Optaflu - summary of medicine characteristics

1. NAME OF THE MEDICINAL PRODUCT

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

3. PHARMACEUTICAL FORM

4. CLINICAL PARTICULARSuenza for adults, especially in those who run an increased risk of associatedProphylaxis of co lications.4.1 Therapeutic indications flu should be used in accordance to Official guidance.

2 Posology and method of administration

Posology

Adults from the age of 18 years: One dose of 0.5 ml

Paediatric population

The safety and efficacy of Optaflu in children and adolescents less than 18 years of age have not yet been established. No data are available. Therefore, Optaflu is not recommended for use in children and adolescents less than 18 years of age (see section 5.1).

Method of administration

Immunisation should be carried out by intramuscular injection into the deltoid muscle.

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. Immunisation shall be postponed in patients with febrile illness or acute infection.

4.4 Special warnings and precautions for use

As with all injectable vaccines, appropriate medical treatment and supervision shouays be readily available in case of a rare anaphylactic event following the administration of the vaccine.

Optaflu should under no circumstances be administered intravascularly.

Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that procedures are in place to avoid injury from faints.

Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient.

4.5 Interaction with other medicinal products and other forms of interaction

Optaflu may be given at the same time as other vaccines. Immunisation should be carried out on separate limbs. It should be noted that adverse reactions may be intensified.

The immunological response may be diminished if the patient is undergoing immunosuppressant treatment.

Following influenza vaccination, false-positive serology test results may be obtained by the ELISA method for antibody to human immunodeficiency virus-1 (HIV-1), hepatitis C virus and, especially, HTLV-1. In such cases, the Western blot method is negative. These transitory false-positive results

uction in response to the vaccine.

ptaflu in pregnancy and breast-feeding has not been assessed in clinical trials.

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In general data from influenza vaccinations in pregnant women do not indicate adverse foetal and maternal outcomes attributable to the vaccine. Animal studies do not indicate reproductive toxicity (see Section 5.3 – Preclinical safety data). The use of Optaflu may be considered from the second trimester of pregnancy. For pregnant women with medical conditions that increase their risk of complications from influenza, administration of the vaccine is recommended, irrespective of their stage of pregnancy.

Breast-feeding

There is no human data on use of Optaflu during lactation. No effects on the breastfed newborn /infant are anticipated. Optaflu may be used during lactation

Fertility

No human fertility data are available. Animal data have not shown effects on female fertility (see section 5.3). Male fertility has not been assessed in animals (see section 5.3).

4.7 Effects on ability to drive and use machines

Optaflu has minor influence on the ability to drive and use machines.

4.8 Undesirable effects

• a) Summary of safety profile                 ।

The safety of Optaflu has been assessed in seven randomized, active controlled clinical trials performed as part of the development program. Overall 7253 single doses of Optaflu were administered to 6180 adults aged 18 – 60 years of age and to 1073 elderly (aged 61 years cr older). Safety and reactogenicity evaluations were performed for all subjects during the first 3 weeks following vaccination and SAEs have been collected for approximately 6700 vaccinees during six months of follow-up.

• b) Summary of adverse reactions

Adverse reactions are listed according to the following frequency:

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)

Not known (cannot be estimated from the available data)

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. The following adverse reactions have been observed:

Table 1: Frequency in adults (18–60 years of age)

Organ class	Very common > 1/10 <	C ommon > 1/100 to < 1/10	Uncommon > 1/1000 to < 1/100	Rare > 1/10,000 to <1/1000	Very rare <1/ 10,000	Not known (cannot be estimated from available data)
Nervous system disorders . r'X	– Headache* ▼				– Neurological disorders, such as Guillain Barré syndrome, encephalomyelitis and neuritis	– Paraesthesia
Vascular diso ders					– Vasculitis, possibly associated with transient renal involvement
Immune system disorders					– Allergic reactions, in very rare cases leading to shock	– Angioedema
Blood and lymphatic system disorders				– Local lymphadenopathy	– Thrombocytopenia

In the elderly frequencies were similar, except for myalgia, headache and injection site pain which were classified as ‘common’. The incidence rates for moderate and severe pain after Optaflu vaccination are similar to those of egg-derived influenza vaccines; however a slightly increased risk for mild short-lasting injection site pain was observed with Optaflu in the subgroup of elderly vaccinees (8% compared to 6% with egg-derived influenza vaccine).

Post-marketing surveillance :

So far there is limited post-marketing experience with Optaflu.

The following additional adverse reactions were reported from post-marketing surveillance with egg-based seasonal trivalent vaccines:

Reporting of suspected adverse reactions :

Reporting of suspected adverse reactions after authorisation of the medicinal products is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionols are asked to report any suspected adverse reactions via the national reporting sytem listed in Appendix V.

4.9 Overdose

No case of overdose has been reported for Optaflu.

5. PHARMACOLOGICAL PROPERTIES5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Influenza vaccine, ATC Code: J07BB02

Efficacy against Culture-Confirmed Influenza

A multinational (US, Finland, and Poland), randomized, observer-blinded, placebo-controlled trial was performed to assess clinical efficacy and safety of Optaflu during the 2007–2008 influenza season in adults aged 18 to 49 years. A total of 11,404 subjects were enrolled to receive Optaflu (N=3828), Agrippal (N=3676) or placebo (N=3900) in a 1:1:1 ratio. Among the overall study population enro the mean age was 33 years, 55% were female, 84% were Caucasian, 7% were Black, 7% were Hispanic, and 2% were of other ethnic origin.

Optaflu efficacy was defined as the prevention of culture-confirmed symptomatic influenza illness caused by viruses antigenically matched to those in the vaccine compared to placebo. Influenza cases were identified by active and passive surveillance of influenza-like illness (ILI). ILI was defined according to Centers for Disease Control and Prevention (CDC) case definition, i.e., a fever (oral temperature > 100.0°F / 38°C) and cough or sore throat. After an episode of Ilt, nose and throat swab samples were collected for analysis. Vaccine efficacies against vaccine-matched influenza viral

strains, against all influenza viral strains, and against individual influenza viral subtypes were calculated (Tables 2 and 3).

Table 2: Vaccine Efficacy against Culture-Confirmed Influ

	Number of subjects per protocol	Number of subjects with influenza	Attack Rate (%)	Vaccine Efficacy*
				%	Lower Limit of OneSided 97.5% CI
Antigenically Matched Strains
Optaflu	3776	V 7	0.19	83.8	61.0
Placebo	3843	44	1.14	--	--
All Culture-Confirmed Influenza V.
Optaflu	3776 k ;      42		1.11	69.5	55.0
Placebo	3843	140	3.64	--	--

Simultaneous one-sided 97.5% confidence intervals for the vaccine efficacy of each influenza vaccine

relative to placebo based on the Sidak-corrected score confidence intervals for the two relative risks. Vaccine Efficacy = (1 – Relative Risk) x 100 %

Table 3: Comparative Efficacy of Optaflu versus Placebo against Culture-Confirmed Influenza by Influenza Viral Subtype

	Optaflu (N=3776)		Placebo (N=3843)		Vaccine Efficacy*
	A Attack Rate (%)	Number of Subjects with Influenza	Attack Rate (%)	Number of Subjects with Influenza	%	Lower Limit of One-Sided 97.5% CI
Antigenically Matched Strains
a/H I3N2”	0. 05	2	0	0	--	--
A/H1N1	0.13	5	1.12	43	88.2	67.4
B	0	0	0.03	1	--	--
All Culture-Confirmed Influenza
A/H3N2	0.16	6	0.65	25	75.6	35.1
A/H1N1	0.16	6	1.48	57	89.3	73.0
B	0.79	30	1.59	61	49.9	18.2

Simultaneous one-sided 97.5% confidence intervals for the vaccine efficacy of each influenza vaccine relative to placebo based on the Sidak-corrected score confidence intervals for the two relative risks.

Vaccine Efficacy = (1 – Relative Risk) x 100 %;

There were too few cases of influenza due to vaccine-matched influenza A/H3N2 or B to adequately assess vaccine efficacy.

Immunogenicity

Seroprotection is generally obtained within 3 weeks, as shown by the pivotal phase III clinical study V58P4 for the adult and elderly population.

In this comparative trial against an egg-derived influenza vaccine the seroprotection rate, seroconversion or significant increase rate** and the geometric mean ratio (GMR) for anti-HA antibody (measured by HI) were assessed according to predefined criteria.

Data for adults were as follows (values in brackets show the 95% confidence intervals):

Data for elderly were as follows (values in brackets show the 95% confidence intervals):

Table 5: Immunogenicity in Elderly

Strain specific anti-HA antibody	AJH1N’ 5\ 672	A/H3N2 N= 672	B N=672
Seroprotection rate	76% !_ (72, 79)	97% (96, 98)	84% (81, 87)
Seroconversion/Sig­nificant increase rate	48% (44, 52)	65% (61, 68)	76% (72, 79)
GMR	4.62	5.91	9.63
	(4.2, 5.08)	(5.35, 6.53)	(8.77, 11)

Seroprotection = HI titers > 40

Seroconversion = negative pre-vaccination HI titer and post-vaccination HI titer >40; significant increase = positive pre-vaccination HI titer and at least a 4-fold increase in post-vaccination HI titer.

No differences were observed between the cell-culture and the comparator egg-derived vaccine. Across all three influenza strains, for the egg-derived vaccine seroprotection rates ranged between 85% and 98%, seroconversion or significant increase rates ranged between 62% and 73% and GMRs ranged between 5.52– and 8.76-fold over baseline HI titers.

The persistence of postvaccination antibodies to strains included in the vaccine is usually 6–12 months, as shown by studies performed during the clinical development of this vaccine.

Paediatric population

Optaflu has not been studied in the paediatric population and therefore, data on immune response are not available for this age group.

The European Medicines Agency has deferred the obligation to submit the results of studies withOptaflu in one or more subsets of the paediatric population in the prevention of influenza (see section 4.2 for information on paediatric use).

5.2 Pharmacokinetic properties

Not applicable

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional repeat dose toxicity studies. Optaflu was well tolerated and immunogenic in mice and ferrets. In a repeated-dose toxicity study in rabbits there was no evidence of systemic toxicity and the vaccine was locally well tolerated.

No evidence of reproductive or developmental toxicity was seen in a study where the human dose of Optaflu was administered prior to and during gestatioin to female rabbits.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

1 year

6.4 Special precautions for storage

Store in a refrigerator (2 °C – 8 °C).

Do not freeze.

Keep the pre-filled syringe in the outer carton in order to protect from light.

6.5 Nature and contents of container

0.5 ml suspension in pre-filled syringes (type I glass), with a plunger stopper (bromobutyl rubber). Pack sizes of 1, 10 or multipacks containing 20 (2 packs of 10) pre-filled syringes, each with or without needle.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

The vaccine should be allowed to reach room temperature before use.

Shake before use.

Visually inspect the contents of each Optaflu syringe for particulate matter and/or change in colour prior to administration. If either condition exists, do not administer the vaccine.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

Seqirus GmbH

Emil-von-Behring-Strasse 76

D-35041 Marburg

Germany

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/07/394/001 – EU/1/07/394/011

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 01 June 2007

Date of latest renewal: 01 June 2012