Adverse reactions : תופעות לוואי

4.8     Undesirable effects

Summary of the safety profile
In 7 clinical trials, individuals were administered Gardasil 9 on the day of enrolment and approximately 2 and 6 months thereafter. Safety was evaluated using vaccination report card (VRC)-aided surveillance for 14 days after each injection of Gardasil 9. A total of 15,776 individuals (10,495 subjects aged 16 to 26 years and 5,281 adolescents aged 9 to 15 years at enrolment) received Gardasil 9. Few individuals (0.1 %) discontinued due to adverse experiences.

In one of these clinical trials which enrolled 1,053 healthy adolescents aged 11 to 15 years, administration of the first dose of Gardasil 9 concomitantly with a combined diphtheria, tetanus, pertussis [acellular, component] and poliomyelitis [inactivated] booster vaccine showed that more injection-site reactions (swelling, erythema), headache and pyrexia were reported. The differences observed were < 10 % and in the majority of subjects, the adverse events were reported as mild to moderate in intensity (see section 4.5).

In a clinical trial that included 640 individuals aged 27 to 45 years and 570 individuals aged 16 to 26 years who received Gardasil 9, the safety profile of Gardasil 9 was comparable between the two age groups.

The most common adverse reactions observed with Gardasil 9 were injection-site adverse reactions (84.8 % of vaccinees within 5 days following any vaccination visit) and headache (13.2 % of the vaccinees within 15 days following any vaccination visit). These adverse reactions usually were mild or moderate in intensity.

Tabulated summary of adverse reactions

The adverse reactions are categorised by frequency using the following convention: 
-       Very common (≥1/10)
-       Common (≥1/100 to <1/10)
-       Uncommon (≥1/1,000 to <1/100)
-       Rare (≥1/10,000 to <1/1,000)
-       Not known (cannot be estimated from the available data)

Clinical trials
Table 1 presents adverse reactions considered as being at least possibly related to vaccination and observed in recipients of Gardasil 9 at a frequency of at least 1.0 % from 7 clinical trials (PN 001, 002, 003, 005, 006, 007 and 009, N=15,776 individuals) (see section 5.1 for description of the clinical trials).


Post-marketing experience
Table 1 also includes adverse events which have been spontaneously reported during the post-marketing use of Gardasil 9 worldwide. Their frequencies were estimated based on relevant clinical trials.

Table 1: Adverse reactions following administration of Gardasil 9 from clinical trials and adverse events from post-marketing data
System organ class                Frequency                      Adverse reactions Uncommon              Lymphadenopathy*
Blood and lymphatic system
disorders
Rare                      Hypersensitivity*
Immune system disorders                     Not known                 Anaphylactic reactions* Very common               Headache
Nervous system disorders
Common                    Dizziness
Uncommon                  Syncope sometimes accompanied by tonic- clonic movements*
Gastrointestinal disorders                  Common                    Nausea Uncommon                  Vomiting*
Skin and subcutaneous tissue                Uncommon                  Urticaria* disorders
Musculoskeletal and connective              Uncommon                  Arthralgia*, myalgia* tissue disorders
Very common               At the injection site: pain, swelling, erythema General disorders and administration site conditions              Common                    Pyrexia, fatigue, At the injection site: pruritus, bruising
Uncommon                  Asthenia*, chills*, malaise*, injection site nodule*
*Adverse events reported during post-marketing use of Gardasil 9. The frequency was estimated based on relevant clinical trials.
For events not observed in clinical trials the frequency is indicated as ‘Not known’.
 qHPV vaccine

Table 2 includes adverse experiences that have been spontaneously reported during post-approval use of qHPV vaccine. The post-marketing safety experience with qHPV vaccine is relevant to Gardasil 9 since the vaccines contain L1HPV proteins of 4 of the same HPV types.

Because these events were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or to establish, for all events, a causal relationship to vaccine exposure.

Table 2: Adverse reactions reported from post-marketing experience with qHPV vaccine System organ class          Frequency                   Adverse reactions 
Infections and                  Not known                   Injection-site cellulitis infestations

Blood and lymphatic             Not known                   Idiopathic thrombocytopaenic purpura system disorders

Immune system                   Not known                   Anaphylactoid reactions, bronchospasm disorders

Nervous system                  Not known                   Acute disseminated encephalomyelitis, disorders                                                   Guillain-Barré syndrome 
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. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il.