Poliovirus Vaccine

DESCRIPTION

IPOL^Ò, Poliovirus Vaccine Inactivated, produced by Pasteur Mérieux Sérums Vaccins S.A., is a sterile suspension of three types of poliovirus: Type 1 (Mahoney), Type 2 (MEF-1), and Type 3 (Saukett). IPOL^Ò is a highly purified, inactivated poliovirus vaccine produced by microcarrier culture.^1,2 This culture technique and improvements in purification, concentration and standardization of poliovirus antigen produce a more potent and consistent immunogenic vaccine than the IPV available in the US prior to 1988. The viruses are grown in cultures of V.R. cells, a continuous line of monkey kidney cells, by the microcarrier technique. The cells are grown in Eagle MEM modified medium, supplemented with newborn calf serum tested for adventitious agents prior to use, originated from countries free of bovine spongiform encephalopathy. For viral growth the culture medium is replaced by M-199, without calf serum.

After clarification and filtration, viral suspensions are concentrated by ultrafiltration, and purified by three liquid chromatography steps; one column of anion exchanger, one column of gel filtration and again one column of anion exchanger. After re-equilibration of the purified viral suspension, with Medium M-199 and adjustment of the antigen titer, the monovalent viral suspensions are inactivated at +37⁰C for at least 12 days with 1:4000 formalin.

Each sterile immunizing dose (0.5 mL) of trivalent vaccine is formulated to contain 40 D antigen units of Type 1, 8 D antigen units of Type 2, and 32 D antigen units of Type 3 poliovirus. For each lot of IPOL^Ò, D-antigen content is determined in vitro using the D-antigen ELISA assay and immunogenicity is determined by in vivo testing in animals. IPOL^Ò is produced from vaccine concentrates diluted with M-199 medium. Also present are 0.5% of 2-phenoxyethanol and a maximum of 0.02% of formaldehyde per dose as preservatives. Neomycin, streptomycin and polymyxin B are used in vaccine production, and although purification procedures eliminate measurable amounts, less than 5 ng neomycin, 200 ng streptomycin and 25 ng polymyxin B per dose may still be present. The residual calf serum protein is less than 1 ppm in the final vaccine.

The vaccine is clear and colorless and should be administered intramuscularly or subcutaneously.

CLINICAL PHARMACOLOGY

Poliomyelitis is caused by poliovirus types 1, 2, or 3. It is primarily spread by the fecal-oral route of transmission but may also be spread by the pharyngeal route.

Approximately 90% to 95% of poliovirus infections are asymptomatic. Nonspecific illness with low-grade fever and sore throat (minor illness) occurs in 4% to 8% of infections. Aseptic meningitis occurs in 1% to 5% of patients a few days after the minor illness has resolved. Rapid onset of asymmetric acute flaccid paralysis occurs in 0.1% to 2% of infections, and residual paralytic disease involving motor neurons (paralytic poliomyelitis) occurs in approximately 1 per 1,000 infections.³

Prior to the introduction of conventional (non-enhanced) inactivated poliovirus vaccines in 1955, large outbreaks of poliomyelitis occurred each year in the United States (US). The annual incidence of paralytic disease of 11.4 cases/100,000 population declined to 0.5 cases by the time oral poliovirus vaccine (OPV) was introduced in 1961. Incidence continued to decline thereafter to its present rate of 0.002 to 0.005 cases per 100,000 population. Of the 127 cases of paralytic poliomyelitis reported in the US between 1980 and 1994, six were imported cases (caused by wild polioviruses), two were "indeterminant" cases, and 119 were vaccine associated paralytic poliomyelitis (VAPP) cases associated with the use of live, attenuated oral poliovirus vaccine (OPV).⁴

Poliovirus Vaccine Inactivated induces the production of neutralizing antibodies against each type of virus which are related to protective efficacy and induces antibody responses in most children after administering fewer doses⁵ than the vaccine available in the United States prior to 1988.

Studies in developed⁵ and developing^6,7 countries with a similar enhanced inactivated poliovirus vaccine produced by the same technology with the use of different cell substrate (primary kidney cells) have shown that a direct relationship exists between the antigenic content of the vaccine, the frequency of seroconversion, and resulting antibody titer. Approval in the US was based upon demonstration of immunogenicity and safety in US children.⁸

In the US, 219 infants received three doses of IPV at two, four and eighteen months of age manufactured by the same process as IPOL^Ò except the cell substrate for IPV was primary monkey kidney cells. Seroconversion to all three types of poliovirus was demonstrated in 99% of these infants after two doses of vaccine given at 2 and 4 months of age. Following the third dose of vaccine at 18 months of age, neutralizing antibodies were present at a level of ³1:10 in 99.1% of children to Type 1 and 100% of children to Types 2 and 3 polioviruses.⁹

IPOL^Ò was administered to more than 700 infants between 2 to 18 months of age during three clinical studies conducted in the US using IPV only schedules and sequential IPV-OPV schedules.^10,11 Seroprevalence rates for detectable serum neutralizing antibody (DA) at a ³1:4 dilution were 95% to 100% (Type 1); 97% to 100% (Type 2) and 96% to 100% (Type 3) after two doses of IPOL^Ò depending on studies.

* N = Number of children from whom serum was available

** Detectable antibody (neutralizing titer ³1:4)

† NA - No poliovirus vaccine administered

¶ IPOL^Ò given subcutaneously

§ IPOL^Ò given intramuscularly

I IPOL^Ò given either separately in association with DTP in two sites (s) or combined © with DTP in a dual chambered syringe

O OPV

In one study¹¹ the persistence of DA in infants receiving two doses of IPOL^Ò at 2 and 4 months of age was 91% to 100% (Type 1), 97% to 100% (Type 2), and 93% to 94% (Type 3) at twelve months of age. In another study.¹⁰ 86% to 100% (Type 1), 95% to 100% (Type 2), and 82% to 94% (Type 3) of infants still had DA at 18 months of age.

IPV ONLY SCHEDULES

Poliomyelitis vaccination based on IPV only schedules using IPOL^Òor other IPV vaccines implemented in numerous countries.^14,15 None of these countries use the schedule proposed for the US.

In trials and field studies conducted outside the US, IPOL^Ò, or a combination vaccine containing IPOL^Ò and D.P. was administered to more than 3,000 infants between 2 to 18 months of age using IPV only schedules and immunogenicity data are available from 1,485 infants. After two doses of vaccine given during the first year of life, seroprevalence rates for detectable serum neutralizing antibody (neutralizing titer >/=1:4) were 88% to 100% (Type 1); 84% to 100% (Type 2) and 94% to 100% (Type 3) of infants, depending on studies. When three doses were given during the first year of life, post-dose 3 DA ranged between 93% to 100% (Type 1); 89% to 100% (Type 2) and 97% to 100% (Type 3) and reached 100% for Types 1, 2, and 3 after the fourth dose given during the second year of life (12 to 18 months of age).¹²
In infants immunized with three doses of an unlicensed combination vaccine containing IPOL^Ò and DTP given during the first year of life, and a fourth dose given during the second year of life, the persistence of detectable neutralizing antibodies was 96%, 96% and 97% against poliovirus types 1, 2, and 3, respectively, at six years of age. DA reached 100% for all types after a booster dose of IPOL^Ò combined with DTP vaccine.⁸ A survey of Swedish children and young adults given a Swedish IPV only schedule demonstrated persistence of detectable serum neutralizing antibody for at least 10 years to all three types of poliovirus.¹³

IPV is able to induce secretory antibody (IgA) produced in the pharynx and gut and reduces pharyngeal excretion of poliovirus type 1 from 75% in children with neutralizing antibodies at levels less than 1:8 to 25% in children with neutralizing antibodies at levels more than 1:64.^12,14-21 There is also evidence of induction of herd immunity with IPV,^13,22-25 and that this herd immunity is sufficiently maintained in a population vaccinated only with IPV.²⁵

Paralytic polio and VAPP have not been reported in association with administration of IPOL^Ò.

SEQUENTIAL IPV OPV SCHEDULES

In an effort to obtain the benefits of both of the available poliomyelitis vaccines, several countries, including Denmark and Israel, have implemented schedules using IPV and OPV. Although none of these countries uses the sequential IPV-OPV schedule recommended for the US, certain general conclusions can be drawn from this experience along with other, more limited studies of IPV-OPV schedules.

Induction of serum neutralizing antibody: It is expected, based on the overall experience with various schedules of IPV and OPV, that administration of two doses of IPV followed by two doses of OPV will induce detectable levels of serum neutralizing antibody against all three poliovirus types in at least 90% of recipients.

Induction of secretory antibody: It is expected, based on the overall experience with various schedules of IPV and OPV, that administration of two doses of IPV followed by two doses of OPV will induce higher levels of secretory antibody in the gut - and therefore potentially reduce virus excretion - when compared with schedules using IPV alone. One study comparing OPV alone with a sequential schedule of MRC-5 cell-derived IPV at 2 months and 4 months, followed by OPV at 6 and 15 months, found similar levels of virus excretion when subjects were challenged with OPV at 28 months of age.²⁶

Potential reduction in recipient cases of VAPP: It is expected, based on high percentage levels of seroconversion following two doses of IPOL^Ò, that the risk of recipient VAPP will be lower with the sequential schedule shown in Table 3 when compared to schedules using OPV alone. No recipient cases were reported in children who previously received two or more doses of "conventional" or non-enhanced IPV, and only one case was reported in (1969) in a child who had previously received one dose of "conventional" IPV.²⁷ VAPP has also been reported prior to 1969 in a few OPV recipients who had previously received conventional IPV.²⁸

Effect on contact cases of VAPP: It is unknown whether the sequential IPV-OPV schedule will reduce the risk of contact VAPP. However, three studies conducted to date indicate that prior vaccination with IPV will not significantly increase the number of children excreting revertant poliovirus (as determined by genomic sequencing studies) after subsequent vaccination with OPV.^15,29,30

Persistence of serum neutralizing antibody: It is expected, but not yet known, that sequential IPV-OPV schedules will provide a similar degree of long-term protection when compared with schedules using IPV or OPV alone.

INDICATIONS

IPOL^Ò is indicated for active immunization of infants (as young as 6 weeks of age), children and adults for the prevention of poliomyelitis caused by poliovirus Types 1, 2, and 3.³¹

INFANTS, CHILDREN AND ADOLESCENTS

General Recommendations

It is recommended that all infants (as young as 6 weeks of age), unimmunized children and adolescents not previously immunized be vaccinated routinely against paralytic poliomyelitis.³² Following the eradication of poliomyelitis caused by wild poliovirus from the Western Hemisphere (including North and South America)³³ VAPP is the only cause of paralytic poliomyelitis in the US.³⁴ The use of IPV has been suggested as a way to reduce VAPP incidence.³⁴ The Advisory Committee on Immunization Practices (ACIP) recommends a preference for poliomyelitis vaccination based on sequential use of two doses of IPV followed by two doses of OPV.³¹ The first two doses of IPV are administered at two and four months of age. Subsequent OPV doses can be given at 12 to 18 months of age and 4 to 6 years of age. Alternatively, IPV only or OPV only schedules may be used. If an IPV only schedule is used, IPV may be given at 2, 4K, 6 to 18 months of age and 4 to 6 years of age. If an OPV- only schedule is used, refer to the manufacturer's latest package insert for the appropriate administration schedule and all other issues related to the use of OPV.

Previous clinical poliomyelitis (usually due to only a single poliovirus type) or incomplete immunization with OPV are not contraindications to completing the primary series of immunization with IPOL^Ò.

IPV also is recommended for every dose of the polio vaccination schedule if the vaccinee is immunodeficient or a member of the immediate household is immunodeficient. OPV is excreted in the stool by healthy vaccinees and can infect an immunocompromised household member, which may result in paralytic disease. In a household with an immunocompromised member, only IPV should be used for all those requiring poliovirus immunization.³¹

Children Incompletely Immunized

Children of all ages should have their immunization status reviewed and be considered for supplemental immunization as follows for adults. Time intervals between doses longer than those recommended for routine primary immunization do not necessitate additional doses as long as a final total of four doses is reached (see

DOSAGE AND ADMINISTRATION

ADULTS

General Recommendations

Routine primary poliovirus vaccination of adults (generally those 18 years of age or older) residing in the US is not recommended. Unimmunized adults residing in a household when a child is receiving OPV and/or adults who have increased risk of exposure to either oral vaccine or wild poliovirus and have not been adequately immunized should receive polio vaccination in accordance with the schedule given in the

DOSAGE AND ADMINISTRATION

Persons with previous wild poliovirus disease who are incompletely immunized or unimmunized should be given additional doses of IPOL^Ò if they fall into one or more categories listed previously.

The following categories of adults are at an increased risk of exposure to wild polioviruses:^31,35

• Travelers to regions or countries where poliomyelitis is endemic or epidemic.

• Health-care workers in close contact with patients who may be excreting polioviruses.

• Laboratory workers handling specimens that may contain polioviruses.

• Members of communities or specific population groups with disease caused by wild polioviruses.

• Incompletely vaccinated or unvaccinated adults in a household (or other close contacts) with children given OPV. The adult should be informed of the risk of VAPP associated with contact of those receiving OPV.

IMMUNODEFICIENCY AND ALTERED IMMUNE STATUS

Patients with recognized immunodeficiency are at greater risk of developing paralysis when exposed to live poliovirus than persons with a normal immune system. Under no circumstances should oral poliovirus vaccine be used in such patients or introduced into a household where such a patient resides.³¹

IPOL^Ò should be used in all patients with immunodeficiency diseases and members of such patients households when vaccination of such persons is indicated. This includes patients with asymptomatic HIV infection, AIDS or AIDS-Related Complex, severe combined immunodeficiency, hypogammaglobulinemia, or aggammaglobulinemia; altered immune states due to diseases such as leukemia, lymphoma, or generalized malignancy; or an immune system compromised by treatment with corticosteroids, alkylating drugs, antimetabolites or radiation. Immunogenicity of IPOL^Ò in individuals receiving immunoglobulin could be impaired and patients with an altered immune state may or may not develop a protective response against paralytic poliomyelitis after administration of IPV.³⁶

As with any vaccine, vaccination with IPOL^Ò may not protect 100% of susceptible individuals.

Use with other vaccines: refer to

DOSAGE AND ADMINISTRATION

DOSAGE AND ADMINISTRATION

Parenteral drug products should be inspected visually for particulate matter and/or discoloration prior to administration whenever solution and container permit. If these conditions exist the vaccine should not be administered.

After preparation of the injection site, immediately administer IPOL^Ò intramuscularly or subcutaneously. In infants and small children, the mid-lateral aspect of the thigh is the preferred site. In adults IPOL^Ò should be administered intramuscularly or subcutaneously in the deltoid area.

Care should be taken to avoid administering the injection into or near blood vessels and nerves. After aspiration, if blood or any suspicious discoloration appears in the syringe, do not inject but discard contents and repeat procedures using a new dose of vaccine administered at a different site.

DO NOT ADMINISTER VACCINE INTRAVENOUSLY.

Children

Primary Immunization

A primary series of IPOL^Ò consists of two 0.5 mL doses administered intramuscularly or subcutaneously in accordance with the schedules indicated in Table 3.³¹ The interval between the first two doses should be at least four weeks, but preferably eight weeks. The first two doses of IPOL^Ò are usually administered at two and four months of age. The first immunization may be administered as early as six weeks of age.

If a sequential IPV-OPV schedule is used, OPV has been recommended by the ACIP to be given at 12 to 18 months of age and 4 to 6 years of age. The third dose of oral poliovirus vaccine, (OPV), should follow at least six months but not more than twelve months after the second IPOL^Ò dose.

Patients with recognized immunodeficiency are at greater risk of developing paralysis when exposed to OPV than persons with a normal immune system. Under no circumstances should OPV be used in such patients or introduced in a household where such a patient resides.³¹

If a full (IPV only) IPOL^Ò schedule is used, the third dose of IPOL^Ò should be given at 6 to 18 months of age and 4 to 6 years of age. The third dose of IPOL^Ò should follow at least two months but not more than 12 months after the second IPOL^Ò dose. If this third dose is given at 6 months of age, it would be preferable to administer this dose two months after the second IPOL^Ò dose simultaneously with DTP or acellular pertussis and Hib or hepatitis B vaccines using separate syringes at separate sites. From historical data on the antibody responses to diphtheria, tetanus, whole-cell or acellular pertussis, Hib, or hepatitis B vaccines used concomitantly or in combination with IPOL^Ò, no interferences have been observed on the immunological end points accepted for clinical protection.^8,12,40 (See DRUG INTERACTIONS section). If the third dose is given between 12 to 18 months of age, it may be desirable to administer this dose with Measles, Mumps, and Rubella (MMR) and other vaccines using separate syringes at separate sites,³¹ but no data on the immunological interference between IPOL^Ò and these vaccines exist. The fourth dose of IPOL^Ò should be given before entering school at 4 to 6 years of age.

* This schedule should be used for individuals and household contacts who are immunocompromised. (See

INDICATIONS

The need to routinely administer additional doses is unknown at this time.³¹

Two doses of IPOL^Ò followed by two doses of OPV (or alternatively four doses of IPV or four doses of OPV) are necessary to complete the ACIP recommended series of primary and booster doses. Children and adolescents with a previously incomplete series of IPOL^Ò/OPV or IPOL^Ò alone should receive sufficient additional doses of IPOL^Ò or OPV to complete the series.

The preferred site of injection in infants and children is the mid lateral aspect of the thigh.

Interruption of the recommended schedule with a delay between doses does not interfere with the final immunity. There is no need to start the series over again regardless of the time elapsed between doses.

Adults

Unvaccinated Adults

A primary series of IPOL^Ò is recommended for unvaccinated adults at increased risk of exposure to poliovirus. While the responses of adults to primary series have not been studied, the recommended schedule for adults is two doses given at a 1 to 2 month interval and a third dose given 6 to 12 months later. If less than 3 months but more than 2 months are available before protection is needed, three doses of IPOL^Ò should be given at least 1 month apart. Likewise, if only 1 or 2 months are available, two doses of IPOL^Ò should be given at least 1 month apart. If less than 1 month is available, a single dose of IPOL^Ò is recommended.³¹

Incompletely Vaccinated Adults

Adults who are at an increased risk of exposure to poliovirus and who have had at least one dose of OPV, fewer than three doses of conventional IPV or a combination of conventional IPV or OPV totaling fewer than three doses should receive at least one dose of IPOL^Ò. Additional doses needed to complete a primary series should be given if time permits.³¹

Completely Vaccinated Adults

Adults who are at an increased risk of exposure to poliovirus and who have previously completed a primary series with one or a combination of polio vaccines can be given a dose of either OPV or IPOL^Ò.³¹

The preferred injection site of IPOL^Ò for adults is in the tissue of the deltoid area.

HOW SUPPLIED

Syringe, 0.5 mL with integrated needle (1 x 1 Dose package - Product No. 49281-860-51) (10 x 1 Dose package Product No. 49281-860-52)

Vial 10 Dose - Product No. 49281-860-10

STORAGE

The vaccine is stable if stored in the refrigerator between 2⁰C and 8⁰C (35⁰F and 46⁰F). The vaccine must not be frozen.

REFERENCES

1. van Wezel AL, et al. Inactivated poliovirus vaccine; Current production methods and new developments. Rev Infect Dis 6 (Suppl 2): S335-S340, 1984
2. Montagnon BJ, et al. Industrial scale production of inactivated poliovirus vaccine prepared by culture of Vero cells on microcarrier. Rev Infect Dis 6 (Suppl 2): S341-S344, 1984
3. Sabin AB. Poliomyelitis. In Brande AI, Davis CE, Fierer J (eds) International Textbook of Medicine, Vol II. Infectious Diseases and Medical Microbiology. 2nd ed. Philadelphia, WBSaunders, 1986
4. Prevots DR, et al. Vaccine-associated paralytic poliomyelitis in the United States, l980- 1994: current risk and potential impact of a proposed sequential schedule of IPV followed by OPV (Abstract #H90). In: Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC. American Society for Microbiology, 179, 1996
5. Salk J, et al. Antigen content of inactivated poliovirus vaccine for use in a one- or two- dose regimen. Ann Clin Res 14: 204-212, 1982
6. Salk J, et al. Killed poliovirus antigen titration in humans. Develop Biol Standard 41: 110- 132, 1978
7. Salk J, et al. Theoretical and practical considerations in the application of killed poliovirus vaccine for the control of paralytic poliomyelitis. Develop Biol Standard 47: 181-198, 1981
8. Unpublished data available from Pasteur Mérieux Sérums & Vaccins S. A.
9. McBean AM, et al. Serologic response to oral polio vaccine and enhanced-potency inactivated polio vaccines. Am J Epidemiol 128:615-628, 1988
10. Unpublished data available from Connaught Laboratories, Inc.
11. Faden H, et al. Comparative evaluation of immunization with live attenuated and enhanced potency inactivated trivalent poliovirus vaccines in childhood: Systemic and local immune responses. J Infect Dis 162:1291-1297, 1990
12. Vidor E, et al. The place of DTP/eIPV vaccine in routine paediatric vaccination. Rev Med Virol 4:261-277, 1994
13. Bottiger M. Long-term immunity following vaccination with killed poliovirus vaccine in Sweden, a country with no circulating poliovirus. Rev Infect Dis 6 (Suppl 2): S545-S551, 1984
14. Plotkin SA, et al. Inactivated polio vaccine for the United States: a missed vaccination opportunity. Pediatr Infect Dis J 14:835-839, 1995
15. Murdin AD, et al. Inactivated poliovirus vaccine: past and present experience. Vaccine 8: 735-746, 1996
16. Marine WM, et al. Limitation of fecal and pharyngeal poliovirus excretion in Salk- vaccinated children. A family study during a Type 1 poliomyelitis epidemic. Amer J Hyg 76: 173-175, 1962
17. Bottiger M, et al. Vaccination with attenuated Type 1 poliovirus, the Chat strain. II. Transmission of virus in relation to age. Acta Paed Scand 55: 416-421, 1966
18. Dick GWA, et al. Vaccination against poliomyelitis with live virus vaccines. Effect of previous Salk vaccination on virus excretion. Brit Med J 2: 266-269, 1961
19. Wehrle PF, et al. Transmission of poliovirus; III. Prevalence of polioviruses in pharyngeal secretions of infected household contacts of patients with clinical disease. Pediatrics 27: 762-764, 1961
20. Adenyi-Jones SC, et al. Systemic and local immune responses to enhanced-potency inactivated poliovirus vaccine in premature and term infants. J Pediatr 120:No 5, 686-689, 1992
21. Chin TDY. Immunity induced by inactivated poliovirus vaccine and excretion of virus. Rev Infect Dis 6 (Suppl 2): S369-S370, 1984
22. Salk D. Herd effect and virus eradication with use of killed poliovirus vaccine. Develop Biol Standard 47:247-255, 1981
23. Bijerk H. Surveillance and control of poliomyelitis in the Netherlands. Rev Infect Dis 6 (Suppl 2): S451-S456, 1984
24. Lapinleimu K. Elimination of poliomyelitis in Finland. Rev Infect Dis 6 (Suppl 2): S457-S460, 1984
25. Conyn van Spaendonck M, et al. Circulation of Poliovirus during the poliomyelitis outbreak in the Netherlands in 1992-1993 - Amer J Epidemiology 143: 929-935, 1996
26. Modlin JF, et al. Serum neutralizing antibody response to three experimental sequential IPV- OPV immunization schedules. J Infec Dis (in press)
27. von Magnus H, et al. Vaccination with inactivated poliovirus vaccine and oral poliovirus vaccine in Denmark. Rev Infect Dis 6 (suppl):S471-S474, 1984
28. Henderson DA, et al Paralytic disease associated with oral polio vaccines. JAMA 190:41- 48, 1964
29. Ogra PL, et al. Effect of prior immunity on the shedding of virulent revertant virus in feces after oral immunization with live attenuated poliovirus vaccines. J Infect Dis 164:191-194, 1991
30. Abraham R, et al. Shedding of virulent poliovirus revertants during immunization with oral poliovirus vaccine after immunization with inactivated polio vaccine. J Infect Dis 168:1105- 1109, 1993
31. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Poliomyelitis Prevention in the United States: Introduction of a Sequential Vaccination Schedule of Inactivated Poliovirus Vaccine Followed by Oral Poliovirus Vaccine. MMWR 46:No. RR-3, 1997
32. WHO. Weekly Epidemiology Record 54: 82-83, 1979
33. Certification of poliomyelitis eradication - the Americas, 1994. MMWR 43:720-722, 1994
34. Strebel PM, et al. Epidemiology of poliomyelitis in the United States one decade after the last reported case of indegenous wild virus associated disease. Clin Infect Dis 14:568-579, 1992
35. Institute of Medicine. An evaluation of poliomyelitis vaccine policy options. Washington, DC. National Academy of Sciences, 1988
36. ACIP. Immunization of children infected with human T-lymphotropic virus type III/ lymphadenopathy-associated virus. MMWR 35: 595-606, 1986
37. ACIP. General recommendations on immunization. MMWR 43: No. RR-1, 1994
38. Barbi M, et al. Antibody response to inactivated polio vaccine (Eipv) in children born to HIV positive mothers. Eur J Epidemiol 8: 211-216, 1992
39. Varon D, et al. Response to hemophilic patients to poliovirus vaccination: Correlation with HIV serology and with immunological parameters. J Med Virol 40:91-95, 1993
40. Vidor E, et al. Fifteen-years experience with vero-produced enhanced potency inactivated poliovirus vaccine (eIPV). Ped Infect Dis J 1997 (In Press)
41. CDC. Vaccine Adverse Event Reporting System - United States. MMWR 39:730-733, 1990
42. CDC. National Childhood Vaccine Injury Act. Requirements for permanent vaccination records and for reporting of selected events after vaccination. MMWR 37:197-200, 1988
43. Food & Drug Administration. New Reporting Requirements for Vaccine Adverse Events. FDA Drug Bull 18 (2), 16-18, 1988

SIDE EFFECTS

BODY SYSTEM AS A WHOLE

In earlier studies with the vaccine grown in primary monkey kidney cells, transient local reactions at the site of injection were observed.⁹ Erythema, induration and pain occurred in 3.2%, 1% and 13%, respectively, of vaccinees within 48 hours post-vaccination. Temperatures of ³39⁰C (³102⁰F) were reported in 38% of vaccinees. Other symptoms included irritability, sleepiness, fussiness, and crying. Because IPV was given in a different site but concurrently with Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed (DTP), these systemic reactions could not be attributed to a specific vaccine. However, these systemic reactions were comparable in frequency and severity to that reported for DTP given alone without IPV.¹⁰ Although no causal relationship has been established, deaths have occurred in temporal association after vaccination of infants with IPV.

Four additional US studies using IPOL⁰ in more than 1,300 infants,¹⁰ between two to eighteen months of age administered with DTP at the same time at separate sites or combined have demonstrated that local and systemic reactions were similar when DTP was given alone.

§ Data are from the IPOL^Ò administration site, given intramuscularly.

* The adverse reaction profile includes the concomitant use of CLI whole-cell DTP vaccine or Tripedia^Ò with IPOL^Ò. Rates are comparable in frequency and severity to that reported for whole-cell DTP given alone.

† Children vaccinated with Tripedia^Ò vaccine.

DIGESTIVE SYSTEM

Anorexia and vomiting occurred with frequencies not significantly different as reported when DTP was given alone without IPV or OPV.¹⁰

NERVOUS SYSTEM

Although no causal relationship between IPOL^Ò and GBS has been established,³² GBS has been temporally related to administration of another inactivated poliovirus vaccine.

Reporting of Adverse Events

The National Vaccine Injury Compensation Program, established by the National Childhood Vaccine Injury Act of 1986, requires physicians and other health-care providers who administer vaccines to maintain permanent vaccination records and to report occurrences of certain adverse events to the US Department of Health and Human Services. Reportable events include those listed in the Act for each vaccine and events specified in the package insert as contraindications to further doses of that vaccine.^41,42,43

Reporting by parents or guardians of all adverse events after vaccine administration should be encouraged. Adverse events following immunization with vaccine should be reported by health- care providers to the US Department of Health and Human Services (DHHS) Vaccine Adverse Event Reporting System (VAERS). Reporting forms and information about reporting requirements or completion of the form can be obtained from VAERS through a toll-free number 1-800-822-7967.^41,42,43

Health care providers also should report these events to the Director of Medical Affairs, Connaught Laboratories, Inc., Route 611, PO Box 187, Swiftwater, PA 18370 or call 1-800-822-2463.

DRUG INTERACTIONS

There are no known interactions of IPOL^Ò with drugs or foods. Simultaneous administration, with separate syringes at separate sites, of other parenteral vaccines is not contraindicated. The first two doses of IPOL^Ò may be administered at separate sites using separate syringes concomitantly with D.P. acellular pertussis, Haemophilus influenzae type b (Hib), and hepatitis B vaccines. From historical data on the antibody responses to diphtheria, tetanus, whole-cell or acellular pertussis, Hib, or hepatitis B vaccines used concomitantly or in combination with IPOL^Ò, no interferences have been observed on the immunological end points accepted for clinical protection.^8,12,40 (See DOSAGE AND ADMINISTRATION section).

If IPOL^Ò has been administered to persons receiving immunosuppressive therapy, an adequate immunologic response may not be obtained. (See PRECAUTIONS - General)

WARNINGS

Neomycin, streptomycin, and polymyxin B are used in the production of this vaccine. Although purification procedures eliminate measurable amounts of these substances, traces may be present (see DESCRIPTION section) and allergic reactions may occur in persons sensitive to these substances (see CONTRAINDICATIONS section).

Systemic adverse reactions reported in infants receiving IPV concomitantly at separate sites or combined with DTP have been similar to those associated with administration of DTP alone.⁸ Local reactions are usually mild and transient in nature.

Although no causal relationship between IPOL^Ò and Guillain-Barré Syndrome (GBS) has been established,³¹ GBS has been temporally related to administration of another inactivated poliovirus vaccine. Deaths have been reported in temporal association with the administration of IPV (see ADVERSE REACTIONS section).

PRECAUTIONS

General

Before injection of the vaccine, the physician should carefully review the recommendations for vaccine use and the patient's medical history including possible hypersensitivities and side effects that may have occurred following previous doses of the vaccine.

Health-care providers should question the patient, parent or guardian about reactions to a previous dose of this product, or similar product.

Epinephrine Injection (1:1000) and other appropriate agents should be available to control immediate allergic reactions.

Health-care providers should obtain the previous immunization history of the vaccinee, and inquire about the current health status of the vaccinee.

Immunodeficient patients or patients under immunosuppressive therapy may not develop a protective immune response against paralytic poliomyelitis after administration of IPV.

Administration of IPOL^Ò is not contraindicated in individuals infected with HIV. ^37,38,39

Special care should be taken to ensure that the injection does not enter a blood vessel.

A separate, sterile syringe and needle or a sterile disposable unit must be used for each patient to prevent transmission of hepatitis or other infectious agents from person to person. Needles should not be recapped and should be disposed of according to biohazard waste guidelines.

Information for Patients

See PATIENT INFORMATION section.

Drug Interactions

See DRUG INTERACTIONS section.

Carcinogenecis, Mutagenesis, Impairment of Fertility

Long-term studies in animals to evaluate carcinogenic potential or impairment of fertility have not been conducted.

Pregnancy

Pregnancy Category C

Animal reproduction studies have not been conducted with IPOL^Ò. It is also not known whether IPOL^Ò can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. IPOL^Ò should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether IPOL^Ò is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when IPOL^Ò is administered to a nursing woman.

Pediatric Use

SAFETY AND EFFECTIVENESS OF IPOL^Ò IN INFANTS BELOW SIX WEEKS OF AGE HAVE NOT BEEN ESTABLISHED.^10,19 (See DOSAGE AND ADMINISTRATION section).

In the US, infants receiving two doses of IPV at 2 and 4 months of age, the seroconversion to all three types of poliovirus was demonstrated in 95% to 100% of these infants after two doses of vaccine.^10,11