Medication Guide App

Influenza A (H1N1) 2009 Monovalent Vaccine Inactivated

Class: Vaccines
VA Class: IM100

Introduction

Inactivated virus vaccine.97 98 99 Influenza A (H1N1) 2009 monovalent vaccine inactivated contains noninfectious, suitably inactivated 2009 influenza type A (H1N1) virus and is used to stimulate active immunity to the influenza virus strain contained in the vaccine.97 98 99

Uses for Influenza A (H1N1) 2009 Monovalent Vaccine Inactivated

Prevention of 2009 Influenza A (H1N1) Virus Infection

Prevention of 2009 pandemic influenza A (H1N1) virus infection in adults,97 98 99 adolescents,97 98 and children ≥6 months of age.97

Influenza outbreaks caused by the 2009 influenza A (H1N1) virus, previously referred to as the novel 2009 influenza A (H1N1) virus or swine-origin influenza A (H1N1) virus, were initially reported in several countries, including the US, beginning in March and April 2009.100 508 513 514 515 516 517 532 On June 11, 2009, the WHO declared that the first global influenza pandemic in 41 years was occurring and issued a phase 6 pandemic alert regarding 2009 influenza A (H1N1).513 529 A phase 6 pandemic is characterized by human-to-human transmission of an animal or human-animal reassortant virus and sustained community level outbreaks of the virus in 2 or more countries in a single WHO region and sustained community level outbreaks in at least one other country in a different WHO region.521

Influenza viruses can cause seasonal epidemics and, occasionally, global pandemics (an epidemic that affects the whole population).100 437 521 Prior to 2009, the 3 most recent influenza pandemics were the 1918 Spanish flu pandemic (caused 20–50 million deaths worldwide including about 500,000 deaths in the US), the 1957 Asian flu pandemic (caused 1–4 million deaths worldwide including about 70,000 deaths in the US), and the 1968 Hong Kong flu pandemic (1–4 million deaths worldwide including about 34,000 deaths in the US).437 521

The 2009 influenza A (H1N1) virus appears to be a triple-reassortant swine influenza virus containing genes from human, swine, and avian influenza A viruses.517 522 532 The virus contains a unique combination of gene segments not previously reported among human or swine influenza A in the US or elsewhere.514 517 522 532 The virus, however, may be antigenically similar to classical swine influenza A (H1N1) viruses and triple reassortant swine influenza A (H1N1) viruses that circulate in pigs and have been associated with sporadic human infections.522 532

The 2009 influenza A (H1N1) virus is antigenically and genetically distinct from circulating seasonal human influenza A (H1N1) viruses, and preliminary studies indicate that a majority of the population may be susceptible to the virus.508 522 This virus is expected to continue to circulate worldwide, including in the US, during the 2009–2010 influenza season in addition to strains of seasonal influenza A and B.100 465 508 512 513 526

Vaccination using an appropriate vaccine is the most effective strategy for preventing influenza and its complications.100 508

Seasonal influenza virus vaccines used for prevention of seasonal influenza are reformulated each year to contain antigens representative of the strains of influenza A and B viruses likely to circulate in the US during the upcoming influenza season.100 510 511 Seasonal influenza vaccines for the 2009–2010 influenza season are not expected to provide protection against 2009 influenza A (H1N1) virus infection.100 508

For prevention of 2009 influenza A (H1N1) virus infection, 2 different types of monovalent influenza vaccine are commercially available in the US: parenteral vaccine containing inactivated virus97 98 99 and intranasal vaccine containing live, attenuated virus.523 Both vaccine types are produced using an A/California/7/2009 (H1N1)v-like strain.97 98 99 508 523 (See Actions.)

Initial FDA approval of each of the commercially available inactivated influenza A (H1N1) 2009 monovalent vaccines was based on safety and efficacy data for the seasonal inactivated trivalent influenza vaccine produced by the same manufacturer (Afluria, manufactured by CSL; Fluvirin, manufactured by Novartis; Fluzone, manufactured by Sanofi Pasteur) and was considered a strain change to each manufacturer's FDA-approved seasonal inactivated influenza vaccine.97 98 99 528 Studies are ongoing to evaluate safety and efficacy of monovalent influenza A (H1N1) 2009 vaccines.97 98 508 524 528

Although influenza vaccination using an appropriate vaccine is the most effective method for preventing influenza and influenza-related complications,100 508 there may be some situations, including during influenza pandemics, when use of antiviral agents may be indicated for prevention or treatment of influenza.100 437 465 512 513 520 521 CDC has issued updated interim recommendations concerning the use of antiviral agents for prevention and treatment of influenza, including 2009 influenza A (H1N1) and seasonal influenza.512 The CDC recommendations are available at and should be used to guide selection of the most appropriate antivirals for prevention and treatment of influenza and to prioritize use of such agents in patients at higher risk for influenza-related complications.512

Because initial supplies of influenza A (H1N1) 2009 vaccine may not be sufficient to meet demands for the vaccine, the USPHS Advisory Committee on Immunization Practices (ACIP) identified initial target groups for priority vaccination.508 These individuals are at higher risk for influenza or influenza-related complications, are likely to come in contact with influenza viruses as part of their occupation and could transmit the viruses to others in medical care settings, or are close contacts of infants too young to be vaccinated (<6 months of age).508 (See table.) As supplies of the vaccine increase and demand for vaccine among individuals in initial priority target groups is met, CDC or ACIP is likely to revise recommendations to include additional target groups (e.g., all individuals 25 through 64 years of age, adults ≥65 years of age).508 533

ACIP Recommendations for Priority Vaccination Against 2009 Pandemic Influenza A (H1N1) Virus:508

Initial Target Groups for Vaccine Supplies

Pregnant women

Individuals who live with or provide care for infants <6 months of age (e.g., parents, siblings, day-care providers)

Health-care and emergency medical services personnel

Individuals 6 months through 24 years of age

Adults 25 through 64 years of age with medical conditions that put them at higher risk for influenza-related complications, including chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, cognitive, neurologic/neuromuscular, hematologic, or metabolic (including diabetes mellitus) disorders

Adults 25 through 64 years of age who are immunosuppressed, including those receiving immunosuppressive drugs and those with HIV infection

Subset of Initial Target Groups for Priority Vaccination if Vaccine Supplies are Limited

Pregnant women

Individuals who live with or provide care for infants <6 months of age (e.g., parents, siblings, day-care providers)

Health-care and emergency medical services personnel who have direct contact with patients or infectious materials

Children 6 months through 4 years of age

Children and adolescents 5–18 years of age who have medical conditions that put them at higher risk for influenza complications, including chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, cognitive, neurologic/neuromuscular, hematologic, or metabolic (including diabetes mellitus) disorders

Based on current prescribing information, parenteral inactivated influenza A (H1N1) 2009 vaccine can be used for prevention of 2009 influenza A (H1N1) virus infection in any of the target groups identified for priority vaccination, unless contraindicated.97 98 99 Based on current prescribing information, the intranasal live influenza A (H1N1) 2009 vaccine may be used in some (but not all) of the target groups.523

Information regarding influenza surveillance and updated recommendations for prevention and treatment of 2009 influenza A (H1N1) virus infection is available at . CDC information on treatment and prevention of seasonal influenza is available at .

Influenza A (H1N1) 2009 Monovalent Vaccine Inactivated Dosage and Administration

Administration

IM Administration

Administer by IM injection.97 98 99

Shake vaccine vial before withdrawing a dose.97 98 99 Shake prefilled syringe immediately before administering a dose.97 98 99 Discard vaccine if it contains particulates, appears discolored, or cannot be resuspended with thorough agitation.97 98 99

Do not mix with any other vaccine or solution.97 98 99

To ensure delivery into muscle, IM injections should be made at a 90° angle to the skin using a needle length appropriate for the individual's age and body mass.475 For adults and adolescents, administer IM into the deltoid muscle.97 98 99 475 In children ≥3 years of age, IM injections should be made into the deltoid muscle if muscle mass is adequate; alternatively, the anterolateral thigh can be used.97 98 475 In children 6 months to 2 years of age, IM injections should preferably be made in the anterolateral aspect of the thigh.97 475

Do not administer into buttock muscle because of potential for injection-associated injury to sciatic nerve.97 98 475 Do not administer into any area where there may be a major nerve trunk.97 98

ACIP states that aspiration (i.e., pulling back on the syringe plunger after needle insertion and before injection) is not required because large blood vessels are not present at recommended IM injection sites.475

Since syncope may occur following vaccination, observe vaccinees for approximately 15 minutes after the dose.112 475 Syncope occurs most frequently in adolescents and young adults,112 475 and may be averted if vaccinees sit or lie down for 15 minutes after vaccination.112 If syncope occurs, observe patient until symptoms resolve.112 475

May be administered simultaneously with other age-appropriate vaccines.533 If given at the same time as other parenteral vaccines during a single health-care visit, each vaccine should be given with a different syringe and at different injection sites.97 (See Other Vaccines under Interactions.)

ACIP has identified specific target groups who should receive influenza A (H1N1) 2009 vaccine beginning as soon as initial supplies become available in October, unless contraindicated.508 These individuals are at higher risk for influenza or influenza-related complications, are likely to come in contact with influenza viruses as part of their occupation and could transmit influenza viruses to others in medical care settings, or are close contacts of infants too young to be vaccinated (<6 months of age).508 (See Uses.)

Dosage

Clinical studies are ongoing to determine the optimal dosage, number of doses, and vaccination schedule for parenteral inactivated influenza A (H1N1) 2009 monovalent vaccine.97 98 99 508 528 The following dosages are based on available data to date.97 98

A single-dose regimen is recommended for adults and children ≥10 years of age.97 98 99 A 2-dose regimen is recommended for children 6 months through 9 years of age.97 98

Influenza A (H1N1) 2009 vaccine inactivated manufactured by CSL is used only in adults ≥18 years of age.99

Influenza A (H1N1) 2009 vaccine inactivated manufactured by Sanofi Pasteur may be used in adults, adolescents, and children ≥6 months of age.97

Influenza A (H1N1) 2009 vaccine inactivated manufactured by Novartis may be used in adults, adolescents, and children ≥4 years of age.98

Pediatric Patients

Prevention of 2009 Influenza A (H1N1) Virus Infection
Children and Adolescents 6 Months through 17 Years of Age (Influenza A (H1N1) 2009 Vaccine Inactivated Manufactured by Sanofi Pasteur)
IM

Children 6 through 35 months of age: Two 0.25-mL doses administered approximately 1 month apart.97

Children 36 months through 9 years of age: Two 0.5-mL doses administered approximately 1 month apart.97

Children and adolescents 10 through 17 years of age: Single 0.5-mL dose.97

Children and Adolescents 4 through 17 Years of Age (Influenza A (H1N1) 2009 Vaccine Inactivated Manufactured by Novartis)
IM

Children 4 through 9 years of age: Two 0.5-mL doses administered approximately 1 month apart.98

Children and adolescents 10 through 17 years of age: Single 0.5-mL dose.98

Adults

Prevention of 2009 Influenza A (H1N1)Virus Infection
Adults 18 Years of Age or Older
IM

Single 0.5-mL dose.97 98 99

Special Populations

Hepatic Impairment

No specific dosage recommendations.97 98 99

Renal Impairment

No specific dosage recommendations.97 98 99

Geriatric Patients

No specific dosage recommendations.97 98 99 (See Geriatric Use under Cautions.)

Cautions for Influenza A (H1N1) 2009 Monovalent Vaccine Inactivated

Contraindications

  • Hypersensitivity to eggs,98 99 egg protein,97 98 chicken protein,99 or any vaccine component.97 98 (See Sensitivity Reactions under Cautions.)

  • Life-threatening reaction to previous dose of any influenza vaccine.97 98 99

  • Influenza A (H1N1) 2009 vaccine inactivated manufactured by CSL: Hypersensitivity to neomycin or polymyxin.99 (See Neomycin and/or Polymyxin B Allergy under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Studies using seasonal parenteral inactivated influenza vaccine indicate rare reports of immediate, presumably allergic reactions (e.g., urticaria, angioedema, anaphylaxis, allergic asthma).97 98 99 103 143 441 463 473 Reactions may result from sensitivity to some vaccine component, including residual egg protein.97 98 99 103 143 441 463 473

Parenteral inactivated influenza A (H1N1) 2009 vaccine is produced using embryonated chicken eggs (the same process used for manufacture of seasonal parenteral inactivated influenza vaccine) and can contain residual egg protein that may induce immediate hypersensitivity reactions, including anaphylaxis, in individuals with severe egg allergy.97 98 99 CDC and ACIP state that asking patients if they can eat eggs without adverse effects is a reasonable way to identify those who may be at risk for allergic reactions if they receive the vaccine.475 533 Those who are able to eat eggs or egg products safely usually can receive vaccines produced using chicken eggs; those with a history of anaphylactic or other immediate hypersensitivity reaction (e.g., hives, angioedema, allergic asthma) to eggs or egg proteins should not receive such vaccines.475 (See Contraindications under Cautions.)

Prior to administration, review patient’s history with respect to possible hypersensitivity to vaccine components, including egg and egg products.98 Epinephrine and other appropriate agents should be readily available in case anaphylaxis occurs.97 98 99

Do not administer additional vaccine doses to any individual who experienced life-threatening reactions to a previous dose.97 98 99 (See Contraindications under Cautions.)

Neomycin and/or Polymyxin B Allergy

Influenza A (H1N1) 2009 vaccine inactivated manufactured by CSL: Contains trace amounts of neomycin sulfate (≤0.2 picograms) and polymyxin B (≤0.03 picograms).99 Manufacturer states the vaccine is contraindicated in individuals hypersensitive to neomycin or polymyxin.99

Influenza A (H1N1) 2009 vaccine inactivated manufactured by Novartis: Contains neomycin sulfate (≤2.5 mcg) and polymyxin B (≤3.75 mcg).98

Neomycin allergy usually results in delayed-type (cell-mediated) hypersensitivity reactions manifested as contact dermatitis.475 ACIP and AAP state that vaccines containing trace amounts of neomycin should not be used in individuals with a history of anaphylactic reaction to neomycin, but may be considered in those with a history of delayed-type neomycin hypersensitivity if benefits of vaccination outweigh risks.112 475

Thimerosal Allergy

All multiple-dose vials of influenza A (H1N1) 2009 vaccine inactivated contain thimerosal as a preservative;97 98 99 some preparations of the vaccine in prefilled syringes are preservative-free but contain trace amounts of thimerosal from the manufacturing process.98 (See Thimerosal Precautions under Cautions.) Hypersensitivity reactions to thimerosal contained in vaccines have been reported in some individuals.100 140 427 498 500 These reactions usually manifest as local, delayed-type hypersensitivity reactions (e.g., erythema, swelling),100 140 427 475 but a generalized reaction manifested as pruritus and an erythematous, maculopapular rash on all 4 extremities has been reported rarely.500 Even when patch or intradermal tests for thimerosal sensitivity are positive, most individuals do not develop hypersensitivity reactions to thimerosal administered as a component of vaccines.100 140 475

ACIP states that a history of delayed-type hypersensitivity to thimerosal is not a contraindication to use of vaccines that contain thimerosal.475

Ongoing Safety Review

Safety and adverse effects reported with parenteral inactivated influenza A (H1N1) 2009 vaccine are expected to be similar to those reported for seasonal parenteral inactivated influenza vaccines (e.g., mild fever, body aches, fatigue, soreness at injection site).528 However, as with any medical product, serious adverse events may occur.528

FDA and CDC are closely monitoring safety of influenza A (H1N1) 2009 vaccines through a collaborative effort between CDC, US Department of Health and Human Services (HHS), and other government agencies.528 Only limited data are available to date regarding adverse effects reported with influenza A (H1N1) 2009 vaccine.524 (See Common Adverse Effects.)

Guillain-Barré Syndrome

In 1976, a temporal association was noted between administration of A/New Jersey/76 (swine) influenza vaccine and Guillain-Barré syndrome (GBS, polyradiculoneuritis).97 98 99 100 278 279 364 365 The annual incidence of GBS is 10–20 cases per million in adults; the increased risk of GBS in individuals who received A/New Jersey/76 (swine) influenza vaccine was estimated to be 1 additional case of GBS per 100,000 vaccinees.100 192 275 276 277 278 279 Epidemiologic evidence indicates that the associated risk between administration of the A/New Jersey/76 (swine) influenza vaccine and GBS did not extend beyond 6 weeks after vaccination,191 and vaccinees who received the 1976 swine influenza vaccine have not been shown to exhibit an increased risk of GBS with subsequent vaccine formulations.280

Evidence for an increased risk of developing GBS with subsequent influenza vaccine formulations prepared from other virus strains is unclear;97 98 99 100 192 275 276 277 280 however, it is difficult to estimate precisely the risk for a condition as rare as GBS.100 192 275 276 277 280

If influenza vaccine does pose a risk, the estimated risk for GBS probably is slightly more than 1 additional case per million vaccinees.97 98 99 100 152 364 365 ACIP states that there is no evidence that the case-fatality ratio for GBS differs among vaccinated and unvaccinated individuals.100

Carefully consider possible benefits and potential risks of influenza A (H1N1) 2009 vaccine in individuals who experienced GBS within 6 weeks of previous influenza vaccination.97 98 99 441 463

AAP states that influenza vaccines should not be used in children who developed GBS within 6 weeks after a dose of any influenza vaccine.465 ACIP states that benefits of influenza vaccine may outweigh risks in individuals with a history of GBS who are at high risk for severe influenza-related complications.100 However, it may be prudent to avoid influenza vaccine in individuals who are not at high risk for severe influenza complications if they experienced GBS within 6 weeks after previous influenza vaccination.100

Other Neurologic Effects

Neurologic disorders (not defined as GBS) have been temporally associated with seasonal inactivated influenza vaccine, including encephalopathy,97 98 99 103 143 441 463 473 encephalomyelitis,441 neuralgia,99 143 473 optic neuritis/neuropathy,97 98 99 103 143 441 463 473 partial facial paralysis,97 98 99 103 143 441 463 473 Bell's palsy,97 98 103 143 neuritis or neuropathy,98 99 143 473 paresthesia,99 103 143 463 473 hypoesthesia,463 and brachial plexus neuropathy.97 98 99 103 143 203 204 205 206 207 208 441 463 473 Seizures97 98 103 143 463 473 and myelitis (including encephalomyelitis and transverse myelitis)97 98 99 103 143 473 358 also reported rarely with seasonal inactivated influenza vaccine.

Individuals with Altered Immunocompetence

May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy.508 Immunocompromised individuals may be at increased risk of severe infections and should be vaccinated against influenza A (H1N1) infection.508 Consider possibility that immune response to the vaccine may be reduced in these individuals.97 98 99

In recommendations regarding seasonal influenza, CDC, National Institutes of Health (NIH), IDSA, AAP, and other experts state that HIV-infected children, adolescents, and adults should be vaccinated against influenza; however, parenteral inactivated influenza vaccine (not intranasal live vaccine) should be used in HIV-infected individuals.378 509 Studies using seasonal influenza virus vaccine inactivated indicate antibody response may be inversely correlated with severity of the disease.100 101 106 109 110 112 116 232 233 255 260 310 375 376 428 Although seasonal parenteral inactivated influenza vaccine has been highly effective in preventing symptomatic, laboratory-confirmed influenza infection in HIV-infected individuals with mean CD4+ T-cell counts of 400/mm3, the vaccine may be less effective in those with more advanced disease and lower CD4+ T-cell counts (e.g., <100/mm3).100 A second dose of seasonal influenza vaccine does not appear to improve immune response in these individuals.100

Individuals with a History of Influenza

May be administered to individuals who have had an influenza-like illness.531 533 The vaccine is not harmful in individuals who previously had diagnosed or undiagnosed influenza illness, including 2009 influenza A (H1N1) infection,531 533 and is not harmful in individuals who already have some existing immunity to the 2009 influenza A (H1N1) virus.533

If influenza A (H1N1) 2009 vaccine is indicated (see Uses), CDC recommends that the vaccine be administered even in individuals who have had an influenza-like illness previously, unless such individuals had a confirmed diagnosis of 2009 influenza A (H1N1) infection based on results of a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test for 2009 influenza A (H1N1) virus.531 533 Individuals who had an influenza-like illness and were tested using a less specific test (e.g., rapid antigen detection assay) should not assume they had 2009 influenza A (H1N1) infection, even if they became ill after being exposed to an individual with confirmed 2009 influenza A (H1N1) infection.533

Thimerosal Precautions

Although it was suggested that thimerosal in vaccines theoretically could have adverse effects in vaccine recipients, there is no conclusive evidence that the low levels of thimerosal contained in vaccines cause harm in vaccine recipients.100 475 492 493 494 499 501 502 503 504 505 506 A link between thimerosal in vaccines and neurodevelopmental disorders in children (autism, attention deficit/hyperactivity disorder [AHDH], speech or language delay) possibly related to mercury neurotoxicity has been theorized; however, considerable evidence has accumulated that supports the absence of substantial risk for neurodevelopmental disorders or other harm resulting from exposure to thimerosal-containing vaccines.100 493 494 499 501 502 503 504 505 506 In 2004, the Immunization Safety Review Committee of the Institute of Medicine (IOM) examined the hypothesis that thimerosal-containing vaccines are causally associated with autism and concluded that the body of epidemiologic evidence favors rejection of a causal relationship between these vaccines and autism.506

Analysis of adverse effects reported to the Vaccine Adverse Event Reporting System (VAERS) indicates that there is no difference in the incidence of injection site reactions, rash, or infections in infants 6–23 months of age who received preservative-containing (thimerosal-containing) seasonal inactivated influenza vaccine compared with those who received preservative-free preparations of the vaccine.100 497 To date, the only adverse effects known to be caused by thimerosal contained in vaccines are hypersensitivity reactions.100 140 427 475 493 (See Thimerosal Allergy under Cautions.)

USPHS, ACIP, AAP, American Association of Family Physicians (AAFP), and other experts state that use of vaccines that contain thimerosal is preferable to withholding vaccination since failure to provide protection against vaccine-preventable diseases may represent an immediate threat, especially in infants.100 401 402 403 465 ACIP states that benefits of influenza vaccination for all recommended groups (including pregnant women and young children) outweigh concerns related to theoretical risks of thimerosal exposure from vaccination with preparations containing thimerosal.100 AAP states that the benefits of protecting children (including children at high risk with underlying CNS disorders) outweigh the hypothetical risks associated with the minute amounts of thimerosal contained in some currently available influenza vaccine preparations.465

Influenza A (H1N1) 2009 vaccine inactivated manufactured by CSL: Commercially available in 0.5-mL prefilled syringes as a preservative-free formulation (thimerosal not used in manufacturing process).99 Also available in multiple-dose vials containing thimerosal as a preservative (24.5 mcg of mercury per 0.5-mL dose).99

Influenza A (H1N1) 2009 vaccine inactivated manufactured by Novartis: Commercially available in prefilled syringes in a preservative-free formulation containing only trace amounts of thimerosal from the manufacturing process (≤1 mcg of mercury per 0.5 mL).98 Also available in multiple-dose vials containing thimerosal as a preservative (25 mcg of mercury per 0.5-mL dose).98

Influenza A (H1N1) 2009 vaccine inactivated manufactured by Sanofi Pasteur: Commercially available in 0.25- and 0.5-mL prefilled syringes and single-dose 0.5-mL vials as a preservative-free formulation (thimerosal not used in manufacturing process).97 Also available in multiple-dose vials containing thimerosal as a preservative (25 mcg of mercury per 0.5-mL dose).97

Limitations of Vaccine Effectiveness

Studies using seasonal influenza vaccines indicate up to 2 weeks may be required for protection to develop following influenza vaccination.100 Preliminary studies using parenteral inactivated influenza A (H1N1) 2009 vaccine indicate an immune response can occur as early as 8–10 days after vaccination.530

May not protect all vaccine recipients against 2009 influenza A (H1N1) virus infection.97 98 99

Does not provide protection against seasonal influenza A and B viruses;508 seasonal influenza vaccine for the 2009–2010 influenza season is indicated to provide protection against seasonal influenza.100 508 531

Duration of Immunity

Studies using seasonal influenza vaccines indicate that immunity declines during the year after influenza vaccination.100 488 Data are not available to date regarding the duration of protection following vaccination with parenteral inactivated influenza A (H1N1) 2009 vaccine.

Concomitant Illness

Vaccination generally should be delayed in individuals with moderate to severe acute febrile illness until symptoms have subsided.100 475 ACIP states that minor acute illness (with or without fever), generally does not preclude vaccination.100 475

Individuals with Bleeding Disorders

ACIP states that vaccines may be given IM to individuals who have bleeding disorders or are receiving anticoagulant therapy if a clinician familiar with the patient's bleeding risk determines that the preparation can be administered with reasonable safety.475 In these cases, use a fine needle (23 gauge) to administer the vaccine and apply firm pressure to the injection site (without rubbing) for ≥2 minutes.475 If patient is receiving antihemophilia therapy, administer the IM vaccine shortly after a scheduled dose of such therapy.475

Advise individual and/or their family about the risk of hematoma from IM injections.475

Improper Storage and Handling

Improper storage or handling of vaccines may result in loss of vaccine potency and reduced immune response in vaccinees.475

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.99 475 476

Do not administer vaccine that has been mishandled or has not been stored at the recommended temperature.99 475 (See Storage under Stability.) If there are concerns about mishandling, contact the manufacturer or state or local health departments for guidance on whether the vaccine is usable.475 476

Specific Populations

Pregnancy

Category C.97 98 99

Manufacturers state that parenteral inactivated influenza A (H1N1) 2009 vaccine should be used in pregnant women only when clearly needed.97 98 99

CDC, ACIP, American College of Obstetricians and Gynecologists (ACOG), American College of Physicians (ACP), NIH, IDSA, and other experts state that parenteral inactivated influenza vaccine (not intranasal live influenza vaccine) should be used for prevention of seasonal influenza in pregnant women.100 378 479 531

Because pregnant women are at risk for influenza complications, CDC and ACIP recommend that pregnant women receive priority vaccination against 2009 influenza A (H1N1) virus infection, unless contraindicated.508 531 (See Uses.)

ACIP states that benefits of influenza vaccination for pregnant women outweigh theoretical risks from thimerosal exposure by vaccination with preparations containing thimerosal;100 CDC states that pregnant women may receive influenza A (H1N1) 2009 vaccine with or without thimerosal.531 (See Thimerosal Precautions under Cautions.)

Lactation

Safety and efficacy not established in breastfeeding mothers.97 98 99

Not known whether parenteral inactivated influenza A (H1N1) vaccine is distributed into milk.97 98 99 Manufacturers recommend caution.97 98 99

Inactivated vaccines do not affect safety of breastfeeding for lactating women or their infants.475 ACIP and CDC state that breastfeeding does not adversely affect immune response and is not a contraindication to vaccination.100 117 475

Pediatric Use

Influenza A (H1N1) 2009 vaccine inactivated manufactured by CSL: Safety and efficacy not established in children <18 years of age.99

Influenza A (H1N1) 2009 vaccine inactivated manufactured by Novartis: Safety and efficacy not established in children <4 years of age.98

Influenza A (H1N1) 2009 vaccine inactivated manufactured by Sanofi Pasteur: Safety and efficacy not established in infants <6 months of age.97

ACIP states that benefits of influenza vaccination for children outweigh theoretical risks from thimerosal exposure by vaccination with preparations containing thimerosal and any available age-appropriate inactivated influenza vaccine can be used in children.100 AAP states that the benefits of protecting children against the known risks of influenza outweigh the hypothetical risks associated with the minute amounts of thimerosal contained in some currently available influenza vaccine preparations.465 (See Thimerosal Precautions under Cautions.)

Because influenza A (H1N1) 2009 vaccine is not indicated in infants <6 months of age and because these infants are at risk for influenza and influenza-related complications, ACIP recommends that household and other close contacts (e.g., day-care providers) of infants <6 months of age receive priority vaccination with influenza A (H1N1) 2009 vaccine using a vaccine appropriate for their age and target group since this may provide some protection for these young infants.508 (See Uses.)

Geriatric Use

Studies using seasonal parenteral inactivated influenza vaccine indicate no substantial differences in safety relative to younger adults.97 98 99 103 143 441 463 473

Common Adverse Effects

Only limited data available to date regarding adverse effects of parenteral inactivated influenza A (H1N1) 2009 monovalent vaccine.524 (See Ongoing Safety Review under Cautions.) Adverse effects expected to be similar to those reported with seasonal parenteral trivalent inactivated influenza vaccine.524 528 Most common adverse effects reported with seasonal parenteral inactivated influenza vaccine are injection site reactions (i.e., tenderness, pain, redness, swelling), hypersensitivity reactions (e.g., rash), influenza-like symptoms, headache, fatigue, myalgia, fever, malaise.97 98 99 103 143 162 243 473

Data to date indicate the most common solicited adverse effects in healthy adults 18–64 years of age who received a single dose of parenteral inactivated influenza A (H1N1) 2009 vaccine were tenderness at the injection site (36.7%), pain at the injection site (21.7%), headache (31.3%), malaise (17.5%), and myalgia (17.1%).524

Interactions for Influenza A (H1N1) 2009 Monovalent Vaccine Inactivated

Other Vaccines

Data are not available to date regarding concomitant administration of parenteral inactivated influenza A (H1N1) 2009 vaccine and other vaccines.97 98 99 CDC states that parenteral inactivated influenza A (H1N1) 2009 vaccine may be administered concomitantly with or at any interval before or after other live or inactivated vaccines, including seasonal intranasal live influenza vaccine or seasonal parenteral inactivated influenza vaccine.533 If the parenteral inactivated influenza A (H1N1) 2009 vaccine is given at the same time as another parenteral vaccine, each vaccine should be administered using different syringes and at a different injection site.97 98 99 \

Specific Drugs

Drug

Interaction

Comments

Anticoagulants (e.g., warfarin)

Increased PT, GI bleeding, hematuria, muscle hematoma, and epistaxis reported rarely in patients stabilized on warfarin who received seasonal parenteral inactivated influenza vaccine;423 conflicting reports regarding whether the vaccine inhibits warfarin metabolism or clearance, 175 176 441 463 but most studies failed to show any clinically important adverse effects in anticoagulated patients175 176 177 210 211

ACIP states that IM vaccines are not contraindicated in patients receiving anticoagulants if a clinician familiar with the patient's bleeding risk determines that the preparation can be administered with reasonable safety;475 some clinicians suggest closely monitoring for enhanced anticoagulant effects423

Antiviral agents active against influenza (amantadine, rimantadine, oseltamivir, zanamivir)

Amantadine, rimantadine, zanamivir: Studies using seasonal parenteral inactivated influenza vaccine indicate no interference with antibody response to the vaccine122 158 408 475

Oseltamivir: No specific studies, but interference with antibody response to parenteral inactivated influenza vaccine not expected;407 oseltamivir does not interfere with humoral antibody response to influenza infection407

Immune globulin (immune globulin IM [IGIM], immune globulin IV [IGIV]) or specific immune globulin (hepatitis B immune globulin [HBIG], rabies immune globulin [RIG], tetanus immune globulin [TIG], varicella zoster immune globulin [VZIG])

No evidence that immune globulin preparations interfere with immune response to inactivated vaccines475

Inactivated vaccines may be given simultaneously with or at any interval before or after immune globulin preparations475

Immunosuppressive agents (e.g., alkylating agents, antimetabolites, corticosteroids, radiation)

Potential for decreased antibody response97 98 99

Studies using seasonal parenteral inactivated influenza vaccine indicate corticosteroids administered for brief periods or every other day have only a minimal effect on antibody response to the vaccine, but corticosteroid therapy (prednisone or equivalent) in a dosage ≥2 mg/kg daily or ≥20 mg daily given for ≥2 weeks may impair antibody response112 475

Influenza vaccine (seasonal)

Seasonal parenteral inactivated influenza vaccine: May be administered simultaneously with508 or at any interval before or after parenteral inactivated influenza A (H1N1) 2009 vaccine;533 if given simultaneously, use different syringes and different anatomic sites508

Seasonal intranasal live influenza vaccine: May be administered simultaneously with or at any interval before or after parenteral inactivated influenza A (H1N1) 2009 vaccine533

Pneumococcal vaccine

May be administered simultaneously with or at any interval before or after parenteral inactivated influenza A (H1N1) 2009 vaccine;533 if given simultaneously, use different syringes and different anatomic sites533

Stability

Storage

Parenteral

Injectable Suspension, for IM Use

2–8°C;97 98 99 476 protect from light;98 99 476 do not freeze.97 98 99 476 If freezing occurs, discard vaccine.97 98

Return multiple-dose vials to 2–8ºC between uses.97 98 99 476 Discard if not used by the expiration date noted on the vial.97 98 99 476

Depending on the manufacturer, single-dose syringes and vials are preservative-free97 99 or contain only trace amounts of thimerosal from the manufacturing process.98 Multiple-dose vials contain thimerosal as a preservative.97 98 99 (See Thimerosal Precautions under Cautions.)

Actions

  • Parenteral inactivated influenza A (H1N1) 2009 vaccines that are used for prevention of infections caused by 2009 influenza A (H1N1) virus, previously referred to as the novel 2009 influenza A (H1N1) virus or swine-origin influenza A (H1N1) virus, are monovalent vaccines containing noninfectious, sterile suspensions of suitably inactivated 2009 pandemic influenza A (H1N1) virus.97 98 99

  • Parenteral inactivated influenza A (H1N1) 2009 vaccines are sterile, clear to colorless opalescent suspensions97 98 99 that may contain some sediment that resuspends when shaken to form a homogeneous suspension.99

  • Parenteral inactivated influenza A (H1N1) 2009 vaccines commercially available in the US are prepared from formaldehyde- or propiolactone-inactivated influenza virus harvested from allantoic fluids of chick embryos infected with the virus and are split-virus preparations (i.e., contain purified subvirion or purified surface antigen).97 The monovalent influenza A (H1N1) 2009 vaccines are manufactured using the same methods used for the manufacture of trivalent seasonal parenteral inactivated influenza vaccines.97 98 99 508

  • Influenza vaccines stimulate active immunity to influenza virus strains represented in the vaccine.97 98 99 Parenteral inactivated influenza A (H1N1) 2009 vaccines commercially available in the US contain A/California/7/2009 (H1N1)v-like virus,97 98 99 the virus selected by the FDA and WHO to represent circulating strains of 2009 pandemic influenza A (H1N1).508 Between May and September 2009, the majority of influenza viruses circulating in the US were the 2009 influenza A (H1N1) strain, and all isolates of the virus characterized at CDC were antigenically related to the A/California/7/2009 (H1N1)v-like strain.526

  • Studies are ongoing to evaluate the immunologic response to parenteral inactivated influenza A (H1N1) 2009 vaccine and efficacy of the vaccine for prevention of 2009 influenza A (H1N1) infection.528

  • In a limited ongoing study in healthy adults 18–64 years of age who received a single dose of parenteral inactivated influenza A (H1N1) 2009 vaccine containing 15 mcg hemagglutinin of A/California/7/2009 (H1N1)v-like virus, preliminary results indicate that 96.7% of vaccinees had an immune response (antibody titer 1:40 or greater) and 74.2% had seroconversion when tested 21 days after the dose.524

  • Preliminary results from an ongoing study evaluating the immunologic response in children who received parenteral inactivated influenza A (H1N1) 2009 vaccine containing 15 mcg hemagglutinin of A/California/7/2009 (H1N1)v-like virus indicate that a single vaccine dose may provide an immune response in the majority of children and adolescents 10–17 years of age at 8–10 days after the dose.530 However, the immune response to a single vaccine dose was lower in children 6 months to 9 years of age.530

Advice to Patients

  • Prior to administration, provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient's legal representative (VISs are available at ).

  • Advise patients that influenza A (H1N1) 2009 vaccine inactivated contains noninfectious killed viruses and cannot cause influenza.97 98 99

  • Advise patients that influenza A (H1N1) 2009 vaccine, formulated to provide protection against 2009 pandemic influenza A (H1N1) virus infections, and seasonal influenza vaccine 2009–2010, formulated to provide protection against seasonal influenza A and B viruses, are available for prevention of influenza97 98 99 and that both vaccines may be indicated in some individuals.100 508 (See Uses.)

  • Advise patients that influenza vaccines only provide protection against illness due to influenza viruses represented in the vaccines and cannot provide protection against all respiratory illness.97 98

  • Advise patient and/or patient's parent or guardian of the risks and benefits of vaccine administration.97 98 99

  • Advise patient and/or patient's parent or guardian that a single dose of parenteral inactivated influenza A (H1N1) vaccine is recommended in adults, adolescents, and children 10 years of age or older, but that 2 doses are recommended in children 6 months through 9 years of age.97 98 99

  • Importance of informing clinicians of any severe or unusual adverse effects.97 98 99 Clinicians or individuals can report any adverse reactions that occur following vaccination to the Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or .97 98 99

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant medical problems (e.g., GBS).97 98 99

  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.97 98 99

  • Importance of informing patients of other precautionary information.97 98 99 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Influenza A (H1N1) 2009 monovalent vaccine is supplied through a centralized distribution system to designated providers (e.g., hospitals, clinics, physician offices, health departments) and is not available directly from the manufacturers.533 State/local public health departments are responsible for identifying and designating providers, facilitating vaccine orders, and allocating and directing the flow of vaccine to providers within each state.533 Consult the CDC website () and state/local health authorities for additional information.533

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Influenza A (H1N1) 2009 Monovalent Vaccine Inactivated

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injectable suspension, for IM use

15 mcg hemagglutinin of A/California/7/2009 (H1N1)v-like per 0.5 mL*

Influenza A (H1N1) 2009 Monovalent Vaccine Inactivated (preservative-free; available in 0.5 mL prefilled disposable syringes or with thimerosal [24.5 mcg of mercury per 0.5 mL]; available in multiple-dose vials)

CSL Biotherapies

Influenza A (H1N1) 2009 Monovalent Vaccine Inactivated (preservative-free with thimerosal [≤1 mcg of mercury per 0.5 mL]; available in 0.5 mL prefilled disposable syringes or with thimerosal [25 mcg of mercury per 0.5 mL]; available in multiple-dose vials)

Novartis Vaccines

Influenza A (H1N1) 2009 Monovalent Vaccine Inactivated (preservative-free; available in 0.25 mL prefilled disposable syringes, 0.5 mL prefilled disposable syringes, and 0.5 mL vials or with thimerosal [25 mcg of mercury per 0.5 mL]; available in multiple-dose vials)

Sanofi Pasteur

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2010, Selected Revisions October 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

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98. Novartis Vaccines and Diagnostics. Influenza A (H1N1) 2009 monovalent vaccine prescribing information. Cambridge, MA; 2009 Sep.

99. CSL Biotherapies. Influenza A (H1N1) 2009 monovalent vaccine prescribing information. King of Prussia, PA; 2009 Sep.

100. Fiore AE, Shay DK, Broder K et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR Recomm Rep. 2009; 58:1-52. [PubMed 19644442]

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351. Miller AE, Morgante LA, Buchwald Ly et al. A multicenter, randomized, double-blind, placebo-controlled trial of influenza immunization in multiple sclerosis. Neurology. 1997; 48:312-4. [IDIS 382280] [PubMed 9040712]

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523. MedImmune, LLC. Influenza A (H1N1) 2009 monovalent vaccine live, intranasal prescribing information. Gaithersburg, MD; 2009 Sep.

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525. Neuzil KM. Pandemic Influenza Vaccine Policy -- Considering the Early Evidence. N Engl J Med. 2009; :. [PubMed 19745213]

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528. Food and Drug Administration. Influenza A (H1N1) 2009 monovalent vaccines questions and answers. From FDA website. Accessed 2009 Sep 18.

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530. National Institute of Allergy and Infectious Diseases (NIAID). Early results: in childrne, 2009 H1N1 influenza vaccine works like seasonal flu vaccine. Sept 21, 2009. From NIAID website.

531. Centers for Disease Control and Prevention. 2009 H1N1 influenza vaccine and pregnant women. September 18, 2009. From CDC website.

532. Garten RJ, Davis CT, Russell CA et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009; 325:197-201. [PubMed 19465683]

533. Centers for Disease Control and Prevention. H1N1 clinicians questions and answers. September 21, 2009. From CDC website.

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