Drug Interactions
In the literature, some studies and case reports have suggested a possible interaction between influenza vaccine and the use of theophylline. However, literature reviews on the subject have not scientifically substantiated these interactions. Based on the available evidence, the fact that most countries do not issue a warning regarding a possible interaction seems justified.
INFLUVAC is unlikely to produce an effect on the ability to drive and use machines.
INFLUVAC may be given at the same time as other vaccines. Immunization should be carried out on separate limbs. It should be noted that the adverse reactions may be intensified.
The immunological response may be diminished if the patient is undergoing immunosuppressant treatment.
In the literature, some studies and case reports have suggested a possible interaction between influenza vaccine and the use of anticoagulants such as warfarin. However, literature reviews on the subject have not scientifically substantiated these interactions. Based on the available evidence, the fact that most countries do not issue a warning regarding a possible interaction seems justified.
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.
No interaction between INFLUVAC (influenza vaccine, surface antigen, inactivated) and other vaccines or medication are known.
Information for the Patient
Influvac
Special Handling Instructions
INFLUVAC (influenza vaccine, surface antigen, inactivated) should be allowed to reach room temperature before use. Shake well before use. For administration of a 0.25 mL dose from a syringe, push the front side of the plunger exactly to the edge of the hub (the knurled polypropylene ring); a reproducible volume of vaccine remains in the syringe, suitable for administration.
Dosage and Administration
INFLUVAC comes as 0.5 mL suspension ready for injection.
The recommended dose of INFLUVAC for adults above 18 years is 0.5 mL.
Parenteral biological products should be inspected visually for extraneous particulate matter and/or discolouration before administration. If these conditions exist, the product should not be administered.
For information on vaccine administration, see the current Canadian Immunization Guide and the Health Canada Website.
The patient should be given a permanent personal immunization record. In addition, it is essential that the physician or nurse record the immunization history in the permanent medical record of each patient. Thus the permanent office record should contain the name of the vaccine, date given, dose, manufacturer and lot number.
INFLUVAC should be administered by intramuscular or deep subcutaneous injection.
INFLUVAC is a colourless clear liquid, in pre-filled single-dose syringes.
INFLUVAC should be allowed to reach room temperature before use. Shake the pre-filled syringe well to uniformly distribute the suspension before administration.
Remove the needle protection, and bleed the syringe of air while holding the needle pointing vertically upward by pressing the plunger in slowly.
Do not administer intravascularly.
Needles should not be recapped, and the syringe should be disposed of properly.
Adverse Reactions
Vaccination with INFLUVAC (influenza vaccine, surface antigen, inactivated) cannot cause influenza because the vaccine does not contain live virus.
Local reactions include: redness, swelling, itching, warmth, pain on contact, continuous pain, restriction in arm movement, induration and blue spots. The most frequent local reaction is soreness at the injection site lasting up to 2 days in adults but rarely interferes with normal activities. Prophylactic acetaminophen may decrease the frequency of pain at the injection site.
Systemic reactions: fever, increased sweating, headache, malaise, insomnia, shivering, myalgia, arthralgia, and fatigue. The most frequent systemic reaction is headache.
Allergic responses to influenza vaccine, in rare cases could lead to anaphylactic shocks, are probably a consequence of hypersensitivity to some vaccine component, most likely residual egg protein, which is present in minute quantities.
Neurological disorders with influenza vaccination include neuritis, encephalomyelitis, convulsions and paraesthesia.
Rare cases of systemic vasculitis have been reported in persons after influenza vaccination, but a causal relation has not been assess.
Guillain-Barré Syndrome (GBS) occurred in adults in association with the 1976 swine influenza vaccine, and evidence favours the existence of a causal relation between the vaccine and GBS during that season. In an extensive review of studies since 1976, the United States Institute of Medicine concluded that the evidence is inadequate to accept or reject a causal relation between GBS in adults and influenza vaccines administered after the swine influenza vaccine program in 1976.
In Canada the background incidence of GBS was estimated at just over 20 cases per million population in a study done in Ontario and Quebec. A variety of infectious agents, such as C. jejuni, have been associated with GBS. It is not known whether influenza virus infection itself is associated with GBS. Neither is it known whether influenza vaccination is causally associated with increased risk of recurrent GBS in persons with a previous history of GBS. Avoiding subsequent influenza vaccination of persons known to have developed GBS within 6 to 8 weeks of a previous influenza vaccination appears prudent at this time. In the past 11 years, for INFLUVAC, 40 cases of Guillain-Barré Syndrome (GBS) and one case of possible GBS, classified as ascending neuron paralysis (flaccid paralysis) were reported. The reporting rate of GBS associated with INFLUVAC is concluded to remain within the expected background incidence. Influenza vaccine is not known to predispose to Reye's Syndrome.
Oculorespiratory Syndrome (ORS) has been reported sporadically in Canada, US and Europe following influenza immunization. Starting in the 2000/2001 season, ORS is defined as the onset of bilateral red eyes and/or respiratory symptoms (cough, wheeze, chest tightness, difficulty breathing, difficulty swallowing, hoarseness or sore throat) and/or facial swelling occurring within 24 hours of influenza immunization. The pathophysiologic mechanism underlying ORS remains unknown.
After the 2000-2001 influenza season, fewer ORS cases have been reported to Health Canada. One case of ORS has been seen with the vaccination with INFLUVAC but a causal relation has not been assessed.
Please refer to the Canadian Immunization Guide for further details about administration of vaccine and management of adverse events.
Physicians, nurses and pharmacists should report any immediate adverse reactions arising from any vaccination, or following shortly thereafter, in accordance with local requirements and to the manufacturer: Drug Safety, Solvay Pharma Inc., 60 Columbia Way, Suite 102, Markham, Ontario L3R 0C9 Canada. Telephone: 1-800-268-4276.
Since the 1992 season, over 130.5 million doses of INFLUVAC have been administered. A total of 878 adverse event reports, including 421 serious reports, associated with the use of INFLUVAC have been reported.
These reports include all adverse events reported from the market, health authorities, all published cases, serious adverse event from clinical studies and spontaneous reports, irrespective of any causality assessment.
In adults/elderly the most frequently (45 or more) reported symptoms listed in the adverse reaction reports for the production years 1992 to 2002 were 'injection and infusion site reactions' (102), 'febrile disorders' (92), 'asthenic conditions' (67), 'joint related signs and symptoms' (65), 'nausea and vomiting symptoms' (56), 'headaches NEC' (48), 'general signs and symptoms NEC (46). All of these reactions are considered to be in line with the information in the INFLUVAC global labeling.
From post-marketing surveillance additionally, the following adverse events have been reported:
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Uncommon (>1/1000 and <1/100): generalised skin reactions including pruritus, urticaria or non-specific rash.
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Rare (>1/10 000 and <1/1000): neuralgia, paraesthesia, transient thrombocytopenia. Allergic reactions, in rare cases leading to shock, have been reported.
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Very rare (<1/10 000): vasculitis with transient renal involvement. Neurological disorders, such as encephalomyelitis, neuritis and Guillain-Barré syndrome.
Other adverse reactions reported during post-marketing surveillance include transient lymphadenopathy, febrile convulsions and angioedema.
A clinical study in high-risk children with chronic respiratory or congenital heart disease aged 6 months to 4 years with thimerosal-containing INFLUVAC showed that following either of the two vaccinations, the incidence of any local (23%) and any systemic reactions (48%) in this particular group was considered comparable with those reported in healthy adults.
These children received two separate vaccinations and had the added parameters of loss of appetite, increased crying and irritability. All reactions were recorded in the questionnaire by the parent/guardian (instead of direct reporting).
The reactions recorded were relatively minor in nature and were resolved within a few days.
Indications and Clinical Use
A clinical trial in high-risk children with chronic respiratory or congenital heart disease aged 6 months to 4 years showed that the vaccine was well tolerated and induced an immunogenic response against all three hemagglutinin antigens.
Studies on healthy elderly showed that INFLUVAC is well tolerated.
Seroprotection is generally obtained within 2 to 3 weeks. The duration of post-vaccinal immunity to homologous strains or to strains closely related to the vaccine strains varies but is usually 6 to 12 months.
People who could transmit influenza to those at high risk should receive annual vaccination, regardless of whether the high-risk person(s) has been immunized:
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Health care providers who work in facilities and community settings, such as physicians, nurses, and emergency response workers.
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Health care and other service providers who have contact with residents of continuing care facilities or residences.
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Those who provide home care for persons in high-risk groups.
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Those who provide services within closed or relatively closed settings to persons at high risk (e.g. crew on ships).
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Household contacts (adults and children) of people at high risk of influenza complications. This includes household contacts of children <6 months of age, who are at high risk of complications from influenza but for whom there is no currently licensed vaccine, and of children aged 6 to 23 months whether or not they have been immunized. Pregnant women should be immunized in their third trimester if they are expected to deliver during influenza season, as they will become household contacts of their newborn (unless adoption occurs).
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Those providing regular child care to children aged 0 to 23 months, whether in or out of the home.
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People who provide essential community services. Vaccination for these individuals should be encouraged in order to minimize the disruption of routine activities in epidemics. Employers and their employees should consider yearly influenza immunization for healthy working adults, as this has been shown to decrease work absenteeism due to respiratory and other illnesses.
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People in direct contact with poultry infected with avian influenza during culling operations. The relevant individuals include those performing the cull as well as others (such as supervising veterinarians and inspectors) who may be directly exposed to the avian virus.
Those persons who would be expected by reason of their employment to come into direct contact with infected poultry during culling operations in the event of potential avian influenza outbreaks should be immunized with TIV on a yearly basis prior to the human influenza season. Those who are immunized with TIV just before exposure to avian influenza will not produce protective antibodies against the human vaccine strains for approximately 10 to 14 days. Antiviral prophylaxis should be used as an adjunct to TIV immunization in order to prevent infection with either avian or human influenza during the culling operation. Advice should be sought from the local medical health officer regarding the use of TIV and influenza antiviral prophylaxis in the control of avian influenza outbreaks. This is a theoretical concern. For further information, please refer to NACI guidelines.
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Healthy persons aged 2 to 64 years. Individuals in this age group should be encouraged to receive the vaccine, even if they are not in one of the aforementioned priority groups.
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Pregnant and breast-feeding women who are characterized by any of the conditions listed under “Recommended Recipients”. This includes pregnant and breast-feeding women who have chronic conditions that put them at high risk of complications from influenza, as well as those who are close contacts of high-risk individuals. (Refer to Warnings and Precautions, Special Populations, Pregnant Women.)
Healthy children aged 6 to 23 months are at increased risk of influenza-associated hospitalization compared with healthy older children and young adults.
Adults and children with chronic cardiac or pulmonary disorders (including bronchopulmonary dysplasia, cystic fibrosis, and asthma) severe enough to require medical follow-up or hospital care.
People of any age who are residents of nursing homes or chronic care facilities.
People 65 years of age and over.
Adults and children with chronic conditions such as diabetes mellitus and other metabolic diseases, cancer, immunodeficiency, immunosuppression (due to underlying disease and/or therapy), renal disease, anemia, and hemoglobinopathy. Although some immunosuppressed individuals may have a suboptimal immune response, influenza vaccination is safe and can induce protective antibody levels in a substantial proportion of adults and children, including transplant recipients, those with proliferative diseases of the hematopoietic and lymphatic systems, and HIV-infected patients.
Children and adolescents (aged 6 months to 18 years) with conditions treated for long periods with acetylsalicylic acid (ASA).
People at high risk of influenza complications who are embarking on travel to destinations where influenza is likely to be circulating.
Overdosage
For management of a suspected drug overdose, CPhA recommends that you contact your regional Poison Control Centre. See the eCPS Directories section for a list of Poison Control Centres.
Overdosage is unlikely to have any untoward effect.
Dosage Forms, Composition and Packaging
INFLUVAC (influenza vaccine, surface antigen, inactivated) comes in a 0.5 mL suspension for injection in pre-filled syringes (glass, type I) in the following format: single pack—syringe is packed in a tamper evident carton box; ten pack—syringes are packed in a tamper evident carton box for 10 syringes.
For the 2008/2009 season, each dose of INFLUVAC contains: neuraminidase and 15 µg of hemagglutinin of the following virus strains: reassortant virus IVR-148 which is derived from A/Brisbane/59/2007 as an A/Brisbane/59/2007-like strain; reassortant virus NYMC X-175C which is derived from A/Uruguay/716/2007 as an A/Brisbane/10/2007-like strain; B/Florida/4/2006 as a B/Florida/4/2006-like strain.
Nonmedicinal ingredients: potassium chloride, potassium dihydrogen phosphate, disodium phosphate dihydrate, sodium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate and water for injections. INFLUVAC also contains trace amounts of eggs, chicken protein, formaldehyde, cetyltrimethylammonium bromide, polysorbate 80 and gentamicin. INFLUVAC is thimerosal-free, mercury-free, and contains no preservative.
Warnings and Precautions
INFLUVAC is indicated in people 65 years of age and over (see Indications and Clinical Use).
If INFLUVAC (influenza vaccine, surface antigen, inactivated) is used in persons receiving immunosuppressive therapy, including corticosteroid therapy, the expected immunological response may be diminished. Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient.
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 into the buttocks due to varying amounts of fatty tissue in this region, nor by the intradermal route, since these methods of administration may induce a weaker response.
INFLUVAC must not be administered intravascularly.
Sterile epinephrine HCl solution (1:1000) and other appropriate agents should be made available for immediate use in case of anaphylactic reaction or acute hypersensitivity to the vaccine occurs. Health care providers should be familiar with current recommendations for the initial management of anaphylaxis in non-hospital settings, including proper airway management. Before administration of any vaccine, all appropriate precautions should be taken to prevent adverse reactions. This includes a review of the patient's history with respect to possible hypersensitivity to the vaccine or similar vaccine, determination of previous immunization history, and the presence of any contraindications to immunization, current health status, and a current knowledge of the literature concerning the use of the vaccine under consideration.
Intramuscular injections should be given with care in persons suffering from coagulation disorders or on anticoagulant therapy because of risk of hemorrhage.
Pneumonococcal vaccine and influenza vaccine can be given at the same visit but at different sites with separate sterile needles and syringes without an increase in side effects. Whereas influenza vaccine is given annually, pneumonococcal vaccine should be given only once to adults. It should be noted that the adverse reactions may be intensified.
Influenza virus undergoes significant antigenic changes from time to time, so different vaccines are made every year. INFLUVAC, as now constituted, is not effective against all possible strains of influenza virus. Protection is limited to those strains of virus from which the vaccine is prepared or against closely-related strains.
The use of fractional doses in an attempt to reduce the severity of adverse reactions cannot be recommended because there is insufficient evidence on the safety or efficacy of such smaller doses.
As with any vaccine, immunization with INFLUVAC may not protect 100% of susceptible individuals.
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.
Limited data from vaccinations in pregnant women do not indicate that adverse fetal and maternal outcomes were attributable to the vaccine. The use of this vaccine 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 (see Indications and Clinical Use).
Evidence indicates that influenza vaccine is safe for pregnant women at all stages of pregnancy and for breast-feeding mothers.
Storage and Stability
INFLUVAC (influenza vaccine, surface antigen, inactivated) should be stored at 2 to 8°C (in a refrigerator). Do not freeze. Protect from light.
Do not use vaccine after expiration date as stated on the label.
Action and Clinical Pharmacology
As this is a vaccine product, pharmacokinetic studies are not applicable.
INFLUVAC (influenza vaccine, surface antigen, inactivated) is an egg-grown, inactivated influenza virus subunit, trivalent vaccine based on isolated surface antigens of A and B strains of myxovirus influenza. The inoculation of antigen prepared from inactivated influenza virus stimulates the production of specific antibodies. Protection is afforded only against those strains of virus from which the vaccine is prepared or closely related strains.
Influenza A viruses are classified into subtypes on the basis of 2 surface antigens: hemagglutinin (H) and neuraminidase (N). Three subtypes of hemagglutinin (H1, H2, H3) and 2 subtypes of neuraminidase (N1, N2) are recognized among influenza A viruses that have caused widespread human disease. Immunity to these antigens, especially to the hemagglutinin, reduces the likelihood of infection and lessens the severity of disease if infection occurs. Infection with a virus of one subtype confers little or no protection against viruses of other subtypes. Antigenic variation over time within a subtype may be so marked that infection or vaccination with one strain may not induce immunity to distantly related strains of the same subtype. Although influenza B viruses have shown more antigenic stability than influenza A viruses, antigenic variation does occur. For these reasons, major epidemics of respiratory disease caused by variants of influenza still occur. The antigenic characteristics of current and emerging influenza virus strains provide the basis for selecting the virus strains included in each year's vaccine.
Each year's influenza vaccine contains 3 virus strains representing the influenza viruses that are likely to be circulating in Canada on the basis of the recommendation from the World Health Organization for the northern hemisphere.
Protective antibody titres generally last for at least 6 months and may last up to one year or longer. New influenza vaccines are produced each year according to the WHO recommended composition. Patients vaccinated a short time before the start of the expected influenza activity (November in the Northern Hemisphere) may therefore be expected to be protected for influenza infections or its complications during the whole influenza season (November to April).
Serological data over a 52-week period since vaccination in healthy adult subjects aged 18 to 60 years showed a substantial decrease in antibody titres, as is to be expected for Influenza vaccines. Still the 52-week GMT values are markedly elevated as compared to the prevaccination values. The observed decline in GMT values over a one year period was approximately 50-70% for both strains. The sustained levels of protective antibody titres are in line with the expectation of protection during an influenza season up to 6 months after vaccination.
Protective antibody levels are generally obtained within 2 to 3 weeks after vaccination.
Contraindications
The influenza virus for INFLUVAC (influenza vaccine, surface antigen, inactivated) is propagated in chicken eggs; therefore, this vaccine should not be administered to anyone with a history of hypersensitivity (allergy) and especially anaphylactic reactions to eggs or egg products.
Allergic reactions are extremely rare and are usually attributable to extreme sensitivity to certain components of the vaccine, probably to trace amounts of residual egg protein.
INFLUVAC should not be given to people who have a hypersensitivity to the active substance, to any of the excipients and to chicken protein, formaldehyde, cetyltrimethylammonium bromide, polysorbate 80, or gentamicin. For a complete listing, see Dosage Forms, Composition and Packaging.
Allergic or anaphylactic reactions to a previous dose of influenza vaccine are contraindications for vaccination.
Immunization with INFLUVAC should be deferred in the presence of any acute illness, including acute or unstable neurologic illness, febrile illness, or active infection.
A minor febrile illness such as mild upper respiratory infection is not usually reason to defer immunization.
Description
INFLUVAC (influenza vaccine, surface antigen, inactivated) is a trivalent subunit influenza vaccine. Each 0.5 mL dose contains neuraminidase and 15 µg of hemagglutinin antigen for each virus strain present in the vaccine. The composition is adapted annually according to WHO and the National Advisory Committee on Immunization (NACI). The virus strains used in the vaccine for 2008/2009 are: an A/Brisbane/59/2007 (H1N1)-like strain, an A/Brisbane/10/2007 (H3N2)-like strain, a B/Florida/4/2006-like strain.
INFLUVAC is a clear to slightly opalescent liquid. INFLUVAC is thimerosal-free, mercury-free, and contains no preservative.
