4.6 Pregnancy and lactation

 Pregnancy

For romiplostim no clinical data on exposed pregnancies are available.

Studies in animals have shown reproductive toxicity, such as transplacental passage and increased foetal platelet counts in rats (see section 5.3). The potential risk for humans is unknown.

Romiplostim should not be used during pregnancy unless clearly necessary.

Breast-feeding

There are no data on excretion of romiplostim in human milk. However, excretion is likely and a risk to the suckling child cannot be excluded. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with romiplostim should be made taking into account the benefit of breast-feeding to the child and the benefit of romiplostim therapy to the woman.

4.7 Effects on ability to drive and use machines

 No studies on the effects on the ability to drive and use machines have been performed. However, patients should be informed that in clinical trials mild to moderate, transient bouts of dizziness were experienced by some patients, which may affect the ability to drive or use machines.

4.8 Undesirable effects

 a. Summary of the safety profile

Based on an analysis of all adult ITP patients receiving romiplostim in 4 controlled and 5 uncontrolled clinical studies, 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.

b. Tabulated list of adverse reactions

Frequencies are defined as: Very common ( 1/10), Common ( 1/100 to < 1/10) and Uncommon ( 1/1000 to < 1/100). 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
 
Blood and lymphatic system disorders
   Bone marrow disorder*

Thrombocytopenia*
 Anaemia

Aplastic anaemia

Bone marrow failure

Leukocytosis

Splenomegaly

Thrombocythaemia

Platelet count increased

Platelet count abnormal
 
Cardiac disorders
     Myocardial infarction

Heart rate increased
 
Ear and labyrinth disorders
     Vertigo
 
Eye disorders
     Conjunctival haemorrhage

Accommodation disorder

Blindness

Eye disorder

Eye pruritus

Lacrimation increased

Papilloedema

Visual disturbances
 
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
 
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 jitter