Influfac

Inactivated influenza vaccine (surface antigen)

Composition Active:
Inactivated influenza vaccine (surface antigen)

Inactive:
Potassium chloride, potassium dihydrogen phosphate, sodium phosphate-dibasic dihydrate, sodium chloride, calcium chloride, magnesium chloride and water for injections.

Description
Influvac is a clear colourless suspension for injection. It is an egg-grown, inactivated influenza virus vaccine based on isolated surface antigens of A and B strains of myxovirus influenza. The type and amount of viral antigens in Influvac conform to the requirements of the Australian Influenza Vaccine Committee (AIVC) and the New Zealand Ministry of Health for the winter of 2007. The strains chosen for vaccine manufacture are endorsed by the AIVC as being antigenically equivalent to the reference virus. The currently recommended strains are: A/Wisconsin/67/2005 (H3N2)-like strain (A/Hiroshima/52/2005 IVR-142) (15 micrograms haemagglutinin/dose), A/New Caledonia/20/99 (H1N1)-like strain (A/New Caledonia/20/99 IVR-116) (15 micrograms haemagglutinin/dose), B/Malaysia/2506/2004- like strain (B/Malaysia/2506/2004) (15 micrograms haemagglutinin/dose).

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Pharmacology
This vaccine is used for active immunisation against influenza virus, types A and B, principally for the vaccination of those groups regarded as being at special risk, especially the elderly.

The vaccine stimulates production of antibodies with a specific capacity against influenza. Protection is only against those strains of the virus from which the vaccine is prepared or closely related strains.

Seroprotection is obtained within 2-3 weeks. The duration of post-vaccination immunity varies, but is between 6-12 months.

Indications
For the prevention of influenza caused by influenza virus, types A and B, in adults aged 18 years and older.

The current New Zealand Immunisation Handbook 2002 recommends annual vaccination for the following persons:

1. All people 65 years and older.
2. People under 65 years with:
   • Cardiovascular disease - ischaemic heart disease, congestive heart failure, rheumatic heart disease, congenital heart disease, cerebrovascular disease.
   • Chronic respiratory disease - Asthma if on regular preventative therapy; other chronic respiratory disease with impaired lung condition.
   • Diabetes.
   • Chronic renal disease.
   • Any cancer, excluding basal or squamous skin cancers if not invasive.
   • Other conditions - autoimmune disease, immune suppression, HIV, transplant recipients, neuromuscular and CNS diseases, haemoglobinopathies, children on long-term aspirin.

Pregnant women
Influenza vaccine should be offered, and is funded, for pregnant women with a medical condition (as above). The vaccine should be given before the influenza season. Although the inactivated influenza vaccine is considered by many experts to be safe at any stage of pregnancy, others prefer to administer the influenza vaccine in the second trimester to avoid a coincidental association with spontaneous abortion. Practitioners should assess the risk for individual women. Although the publicly funded vaccine is not yet available for pregnant women (without a risk condition) the Infectious Diseases Advisory Committee to the Ministry of Health makes the following recommendations for pregnant women:

Women in the first trimester of pregnancy should not be vaccinated.

Influenza vaccination is recommended for women who are beyond the first trimester of pregnancy (ie, greater than 14 weeks gestation) during the influenza season.

Other adults
Healthy individuals should also consider the use of the vaccine, especially if they are in close contact with individuals at high risk of complications. Employers should consider providing influenza vaccine to avoid illness in their employees, especially those engaged in health care and other essential community services. Immunizing healthy individuals has been shown to be cost effective.

Contraindications
Hypersensitivity to eggs, chicken protein, chicken feathers, or any other constituent of the vaccine (See 'Description').

Immunisation should be postponed in patients with an acute febrile illness. The presence of a minor illness with or without fever should not contraindicate the use of Influvac.

Precautions
As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine. Influvac should not be administered intravascularly.

Influvac should be administered subcutaneously to subjects with thrombocytopenia or a bleeding disorder, since bleeding may occur following an intramuscular injection.

Patients with impaired immune responsiveness, whether due to the use of immunosuppressive therapy, a genetic defect, human immunodeficiency virus (HIV) infection, or other causes, may have a reduced antibody response in active immunisation procedures. The vaccine may contain non-detectable residual amounts of gentamicin. Use with caution in patients known to be hypersensitive to this antibiotic.

Patients with a history of Guillain-Barre syndrome (GBS) with an onset related in time to influenza vaccination may be at increased risk of again developing GBS if given influenza vaccine. While this risk should be weighed against the benefits to the individual patient of influenza vaccination, it would seem prudent to avoid subsequent influenza vaccination in this group. Because patients with a history of GBS have an increased likelihood of again developing the syndrome, the chance of them coincidentally developing the syndrome following influenza vaccination may be higher than in individuals with no history of GBS.

Interactions
Influenza vaccine can impair the metabolism of warfarin, theophylline, phenytoin, phenobarbitone and carbamazepine by the hepatic P450 system. Results from studies have been variable in degree of interaction and time after vaccination for the interaction to take effect. The interaction may be idiosyncratic. Patients taking warfarin, theophylline, phenytoin, phenobarbitone, or carbamazepine should be advised of the possibility of an interaction and told to look out for signs of elevated levels of medication.

Influvac should not be mixed with other vaccines in the same syringe.

Effects on laboratory tests
Following influenza vaccination, false positive results in serology tests using the ELISA method to detect antibodies against HIV1, Hepatitis C and especially HTLV1 have been observed. The Western Blot technique disproves the results. The transient false positive reactions could be due to the IgM response by the vaccine.

Carcinogenesis, mutagenesis, impairment of fertility
Animal studies have not been conducted and therefore the effects of vaccination are unknown.

Use in pregnancy

Category B2.

No relevant animal data is available. There is no convincing evidence of risk to the foetus from immunisation of pregnant women using inactivated virus vaccines, bacterial vaccines, or toxoids. In pregnant high risk patients the possible risks of clinical influenza infection should be weighed against the possible risks of vaccination.

There is evidence from a number of studies that pregnant women, particularly during the second and third trimester, are at increased risk of influenza associated complications. It is therefore recommended that all women who will be in the second or third trimester of pregnancy during the influenza season be vaccinated in advance, so they are protected during that season.

Use in lactation No relevant animal data is available. There are no known contraindications to the use of Influvac by lactating women.

Adverse reactions In clinical studies Influvac was administered to 1101 subjects. No serious adverse reactions attributable to vaccine administration were reported. Local and general symptoms were recorded for a period of 3 days following vaccination and reactions usually disappeared within 1-2 days without treatment.

During clinical studies, local and general signs and symptoms reported by the vaccinee were recorded.

The events are categorised by frequency according to the following definitions:

Very common: (frequency ≥ 10 %)
Common (frequency ≥ 1 and <10 %)
Uncommon (frequency ≥ 0.1% and < 1 %)
Rare (frequency ≥ 0.01% and < 0.1 %)
Very rare (frequency < 0.01 %)

Local reactions
Very common: redness, swelling, pain.

Common: ecchymosis, induration.

Body as a whole Very common: headache.

Common: fever, malaise.

Uncommon: shivering, fatigue, sweating, myalgia, arthralgia.

Very rare: neuralgia, paraesthesia, convulsions, transient thrombocytopenia, allergic reactions (such as angioedema) leading to shock.

As with most biological products very rare post-vaccination neurological disorders such as encephalomyelitis, neuritis and Guillain-Barre syndrome (GBS) have been reported. Guillain-Barre syndrome (GBS) has been very rarely reported in temporal association with administration of influenza vaccines. In the 1976 swine influenza vaccination program, the US Public Health Advisory Committee on Immunization Procedures (ACIP) found that GBS occurred at an incidence of approximately 1 in 100,000 after immunisation and that the death rate in this 'series' was approximately 1 in 2,000,000. Such an excess incidence of GBS was not demonstrated in subsequent years when recipients of the 1978 or 1979 vaccines were studied. However, in 1998, ACIP reported that a study of the 1992-93 and 1993-94 seasons found an elevation in the overall relative risk for GBS which represents an excess of an estimated one to two cases of GBS per million persons vaccinated.

Post-marketing Experience Very rarely cases of rash, asthenia and vasculitis with transient renal involvement have been reported.

Dosage and Administration

Adults: 0.5 mL

One dose is sufficient for persons previously exposed to viruses of similar antigenic composition to the strain(s) present in the vaccine. In those with some impairment of immune mechanisms, two doses separated by an interval of at least four weeks are recommended.

Administration
Influvac should be administered by intramuscular or deep subcutaneous injection. Influvac should not be administered intravenously.

Influvac should not be mixed with other injection fluids.

Data on the administration of Influvac with other vaccines is not available.

The syringe is for use in a single patient on one occasion only. Remaining contents should be discarded.

Instructions for use/handling
Influvac should be allowed to reach room temperature and shaken well before use.

Vaccination schedule
Influvac should be administered before the beginning of the influenza season or as required by the epidemiological situation. Vaccination should be repeated every year with an age appropriate dose of vaccine of updated antigen composition.

Overdosage
Given the nature of the product and mode of administration the probability of overdosage is negligible.

Presentation
Single-dose 0.5 mL pre-filled glass syringe, 1's and 10's (AUST R: 81465)

Storage
Store between 2 and 8 degrees Celsius. Refrigerate, Do not freeze. Protect from light.