PREVNAR 13

General Administration Information
For storage information, see the specific product information within the How Supplied section.

-Inform the patient, parent, guardian, or responsible adult of the benefits and risks of the vaccine. Provide the Vaccine Information Statements from the manufacturer to the recipient or guardian before each immunization. These actions are required by the National Childhood Vaccine Injury Act of 1986.
-Record the manufacturer and lot number of the vaccine; date of administration; and the name, address, and title of the person who administered the vaccine in the recipient's permanent medical record. These actions are required by the National Childhood Vaccine Injury Act of 1986.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Do not mix with any other vaccine.
-When concomitant administration of other vaccines or immunoglobulin is required, they should be given with different syringes and at different injection sites.
Intramuscular Administration
Preparation
-Use vaccine as supplied; reconstitution is not necessary.
-PCV13 (Prevnar 13): Shake vigorously just prior to administration to obtain a homogenous, white suspension. Do not use the vaccine if it cannot be resuspended.
-PCV15 (Vaxneuvance): Shake vigorously just prior to administration to obtain an opalescent suspension. Do not use the vaccine if it cannot be resuspended.
-PPSV23 (Pneumovax 23): Pneumovax 23 is a clear solution that does not require shaking prior to administration.

Intramuscular Injection
-For vials, use a sterile syringe and needle to withdraw the vaccine from the vial. For prefilled syringes, attach a sterile needle.
-Inject IM into the anterolateral aspect of the mid-thigh (for infants younger than 1 year) or the deltoid muscle of the upper arm (usually suitable for older children). Do NOT administer in the gluteal muscle or other areas where there may be a major nerve trunk.

Subcutaneous Administration
-Only PPSV23 (Pneumovax 23) is approved for subcutaneous administration.
-Use vaccine as supplied; reconstitution is not necessary. The vaccine is a clear solution.
-Use a sterile syringe and needle to withdraw solution from the vial.
-Inject subcutaneously into the outer aspect of the upper arm. Care should be taken to avoid intradermal injection.

Report all adverse reactions to the Vaccine Adverse Event Reporting System (VAERS), as well as to the manufacturer. The toll-free number for VAERS is 1-800-822-7967. Educate the responsible adult(s) to promptly report any adverse reaction after vaccine administration to a health care provider.

The most frequent adverse reaction of pneumococcal vaccine, polyvalent administration in infants and children is an injection site reaction, which usually is of minor consequence. During clinical trials of PCV13 (Prevnar 13), patients experienced erythema (24.3% to 70%), swelling (19.6% to 44.5%), warmth, and tenderness (15.1% to 89%) at the injection site. Significant tenderness that interfered with limb movement was reported in up to 43.8% of patients. Skin necrosis at the injection site, itching or hives at the injection site, injection site dermatitis, and peripheral edema in the injected extremity have been observed during postmarketing experience; frequency of these reactions is not established.

During pre-marketing clinical trials of conjugated pneumococcal vaccine, polyvalent (PCV13 or Prevnar 13), < 1% of infant and children vaccinees experienced seizures (including febrile seizures); vaccinees also received other standard childhood vaccines concomitantly. Febrile convulsions have also been observed during post-marketing experience with PPSV23 (Pneumovax 23). During the first 2 years of licensure of PCV7, and epidemiologic study described 393 reports of seizures (including 94 febrile seizures) that were reported to the Vaccine Adverse Event Reporting System; Of the 393 seizure cases, 57 occurred after receipt of only PCV7. During focused follow-up of the first 98 seizures reported during the surveillance period, 80.6% of seizures occurred in patients with previous seizure history or patients who were febrile. During the 2010-2011 influenza season, there were increased reports of febrile seizures in children 6 months to 4 years of age receiving the inactivated influenza vaccine and PCV13 concomitantly. The CDC found that febrile seizures were rare in this group with approximately one additional seizure occurring for every 2000-3000 children vaccinated. Febrile seizures occurred most commonly in children 12-23 months of age who received both vaccines at the same healthcare visit. No changes to the recommended childhood immunization schedule were recommended.

Lymphadenitis, lymphadenopathy, hemolytic anemia, and leukocytosis have been reported with post-marketing use of pneumococcal vaccine, polyvalent; however, a causal relationship to the vaccine has not been established. Ecchymosis occurred in 1.1% of adults after pneumococcal vaccination with PPSV23 (Pneumovax 23) in clinical trials. Pneumococcal vaccination has been associated with relapse of idiopathic thrombocytopenic purpura (ITP) in previously stabilized patients. A report of a patient that developed a platelet count less than 150,000 mm3, immune thrombocytopenic purpura, and aplastic anemia 1 week after her first dose of PCV7 (Prevnar) given alone has been received through the Vaccine Adverse Event Reporting System (VAERS). Over the first 2 years after approval of PCV7, 78 reports of possible thrombocytopenia (e.g., petechiae, purpura, or ecchymosis) were received through VAERS. Most patients developed symptoms 1-35 days after immunization. Twelve patients had a documented platelet count < 20,000 mm3, but at least 8 patients had multiple potential causes of the thrombocytopenia (e.g., vaccines, medications, or viral or bacterial infections).

Paresthesias and acute radiculoneuropathy, such as Guillain-Barre syndrome, have occurred after immunization with pneumococcal vaccine, polyvalent, but such reactions are rare, and a causal relationship cannot be established.

Myalgia (11.9-61.8%), arthralgia (9.7-31.5%), neck pain (0.7-1.5%), and back pain (0.9%) have been reported in clinical trials of pneumococcal vaccine, polyvalent in the adult population; these reactions may also occur in the pediatric population. Over the first 2 years after approval of PCV7 (Prevnar), 5 reports of serum sickness in patients who only received PCV7 were received through the Vaccine Adverse Event Reporting System. Symptoms occurred within 1 day of vaccination in half of the cases, and with the initial dose in 3 patients. Arthus reaction has occurred and is more likely to occur with repeat vaccination. In addition, 26 reports of arthritis or arthralgia have been received. Although these events have not been specifically reported with PCV13 (Prevnar 13), they should still be considered potential reactions because of the similarity of the PCV13 product to PCV7.

Development of a rash (unspecified) has occurred after vaccination with pneumococcal vaccine, polyvalent. During pre-marketing trials of PCV13 (Prevnar 13), rash occurred in >= 1% of infants and children and 7.3-16.5% of adults who received the vaccine. Rash has also been reported with post-marketing use of PPSV23 (Pneumovax 23); however, a causal relationship has not been established. Over the first 2 years after approval of PCV7 (Prevnar), 796 reports of a rash were received through the Vaccine Adverse Event Reporting System. Of the 796 cases, 183 patients had only received vaccination with PCV7. Also, there were 39 reports of erythema multiforme of which 9 patients had received vaccination only with PCV7.

During pre-marketing clinical trials of conjugated pneumococcal vaccine, polyvalent (PCV13 or Prevnar 13), < 1% of vaccinees experienced a hypersensitivity or allergic reaction that included facial edema, dyspnea, and bronchospasm. Urticaria was observed in 1.4-1.9% of patients aged 5-17 years who received the vaccine without other concomitant vaccinations. Anaphylactoid reactions, angioedema, and urticaria have also been reported with post-marketing use of Pneumovax 23; however, a causal relationship has not been established. Of 4154 reports to the Vaccine Adverse Event Reporting System over 2 years during experience with PCV7 (Prevnar), about a third were in regard to allergic reactions (e.g., anaphylactic shock, urticaria, pruritus, facial edema, angioedema, asthma, dyspnea, bronchospasm, anaphylactic or anaphylactoid reactions). Symptoms of anaphylaxis began after 1 dose of PCV7 in 12 patients, and symptoms began 5 minutes to 4 hours after vaccination.

Anorexia (decreased appetite) occurred in 16.3-44.4% of infants and children who received the conjugated pneumococcal vaccine, polyvalent (PCV13 or Prevnar 13) alone in clinical trials. Vomiting (0.9-6.9% adults; > 1% pediatrics), diarrhea (0.7-1.1% adults; > 1% pediatrics), nausea (1.8% adults), and dyspepsia (1.1% adults) have also been reported to occur in patients receiving the pneumococcal vaccine. Intussusception has been reported in 5 patients that received a dose of PCV7 (Prevnar); one patient developed the adverse event after receipt of only PCV7. Symptoms of intussusception occurred within 2 days of vaccination in 4 patients and within 2 weeks in the other patient. One patient died after months of frequent diarrhea.

The most frequent neurological adverse reactions in pediatric patients who received conjugated pneumococcal vaccine, polyvalent (PCV13 or Prevnar 13) during clinical trials included increases and decreases in sleep, reported in 2.6-35.3% and 5.7-29.7% of vaccinees who received PCV13 without other concurrent vaccines, respectively. Headache has been reported with PCV13 use in up to 65.9% of adults, and with Pneumovax 23 use in up to 18.1% of adults. During the first 2 years of licensure of PCV7, an epidemiologic study described 144 cases of pallor, syncope, or dizziness that were reported to the Vaccine Adverse Event Reporting System. Eight patients experienced a hypotonic, hyporesponsive episode, hypotonia, or hyporesponsiveness after receipt of a PCV7 dose. As these reports are collected from a population of uncertain size, reaction frequency is unknown. One (0.015%) hypotonic-hyporesponsive episode was reported with Prevnar 13 from infant and toddler clinical studies.

In clinical trials comparing 2 conjugated pneumococcal vaccines (PCV7 and PCV13), the most commonly reported serious adverse effect was infection. Bronchiolitis, gastroenteritis, and pneumonia were reported in 0.9% of children who received PCV 13. Upper respiratory tract infection and pharyngitis were reported in clinical trials of adults receiving pneumococcal vaccine, polyvalent (PPSV23).

Apnea following intramuscular administration of vaccines has been observed in some infants born prematurely. Consider the medical status of the infant and risks and benefits of immunization with pneumococcal vaccine in this patient population.

Fever is a relatively common adverse effect of immunization with pneumococcal vaccine, polyvalent (PCV13) reported in 0.7-19.9% of infants and children during clinical trials. With concomitant administration with other standard childhood vaccines, the incidence increased up to 35.5%. The incidence of fever associated with the primary childhood series is lower with the first dose compared to fevers associated with the second, third, or fourth dose. The majority of fevers experienced are <= 39 degrees C (102.2 degrees F); however, fevers > 40 degrees C (104 degrees F) have been reported in a small number of children (<= 1%). Fever > 102 degrees F has been reported during post-marketing experience with PPSV23 (Pneumovax 23). Pediatric patients aged 6-23 months receiving simultaneous trivalent inactivated influenza vaccine (TIV) and 13-valent pneumococcal vaccine (PCV13) are 2.67 times (CI 1.25-5.66) more likely to have a day 0 to 1 temperature of >= 100.4 degrees F than those receiving PCV13 without TIV. A temperature of 102.2 degrees F is 2.53 times (CI 0.76-8.42) more likely to occur on day 0 to 1 when TIV and PCV13 are administered together vs. PCV13 alone. Chills have been reported with PCV13 use in adult patients. Irritability was noted in 14.3-73.3% of infant and children vaccinees who received PCV13 without other concomitant vaccinations. Counsel patients to report any signs or symptoms of a systemic reaction to their health care provider.

Fatigue and asthenia have been noted in up to 63.3% and 17.9% of adults who received pneumococcal vaccine, polyvalent during clinical trials (PCV13 or PPSV23). Malaise has been noted during post-marketing observation. Counsel patients to report signs or symptoms of a systemic reaction to their health care provider.

Prior to administration, inform the patient, parent, guardian, or responsible adult of the benefits and risks of the vaccine, and provide the Vaccine Information Statement, accessible at the Centers for Disease Control and Prevention (CDC) website. These actions are required by the National Childhood Vaccine Injury Act of 1986. If a dose of pneumococcal vaccine, polyvalent has been previously given, question the parent or guardian about previous adverse reactions that may preclude further administration. Report all adverse reactions to the Vaccine Adverse Event Reporting System (VAERS), as well as the manufacturer. The toll-free number for VAERS is 1-800-822-7967. Educate the responsible adult(s) to promptly report any adverse reaction after vaccine administration to a health care provider.

Pneumococcal vaccines are contraindicated in patients who have had a previous hypersensitivity reaction to the vaccine to be administered or to any components of the vaccine. PCV13 (Prevnar 13) and PCV15 (Vaxneuvance) are contraindicated in patients who have had a hypersensitivity reaction to any diphtheria toxoid-containing vaccine. As with any biologic product, the prescriber or health care professional should have procedures in place to manage allergic reactions. The health care professional should have immediate availability of epinephrine (1 mg/mL) injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction to the pneumococcal vaccines.

The conjugated pneumococcal vaccines (PCV13 [Prevnar 13] and PCV15 [Vaxneuvance]) are only indicated for intramuscular administration; do not give via intravenous administration, subcutaneous administration, or intradermal administration. PPSV23 (Pneumovax 23) may be administered via intramuscular or subcutaneous routes. Incorrect administration may result in inadequate immunity.

The decision to administer or delay vaccination with the pneumococcal vaccine because of current or recent febrile illness depends on the severity of symptoms and on the etiology of the disease. The Advisory Committee on Immunization Practices recommends that vaccinations be delayed during the course of a moderate or severe acute illness with or without fever and administered after the acute phase of illness has resolved. All vaccines can be given to persons with minor illnesses such as diarrhea, mild upper-respiratory infection with or without low-grade fever, or other low-grade febrile illness.

Use pneumococcal vaccines with caution in patients with immune thrombocytopenic purpura (ITP) because pneumococcal vaccination has been associated with relapse of this condition in previously stabilized patients. Monitor patients for relapse after vaccination.

Use pneumococcal vaccines cautiously in patients with severe cardiac disease or pulmonary disease because systemic reactions may pose significant risks in these patient populations. In patients at higher risk for pneumococcal infection, including those with chronic heart or lung disease, diabetes mellitus, cochlear implants, or cerebrospinal fluid leaks (due to congential lesions, skull fractures, or neurosurgical procedures), give the pneumococcal vaccine in accordance with current immunization schedules. Pneumococcal meningitis may not be prevented with pneumococcal immunization in patients with cerebrospinal fluid leaks.

Patients with significant immunosuppression may not have an adequate antibody response to pneumococcal vaccines. Immunosuppressed persons may include those with: absent or deficient splenic function (including sickle cell disease); severe combined immunodeficiency (SCID); hypogammaglobulinemia; agammaglobulinemia; chronic renal failure and nephrotic syndrome; allogeneic stem cell transplant; organ transplant; altered immune states due to generalized neoplastic disease (i.e., leukemia, lymphoma, Hodgkin lymphoma); or an immune system compromised by radiation therapy or drug therapy (e.g., chemotherapy or corticosteroid therapy with greater than physiologic doses). Short-term (less than 2 weeks) corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive. In a study evaluating antibody response to the pneumococcal conjugate vaccine (PCV13) in pediatric patients with sickle cell disease, antipneumococcal opsonophagocytic activity (OPA) geometric mean antibody titers (GMTs) for all vaccine serotypes were higher than prevaccination concentrations after the first dose, and were generally comparable after subsequent doses. In patients (age 2 to 71 years) who received an allogeneic hematopoietic stem cell transplant 3 to 6 months prior to a series of PCV13 vaccines, sera was obtained approximately 1 month after each vaccination. Immune responses (IgG GMCs) were numerically higher after the first dose compared with baseline and were, similarly, numerically higher after each subsequent dose compared to the previous dose. Invasive pneumococcal disease has decreased substantially among pediatric patients with sickle cell disease since the introduction of PCVs; however, risk still remains higher compared to healthy patients. Patients with chronic immunodeficiency should receive PCV13 in addition to PPSV23 (23-valent pneumococcal polysaccharide vaccine) according to current immunization schedules. If elective splenectomy or immunosuppressive therapy is planned, complete necessary pneumococcal immunization at least 2 weeks before surgery or therapy initiation.

The pneumococcal vaccines are indicated for intramuscular (IM) administration. Therefore, administer with caution to persons receiving anticoagulant therapy. Also, monitor patients with thrombocytopenia, coagulopathy (e.g., hemophilia), other bleeding disorders, or vitamin K deficiency closely for bleeding at the IM injection site. Steps to avoid hematoma formation are recommended.

Safety and efficacy of the pneumococcal conjugate vaccine 13 (PCV13 or Prevnar 13), pneumococcal conjugate vaccine 15 (PCV15 or Vaxneuvance), or pneumococcal conjugate vaccine 20 (PCV20 or Prevnar 20) have not been established in neonates and infants younger than 6 weeks of age. Safety and efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPSV23 or Pneumovax 23) have not been established in children younger than 2 years of age. Patients in this age group do not develop an effective immune response to the capsular types contained in this polysaccharide vaccine. Apnea has occurred in some premature neonates and infants after intramuscular injections. The risks and benefits of intramuscular injections, including vaccination with the pneumococcal vaccine, must be considered on an individual patient basis. In addition, health care providers are advised that immunogenicity may be lower in premature neonates. In 1 study, premature neonates (younger than 37 weeks gestation; n = 100) receiving Prevnar 13 on a non-United States 4-dose schedule displayed lower serotype-specific IgG antibody responses after the third and fourth doses when compared to term neonates (37 weeks gestation and older; n = 100).

Compared to healthy individuals, patients with human immunodeficiency virus (HIV) infection generally have lower vaccine-induced antibody concentrations, which are proportional to the severity of infection (i.e., CD4 counts) and are lowest in those with acquired immunodeficiency syndrome (AIDS). The 13-valent pneumococcal conjugate vaccine (PCV13) may be administered to all persons with HIV, regardless of CD4 counts. In those who receive the PCV13 dose when the CD4 count is less than 200 cells/mm3, some experts may choose to defer the 23-valent pneumococcal polysaccharide vaccine (PPSV23) until CD4 counts are above 200 cells/mm3 in order to optimize vaccine efficacy. Vaccination is increasingly pertinent with the rising incidence of drug-resistant S. pneumoniae infections. In studies evaluating antibody response to the pneumococcal conjugate vaccine (PCV13) in pediatric patients with HIV infection, antipneumococcal opsonophagocytic activity (OPA) geometric mean antibody titers (GMTs) for all vaccine serotypes were higher than prevaccination concentrations after the first dose, and were generally comparable after subsequent doses. In other studies involving pediatric patients with HIV, antibody response to various formulations of pneumococcal conjugate vaccines (PCV) have been slightly lower but comparable to patients who are not infected.

Description: Pneumococcal vaccines provide immunity against pneumococcal disease, which may manifest as, but is not limited to, otitis media, pneumonia, bacteremia, or meningitis. The prevention of serious pneumococcal disease has become an increasingly important health issue due to the increased number of Streptococcus pneumoniae isolates that are drug resistant. Four different polyvalent pneumococcal vaccines, each containing highly purified capsular polysaccharides from S. pneumoniae, are available for use in pediatric patients: conjugated (13-valent pneumococcal conjugate vaccine [PCV13 or Prevnar 13], 15-valent pneumococcal conjugate vaccine [PCV15 or Vaxneuvance], and 20-valent pneumococcal conjugate vaccine [PCV20 or Prevnar 20]) and non-conjugated (23-valent pneumococcal polysaccharide vaccine [PPSV23 or Pneumovax 23]). The vaccines are designed to protect against the most frequent bacterial serotypes associated with pneumococcal infection. In the conjugated vaccines, coupling of the capsular polysaccharides to another antigen (nontoxic diphtheria CRM197) in the vaccine induces T-cell dependent immune responses that are immunogenic in patients younger than 2 years of age whose immune systems are not fully mature. In contrast, non-conjugated PPSV23 (Pneumovax 23) elicits an independent T-cell response and is only used in pediatric patients at high risk of pneumococcal disease. During randomized trials in fully vaccinated infants and children, the efficacy of pneumococcal conjugate vaccines (PCVs) against invasive pneumococcal disease was 97.4%; efficacy against acute otitis media episodes in fully vaccinated infants was 57%. PCVs were associated with a 20% reduction in tympanostomy tube placement. In clinical trials with PCV15 (Vaxneuvance), immune responses produced by the PCV15 vaccine after 4 doses were non-inferior to PCV13 for the 13 shared serotypes based on serotype-specific immunoglobulin G geometric mean concentrations. Routine vaccination with pneumococcal vaccine is recommended by ACIP for all infants and children up to 5 years of age. Vaccination is also recommended for patients 2 years and older with underlying medical conditions. PCV13 (Prevnar 13), PCV15 (Vaxneuvance), and PCV20 (Prevnar 20) are approved for use in infants as young as 6 weeks. PPSV23 (Pneumovax 23) is approved for use in children as young as 2 years.

General Dosing Information
-Pneumococcal conjugate vaccines (PCV13 [Prevnar 13], PCV15 [Vaxneuvance], and PCV20 [Prevnar 20]) are used for routine immunization in infants and children.
-PCV13 (Prevnar 13) is indicated for immunization for prevention of invasive disease caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F; the vaccine is also indicated for immunization against serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F for otitis media prevention. No efficacy data for otitis media prevention are available for serotypes 1, 3, 5, 6A, 7F, and 19A.
-PCV15 (Vaxneuvance) is indicated for immunization for prevention of invasive disease caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F.
-PCV20 (Prevnar 20) is indicated for immunization for prevention of invasive disease caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F; the vaccine is also indicated for immunization against serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F for otitis media prevention.
-Non-conjugated PPSV23 (23-valent pneumococcal polysaccharide vaccine or Pneumovax 23) is indicated for immunization against S. pneumoniae serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F for prevention of pneumococcal disease. It is only used in patients 2 years and older with a high risk of pneumococcal disease due to certain underlying medical or immunocompromising conditions.
-The safety and efficacy of concomitant administration of PCV13 and PPSV23 have not been studied and is therefore not recommended.
-Interruption of the recommended schedule with a delay between doses should not interfere with the final immunity achieved with the pneumococcal vaccine. There is no need to start a primary series over again, regardless of the time between doses.
-Premature infants should be immunized according to their chronological age, regardless of birth weight.

For pneumocoocal prophylaxis:
-for routine immunization:
Intramuscular dosage (PCV13 or Prevnar 13):
Infants 6 weeks to 6 months at first dose: 0.5 mL IM for a total of 4 doses. Give the first 3 doses at intervals of 4 to 8 weeks, ideally at 2, 4, and 6 months of age; the first dose can be given as young as 6 weeks. The fourth dose is given as a booster between 12 and 15 months of age and at least 8 weeks after the third dose.
Infants 7 to 11 months at first dose: 0.5 mL IM for 3 doses. Give the first 2 doses at least 4 weeks apart. The third dose should ideally be given after the first birthday, separated from the second dose by at least 8 weeks.
Children 12 to 23 months at first dose: 0.5 mL IM for 2 doses administered at least 8 weeks apart.
Children 24 to 59 months at first dose: 0.5 mL IM as a single dose.
Children and Adolescents 5 to 17 years: ACIP does not include recommendations for pneumococcal vaccine for healthy children and adolescents 5 years and older. Vaccination is only recommended in patients with underlying medical conditions. The FDA-approved product labeling recommends a single 0.5 mL IM dose.
Intramuscular dosage (PCV15 or Vaxneuvance):
Infants 6 weeks to 6 months at first dose: 0.5 mL IM for a total of 4 doses. Give the first 3 doses at intervals of 4 to 8 weeks, ideally at 2, 4, and 6 months of age; the first dose can be given as young as 6 weeks. The fourth dose is given as a booster between 12 and 15 months of age and at least 8 weeks after the third dose. The 4-dose series initiated with a lower valency pneumococcal conjugate vaccine (i.e., PCV13) can be completed with Vaxneuvance.
Infants 7 to 11 months at first dose: 0.5 mL IM for 3 doses. Give the first 2 doses at least 4 weeks apart. The third dose should ideally be given after the first birthday, separated from the second dose by at least 8 weeks.
Children 12 to 23 months at first dose: 0.5 mL IM for 2 doses, separated by at least 8 weeks.
Children 24 to 59 months at first dose: 0.5 mL IM as a single dose. Administer a single dose to children who have received an incomplete series of another pneumococcal conjugate vaccine. At least 8 weeks should elapse between receipt of the last dose of another pneumococcal conjugate vaccine and administration of Vaxneuvance.
Children and Adolescents 5 to 17 years at first dose: ACIP does not include recommendations for pneumococcal vaccine for healthy children and adolescents 5 years and older. Vaccination is only recommended in patients with underlying medical conditions. The FDA-approved product labeling recommends a single 0.5 mL IM dose.
Intramuscular dosage (PCV20 or Prevnar 20):
Infants 6 weeks to 6 months at first dose: 0.5 mL IM for a total of 4 doses. Administer at 2, 4, and 6 months of age; the first dose can be given as young as 6 weeks. The fourth dose is given as a booster between 12 and 15 months of age and at least 2 months after the third dose.
Infants 7 to 11 months at first dose: 0.5 mL IM for 3 doses. Give the first 2 doses at least 4 weeks apart. The third dose should ideally be given after the first birthday, separated from the second dose by at least 2 months.
Children 12 to 23 months at first dose: 0.5 mL IM for 2 doses, separated by at least 2 months.
Children 24 to 59 months at first dose: 0.5 mL IM as a single dose.
Children and Adolescents 5 to 17 years at first dose: ACIP does not include recommendations for pneumococcal vaccine for healthy children and adolescents 5 years and older. Vaccination is only recommended in patients with underlying medical conditions. The FDA-approved product labeling recommends a single 0.5 mL IM dose.
Children and Adolescents 15 months to 17 years previously vaccinated with at least 1 dose of a lower valency pneumococcal conjugate vaccine: 0.5 mL IM as a single dose at least 8 weeks after receipt of a lower valency pneumococcal conjugate vaccine.
-for invasive pneumococcal prophylaxis in patients with high-risk conditions such as chronic heart disease, chronic lung disease (e.g., asthma treated with high-dose oral corticosteroids), and diabetes mellitus:
Intramuscular dosage (PCV13 or Prevnar 13):
Children 2 to 5 years: If 3 doses of PCV13 were received previously, give one 0.5 mL dose IM at least 8 weeks after the last PCV13 dose. If less than 3 doses of PCV13 were received previously, give 2 doses at least 8 weeks apart. Children who have received a dose of PPSV23 should also receive the recommended PCV13 doses. If not previously received, a dose of PPSV23 is needed at least 8 weeks after the last PCV13 dose.
Intramuscular or Subcutaneous dosage (PPSV23 or Pneumovax 23):
Children and Adolescents 2 to 17 years who are PPSV23-naive: 0.5 mL IM or subcutaneously as a single dose at least 8 weeks after the last dose of PCV13.
-for invasive pneumococcal prophylaxis in patients with immunocompromising conditions (i.e., sickle cell disease and other hemoglobinopathies, anatomic or functional asplenia, congenital or acquired immunodeficiency, HIV infection, chronic renal failure, nephrotic syndrome, malignant neoplasms, leukemias, lymphomas, Hodgkin disease, solid organ transplantation, multiple myeloma, iatrogenic immunosuppression from drug or radiation therapy):
Intramuscular dosage (PCV13 or Prevnar 13):
Children 2 to 5 years: If 3 doses of PCV13 were received previously, give one 0.5 mL dose IM at least 8 weeks after the last PCV13 dose. If less than 3 doses of PCV13 were received previously, give 2 doses at least 8 weeks apart. Children who have received a dose of PPSV23 should also receive the recommended PCV13 doses. If not previously received, 2 doses of PPSV23 are needed; first PPSV23 dose at least 8 weeks after the last PCV13 dose and second PPSV23 dose 5 years later.
Children and Adolescents 6 to 17 years who are PCV13-naive and PPSV23-naive: 0.5 mL IM as a single dose, followed at least 8 weeks later by a dose of PPSV23. A second PPSV23 vaccination is recommended 5 years after the first dose of PPSV23 (Max: 2 doses of PPSV23 before age 65 years).
Children and Adolescents 6 to 17 years who received previous vaccination with PPSV23: 0.5 mL IM as a single dose at least 8 weeks after the last PPSV23 dose. A second PPSV23 vaccination is recommended 5 years after the first dose of PPSV23 and at least 8 weeks after a dose of PCV13 (Max: 2 doses of PPSV23 before age 65 years).
Intramuscular or Subcutaneous dosage (PPSV23 or Pneumovax 23):
Children and Adolescents 2 to 17 years who are PPSV23-naive: 0.5 mL IM or subcutaneously as a single dose at least 8 weeks after the last dose of PCV13. A second vaccination is recommended 5 years after the first dose of PPSV23 (Max: 2 doses of PPSV23 before age 65 years). For patients with HIV and CD4 counts less than 200 cells/mm3, the PPSV23 can be offered; however, it may be beneficial to wait until the CD4 count increases to more than 200 cells/mm3.
-for invasive pneumococcal prophylaxis in patients with cerebrospinal fluid leak or cochlear implant:
Intramuscular dosage (PCV13 or Prevnar 13):
Children 2 to 5 years: If 3 doses of PCV13 were received previously, give one 0.5 mL dose IM at least 8 weeks after the last PCV13 dose. If less than 3 doses of PCV13 were received previously, give 2 doses at least 8 weeks apart and at least 8 weeks after the last PCV13 dose. Children who have received a dose of PPSV23 should also receive the recommended PCV13 doses. If not previously received, a dose of PPSV23 is needed at least 8 weeks after the last PCV13 dose.
Children and Adolescents 6 to 17 years who are PCV13-naive and PPSV23-naive: 0.5 mL IM as a single dose, followed at least 8 weeks later by a dose of PPSV23.
Children and Adolescents 6 to 17 years who are PCV13-naive, but received previous vaccination with PPSV23: 0.5 mL IM as a single dose at least 8 weeks after the last PPSV23 dose.
Intramuscular or Subcutaneous dosage (PPSV23 or Pneumovax 23):
Children and Adolescents 2 to 17 years who are PPSV23-naive: 0.5 mL IM or subcutaneously as a single dose at least 8 weeks after the last dose of PCV13.
-for invasive pneumococcal prophylaxis in patients with chronic liver disease or alcoholism:
Intramuscular or Subcutaneous dosage (PPSV23 or Pneumovax 23):
Children and Adolescents 6 to 17 years who are PPSV23-naive: 0.5 mL IM or subcutaneously as a single dose at least 8 weeks after the last dose of PCV13.

For otitis media prophylaxis in infants and children younger than 6 years:
Intramuscular dosage (Prevnar 13 only):
Infants 6 weeks to 6 months at first dose: 0.5 mL IM for a total of 4 doses. Give the first 3 doses at intervals of 4 to 8 weeks, ideally at 2, 4, and 6 months of age; the first dose can be given as young as 6 weeks. The fourth dose is given as a booster between 12 to 15 months of age and at least 8 weeks after the third dose.
Infants 7 to 11 months at first dose: 0.5 mL IM for 3 doses. Give the first 2 doses 4 to 8 weeks apart. The third dose should ideally be given at 12 to 15 months; it must be separated from the second dose by 2 months or more and given after the first birthday.
Children 12 to 23 months at first dose: 0.5 mL IM for 2 doses administered at least 2 months apart.
Children 24 to 71 months at first dose: 0.5 mL IM for 1 dose prior to the sixth birthday. The FDA-approved product labeling recommends a single dose for patients 15 to 71 months of age whereas the ACIP recommends a single dose for all children 14 to 59 months of age and for all children 60 to 71 months of age with underlying medical conditions.
Intramuscular dosage (PCV20 or Prevnar 20):
Infants 6 weeks to 6 months at first dose: 0.5 mL IM for a total of 4 doses. Administer at 2, 4, and 6 months of age; the first dose can be given as young as 6 weeks. The fourth dose is given as a booster between 12 and 15 months of age and at least 2 months after the third dose.
Infants 7 to 11 months at first dose: 0.5 mL IM for 3 doses. Give the first 2 doses at least 4 weeks apart. The third dose should ideally be given after the first birthday, separated from the second dose by at least 2 months.
Children 12 to 23 months at first dose: 0.5 mL IM for 2 doses, separated by at least 2 months.
Children 24 to 71 months at first dose: 0.5 mL IM as a single dose.

Maximum Dosage Limits:
-Neonates
Use not recommended.
-Infants
1 to 5 weeks: Use not recommended.
6 weeks to 11 months: 0.5 mL/dose IM for PCV13 (Prevnar 13), PCV15 (Vaxneuvance), and PCV20 (Prevnar 20); safety and efficacy have not been established for PPSV23 (Pneumovax 23).
-Children
1 year: 0.5 mL/dose IM for PCV13 (Prevnar 13), PCV15 (Vaxneuvance), and PCV20 (Prevnar 20); safety and efficacy have not been established for PPSV23 (Pneumovax 23).
2 to 12 years: 0.5 mL/dose IM for PCV13 (Prevnar 13), PCV15 (Vaxneuvance), and PCV20 (Prevnar 20); 0.5 mL/dose IM or subcutaneously for PPSV23 (Pneumovax 23).
-Adolescents
0.5 mL/dose IM for PCV13 (Prevnar 13), PCV15 (Vaxneuvance), and PCV20 (Prevnar 20); 0.5 mL/dose IM or subcutaneously for PPSV23 (Pneumovax 23).

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. However, consult current immunization schedules for recommended vaccines for use in young dialysis patients; the ACIP states that all routine vaccinations are likely effective in patients with chronic renal disease.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Pneumococcal vaccine, polyvalent confers immunity against the bacteria that cause pneumococcal disease. Levels of antibodies that correlate with disease protection have not been clearly defined.

Non-conjugate pneumococcal vaccine, polyvalent (Pneumovax 23): The high virulence of the pneumococcal organism is largely due to its polysaccharide capsule, which inhibits phagocytosis by white blood cells. Pneumococcal non-conjugated polysaccharide vaccine stimulates a T-cell independent immune response. Vaccine exposure stimulates the immune system to produce pneumococcal capsule-specific antibodies that make the organism more vulnerable to phagocytosis and other host defenses. The antibodies produced by the vaccine are predominantly IgM; the antibodies do not induce T-cell dependent responses associated with immunologic memory. After revaccination, antibody titers increase, but an anamnestic response does not occur.

Conjugated pneumococcal vaccine (Prevnar 13): The high virulence of the pneumococcal organism is largely due to its polysaccharide capsule, which inhibits phagocytosis by white blood cells. In conjugated pneumococcal vaccine, the polysaccharides of the pneumococcal serotypes are bound to a non-toxic diphtheria protein known as CRM197. By coupling the polysaccharides to this carrier protein, a T-cell dependent immune response is generated. The conjugated polysaccharide (antigen) can then be presented by major histocompatibility complex molecules, which signals the activation of T-helper cells. The T-helper cells are then able to stimulate B-cells to mature into antibody-secreting plasma or memory cells. The exposure to the vaccine produces pneumococcal capsule-specific antibodies that make the organism more vulnerable to phagocytosis and other host defenses.

Pharmacokinetics: Pneumococcal vaccine is administered intramuscularly. The PPSV23 (Pneumovax 23) formulation of the vaccine may be administered intramuscularly or subcutaneously. The distribution, metabolism, and excretion of the vaccines have not been well-defined. The immunologic response and duration of immunity conferred by pneumococcal vaccine is dependent upon the serotypes present in the vaccine and whether the polysaccharides are coupled/conjugated to various carrier proteins. In some individuals, immune response to the vaccine may not be sufficient to prevent pneumococcal infection.


-Special Populations
Pediatrics
Premature Neonates younger than 37 weeks
-PCV13 (Prevnar 13): In a study of 100 premature neonates (younger than 37 weeks gestation) who received 4 doses Prevnar 13 on a non-United States dosing schedule, serotype-specific IgG antibody responses were lower after the 3rd and 4th doses compared to responses among term infants (37 weeks gestation and older) for some serotypes. Immune responses elicited by the vaccine administered on the ACIP-recommended schedule to premature neonates are not known.
-PCV15 (Vaxneuvance): In studies of 142 premature neonates (younger than 37 weeks gestation) who received a 4-dose series, serotype-specific IgG and opsonophagocytic activity (OPA) responses at 30 days postdose 3, predose 4, and at 30 days postdose 4 were similar to those observed in term infants.

Infants and Children 2 to 15 months
-PCV13 (Prevnar 13): In the pivotal U.S. non-inferiority trial comparing Prevnar 13 to Prevnar (PCV7), non-inferiority criterion was met for 10 of 13 serotypes after the third dose; the exceptions were serotypes 6B, 9V, and 3. For serotype 6B, 87.3% (95% CI, 82.5% to 91.1%) of patients who received Prevnar 13 achieved an antibody concentration 0.35 mcg/mL or greater 1 month after the third dose compared to 92.8% (95% CI, 88.9% to 95.7%) of those who received Prevnar. For serotype 9V, 90.5% (95% CI, 86.2% to 93.8%) of patients who received Prevnar 13 met the 0.35 mcg/mL threshold compared to 98.4% (95% CI, 96% to 99.6%) of those who received Prevnar. Although the criterion for non-inferiority was not met for serotypes 6B and 9V, the clinical significance of this is unknown. Of patients who received Prevnar 13, 63.5% (95% CI, 57.1% to 69.4%) achieved an antibody concentration of 0.35 mcg/mL or greater after the third dose. Serotype 3 is not included in the original Prevnar vaccine. After the fourth dose of Prevnar 13, non-inferiority criterion was met for 12 of 13 serotypes; the exception was serotype 3. Functional antibody responses, as measured by opsonophagocytic assay (OPA), were elicited for all 13 serotypes after 3 doses of Prevnar 13, and after the fourth dose, the OPA response was quantitatively greater than the responses after the third dose for each serotype.
-PCV15 (Vaxneuvance): In clinical trials, immune responses produced by Vaxneuvance after 4 doses were non-inferior to Prevnar 13 for the 13 shared serotypes based on serotype-specific IgG geometric mean concentrations.
-PCV20 (Prevnar 20): In clinical trials, immune responses 1 month after the fourth dose of Prevnar 20 were non-inferior to Prevnar 13 for all 13 shared serotypes based on serotype-specific IgG geometric mean concentrations. For the additional 7 serotypes, non-inferiority to serotype 1 (the lowest response of the 13 shared serotypes) was demonstrated.
-PPSV23 (Pneumovax 23): The antibody response to most serotypes is poor among pediatric patients younger than 2 years of age. Children, especially those with asplenia, nephrotic syndrome, or sickle cell disease, may have a decline in antibodies to pre-vaccination concentrations within 3 to 5 years.

Other
HIV Infection
-PCV13 (Prevnar 13): In an open-label study, 3 doses of Prevnar 13 were administered 1 month apart to patients 6 years and older with HIV infection and CD4 counts 200 cells/mm3 or higher and serum HIV RNA titer less than 50,000 copies/mL, who had not been previously vaccinated with Pneumovax 23. After the first dose, anti-pneumococcal opsonophagocytic activity (OPA) geometric mean antibody titers (GMTs) for all vaccine serotypes were higher than pre-vaccination concentrations (n = 197 to 257). OPA GMTs after the first, second, and third doses were generally comparable.
-PCV15 (Vaxneuvance): In a double-blind study in patients 6 to 17 years with HIV infection and CD4 counts 200 cells/mm3 or higher and serum HIV RNA titer less than 50,000 copies/mL, patients received a single dose of Vaxneuvance (n = 203) or Prevnar 13 (n = 204), followed by administration of Pneumovax 23 two months later. Serotype-specific IgG geometric mean concentrations (GMCs) and OPA GMTs were higher after vaccination compared to pre-vaccination for all vaccine serotypes included in Vaxneuvance. Serotype-specific IgG GMCs and OPA GMTs were numerically similar for the 13 shared serotypes and higher for the 2 unique serotypes (22F and 33F) at 30 days after vaccination with Vaxneuvance or Prevnar 13 and were numerically similar for all 15 serotypes contained in Vaxneuvance at 30 days after subsequent vaccination with Pneumovax 23. The safety profile of Vaxneuvance was similar to the safety profile of Prevnar 13.

Sickle Cell Disease
-PCV13 (Prevnar 13): In an open-label study, 2 doses of Prevnar 13 were administered 6 months apart to children and adolescents (6 to 17 years of age) with sickle cell disease. All patients had been previously vaccinated with Pneumovax 23 at least 6 months prior to enrollment. After the first Prevnar 13 dose, OPA GMTs for all vaccine serotypes were higher than pre-vaccination concentrations. OPA GMTs after the first and second dose were comparable.
-PCV15 (Vaxneuvance): In a double-blind study in patients 5 to 17 years with sickle cell disease comparing a single dose of Vaxneuvance (n = 70) to Prevnar 13 (n = 34), serotype-specific IgG GMCs and OPA GMTs were higher after vaccination compared to pre-vaccination for all vaccine serotypes included in Vaxneuvance. IgG GMCs and OPA GMTs were numerically similar between the 2 vaccination groups for the 13 shared serotypes and higher in Vaxneuvance for serotypes 22F and 33F. The safety profile of Vaxneuvance was similar to the safety profile of Prevnar 13.

Hematopoietic Stem Cell Transplant (HSCT)
-PCV13 (Prevnar 13): In an open-label study, 4 doses of Prevnar 13 were administered to patients (age 2 to 71 years) who had received an allogeneic hematopoietic stem cell transplant 3 to 6 months prior to enrollment. All had a history of stable engraftment and did not have uncontrolled graft versus host disease. The first 3 doses were administered a month apart and the fourth dose was administered 6 months after the third dose. Sera were obtained approximately 1 month after each vaccination. Immune responses (IgG GMCs) were numerically higher after the first dose of Prevnar 13 compared with baseline. Similarly, IgG GMCs were numerically higher after each subsequent dose compared to the previous dose. A post hoc analysis of immune response (measured by OPA antibody assay) showed the pattern of functional antibody response to be consistent with IgG response for each serotype.