannitol (E421), sucrose, l-histidine, hydrochloric acid (for pH adjustment) and 
polysorbate 20. 
Solvent: water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
1 pack containing: 
Multipack: comprising 4 packs 
Each pack contains: 
1 vial of powder for solution for injection. 
1 pre-filled syringe containing 1.2 mL of solvent. 
1 plunger rod for pre-filled syringe. 
1 sterile vial adapter. 
1 sterile 1 mL Luer lock syringe. 
1 sterile safety needle. 
4 alcohol swabs. 
 
 
5. METHOD AND ROUTE 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 
 
 



 68

8. EXPIRY DATE 
 
EXP 
 
After reconstitution: 24 hours when stored at 25°C or in a refrigerator (2ºC – 8ºC) if kept in the 
original vial and protected from light. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBERS 
 
EU/1/08/497/007 – 1 pack 
EU/1/08/497/008 – 4 pack 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Nplate 500 
 
 



 69

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 70

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
WATER FOR INJECTIONS LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for Nplate 
Water for injections 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1.2 ml 
 
 
6. OTHER 
 
For 500 µg kit 
 



 71

 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



 72

Package leaflet: Information for the user 
 

Nplate 125 micrograms powder for solution for injection 
Nplate 250 micrograms powder for solution for injection 
Nplate 500 micrograms powder for solution for injection 

Romiplostim 
 

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 Nplate is and what it is used for 
2. What you need to know before you use Nplate 
3. How to use Nplate 
4. Possible side effects 
5. How to store Nplate 
6. Contents of the pack and other information 
 
 
1. What Nplate is and what it is used for 
 
Nplate’s active ingredient is romiplostim, which is a protein used to treat low platelet counts in 
patients with immune (idiopathic) thrombocytopenic purpura (called ITP). ITP is a disease in which 
your body’s immune system destroys its own platelets. Platelets are the cells in your blood that help 
seal cuts and form blood clots. Very low platelet counts can cause bruising and serious bleeding. 
 
Nplate is used to treat patients aged 1 year and over who may or may not have had their spleen 
removed for chronic ITP and who have been previously treated with corticosteroids or 
immunoglobulins, where these treatments don’t work. 
 
Nplate works by stimulating the bone marrow (part of the bone which makes blood cells) to produce 
more platelets. This should help to prevent bruising and bleeding associated with ITP. 
 
 
2. What you need to know before you use Nplate 
 
Do not use Nplate: 
 
 if you are allergic to romiplostim or any of the other ingredients of this medicine (listed in 

section 6). 
 if you are allergic to other medicines that are produced by DNA technology using the 

micro-organism Escherichia coli (E. coli). 
 
Warnings and precautions 
 
 If you stop taking Nplate a low blood platelet count (thrombocytopenia) is likely to reoccur. If 

you stop taking Nplate your platelet count will have to be monitored, and your doctor will 
discuss appropriate precautions with you. 



 73

 If you are at risk of blood clots or if blood clots are common in your family. The risk of blood 
clotting may also be increased if you: 
- have liver problems; 
- are elderly (≥ 65 years); 
- are bedridden; 
- have cancer; 
- are taking the contraceptive pill or hormone replacement therapy; 
- have recently had surgery or suffered an injury; 
- are obese (overweight); 
- are a smoker. 

Talk to your doctor, pharmacist or nurse before using Nplate. 
 
If you have very high blood platelet counts this may increase the risk of blood clotting. Your doctor 
will adjust your dose of Nplate to ensure that your platelet count does not become too high. 
 
Bone marrow changes (increased reticulin and possible bone marrow fibrosis) 
 
Long-term use of Nplate may cause changes in your bone marrow. These changes may lead to 
abnormal blood cells or your body making less blood cells. The mild form of these bone marrow 
changes is called “increased reticulin” and has been observed in Nplate clinical trials. It is not known 
if this may progress to a more severe form called “fibrosis.” Signs of bone marrow changes may show 
up as abnormalities in your blood tests. Your doctor will decide if abnormal blood tests mean that you 
should have bone marrow tests or if you should stop taking Nplate. 
 
Worsening of blood cancers 
 
Your doctor may decide to take a bone marrow biopsy if they decide it is necessary to ensure that you 
have ITP, and not another condition such as Myelodysplastic Syndrome (MDS). If you have MDS and 
receive Nplate you may have an increase in your blast cell counts and your MDS condition may 
worsen to become an acute myeloid leukaemia, which is a type of cancer of the blood. 
 
Loss of response to romiplostim 
 
If you experience a loss of response or failure to maintain a platelet response with romiplostim 
treatment, your doctor will investigate the reasons why including whether you are experiencing 
increased bone marrow fibres (reticulin) or have developed antibodies which neutralise romiplostim’s 
activity. 
 
Children and adolescents 
 
Nplate is not recommended for use in children aged under 1 year. 
 
Other medicines and Nplate 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
If you are also taking medicines which prevent blood clots (anticoagulants or antiplatelet therapy) 
there is a greater risk of bleeding. Your doctor will discuss this with you. 
 
If you are taking corticosteroids, danazol, and/or azathioprine, which you may be receiving to treat 
your ITP, these may be reduced or stopped when given together with Nplate. 
 



 74

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 or pharmacist for advice before taking this medicine. Nplate is not recommended for use if 
you are pregnant unless indicated by your doctor. 
 
It is not known whether romiplostim is present in human milk. Nplate is not recommended for use if 
you are breast-feeding. A decision on whether to discontinue breast-feeding or discontinue therapy 
with romiplostim should be made taking into account the benefit of breast-feeding to your child and 
the benefit of romiplostim therapy to you. 
 
Driving and using machines 
 
You should speak with your doctor before driving or using machines, as some side effects (e.g. 
temporary bouts of dizziness) may impair your ability to do so safely. 
 
 
3. How to use Nplate 
 
Adult and children (1 to 17 years): 
 
Nplate will be given under the direct supervision of your doctor, who will closely control the amount 
of Nplate given to you. 
 
Nplate is administered once a week as an injection under the skin (subcutaneous). 
 
Your initial dose is 1 microgram of Nplate per kilogram of your body weight once a week. Your 
doctor will tell you how much you must take. Nplate should be injected once per week in order to keep 
your platelet counts up. Your doctor will take regular blood samples to measure how your platelets are 
responding and may adjust your dose as necessary. 
 
Once your platelet count is under control, your doctor will continue to regularly check your blood. 
Your dose may be adjusted further in order to maintain long-term control of your platelet count. 
 
Children (1 to 17 years old): in addition to adjusting your dose based on platelet counts, your doctor 
will also regularly reassess your body weight in order to adjust your dose. 
 
If you use more Nplate than you should 
 
Your doctor will ensure that you receive the right amount of Nplate. If you have been given more 
Nplate than you should, you may not experience any physical symptoms but your blood platelet counts 
may rise to very high levels and this may increase the risk of blood clotting. Therefore if your doctor 
suspects that you have been given more Nplate than you should, it is recommended that you are 
monitored for any signs or symptoms of side effects and that you are given appropriate treatment 
immediately. 
 
If you use less Nplate than you should 
 
Your doctor will ensure that you receive the right amount of Nplate. If you have been given less 
Nplate than you should, you may not experience any physical symptoms but your blood platelet counts 
may become low and this may increase the risk of bleeding. Therefore if your doctor suspects that you 
have been given less Nplate than you should, it is recommended that you are monitored for any signs 
or symptoms of side effects and that you are given appropriate treatment immediately. 
 



 75

If you forget to use Nplate 
 
If you have missed a dose of Nplate, your doctor will discuss with you when you should have your 
next dose. 
 
If you stop using Nplate 
 
If you stop using Nplate, your low blood platelet count (thrombocytopenia) is likely to reoccur. Your 
doctor will decide if you should stop using Nplate. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Possible side effects in adults with ITP 
 
Very common: may affect more than 1 in 10 people 
 headache; 
 allergic reaction; 
 upper respiratory tract infection. 
 
Common: may affect up to 1 in 10 people 
 bone marrow disorder, including increased bone marrow fibres (reticulin); 
 trouble sleeping (insomnia); 
 dizziness; 
 tingling or numbness of the hands or feet (paraesthesia); 
 migraine; 
 redness of the skin (flushing); 
 blood clot in a lung artery (pulmonary embolism); 
 nausea; 
 diarrhoea; 
 abdominal pain; 
 indigestion (dyspepsia); 
 constipation; 
 itching of the skin (pruritis); 
 bleeding under the skin (ecchymosis); 
 bruising (contusion); 
 rash; 
 joint pain (arthralgia); 
 muscles pain or weakness (myalgia); 
 pain in your hands and feet; 
 muscle spasm; 
 back pain; 
 bone pain; 
 tiredness (fatigue); 
 injection site reactions; 
 swelling in the hands and feet (oedema peripheral); 
 flu like symptoms (influenza like illness); 
 pain; 
 weakness (asthenia); 
 fever (pyrexia); 
 chills; 
 contusion; 



 76

 swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or 
breathing (angioedema); 

 gastroenteritis; 
 palpitations. 

 
Common: may affect up to 1 in 10 people (may show up in blood or urine tests) 
 low blood platelet count (thrombocytopenia) and low blood platelet count (thrombocytopenia) 

after stopping Nplate; 
 higher than normal platelet counts (thrombocytosis); 
 anaemia. 
 
Uncommon: may affect up to 1 in 100 people 
 bone marrow failure; disorder of the bone marrow that causes scarring (myelofibrosis); enlarged 

spleen (splenomegaly); bleeding of the vagina (vaginal haemorrhage), bleeding in the rectum 
(rectal haemorrhage); bleeding mouth (mouth haemorrhage); injection site bleeding (injection 
site haemorrhage); 

 heart attack (myocardial infarction); increased heart rate; 
 dizziness or a spinning sensation (vertigo); 
 problems with the eyes including: bleeding in the eye (conjunctival haemorrhage); difficulty 

focussing or blurred vision (accommodation disorder, papilloedema or eye disorder); blindness; 
itchy eye (eye pruritus); increased tears (lacrimation increased); or visual disturbances; 

 problems with the digestive system including: vomiting; bad breath (breath odour); difficulty 
swallowing (dysphagia); indigestion or heartburn (gastro-oesophageal reflux disease); blood in 
the stools (haematochezia); stomach discomfort; mouth ulcers or mouth blistering (stomatitis); 
discoloured teeth (tooth discolouration); 

 weight decreased; weight increased; intolerance of alcohol; loss of appetite (anorexia or 
decreased appetite); dehydration; 

 generally feeling unwell (malaise); chest pain; irritability; swelling of the face (face oedema); 
feeling hot; increased body temperature; feeling jittery; 

 influenza; localised infection; inflammation of the passages in the nose and throat 
(nasopharyngitis); 

 problems with the nose and throat including: cough; runny nose (rhinorrhoea); dry throat; 
shortness of breath or difficulty breathing (dyspnoea); nasal congestion; painful breathing 
(painful respiration) 

 painful swollen joints caused by uric acid (food breakdown product) (gout); 
 muscle tightness; muscular weakness; shoulder pain; muscle twitching; 
 problems with your nervous system including involuntary muscle contractions (clonus); 

distorted sense of taste (dysgeusia); decrease in sense of taste (hypogeusia); decreased feeling of 
sensitivity, especially in the skin (hypoaesthesia); alteration in the nerve functions in the arms 
and legs (neuropathy peripheral); blood clot in the transverse sinus (transverse sinus 
thrombosis); 

 depression; abnormal dreams; 
 hair loss (alopecia); sensitivity to light (photosensitivity reaction); acne; allergic reaction in the 

skin upon contact with allergen (dermatitis contact); skin manifestation with rash and blisters 
(eczema); dry skin; redness of the skin (erythema); severe flaking or peeling rash (exfoliative 
rash); abnormal hair growth; thickening and itching of the skin due to repeated scratching 
(prurigo); bleeding beneath the surface of the skin or bruising under the skin (purpura); bumpy 
skin rash (rash papular); itchy skin rash (rash pruritic); generalised itchy rash (urticaria); bump 
on the skin (skin nodule); abnormal smell to the skin (skin odour abnormal); 

 problems with the circulation including blood clot in the vein in the liver (portal vein 
thrombosis); deep vein thrombosis; low blood pressure (hypotension); increased blood pressure; 
blocking of a blood vessel or (peripheral embolism); reduced blood flow in the hands, ankles or 
feet (peripheral ischaemia); swelling and clotting in a vein, which may be extremely tender 
when touched (phlebitis or thrombophlebitis superficial); blood clot (thrombosis); 

 a rare disorder characterised by periods of burning pain, redness and warmth in the feet and 
hands (erythromelalgia). 



 77

 
Uncommon: may affect up to 1 in 100 people (may show up in blood or urine tests) 
 a rare type of anaemia in which the red blood cells, white blood cells and platelets are all 

reduced in number (aplastic anaemia); 
 raised white blood cell count (leucocytosis); 
 excess platelet production (thrombocythaemia); increased platelet counts; abnormal count in the 

cells in the blood that prevents bleeding (platelet count abnormal); 
 changes in some blood tests (increase in transaminase; blood lactate dehydrogenase increased); 
 or cancer of white blood cells (multiple myeloma); 
 protein in the urine. 
 
Possible side effects in children with ITP 
 
Very common: may affect more than 1 in 10 people 
 upper respiratory tract infection; 
 pain in the mouth and throat (oropharyngeal pain); 
 itchy, runny or blocked nose (rhinitis); 
 cough; 
 upper abdominal pain; 
 diarrhoea; 
 rash; 
 fever (pyrexia); 
 bruising (contusion). 
 
Common: may affect up to 1 in 10 people 
 gastroenteritis; 
 sore throat and discomfort when swallowing (pharyngitis); 
 inflammation of the eye (conjunctivitis); 
 ear infection; 
 inflammation of the sinuses (sinusitis); 
 swelling in the limbs/hands/feet; 
 bleeding beneath the surface of the skin or bruising under the skin (purpura); 
 itchy rash (urticaria). 
 
Uncommon: may affect up to 1 in 100 people 
 higher than normal platelet counts (thrombocytosis). 
 
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 Nplate 
 
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 vial label after EXP. 
The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2ºC – 8ºC). 
Do not freeze. 
Store in the original carton in order to protect from light. 
 



 78

This medicine may be removed from the refrigerator for a period of 30 days at room temperature (up 
to 25ºC) when stored in the original carton. 
 
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 Nplate contains 
 
- The active substance is romiplostim. 
 

Each vial of Nplate 125 micrograms powder for solution for injection contains a total of 
230 micrograms of romiplostim. An additional overfill is included in each vial to ensure that 
125 micrograms of romiplostim can be delivered. After dissolving, a deliverable amount of 
0.25 mL solution contains 125 micrograms of romiplostim (500 micrograms/mL). 

 
Each vial of Nplate 250 micrograms powder for solution for injection contains a total of 
375 micrograms of romiplostim. An additional overfill is included in each vial to ensure that 
250 micrograms of romiplostim can be delivered. After dissolving, a deliverable amount of 
0.5 mL solution contains 250 micrograms of romiplostim (500 micrograms/mL). 

 
Each vial of Nplate 500 micrograms powder for solution for injection contains a total of 
625 micrograms of romiplostim. An additional overfill is included in each vial to ensure that 
500 micrograms of romiplostim can be delivered. After dissolving, a deliverable amount of 
1 mL solution contains 500 micrograms of romiplostim (500 micrograms/mL). 

 
- The other ingredients are mannitol (E421), sucrose, L-histidine, hydrochloric acid (for pH 

adjustment) and polysorbate 20. 
 
What Nplate looks like and contents of the pack 
 
Nplate is a white powder for solution for injection supplied in a single-dose glass vial. 
 
Carton containing 1 or 4 vials of either 125 micrograms (beige cap), 250 micrograms (red cap) or 
500 micrograms of romiplostim (blue cap). 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
Marketing Authorisation Holder 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 



 79

Manufacturer 
Amgen Technology (Ireland) Unlimited Company 
Pottery Road 
Dun Laoghaire 
Co Dublin 
Ireland 
 
Manufacturer 
Amgen NV 
Telecomlaan 5-7 
1831 Diegem 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
België/Belgique/Belgien 
s.a. Amgen n.v. 
Tel/Tél: +32 (0)2 7752711 
 

Lietuva 
Amgen Switzerland AG Vilniaus filialas 
Tel: +370 5 219 7474 

България 
Амджен България ЕООД 
Тел.: +359 (0)2 424 7440 

Luxembourg/Luxemburg 
s.a. Amgen 
Belgique/Belgien 
Tel/Tél: +32 (0)2 7752711 

Česká republika 
Amgen s.r.o. 
Tel: +420 221 773 500 

Magyarország 
Amgen Kft. 
Tel.: +36 1 35 44 700 

Danmark 
Amgen, filial af Amgen AB, Sverige 
Tlf: +45 39617500 
 

Malta 
Amgen B.V. 
The Netherlands 
Tel: +31 (0)76 5732500 
 

Deutschland 
AMGEN GmbH 
Tel.: +49 89 1490960 
 

Nederland 
Amgen B.V. 
Tel: +31 (0)76 5732500 

Eesti 
Amgen Switzerland AG Vilniaus filialas 
Tel: +372 586 09553 

Norge 
Amgen AB 
Tel: +47 23308000 

Ελλάδα 
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε. 
Τηλ.: +30 210 3447000 

Österreich 
Amgen GmbH 
Tel: +43 (0)1 50 217 
 

España 
Amgen S.A. 
Tel: +34 93 600 18 60 
 

Polska 
Amgen Biotechnologia Sp. z o.o. 
Tel.: +48 22 581 3000 

France 
Amgen S.A.S. 
Tél: +33 (0)9 69 363 363 
 

Portugal 
Amgen Biofarmacêutica, Lda. 
Tel: +351 21 4220606 



 80

Hrvatska 
Amgen d.o.o. 
Tel: +385 (0)1 562 57 20 
 

România 
Amgen România SRL 
Tel: +4021 527 3000 

Ireland 
Amgen Ireland Limited 
Tel: +353 1 8527400 
 

Slovenija 
AMGEN zdravila d.o.o. 
Tel: +386 (0)1 585 1767 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
Amgen Slovakia s.r.o. 
Tel: +421 2 321 114 49 

Italia 
Amgen S.r.l. 
Tel: +39 02 6241121 

Suomi/Finland 
Amgen AB, sivuliike Suomessa/Amgen AB, filial 
i Finland 
Puh/Tel: +358 (0)9 54900500 
 

Kύπρος 
C.A. Papaellinas Ltd 
Τηλ.: +357 22741 741 

Sverige 
Amgen AB 
Tel: +46 (0)8 6951100 

Latvija 
Amgen Switzerland AG Rīgas filiāle 
Tel: +371 257 25888 
 

United Kingdom 
Amgen Limited 
Tel: +44 (0)1223 420305 

 
This leaflet was last revised in 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
 
--------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Reconstitution: 
 
Nplate is a sterile but unpreserved product and is intended for single use only. Nplate should be 
reconstituted in accordance with good aseptic practice. 
 
 Nplate 125 micrograms powder for solution for injection should be reconstituted with 

0.44 mL sterile water for injections, yielding a deliverable volume of 0.25 mL. An additional 
over fill is included in each vial to ensure that 125 mcg of romiplostim can be delivered (see 
vial content table below). 

or 
 Nplate 250 micrograms powder for solution for injection should be reconstituted with 

0.72 mL sterile water for injections, yielding a deliverable volume of 0.5 mL. An additional 
overfill is included in each vial to ensure that 250 mcg of romiplostim can be delivered (see vial 
content table below). 

or 
 Nplate 500 micrograms powder for solution for injection should be reconstituted with 

1.2 mL sterile water for injections, yielding a deliverable volume of 1 mL. An additional 
overfill is included in each vial to ensure that 500 mcg of romiplostim can be delivered (see vial 
content table below). 

 



 81

Vial Content: 
 
Nplate single- 
use vial 

Total vial 
content of 
romiplostim  

 Volume of 
sterile water 
for injection  

 Deliverable 
product and 
volume 

Final 
concentration 

125 mcg 230 mcg + 0.44 mL = 125 mcg in 0.25 mL 500 mcg/mL
250 mcg 375 mcg + 0.72 mL = 250 mcg in 0.50 mL 500 mcg/mL
500 mcg 625 mcg + 1.20 mL = 500 mcg in 1.00 mL 500 mcg/mL
 
Sterile water for injections only should be used when reconstituting the medicinal product. Sodium 
chloride solutions or bacteriostatic water should not be used when reconstituting the medicine. 
 
Water for injections should be injected into the vial. The vial contents may be swirled gently and 
inverted during dissolution. The vial should not be shaken or vigorously agitated. Generally, 
dissolution of Nplate takes less than 2 minutes. Visually inspect the solution for particulate matter and 
discolouration before administration. The reconstituted solution should be clear and colourless and 
should not be administered if particulate matter and/or discolouration are observed. 
 
From a microbiological point of view, the medicine 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 25ºC or 24 hours in a refrigerator (2ºC – 8ºC), protected 
from light. 
 
Any unused medicine or waste material should be disposed of in accordance with local requirements. 
 
Dilution (required when the calculated individual patient dose is less than 23 mcg) 
 
Initial reconstitution of romiplostim with designated volumes of sterile water for injections results in a 
concentration of 500 mcg/mL in all vial sizes. If the calculated individual patient dose is less than 
23 mcg, an additional dilution step to 125 mcg/mL with preservative-free, sterile, sodium chloride 
9 mg/mL (0.9%) solution for injection is required to ensure accurate volume (see table below). 
 
Dilution Guidelines: 
 
Nplate single-use vial Add this volume of preservative-free, sterile, 

sodium chloride 9 mg/mL (0.9%) solution 
for injection to the reconstituted vial 

Concentration after dilution 

125 mcg 1.38 mL 125 mcg/mL 
250 mcg 2.25 mL 125 mcg/mL 
500 mcg 3.75 mL 125 mcg/mL 
 
Preservative-free, sterile, sodium chloride 9 mg/mL (0.9%) solution for injection only must be used 
for dilution. Dextrose (5%) in water or sterile water for injection should not be used for the dilution. 
No other diluents have been tested. 
 
From a microbiological point of view, the diluted 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 4 hours at 25ºC in disposable syringes, or 4 hours in a 
refrigerator (2ºC – 8ºC) in the original vials, protected from light. 
 



 82

Package leaflet: Information for the user 
 

Nplate 250 micrograms powder and solvent for solution for injection 
Nplate 500 micrograms powder and solvent for solution for injection 

Romiplostim 
 

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 Nplate is and what it is used for 
2. What you need to know before you use Nplate 
3. How to use Nplate 
4. Possible side effects 
5. How to store Nplate 
6. Contents of the pack and other information 
7. Instructions for preparing and giving an injection of Nplate 
 
 
1. What Nplate is and what it is used for 
 
Nplate’s active ingredient is romiplostim, which is a protein used to treat low platelet counts in 
patients with immune (idiopathic) thrombocytopenic purpura (called ITP). ITP is a disease in which 
your body’s immune system destroys its own platelets. Platelets are the cells in your blood that help 
seal cuts and form blood clots. Very low platelet counts can cause bruising and serious bleeding. 
 
Nplate is used to treat adult patients (aged 18 years and over) who may or may not have had their 
spleen removed for chronic ITP and who have been previously treated with corticosteroids or 
immunoglobulins, where these treatments don’t work. 
 
Nplate works by stimulating the bone marrow (part of the bone which makes blood cells) to produce 
more platelets. This should help to prevent bruising and bleeding associated with ITP. 
 
 
2. What you need to know before you use Nplate 
 
Do not use Nplate: 
 
 if you are allergic to romiplostim or any of the other ingredients of this medicine (listed in 

section 6). 
 if you are allergic to other medicines that are produced by DNA technology using the 

micro-organism Escherichia coli (E. coli). 
 
Warnings and precautions 
 
 If you stop taking Nplate a low blood platelet count (thrombocytopenia) is likely to reoccur. If 

you stop taking Nplate your platelet count will have to be monitored, and your doctor will 
discuss appropriate precautions with you. 



 83

 If you are at risk of blood clots or if blood clots are common in your family. The risk of blood 
clotting may also be increased if you: 
- have liver problems; 
- are elderly (≥ 65 years); 
- are bedridden; 
- have cancer; 
- are taking the contraceptive pill or hormone replacement therapy; 
- have recently had surgery or suffered an injury; 
- are obese (overweight); 
- are a smoker. 

Talk to your doctor, pharmacist or nurse before using Nplate. 
 
If you have very high blood platelet counts this may increase the risk of blood clotting. Your doctor 
will adjust your dose of Nplate to ensure that your platelet count does not become too high. 
 
Bone marrow changes (increased reticulin and possible bone marrow fibrosis) 
 
Long-term use of Nplate may cause changes in your bone marrow. These changes may lead to 
abnormal blood cells or your body making less blood cells. The mild form of these bone marrow 
changes is called “increased reticulin” and has been observed in Nplate clinical trials. It is not known 
if this may progress to a more severe form called “fibrosis.” Signs of bone marrow changes may show 
up as abnormalities in your blood tests. Your doctor will decide if abnormal blood tests mean that you 
should have bone marrow tests or if you should stop taking Nplate. 
 
Worsening of blood cancers 
 
Your doctor may decide to take a bone marrow biopsy if they decide it is necessary to ensure that you 
have ITP, and not another condition such as Myelodysplastic Syndrome (MDS). If you have MDS and 
receive Nplate you may have an increase in your blast cell counts and your MDS condition may 
worsen to become an acute myeloid leukaemia, which is a type of cancer of the blood. 
 
Loss of response to romiplostim 
 
If you experience a loss of response or failure to maintain a platelet response with romiplostim 
treatment, your doctor will investigate the reasons why including whether you are experiencing 
increased bone marrow fibres (reticulin) or have developed antibodies which neutralise romiplostim’s 
activity. 
 
Children and adolescents 
 
Nplate is not recommended for use in children below age 18. 
 
Other medicines and Nplate 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
If you are also taking medicines which prevent blood clots (anticoagulants or anti-platelet therapy) 
there is a greater risk of bleeding. Your doctor will discuss this with you. 
 
If you are taking corticosteroids, danazol, and/or azathioprine, which you may be receiving to treat 
your ITP, these may be reduced or stopped when given together with Nplate. 
 



 84

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 or pharmacist for advice before taking this medicine. Nplate is not recommended for use if 
you are pregnant unless indicated by your doctor. 
 
It is not known whether romiplostim is present in human milk. Nplate is not recommended for use if 
you are breast-feeding. A decision on whether to discontinue breast-feeding or discontinue therapy 
with romiplostim should be made taking into account the benefit of breast-feeding to your child and 
the benefit of romiplostim therapy to you. 
 
Driving and using machines 
 
You should speak with your doctor before driving or using machines, as some side effects (e.g. 
temporary bouts of dizziness) may impair your ability to do so safely. 
 
 
3. How to use Nplate 
 
Nplate will be given under the direct supervision of your doctor, who will closely control the amount 
of Nplate given to you. 
 
Nplate is administered once a week as an injection under the skin (subcutaneous). 
 
Your initial dose is 1 microgram of Nplate per kilogram of your body weight once a week. Your 
doctor will tell you how much you must take. Nplate should be injected once per week in order to keep 
your platelet counts up. Your doctor will take regular blood samples to measure how your platelets are 
responding and may adjust your dose as necessary. 
 
Once your platelet count is under control, your doctor will continue to regularly check your blood. 
Your dose may be adjusted further in order to maintain long-term control of your platelet count. 
 
Always use Nplate exactly as your doctor has told you. You should check with your doctor or 
pharmacist if you are not sure of how to use Nplate. 
 
Instructions for preparing and giving an injection of Nplate 
 
After suitable training, your doctor may also allow you to inject Nplate yourself. Please read the 
instructions at the end of this leaflet on how to inject Nplate, as discussed with your doctor. If your 
doctor has allowed you to self-inject, you should follow up with your doctor every month to have the 
doctor determine if Nplate is working for you or if another treatment needs to be considered. 
 
After the first month of self-injecting Nplate, you will need to show that you can still prepare and 
inject Nplate correctly. 
 
If you use more Nplate than you should 
 
Your doctor will ensure that you receive the right amount of Nplate. If you have been given more 
Nplate than you should, you may not experience any physical symptoms but your blood platelet counts 
may rise to very high levels and this may increase the risk of blood clotting. Therefore if your doctor 
suspects that you have been given more Nplate than you should, it is recommended that you are 
monitored for any signs or symptoms of side effects and that you are given appropriate treatment 
immediately. 
 
If your doctor has allowed you to self-inject and you use more Nplate than you should, then inform 
your doctor immediately. 
 



 85

If you use less Nplate than you should 
 
Your doctor will ensure that you receive the right amount of Nplate. If you have been given less 
Nplate than you should, you may not experience any physical symptoms but your blood platelet counts 
may become low and this may increase the risk of bleeding. Therefore if your doctor suspects that you 
have been given less Nplate than you should, it is recommended that you are monitored for any signs 
or symptoms of side effects and that you are given appropriate treatment immediately. 
 
If your doctor has allowed you to self-inject and you use less Nplate than you should, then inform your 
doctor immediately. 
 
If you forget to use Nplate 
 
If you have missed a dose of Nplate, your doctor will discuss with you when you should have your 
next dose. 
 
If your doctor has allowed you to self-inject and you forget to give yourself an injection, you should 
inform your doctor immediately. 
 
If you stop using Nplate 
 
If you stop using Nplate, your low blood platelet count (thrombocytopenia) is likely to reoccur. Your 
doctor will decide if you should stop using Nplate. 
 
Injecting Nplate yourself 
 
Your doctor may decide that it is best for you to inject Nplate. Your doctor, nurse or pharmacist will 
show you how to inject yourself with Nplate. Do not try to inject yourself if you have not been trained. 
It is very important that you prepare Nplate properly and take the correct dose (see section 7. 
Instructions for preparing and giving an injection of Nplate, at the end of this leaflet). 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Very common: may affect more than 1 in 10 people 
 headache; 
 allergic reaction; 
 upper respiratory tract infection. 
 
 Common: may affect up to 1 in 10 people 
 bone marrow disorder, including increased bone marrow fibres (reticulin); 
 trouble sleeping (insomnia); 
 dizziness; 
 tingling or numbness of the hands or feet (paraesthesia); 
 migraine; 
 redness of the skin (flushing); 
 blood clot in a lung artery (pulmonary embolism); 
 nausea; 
 diarrhoea; 
 abdominal pain; 
 indigestion (dyspepsia); 
 constipation; 
 itching of the skin (pruritis); 
 bleeding under the skin (ecchymosis); 



 86

 bruising (contusion); 
 rash; 
 joint pain (arthralgia); 
 muscles pain or weakness (myalgia); 
 pain in your hands and feet; 
 muscle spasm; 
 back pain; 
 bone pain; 
 tiredness (fatigue); 
 injection site reactions; 
 swelling in the hands and feet (oedema peripheral); 
 flu like symptoms (influenza like illness); 
 pain; 
 weakness (asthenia); 
 fever (pyrexia); 
 chills; 
 contusion; 
 swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or 

breathing (angioedema); 
 gastroenteritis; 
 palpitations. 

 
Common: may affect up to 1 in 10 people (may show up in blood or urine tests) 
 low blood platelet count (thrombocytopenia) and low blood platelet count (thrombocytopenia) 

after stopping Nplate; 
 higher than normal platelet counts (thrombocytosis); 
 anaemia. 
 
Uncommon: may affect up to 1 in 100 people 
 bone marrow failure; disorder of the bone marrow that causes scarring (myelofibrosis); enlarged 

spleen (splenomegaly); bleeding of the vagina (vaginal haemorrhage), bleeding in the rectum 
(rectal haemorrhage); bleeding mouth (mouth haemorrhage); injection site bleeding (injection 
site haemorrhage); 

 heart attack (myocardial infarction); increased heart rate; 
 dizziness or a spinning sensation (vertigo); 
 problems with the eyes including: bleeding in the eye (conjunctival haemorrhage); difficulty 

focussing or blurred vision (accommodation disorder, papilloedema or eye disorder); blindness; 
itchy eye (eye pruritus); increased tears (lacrimation increased); or visual disturbances; 

 problems with the digestive system including: vomiting; bad breath (breath odour); difficulty 
swallowing (dysphagia); indigestion or heartburn (gastro-oesophageal reflux disease); blood in 
the stools (haematochezia); stomach discomfort; mouth ulcers or mouth blistering (stomatitis); 
discoloured teeth (tooth discolouration); 

 weight decreased; weight increased; intolerance of alcohol; loss of appetite (anorexia or 
decreased appetite); dehydration; 

 generally feeling unwell (malaise); chest pain; irritability; swelling of the face (face oedema); 
feeling hot; increased body temperature; feeling jittery; 

 influenza; localised infection; inflammation of the passages in the nose and throat 
(nasopharyngitis); 

 problems with the nose and throat including: cough; runny nose (rhinorrhoea); dry throat; 
shortness of breath or difficulty breathing (dyspnoea); nasal congestion; painful breathing 
(painful respiration) 

 painful swollen joints caused by uric acid (food breakdown product) (gout); 
 muscle tightness; muscular weakness; shoulder pain; muscle twitching; 
 problems with your nervous system including involuntary muscle contractions (clonus); 

distorted sense of taste (dysgeusia); decrease in sense of taste (hypogeusia); decreased feeling of 



 87

sensitivity, especially in the skin (hypoaesthesia); alteration in the nerve functions in the arms 
and legs (neuropathy peripheral); blood clot in the transverse sinus (transverse sinus 
thrombosis); 

 depression; abnormal dreams; 
 hair loss (alopecia); sensitivity to light (photosensitivity reaction); acne; allergic reaction in the 

skin upon contact with allergen (dermatitis contact); skin manifestation with rash and blisters 
(eczema); dry skin; redness of the skin (erythema); severe flaking or peeling rash (exfoliative 
rash); abnormal hair growth; thickening and itching of the skin due to repeated scratching 
(prurigo); bleeding beneath the surface of the skin or bruising under the skin (purpura); bumpy 
skin rash (rash papular); itchy skin rash (rash pruritic); generalised itchy rash (urticaria); bump 
on the skin (skin nodule); abnormal smell to the skin (skin odour abnormal); 

 problems with the circulation including blood clot in the vein in the liver (portal vein 
thrombosis); deep vein thrombosis; low blood pressure (hypotension); increased blood pressure; 
blocking of a blood vessel or (peripheral embolism); reduced blood flow in the hands, ankles or 
feet (peripheral ischaemia); swelling and clotting in a vein, which may be extremely tender 
when touched (phlebitis or thrombophlebitis superficial); blood clot (thrombosis). 

 a rare disorder characterised by periods of burning pain, redness and warmth in the feet and 
hands (erythromelalgia). 

 
Uncommon: may affect up to 1 in 100 people (may show up in blood or urine tests) 
 a rare type of anaemia in which the red blood cells, white blood cells and platelets are all 

reduced in number (aplastic anaemia); 
 raised white blood cell count (leucocytosis); 
 excess platelet production (thrombocythaemia); increased platelet counts; abnormal count in the 

cells in the blood that prevents bleeding (platelet count abnormal); 
 changes in some blood tests (increase in transaminase; blood lactate dehydrogenase increased); 
 or cancer of white blood cells (multiple myeloma); 
 protein in the urine. 
 
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 Nplate 
 
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 vial label after EXP. The expiry 
date refers to the last day of that month. 
 
Store in a refrigerator (2ºC – 8ºC). 
Do not freeze. 
Store in the original carton in order to protect from light. 
 
This medicine may be removed from the refrigerator for a period of 30 days at room temperature (up 
to 25ºC) when stored in the original carton. 
 
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. 
 
 



 88

6. Contents of the pack and other information 
 
What Nplate contains 
 
- The active substance is romiplostim. 
 

Each vial of Nplate 250 micrograms powder for solution for injection contains a total of 
375 micrograms of romiplostim. An additional overfill is included in each vial to ensure that 
250 micrograms of romiplostim can be delivered. After dissolving, a deliverable amount of 
0.5 mL solution contains 250 micrograms of romiplostim (500 micrograms/mL). 

 
Each vial of Nplate 500 micrograms powder for solution for injection contains a total of 
625 micrograms of romiplostim. An additional overfill is included in each vial to ensure that 
500 micrograms of romiplostim can be delivered. After dissolving, a deliverable amount of 
1 mL solution contains 500 micrograms of romiplostim (500 micrograms/mL). 

 
- The other ingredients are: 

Powder: mannitol (E421), sucrose, L-histidine, hydrochloric acid (for pH adjustment) and 
polysorbate 20. 
Solvent: water for injections. 

 
What Nplate looks like and contents of the pack 
 
Nplate is a white powder for solution for injection supplied in a 5 mL single-dose glass vial. 
 
Nplate is supplied as a 1 pack or multipack comprising 4 packs. Each pack contains: 
1 vial of 250 micrograms or 500 micrograms of romiplostim. 
1 pre-filled syringe containing 0.72 or 1.2 mL of water for injections. 
1 plunger rod for pre-filled syringe. 
1 sterile vial adapter. 
1 sterile 1 mL Luer lock syringe. 
1 sterile safety needle. 
4 alcohol swabs. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
Marketing Authorisation Holder 
Amgen Europe B.V. 
Minervum 7061 
4817 ZK Breda 
The Netherlands 
 
Manufacturer 
Amgen Technology (Ireland) Unlimited Company 
Pottery Road 
Dun Laoghaire 
Co Dublin 
Ireland 
 



 89

Manufacturer 
Amgen NV 
Telecomlaan 5-7 
1831 Diegem 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
België/Belgique/Belgien 
s.a. Amgen n.v. 
Tel/Tél: +32 (0)2 7752711 
 

Lietuva 
Amgen Switzerland AG Vilniaus filialas 
Tel: +370 5 219 7474 

България 
Амджен България ЕООД 
Тел.: +359 (0)2 424 7440 

Luxembourg/Luxemburg 
s.a. Amgen 
Belgique/Belgien 
Tel/Tél: +32 (0)2 7752711 

Česká republika 
Amgen s.r.o. 
Tel: +420 221 773 500 

Magyarország 
Amgen Kft. 
Tel.: +36 1 35 44 700 

Danmark 
Amgen, filial af Amgen AB, Sverige 
Tlf: +45 39617500 
 

Malta 
Amgen B.V. 
The Netherlands 
Tel: +31 (0)76 5732500 
 

Deutschland 
AMGEN GmbH 
Tel.: +49 89 1490960 
 

Nederland 
Amgen B.V. 
Tel: +31 (0)76 5732500 

Eesti 
Amgen Switzerland AG Vilniaus filialas 
Tel: +372 586 09553 

Norge 
Amgen AB 
Tel: +47 23308000 

Ελλάδα 
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε. 
Τηλ.: +30 210 3447000 

Österreich 
Amgen GmbH 
Tel: +43 (0)1 50 217 
 

España 
Amgen S.A. 
Tel: +34 93 600 18 60 
 

Polska 
Amgen Biotechnologia Sp. z o.o. 
Tel.: +48 22 581 3000 

France 
Amgen S.A.S. 
Tél: +33 (0)9 69 363 363 
 

Portugal 
Amgen Biofarmacêutica, Lda. 
Tel: +351 21 4220606 

Hrvatska 
Amgen d.o.o. 
Tel: +385 (0)1 562 57 20 
 

România 
Amgen România SRL 
Tel: +4021 527 3000 

Ireland 
Amgen Ireland Limited 
Tel: +353 1 8527400 
 

Slovenija 
AMGEN zdravila d.o.o. 
Tel: +386 (0)1 585 1767 



 90

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
Amgen Slovakia s.r.o. 
Tel: +421 2 321 114 49 
 

Italia 
Amgen S.r.l. 
Tel: +39 02 6241121 

Suomi/Finland 
Amgen AB, sivuliike Suomessa/Amgen AB, filial 
i Finland 
Puh/Tel: +358 (0)9 54900500 
 

Kύπρος 
C.A. Papaellinas Ltd 
Τηλ.: +357 22741 741 

Sverige 
Amgen AB 
Tel: +46 (0)8 6951100 

Latvija 
Amgen Switzerland AG Rīgas filiāle 
Tel: +371 257 25888 
 

United Kingdom 
Amgen Limited 
Tel: +44 (0)1223 420305 

 
This leaflet was last revised in 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
 
 
7. Instructions for preparing and giving an injection of Nplate 
 
This section contains information on how to give yourself an injection of Nplate. It is important that 
you do not try to give yourself the injection unless you have received training from your doctor, nurse 
or pharmacist. If you have questions about how to inject, please ask your doctor, nurse or pharmacist 
for assistance. It is very important the product is prepared correctly and the correct dose is taken. 
 
This section is divided into the following subsections: 
 
Before you begin 
Step 1. Set up materials for an injection 
Step 2. Prepare vial for use, attach vial adapter 
Step 3. Prepare sterile water syringe 
Step 4. Dissolving Nplate by injecting water into vial 
Step 5. Prepare new syringe for injection 
Step 6. Prepare injection needle 
Step 7. Choose and prepare an injection site 
Step 8. Injecting the Nplate liquid 
Step 9. Disposing of supplies 
 
Before you begin 
 
Read all instructions for use thoroughly. These instructions are for patients who are already trained 
by their healthcare professional, such as your doctor, nurse, or pharmacist, in self injection. If you 
have not been trained, please contact your healthcare professional. 
 
The Nplate self injection kit must be kept in the original package until use in order to protect the 
Nplate vial from light. Keep the Nplate self injection kit refrigerated at 2ºC to 8ºC. 
 
Once Nplate has been dissolved, inject immediately. 



 91

 
You may have excess Nplate left over after administering your prescribed dose. Do not re-use Nplate! 
Any excess dissolved Nplate must be thrown away immediately after completing the injection process. 
Left over Nplate in vial must NEVER be re-used for another injection. 
 
Step 1. Set up materials for an injection 
 
Do the following: 
 
 Select a well lit, flat work surface, such as a table. 
 
 Take the Nplate self injection kit out of the refrigerator. Do not use if frozen. If you have any 

questions about storage, contact your healthcare professional for further instructions. Check the 
expiry date on the self injection kit. If the expiry date has passed, do not use. Stop and 
contact your healthcare professional. 

 
 Note: If your healthcare professional has instructed you that your Nplate dose requires more 

than one injection of Nplate, you will need to use more than one self injection kit. Follow the 
steps as described in this leaflet and use as many self injection kits as necessary to complete 
your prescribed dose of Nplate. 

 
 Make sure you have the following items: 
 
Alcohol swab package x4

 

 

 
A vial of powder, either 250 micrograms OR 
500 micrograms x1 

13 mm vial adapter x1 

  
 
Plunger rod for pre-filled sterile water syringe x1 Pre-filled sterile water syringe x1 

 
 

 

 



 92

1 mL Luer-lock tip syringe x1 Injection safety needle x1 

 
 
 Do not open items until directed in instructions. 
 
 Do not use components that have evidence of tampering or damage. 
 
 Do not re-use items. 
 
Step 2. Prepare vial for use, attach vial adapter 
 
Using: 2 alcohol swab packages, 1 vial, and 1 vial adapter package. 
 
Do the following: 
 
 Wash your hands with soap and warm 

water. 
 
 Clean the flat work surface with a new 

alcohol swab. 
 
 Remove red (250 micrograms) or blue 

(500 micrograms) plastic cap from vial.  
 
 Using a new alcohol swab clean vial 

stopper. 
 
 Do not touch vial stopper after cleaning it. 

 



 93

 Peel off paper backing slowly from vial 
adapter while keeping vial adapter in the 
plastic package. 

 
 Do not touch vial stopper or spike of vial 

adapter. 

 
 
 Keeping the vial on a table, and keeping the 

vial adapter in the plastic packaging, line up 
spike on the vial adapter to the centre of 
the stopper on the vial. 

  
 Push the vial adapter down onto the vial 

until it is firmly in place and you can’t push 
down any more. 

 
 Lift off plastic vial adapter packaging, 

leaving vial adapter on vial. 
 
 Do not touch the top of vial adapter. 

 

 



 94

Step 3. Prepare sterile water syringe 
 
Using: Pre-filled sterile water syringe and plunger rod. 
 
Before you begin Step 3 please note the following: 
 
 The clear plastic plunger rod MUST always be attached first before breaking the white tip off of 

the pre-filled water syringe. Perform step 3a before step 3b. 
 
Do the following: 
 
 Step 3a: Attach clear plastic plunger rod 

to pre-filled sterile water syringe by 
placing the threaded end of the plunger rod 
into the syringe and carefully twisting the 
rod clockwise onto the grey syringe plunger, 
until you feel a slight resistance. Do not over 
tighten. 

 

 
 Step 3b: Holding the syringe with one 

hand, bend the tip of the white plastic 
cover downward with your other hand. 
This will break the seal of the white plastic 
cover. 

 
 Once the seal is broken, pull the white 

plastic cover off. You will see grey rubber 
in the cap. 

 

 
Step 4. Dissolving Nplate by injecting water into vial 
 
Using: Pre-filled sterile water syringe and vial with vial adapter attached. 
 
Before you begin Step 4 please note the following: 
 
 Do dissolve slowly and carefully. This is a protein product and proteins can be easily damaged 

by improper mixing and excessive shaking. 
 



 95

Do the following: 
 
 Keeping the vial on the table, attach 

water-filled syringe to vial adapter by 
holding the side of the vial adapter with one 
hand and twisting the syringe tip clockwise 
onto the adapter with the other hand until 
you feel a slight resistance. 

 
 Very slowly and gently push down on 

plunger rod to inject all water in the 
syringe into the vial. Water must flow 
slowly onto powder. 

 
 Do not force the water into the vial. 
 
 Note: After injecting the water into the vial 

it is common for the plunger to move back 
up. You do not have to maintain pressure on 
the plunger for the rest of Step 4. 

 
 Push slowly and gently 
 



 96

Before continuing: 
 
 Do ensure that all water is injected from the syringe into the vial before dissolving. 
 
 Holding the area where the vial and vial 

adapter connect between your fingers, 
gently swirl the vial by rotating your wrist 
until all of the powder has dissolved and 
the liquid in the vial is clear and 
colourless. 

 
 Do gently swirl the vial. 
 
 Do not shake the vial. 
 
 Do not roll vial between palms. 
 
 Note: It may take up to 2 minutes for the 

powder to completely dissolve. 
 

Correct 
 

 

 Incorrect  
 
Before continuing: 
 
 Do visually inspect the dissolved liquid for particles and/or discolouration. It must be clear and 

colourless and fully dissolved. 
 
 Note: If there is any colour or particles in the liquid, contact your healthcare professional. 
 
 Do make sure liquid is fully dissolved before removing syringe. 
 
 When Nplate is completely dissolved, 

remove the empty syringe by twisting it 
anti-clockwise off of the vial adapter. 

 
 Discard the empty syringe into sharps or hazard container. Keep the dissolved Nplate Vial. 

Immediately prepare new syringe for injection. 
 



 97

 Do not delay injecting Nplate. 
 
Step 5. Prepare new syringe for injection 
 
Using: A new 1 mL syringe package and the vial of dissolved, clear Nplate. 
 
Before continuing: 
 
 Do check your dose before starting this step. 
 
 Note: The Nplate liquid is highly potent which is why accuracy and dose measurement are 

important. 
 
 Do make sure that all air bubbles are removed before injection. 
 
Do the following: 
 
 Remove 1 mL syringe from package. 
 
 Draw air into syringe to 1 mL marking. 
 
 Do not pull plunger back to more than 1 mL. 

 Draw air into syringe to the 1 mL mark 
 
 Attach 1 mL syringe to vial adapter of the 

dissolved Nplate by twisting the syringe tip 
clockwise onto the vial adapter until you feel 
a slight resistance. 

 



 98

A. Push air into vial. 
 
B. Maintain pressure on plunger. 
 
C. Turn vial assembly and syringe upside 

down, so the vial is directly above the 
syringe. 

 A. B. C. 
Flip 

 
 Withdraw the full amount of liquid into 

the syringe. 
 

-  The maximum deliverable volume for 
the 250 microgram vial is 0.5 mL and 
for the 500 microgram vial is 1 mL. 

 
 Do not pull the plunger out of the back of 

the syringe. 
 

 
 
 Do ensure that the plunger remains in the 

syringe. 

 Correct 
 



 99

 Check and remove all air bubbles in the 
syringe. 
-  Gently tap the syringe with your 

fingers to separate the bubbles from 
the liquid. 

 
-  Slowly push the plunger up to force 

the air bubbles out of the syringe. 

 
 Air bubbles: 

Incorrect 
Correct 

 
 Slowly push back on the plunger to leave 

only the amount prescribed by your 
healthcare professional. 

 
 Make sure the top of the plunger head 

lines up with the syringe marking that 
matches your prescribed dose. If necessary 
push liquid back into the vial to achieve the 
desired dose. 

 
 Adjust the amount to your prescribed dose 
 
 Do a final check to ensure the correct 

amount of liquid for your dose is in the 
syringe and all air bubbles have been 
removed. 

 

 
Before continuing: 
 
 Do make sure the correct amount of liquid for your dose remains in the syringe. 
 
 Do make sure all air bubbles are removed from the syringe. 
 



 100

 Once all air bubbles are removed and syringe 
is filled with your correct dose, twist off 
syringe from vial adapter. 

 
 Keep filled syringe in your hand and do 

not touch syringe tip. 
 
 Do not set filled syringe down after 

removing from vial. 

 
 
Step 6. Prepare injection needle 
 
Using: Filled syringe with measured Nplate dose and safety needle. 
 
Do the following: 
 
 Holding the syringe in the palm of your hand 

with the tip facing up, remove the safety 
needle from the package. 

 



 101

 Attach safety needle to filled syringe. 
Apply strong force while twisting to attach 
the safety needle onto syringe. Turn 
clockwise to lock into Luer lock tip. 

 
 The product is now ready for injection. 

IMMEDIATELY continue to step 7. 

 
 
Step 7. Choose and prepare an injection site 
 
Using: New alcohol swab. 
 
Do the following: 
 
 Injection Site 
 Select your injection site. Three 

recommended injection sites for Nplate 
include: 
-  Front of the middle thighs 

 
-  Abdomen, except for the 5 centimetre 

area right around the navel 
 

-  If someone else is giving you the 
injection, they can also use the outer 
area of the upper arms 

 
-  Do rotate the site for each injection.

 

 Front Back 
 
 Do not inject into areas where the skin is 

tender, bruised and hard. 
 
 Do not inject into areas with scars or stretch 

marks. 
 
 Wipe the site where Nplate is to be injected 

with an alcohol swab, using a circular 
motion. 

 
 Do not touch this area again before giving 

the injection. 
 

 



 102

Step 8. Injecting the Nplate liquid 
 
Using: Filled syringe and needle assembly. 
 
Do the following: 
 
 Pull back on the pink safety cover 

(toward the syringe and away from the 
needle). 

 

 
 Remove clear needle shield by holding 

syringe in one hand and carefully pulling 
shield straight off with the other hand. 

 
 Do remove the clear needle shield before 

injecting. 

 
 With one hand, gently pinch the cleaned 

area of skin and hold it firmly. With the 
other hand, hold the syringe (like a 
pencil) at a 45-degree angle to the skin. 

 
 With a short, sharp motion, push the 

needle into the skin. 

 



 103

 Inject the prescribed dose subcutaneously 
as directed by your doctor, nurse or 
pharmacist. 

 
 When the syringe is empty, pull the needle 

out of the skin, being careful to keep it at 
the same angle as inserted. 

 
 There may be a little bleeding at the 

injection site. You can press a cotton ball 
or gauze over the injection site for 
10 seconds. 

 
 Do not rub the injection site. If needed, 

you may cover the injection site with a 
plaster. 

 

 
 After injecting, use your thumb (or tip of 

your finger) to activate the pink safety 
cover by pushing the cover forward using 
the same hand until you hear and/or feel it 
click and lock into place over the needle. 

 
 Visually confirm that the needle tip is 

covered. Always cover the needle with the 
pink safety cover before disposal. 

 
 
Step 9. Disposing of supplies 
 
Do the following: 
 
 Immediately discard syringe with covered needle into a sharps container. 
 Immediately discard used Nplate vial into an appropriate waste container. 
 Make sure all other materials are discarded into proper containers. 
 



 104

The injection device and Nplate vial must NEVER be reused. 
 Do dispose of the used needle and syringe in a puncture-resistant container. 
 Do dispose of any left-over Nplate in proper waste container. Left over Nplate in the vial must 

NEVER be re-used for another injection. 
 
 



 105

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 
 

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS 
OF THE MARKETING AUTHORISATION(S) 

 
 
 
 
 
 



 106

Scientific conclusions 
 
Taking into account the PRAC Assessment Report on the PSUR(s) for romiplostim, the scientific 
conclusions of CHMP are as follows: 
 
A signal was triggered by a positive test of binding and neutralising antibodies to thrombopoietin 
(TPO) in a paediatric clinical trial. The review of the MAH’s clinical trial database identified 
2 subjects with binding and neutralising antibodies to TPO (one paediatric and one adult); 10 subjects 
with binding and neutralising antibodies to romiplostim and binding antibodies to TMP (3 adults and 
7 paediatrics); 2 subjects with binding and neutralising antibodies to romiplostim. In addition, the 
following subjects were identified from the MAH’s global safety database, 2 subjects with binding and 
neutralising antibodies to romiplostim and 4 subjects with binding and / or neutralising antibodies to 
romiplostim and binding antibodies to TPO. 
 
In view of the current new data, an update of the current product information is warranted in order to 
reflect the known information on immunogenicity. 
 
The CHMP agrees with the scientific conclusions made by the PRAC. 
 
 
Grounds for the variation to the terms of the marketing authorisation(s) 
 
On the basis of the scientific conclusions for romiplostim the CHMP is of the opinion that the benefit-
risk balance of the medicinal product(s) containing romiplostim is unchanged subject to the proposed 
changes to the product information. 
 
The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE ANDMANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
	SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMSOF THE MARKETING AUTHORISATION(S)