This information comes from the Medicines and Healthcare Products Regulatory Agency of the UK Government.
Suspected Adverse Reaction Analysis
CERVARIX Human papillomavirus (HPV) vaccine
04 December 2008
This report summarises the adverse reactions suspected to have been caused by Cervarix human
papillomavirus (HPV) vaccine in the UK. This includes reports received between 14 April 2008 and 3rd
December 2008. These reports have been voluntarily submitted to the MHRA by healthcare
professionals and members of the public via the Yellow Card Scheme (visit www.yellowcard.gov.uk)
and by the manufacturers of the vaccine as part of their legal requirements
It is essential to bear in mind that reports to the MHRA relate only to adverse medical events which the
reporter considered could have been caused by the vaccine (i.e. if there was merely a suspicion of
causality). Therefore, cases may be true side-effects or they may have been purely coincidental events
due to underlying or undiagnosed illness that would have occurred anyway in the absence of
vaccination. Events may also have been psychogenic1 in origin. This report therefore cannot be
considered to represent a list of known side-effects of the vaccine. These data also cannot be used to
determine the frequency, or incidence, of known side-effects because they are often under-reported.
The known side-effects, and their frequencies (based on clinical trial data), are available in the product
information (see http://emc.medicines.org.uk/).
The reactions in this report have been broken down into 5 categories based on scientific assessment of
the cases by MHRA assessors: injection-site reactions; allergic reactions; ‘psychogenic’ events; other
recognised reactions; and ‘suspected adverse reactions not currently recognised’ (reactions in this latter
category are divided into the high-level classification of System Organ Class)2.
A single report may contain more than one reaction, more than one sign or symptom of a single
reaction or reactions in more than one of the above categories. Therefore the total number of listed
reactions is greater than the total number of reports and total reports in each of the 5 tables should not
be added together.
Headline summary:
To date, the vast majority of suspected adverse reactions reported to MHRA in association with
Cervarix vaccine have related either to the signs and symptoms of recognised side effects listed
in the product information or were due to the injection process and not the vaccine itself (i.e.
‘psychogenic’ in nature).
For the isolated cases of other medical conditions reported, the available evidence does not
suggest that the vaccine caused the condition and these may have been coincidental events.
The balance of risks and benefits of Cervarix remains positive.
1 For this analysis, defined as non-allergic events which occurred within minutes of, or soon after, vaccination and were
most likely a psychogenic response to, or anticipation of, the injection. These are not side effects to the vaccine as such
and can occur with any needle injection procedure.
2 Using MedDRA terminology
2
SUMMARY OF UK SAFETY EXPERIENCE
Total number of reports received: 623
Total number of suspected reactions: 1416
Estimated number of doses administered to date: unavailable at present
Overall adverse reaction reporting rate: unavailable at present
A. Injection-site reactions
Injection-site reactions including redness, pain and swelling are recognised side-effects of Cervarix
vaccine and are listed in the product information. These may occur at a frequency3 of more than 1 in 10
persons vaccinated. The reported cases of ‘Pain in extremity’ mainly relate to a sore arm.
The cases reported to the MHRA during use of the vaccine in the UK do not indicate any change in the
severity or nature of injection-site reactions.
Reported event (Preferred Term2) Number of cases
Pain in extremity 36
Injection site erythema 15
Limb discomfort 13
Injection site pain 10
Injection site swelling 10
Oedema peripheral 8
Erythema 5
Injection site reaction 5
Hypoaesthesia 4
Skin discolouration 4
Injection site rash 3
Local swelling 3
Pain 3
Rash macular 3
Feeling hot 2
Injection site mass 2
Injection site pruritus 2
Musculoskeletal stiffness 2
Paraesthesia 2
Injection site induration 1
Injection site inflammation 1
Injection site joint pain 1
Injection site papule 1
Injection site vesicles 1
Injection site warmth 1
Limb immobilisation 1
Local reaction 1
Pruritus 1
Total reactions 141
Total reports 106
3 Based on clinical trial data
3
B. Allergic reactions (including skin reactions not directly related to an injection-site
reaction)
Allergic reactions are recognised side-effect of Cervarix vaccine and are listed in the product
information. These may occur at a frequency4 between 1 in 10 persons (for non-serious types of allergic
reaction such as rash and itching) to less than 1 in 10,000 persons vaccinated. Severe allergic
reactions are very rare.
The cases reported to the MHRA during use of the vaccine in the UK do not indicate any change in the
severity or nature of allergic reactions.
Reported event (Preferred Term2) Number of cases
Rash 23
Pruritus 11
Urticaria 11
Swelling face 9
Lip swelling 7
Oedema peripheral 7
Rash pruritic 7
Eye swelling 6
Erythema 5
Dyspnoea 4
Hypersensitivity 4
Paraesthesia 4
Rash generalised 4
Anaphylactic reaction 3
Paraesthesia oral 3
Throat tightness 3
Eye pruritus 2
Ocular hyperaemia 2
Pharyngeal oedema 2
Pruritus generalised 2
Angioedema 1
Blister 1
Chest discomfort 1
Dizziness 1
Dysphagia 1
Eyelid oedema 1
Flushing 1
Gingival swelling 1
Hypoaesthesia 1
Limb discomfort 1
Malaise 1
Musculoskeletal stiffness 1
Neck pain 1
Pain of skin 1
Pallor 1
Peripheral coldness 1
Purpura 1
Rash erythematous 1
Rash macular 1
Skin inflammation 1
4
Sneezing 1
Swelling 1
Swollen tongue 1
Type I hypersensitivity 1
Wheezing 1
Total reactions 144
Total reports 86
C. ‘Psychogenic’ events
Psychogenic events including vasovagal syncope, faints and panic attacks can occur with any injection
procedure, not just vaccination, and can be common in adolescents. These are due to fear and/or
anticipation of the needle injection and are not side-effects of Cervarix vaccine as such. Such events
can be associated with a wide range of temporary signs and symptoms including loss of consciousness,
vision disturbance, injury, limb jerking (often misinterpreted as a seizure/convulsion), limb numbness or
tingling, difficulty in breathing, hyperventilation etc.
The events in the list below were considered ‘psychogenic’ in nature based on MHRA assessment of
the individual case details reported. The reported cases which do not refer specifically to vasovagal
syncope, faint or panic attack (e.g. convulsion, transient blindness which refers to temporary loss of
vision at the start of a faint) were concurrently reported as signs or symptom of the psychogenic event;
i.e. these also were not side-effects of the vaccine itself.
Reported event (Preferred Term2) Number of cases
Syncope 88
Dizziness 71
Headache 43
Nausea 38
Pallor 21
Flushing 19
Malaise 16
Cold sweat 13
Tremor 13
Syncope vasovagal 9
Vomiting 9
Feeling hot 8
Paraesthesia 8
Rash 7
Vision blurred 7
Hyperhidrosis 6
Hypoaesthesia 6
Loss of consciousness 6
Somnolence 6
Unresponsive to stimuli 6
Chills 5
Abdominal pain upper 4
Dyskinesia 4
Feeling cold 4
Feeling of body temperature change 4
Visual impairment 4
5
Abdominal pain 3
Blindness transient 3
Convulsion 3
Dyspnoea 3
Eye rolling 3
Fatigue 3
Heart rate increased 3
Muscle twitching 3
Muscular weakness 3
Nasopharyngitis 3
Tearfulness 3
Asthenia 2
Chest discomfort 2
Confusional state 2
Dysgeusia 2
Erythema 2
Feeling abnormal 2
Hyperventilation 2
Muscle rigidity 2
Myalgia 2
Nervousness 2
Peripheral coldness 2
Pulse abnormal 2
Rash macular 2
Stomach discomfort 2
Tinnitus 2
Abasia 1
Altered state of consciousness 1
Anxiety 1
Blindness 1
Body temperature increased 1
Bruxism 1
Burning sensation 1
Chest pain 1
Colour blindness 1
Cyanosis 1
Deafness 1
Deafness transitory 1
Discomfort 1
Disorientation 1
Dizziness postural 1
Dry mouth 1
Dry throat 1
Dysphagia 1
Dysstasia 1
Ear pain 1
Eye swelling 1
Eyelid oedema 1
Facial spasm 1
Fall 1
Feeling of despair 1
Grand mal convulsion 1
Heart rate irregular 1
6
Hot flush 1
Hypersomnia 1
Lethargy 1
Lip swelling 1
Musculoskeletal stiffness 1
Mydriasis 1
Neck pain 1
Oropharyngeal pain 1
Pain 1
Panic reaction 1
Photophobia 1
Pruritus 1
Pyrexia 1
Rash generalised 1
Respiratory arrest 1
Respiratory rate decreased 1
Respiratory rate increased 1
Salivary hypersecretion 1
Seizure anoxic 1
Sensory loss 1
Shock 1
Swelling face 1
Tachycardia 1
Throat irritation 1
Throat tightness 1
Total reactions 540
Total reports 205
D. ‘Other recognised’ reactions
This section includes other events recognised to be side-effects of Cervarix vaccine and not already
included in sections A and B above. This also includes signs and symptoms of recognised side effects.
The frequencies, where known, are listed in the product information.
The cases reported to the MHRA during use of the vaccine in the UK so far do not indicate any change
in the severity or nature of these reactions.
Reported event (Preferred Term2) Number of cases
Headache 102
Nausea 90
Dizziness 88
Vomiting 35
Abdominal pain upper 18
Fatigue 18
Malaise 18
Pyrexia 12
Abdominal pain 10
Myalgia 7
Chills 5
Feeling hot 5
7
Stomach discomfort 5
Arthralgia 4
Diarrhoea 4
Paraesthesia 4
Body temperature increased 3
Oropharyngeal pain 3
Pain 3
Pain in extremity 3
Back pain 2
Feeling of body temperature change 2
Influenza like illness 2
Musculoskeletal stiffness 2
Neck pain 2
Pallor 2
Pruritus 2
Thirst 2
Asthenia 1
Induration 1
Lethargy 1
Listless 1
Local swelling 1
Lower respiratory tract infection 1
Migraine 1
Musculoskeletal chest pain 1
Nasal congestion 1
Pharyngitis 1
Pruritus generalised 1
Rash 1
Respiratory disorder 1
Skin warm 1
Somnolence 1
Tremor 1
Upper respiratory tract infection 1
Urticaria 1
Wheezing 1
Total reactions 472
Total reports 252
8
E. Suspected adverse reactions not currently recognised
This section includes reports which, based on MHRA assessment of the case details provided, do not fit
into one of the above 4 categories.
These suspected ADRs are not currently recognised as side effects of Cervarix vaccine and the
available evidence does not suggest a causal link with the vaccine. These are isolated medical events
which may have been coincidental with vaccination. These reports are continually assessed by the
MHRA.
System Organ Class Reported event (Preferred Term2) Number of cases
Blood and lymphatic
system disorders Lymphadenopathy 4
Cardiac disorders Palpitations 1
Ear and labyrinth
disorders Ear pain 3
Eye disorders Eye swelling 1
Photophobia 1
Vision blurred 3
Gastrointestinal disorders Abnormal faeces 1
Mouth ulceration 1
Nausea 2
Vomiting 3
General disorders and
administration site
conditions
Abasia 1
Chills 1
Fatigue 1
Feeling cold 1
Influenza like illness 5
Local swelling 1
Malaise 3
Oedema peripheral 2
Pain 1
Peripheral coldness 2
Swelling 1
Infections and
infestations Application site pustules 1
Folliculitis 1
Nasopharyngitis 1
Pneumonia viral 1
Injury, poisoning and
procedural complications Contusion 3
Drug exposure during pregnancy 1
Investigations Blood glucose increased 2
Blood pressure increased 1
Respiratory rate increased 1
Weight decreased 1
Metabolism and nutrition
disorders Anorexia 1
Dehydration 1
Diabetes mellitus inadequate
control 1
9
Diabetic ketoacidosis 1
Hypoglycaemia 1
Musculoskeletal and
connective tissue
disorders
Muscular weakness 2
Musculoskeletal stiffness 1
Myalgia 1
Pain in extremity 5
Nervous system
disorders Complex regional pain syndrome 1
Convulsion 2
Dizziness 2
Facial palsy 1
Grand mal convulsion 1
Hemiparesis 1
Hypoaesthesia 2
Lethargy 1
Migraine 1
Paraesthesia 2
Somnolence 5
Status epilepticus 1
Syncope 2
Tremor 1
Unresponsive to stimuli 1
Pregnancy, puerperium
and perinatal conditions Abortion spontaneous 1
Psychiatric disorders Confusional state 1
Insomnia 1
Sleep disorder 2
Reproductive system and
breast disorders Amenorrhoea 1
Respiratory, thoracic and
mediastinal disorders Asthma 1
Dyspnoea 2
Epistaxis 2
Haemoptysis 1
Hypoventilation 1
Nasal congestion 1
Oropharyngeal pain 3
Wheezing 1
Skin and subcutaneous
tissue disorders Eczema 2
Erythema 1
Guttate psoriasis 1
Rash 2
Rash vesicular 1
Skin discolouration 2
Vascular disorders Flushing 1
Pallor 1
Total reactions 119
Total reports 71
10
In relation to safety in pregnancy, during pre-licensing studies of Cervarix it was found that almost
870 women became pregnant before or after receiving the vaccine. The overall rates of
spontaneous abortion in these clinical trials were no greater than the background rates in the
general population (i.e. regardless of vaccination). There is currently no evidence to suggest that
Cervarix vaccine carries any risks during pregnancy. Nonetheless, Cervarix is not recommended
for use in pregnancy.
www.mhra.gov.uk
