Adverse reactions : תופעות לוואי

4.8   Undesirable effects

A higher incidence of mild post-immunisation reactions has been reported with Fluad compared to non- adjuvanted influenza vaccines.

Adverse reactions observed from clinical trials

The safety of Fluad in elderly subjects was assessed in thirty-six (36) clinical trials in subjects ≥65 years of age, including 19 randomized controlled trials and 17 uncontrolled seasonal studies. This database includes 12730 subjects, 7532 subjects who received Fluad and 5198 subjects who received conventional trivalent influenza vaccines (TIV).
In this pooled analysis, a higher percentage of subjects who received Fluad reported both local and systemic reactions post-immunization compared with those that received conventional TIV. These included pain at injection site (26.1 vs 13.7%), local tenderness (22.2 vs 12.2%), erythema (3.2 vs 1.7%), induration (2.5 vs 1. 2 %) and swelling (1.6 vs 0.6%) in addition to myalgia (11.0 vs 7.9%) chills (5.0 vs 4.0%), fatigue (11.3% vs 10.5%) and malaise (6.3% vs 5.8%).

The following undesirable effects have been observed during clinical trials with the following frequencies: 
Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000), including isolated reports.

Nervous system disorders
Very Common (≥1/10): Headache

Gastrointestinal disorders
Common (≥1/100, <1/10): Nausea, Diarrhoea, Vomiting
Skin and subcutaneous tissue disorders
Common (≥1/100, <1/10): Sweating
Uncommon (≥1/1,000, <1/100): Rash

Musculoskeletal and connective tissue disorders
Very common (≥1/10): Myalgia
Common (≥1/100, <1/10): Arthralgia

General disorders and administration site conditions
Very common (≥1/10): Tenderness, pain at injection site, fatigue
Common (≥1/100, <1/10): Fever, malaise, shivering
Local reactions: redness, swelling, ecchymosis, induration
Most reactions are mild or moderate and resolve spontaneously within 1 to 2 days.

Adverse reactions reported from post-marketing surveillance

Adverse reactions reported from post marketing surveillance are, next to the reactions which have also been observed during the clinical trials, the following:

Blood and lymphatic system disorders
Thrombocytopenia (some very rare cases were severe with platelet counts less than 5,000 per mm3), lymphadenopathy.

General disorders and administration site conditions
Asthenia, Influenza-Like Illness (ILI)

Extensive swelling of injected limb lasting more than one week, injection-site cellulitis-like reaction (some cases of swelling, pain, and redness extending more than 10 cm and lasting more than 1 week).

Immune system disorders
Allergic reactions including anaphylactic shock (in rare cases), anaphylaxis and angioedema.

Musculoskeletal and connective tissue disorders
Pain in the extremity, muscular weakness.
Nervous system disorders
Encephalomyelitis, Guillain-Barré Syndrome, convulsions, neuritis, neuralgia, paraesthesia, syncope, presyncope.

Skin and subcutaneous tissue disorders
Generalised skin reactions including erythema multiforme, urticaria, pruritus or non-specific rash.

Vascular disorders
Vasculitis with transient renal involvement
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 http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.gov.il and emailed to the Registration Holder’s Patient Safety Unit at: drugsafety@neopharmgroup.com