Consumer medicine information

Prevenar 20

Pneumococcal 20 valent polysaccharide conjugate vaccine

BRAND INFORMATION

Brand name

Prevenar 20

Active ingredient

Pneumococcal 20 valent polysaccharide conjugate vaccine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Prevenar 20.

SUMMARY CMI

PREVENAR 20®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

▼ This medicine is new or being used in a different way. Please report side effects. See the full CMI for further details.

1. Why am I being given PREVENAR 20?

PREVENAR 20 contains the active ingredient Pneumococcal polysaccharide conjugate vaccine (20-valent, adsorbed). PREVENAR 20 is a vaccine, which is a type of medicine. PREVENAR 20 helps to protect (immunise) from certain infectious diseases.

For more information, see Section 1. Why am I being given PREVENAR 20? in the full CMI.

2. What should I know before I am given PREVENAR 20?

Do not use if you have ever had an allergic reaction to pneumococcal or diphtheria vaccines, or any of the ingredients listed at the end of this CMI; Tell your doctor if you have a a fever or infection requiring a visit to the doctor; Tell your doctor or clinic nurse if you are having anti-cancer therapy or have an HIV infection or any other condition that affects the immune response; Tell your doctor or clinic nurse if your child being vaccinated was born prematurely. Tell your doctor if you have any other disease or medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I am given PREVENAR 20? in the full CMI.

3. What if I am taking other medicines?

Tell your doctor or nurse if you are taking any other medicines, including medicines you buy without a prescription from a pharmacy, supermarket or health food shop, or if you have recently been given any other vaccine.

For more information, see Section 3. What if I am taking other medicines? in the full CMI.

4. How is PREVENAR 20 given?

  • A doctor or a nurse will give the PREVENAR 20 injection. The dose is injected into a muscle in the upper arm or thigh. Other vaccines might be given at the same time, but not at the same injection site.
  • Adults (18 years and older) are given one single dose. Dosing in children is based on their age.

More instructions can be found in Section 4. How is PREVENAR 20 given? in the full CMI.

5. What should I know after given PREVENAR 20?

Things you should do
  • Check with your doctor before you receive any other vaccines or medicines.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how PREVENAR 20 affects you.
  • PREVENAR 20 has no or negligible effect on your ability to drive and use machine. However, other side effects may influence your ability to drive, such as fatigue or headache.
Looking after your medicine
  • It is unlikely that you will be asked to store PREVENAR 20.
  • Keep PREVENAR 20 in a refrigerator (2°C to 8°C). Do not freeze.

For more information, see Section 5. What should I know while using PREVENAR 20? in the full CMI.

6. Are there any side effects?

Like all vaccines, PREVENAR 20 may cause unwanted side effects.

Common side effects of PREVENAR 20 are local reaction around the injection site such as tenderness or pain, redness, swelling or the formation of hard lumps or scars, headache, fatigue, fever, joint or muscle pain. Serious side effects include allergic reactions.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

▼ This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. You can report side effects to your doctor, or directly at www.tga.gov.au/reporting-problems.



FULL CMI

PREVENAR 20®

Active ingredient(s): Pneumococcal polysaccharide conjugate vaccine (20-valent, adsorbed)

Consumer Medicine Information (CMI)

This leaflet provides important information about using PREVENAR 20. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All vaccinations have risks and benefits. Your doctor has weighed the risks of you or your child receiving this vaccine against the benefits they expect it will have for you.

You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using PREVENAR 20.

Read this leaflet carefully before you use PREVENAR 20 and keep. You may need to read it again.

Where to find information in this leaflet:

1. Why am I being given PREVENAR 20?
2. What should I know before I am given PREVENAR 20?
3. What if I am taking other medicines?
4. How is PREVENAR 20 given?
5. What should I know after given PREVENAR 20?
6. Are there any side effects?
7. Product details

1. Why am I being given PREVENAR 20?

PREVENAR 20 is a vaccine, which is a type of medicine that helps to protect (immunise) people from certain infectious diseases. It does this by preparing the body's defences to fight the infection, before you catch the bacteria or virus.

PREVENAR 20 is a mixture of the outer sugar coating (polysaccharide) from 20 different strains or serotypes of bacteria calledStreptococcus pneumoniae. Each serotype is joined to a non-toxic protein to make it work more effectively.

Streptococcus pneumoniae bacteria are one of the causes of:

  • meningitis (a serious brain infection that could cause death or brain damage)
  • bacteraemia (infection of the blood)
  • pneumonia (infection of the lung)
  • otitis media (an ear infection that can cause pain and temporary hearing loss and may require you or your child to have an ear operation).

PREVENAR 20 can protect against 20 of the strains of Streptococcus pneumoniae that can cause these diseases. PREVENAR 20 does not replace the need for vaccination with Haemophilus influenzae type b (Hib) or meningococcal vaccines that protect against other important causes of meningitis. You cannot catch any of the above diseases from the vaccine itself, because it is not made with live or whole bacteria. As with all vaccines, 100% protection against the above diseases cannot be guaranteed.

Ask your doctor if you have any questions about this vaccine.

2. What should I know before I am given PREVENAR 20?

Warnings

Do not use if:

  • you or your child are allergic to any of the ingredients listed at the end of this leaflet.

Check with your doctor or nurse if:

  • you or your child are sick with a high fever
  • your baby was born prematurely.

There is a higher risk of apnoea (temporarily stopping breathing) when vaccines are given to babies born prematurely.

  • you suspect or know that you or your child may be allergic to anything, including foods, any medicines or other vaccines
  • you or your child have had a reaction to an earlier dose of PREVENAR 20 vaccine or any other pneumococcal vaccine.

In rare cases, the doctor or nurse may decide that the risk of a further reaction may outweigh the benefits of immunisation.

Medical conditions and treatments

Tell your doctor or clinic nurse if the following medical conditions or treatments apply to you or your child being vaccinated. PREVENAR 20 may not be suitable for individuals with certain diseases.

  • you have any bleeding problems
  • you are having anti-cancer therapy or have an HIV infection or any other condition that affects the immune response. PREVENAR 20 may not be as effective in individuals with reduced immune responsiveness due to various causes such as these.

Tell your doctor or clinic nurse if you or your child have any other disease.

During vaccination, you or your child may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?.

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

3. What if I am taking other medicines?

Tell your doctor or nurse if you or your child are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from a pharmacy, supermarket or health food shop.

Tell your doctor or nurse if you or your child have recently been given any other vaccine.

4. How is PREVENAR 20 given?

A doctor or a nurse will give the PREVENAR 20 injection. The dose is 0.5 mL injected into a muscle in the upper arm or thigh muscle. Other vaccines (including other routine adult and childhood vaccines) might be given at the same time, but not at the same injection site.

How many injections will be given

  • Babies and young children up to 5 years: The total number of injections required depends on how old your child is when they receive the first dose of PREVENAR 20. Normally, your child will receive either three or four doses of the vaccine, at least 4 weeks apart, starting at 6 weeks to 2 months of age. Four is the maximum number of doses required. Each dose will be given on a separate occasion. Your doctor or clinic nurse will tell you the correct vaccination schedule for your child. It is important to follow the instructions from the doctor or clinic nurse so that your child completes the course of injections.
  • Premature infants: Your child will receive an initial course of three injections. The first injection may be given as early as six weeks of age with at least one month between doses. A fourth (booster) injection is recommended at approximately 12 months of age.
  • Children 6 - 17 years and adults: One single dose.
  • Special populations: Individuals considered to be at a higher risk of pneumococcal infection may receive at least one dose of Prevenar 20. Your doctor will advise the appropriate vaccination schedule.
  • Adults (18 years and older): One single dose

If you use too much PREVENAR 20

A trained doctor or nurse gives this vaccination, so an overdose is unlikely to occur.

5. What should I know after given PREVENAR 20?

Things you should do

Check with your doctor before you or your child receive any other vaccines or medicines.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how PREVENAR 20 affects you.

PREVENAR 20 has no or negligible effect on your ability to drive and use machine. However, other side effects may influence your ability to drive, such as muscle pain, fatigue or headache.

Looking after your medicine

It is unlikely that you will be asked to store PREVENAR 20. If you are:

Keep this vaccine in the refrigerator at a temperature between 2°C and 8°C where young children cannot reach it. Do not freeze it. If the vaccine has been frozen it should not be used.

Keep PREVENAR 20 in the original pack until it is time to be given.

6. Are there any side effects?

All medicines can have side effects. If you or your child do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Side effects

Side effectWhat to do
General effects:
  • fatigue
  • fever or chills
  • irritability
  • crying
Nervous System reactions:
  • restless sleep or decreased sleep
  • drowsiness or increased sleep
  • headache
Nutritional effects:
  • decreased appetite
Gastrointestinal effects:
  • nausea
  • vomiting
  • diarrhoea
Skin reactions:
  • rash
Joints and muscle:
  • joint or muscle pain
Injection site effects:
  • local reaction around the injection site such as tenderness or pain, redness, rash, itchiness or swelling or formation of hard lumps or scars
Glandular effects:
  • swelling of the glands in the neck, armpit or groin
Speak to your doctor if you have any of these side effects and they worry you.
They are usually mild and short-lived.
Immune reactions:
  • allergic reaction such as rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath or trouble breathing
  • rapid, shallow breathing, cold, clammy skin, a rapid, weak pulse, dizziness, weakness and fainting
Other reactions:
  • temperature higher than 39°C in babies or young children
  • a seizure or convulsion, which may be accompanied by a very high temperature. Symptoms may include rapid uncontrollable shaking of the body, loss of muscle control, drooling, sudden changes in mood or behaviour.
  • your child is pale, limp and does not respond to you.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these side effects.
You may need urgent medical attention or hospitalisation.

Tell your doctor or pharmacist if you notice anything else that may be making you or your child feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you or your child experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

7. Product details

This medicine is only available with a doctor's prescription.

What PREVENAR 20 contains

Active ingredient
(main ingredient)		Pneumococcal purified capsular polysaccharides
diptheria CRM197 protein
Other ingredients
(inactive ingredients)		Aluminium phosphate
Sodium chloride
Succinic acid
Polysorbate 80
Water for injections

You should not be given this vaccine if you are allergic to any of these ingredients.

What PREVENAR 20 looks like

PREVENAR 20 Pre-filled Syringe (Solution for injection)

PREVENAR 20 is a clear liquid with sediment which, after shaking, will look like a white coloured liquid (called a suspension). PREVENAR 20 is supplied as a suspension in 0.5 mL pre-filled syringes in packs of 1 and 10.

(AUST R 376353)

Who distributes PREVENAR 20

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizer.com.au

This leaflet was prepared in January 2024.

®= Registered Trademark

Published by MIMS February 2024

BRAND INFORMATION

Brand name

Prevenar 20

Active ingredient

Pneumococcal 20 valent polysaccharide conjugate vaccine

Schedule

S4

 

1 Name of Medicine

Pneumococcal polysaccharide conjugate vaccine (20-valent, adsorbed).

2 Qualitative and Quantitative Composition

One dose (0.5 mL) contains:
Pneumococcal polysaccharide serotype 11,2 2.2 microgram;
Pneumococcal polysaccharide serotype 31,2 2.2 microgram;
Pneumococcal polysaccharide serotype 41,2 2.2 microgram;
Pneumococcal polysaccharide serotype 51,2 2.2 microgram;
Pneumococcal polysaccharide serotype 6A1,2 2.2 microgram;
Pneumococcal polysaccharide serotype 6B1,2 4.4 microgram;
Pneumococcal polysaccharide serotype 7F1,2 2.2 microgram;
Pneumococcal polysaccharide serotype 81,2 2.2 microgram;
Pneumococcal polysaccharide serotype 9V1,2 2.2 microgram;
Pneumococcal polysaccharide serotype 10A1,2 2.2 microgram;
Pneumococcal polysaccharide serotype 11A1,2 2.2 microgram;
Pneumococcal polysaccharide serotype 12F1,2 2.2 microgram;
Pneumococcal polysaccharide serotype 141,2 2.2 microgram;
Pneumococcal polysaccharide serotype 15B1,2 2.2 microgram;
Pneumococcal polysaccharide serotype 18C1,2 2.2 microgram;
Pneumococcal polysaccharide serotype 19A1,2 2.2 microgram;
Pneumococcal polysaccharide serotype 19F1,2 2.2 microgram;
Pneumococcal polysaccharide serotype 22F1,2 2.2 microgram;
Pneumococcal polysaccharide serotype 23F1,2 2.2 microgram;
Pneumococcal polysaccharide serotype 33F1,2 2.2 microgram.
1Conjugated to diptheria CRM197 protein (approximately 51 microgram per dose).
2Adsorbed on aluminium phosphate (0.125 mg aluminium per dose).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Suspension for injection.
The vaccine is a homogeneous white suspension.

4 Clinical Particulars

4.1 Therapeutic Indications

Active immunisation for the prevention of pneumococcal disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F in individuals from 6 weeks of age and older.
Prevenar 20 may not prevent disease caused by S. pneumoniae serotypes that are not contained in the vaccine.
Prevenar 20 should be used in accordance with official recommendations.

4.2 Dose and Method of Administration

The safety and efficacy of Prevenar 20 in infants below 6 weeks of age have not been established. No data are available.

Infants and children 6 weeks to less than 5 years of age.

It is recommended that infants who receive a first dose of Prevenar 20 complete the vaccination course with Prevenar 20. See Table 1.

Special populations.

There are no data with Prevenar 20 in special populations.
However, safety and immunogenicity studies of Prevenar 13 have been conducted in adults and children at higher risk of pneumococcal infection including immunocompromised adults and children with human immunodeficiency virus (HIV) infection or haematopoietic stem cell transplant (HSCT), and children with sickle cell disease (SCD); these are relevant to Prevenar 20, since the vaccines are manufactured and formulated similarly and contain 13 of the same polysaccharide conjugates.
Individuals at higher risk of pneumococcal infection, including those previously vaccinated with 1 or more doses of 23vPPV, were recommended to receive at least 1 dose of Prevenar 13.
In individuals with a HSCT, the recommended immunisation series with Prevenar 13 consisted of 4 doses of Prevenar 13, each of 0.5 mL. The primary series consisted of 3 doses, with the first dose given 3 to 6 months after HSCT and with an interval of at least 4 weeks between doses. A booster dose was recommended 6 months after the third dose (see Section 5.1 Pharmacodynamic Properties).
The recommended dosing of Prevenar 13 may be considered in guiding vaccination with Prevenar 20 in higher risk populations. For immune responses to pneumococcal vaccines in immunocompromised individuals, see Section 4.4 Special Warnings and Precautions for Use. The use of Prevenar 20 in special populations should be guided by official recommendations.

Method of administration.

Prevenar 20 should be administered as soon as possible after being removed from refrigeration.
For intramuscular use only. Product is for single use in one patient only. Discard any residue.
The dose (0.5 mL) of Prevenar 20 should be administered intramuscularly, preferably in the anterolateral aspect of the thigh (vastus lateralis muscle) in infants or the deltoid muscle of the upper arm in children and adults, with care to avoid injection into or near nerves and blood vessels. The vaccine should not be injected in the gluteal area. Do not inject Prevenar 20 intravascularly.
Preparation for administration.

Step 1. Vaccine resuspension.

Hold the pre-filled syringe horizontally between the thumb and the forefinger and shake vigorously until the contents of the syringe are a homogeneous white suspension. Do not use the vaccine if it cannot be re-suspended.

Step 2. Visual inspection.

Visually inspect the vaccine for large particulate matter and discoloration prior to administration. Do not use if large particulate matter or discolouration is found. If the vaccine is not a homogenous white suspension, repeat Steps 1 and 2.

Step 3. Remove syringe cap.

Remove the syringe cap from the Luer lock adapter by slowly turning the cap counterclockwise while holding the Luer lock adapter.

Note.

Care should be taken to ensure that the extended plunger rod is not depressed while removing the syringe cap.

Step 4. Attach a sterile needle.

Attach a needle appropriate for intramuscular administration to the pre-filled syringe by holding the Luer lock adapter and turning the needle clockwise.

4.3 Contraindications

Hypersensitivity to the active substance, diphtheria toxoid, or to any of the excipients listed in Section 6.1 List of Excipients.

4.4 Special Warnings and Precautions for Use

Traceability.

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be recorded in the Australian Immunisation Register.

Hypersensitivity.

As with all injectable vaccines, appropriate medical treatment and supervision must always be readily available in case of a rare anaphylactic event following the administration of the vaccine (see Section 4.8 Adverse Effects (Undesirable Effects)).

Concurrent illness.

Vaccination should be postponed in individuals suffering from acute severe febrile illness. However, the presence of a minor infection, such as a cold, should not result in the deferral of vaccination.

Thrombocytopenia and coagulation disorders.

The vaccine must be administered with caution to individuals with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration.
The risk of bleeding in patients with coagulation disorders needs to be carefully evaluated before intramuscular administration of any vaccine, and subcutaneous administration should be considered if the potential benefit clearly outweighs the risks.

Protection against pneumococcal disease.

Prevenar 20 will only protect against Streptococcus pneumoniae serotypes included in the vaccine and will not protect against other microorganisms that cause invasive disease, pneumonia or otitis media (OM). As with any vaccine, Prevenar 20 may not protect all individuals receiving the vaccine from pneumococcal disease, OM or pneumonia.

Immunocompromised individuals.

Safety and immunogenicity data on Prevenar 20 are not available for individuals in immunocompromised groups and vaccination should be considered on an individual basis.
Based on experience with pneumococcal vaccines, some individuals with altered immunocompetence may have reduced immune responses to Prevenar 20.
Individuals with impaired immune responsiveness, whether due to the use of immunosuppressive therapy, a genetic defect, HIV infection, or other causes, may have reduced antibody response to active immunisation. The clinical relevance of this is unknown.
Safety and immunogenicity data with Prevenar 13 are available for a limited number of individuals with HIV infection, SCD or with a HSCT (see Section 4.8 Adverse Effects (Undesirable Effects); Section 5.1 Pharmacodynamic Properties).
In adults across all studied age groups, formal non-inferiority criteria were met although numerically lower geometric mean titres were observed with Prevenar 20 for most of the serotypes compared to Prevenar 13 (see Section 5.1), however the clinical relevance of this observation for immunocompromised individuals is unknown.

Paediatric use.

The potential risk of apnoea and the need for respiratory monitoring for 48 to 72 h should be considered when administering the primary immunisation series to very premature infants (born less than or equal to 28 weeks of gestation), and particularly for those with a previous history of respiratory immaturity. As the benefit of vaccination is high in this group of infants, vaccination should not be withheld or delayed.

Use in the elderly.

No dose adjustment or special precautions are applicable to use in the elderly.
Of the 4263 adults in the 3 studies (B7471006, B7471007, B7471008) of the clinical development program who received Prevenar 20, 668 (15.7%) were 65 through 69 years of age, 398 (9.3%) were 70 through 79 years of age, and 72 (1.7%) were 80 years of age and older. Prevenar 20 has been shown to be safe and immunogenic in the geriatric population regardless of prior pneumococcal vaccination (see Section 5.1 Pharmacodynamic Properties).

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Different injectable vaccines should always be given at different vaccination sites.
Do not mix Prevenar 20 with other vaccines/medicinal products in the same syringe.

Paediatric population.

In infants and children 6 weeks to less than 5 years of age, Prevenar 20 can be administered concomitantly with any of the following vaccine antigens, either as monovalent or combination vaccines: diphtheria, tetanus, acellular pertussis, hepatitis B, Haemophilus influenzae type b, inactivated poliomyelitis, measles, mumps, rubella, and varicella vaccines. The vaccine has been safely administered with influenza and rotavirus vaccines.

Individuals 18 years of age and older.

Prevenar 20 can be administered concomitantly with influenza vaccine, adjuvanted (Fluad Quadrivalent [QIV]) and COVID-19 mRNA vaccine (Comirnaty [tozinameran]) (see Section 5.1).
It has been demonstrated in adults 50 years of age and older that Prevenar 13 may be administered concomitantly with the seasonal trivalent or quadrivalent inactivated influenza vaccine (TIV or QIV) with no interference with the immune responses to TIV or QIV. Safety and immunogenicity of Prevenar 13 are relevant to Prevenar 20, since the vaccines are manufactured similarly and contain 13 of the same polysaccharide conjugates.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No human data on the effect of Prevenar 20 on fertility are available. Prevenar 20 showed no adverse effects on mating or fertility in a combined fertility, embryofetal development and pre/postnatal study in which female rabbits were administered the human dose (0.5 mL) of the vaccine intramuscularly 17 and 3 days prior to mating, and on gestation days 10 and 24.
(Category B1)
There are no data from the use of Prevenar 20 in pregnant women.
In an animal study where female rabbits were administered the human dose (0.5 mL) of the vaccine intramuscularly 17 and 3 days prior to mating, and on gestation days 10 and 24, there were no effects on pregnancy, parturition, fetal abnormalities, or pup survival and growth. Serotype-specific antibodies against each of the 20 vaccine serotypes were detected in does, fetuses and pups.
Administration of Prevenar 20 in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus.
 It is unknown whether Prevenar 20 is excreted in human milk.

4.7 Effects on Ability to Drive and Use Machines

Prevenar 20 has no, or negligible, influence on the ability to drive and use machines. However, some of the effects mentioned under Section 4.8 Adverse Effects (Undesirable Effects) may temporarily affect the ability to drive or use machines.

4.8 Adverse Effects (Undesirable Effects)

Summary of the safety profile.

Paediatric population. The safety of Prevenar 20 was evaluated in 5,987 participants 6 weeks of age to less than 18 years of age in four randomised double-blind, active-controlled, clinical trials and one single-arm clinical trial (one Phase 2 and four Phase 3); 3664 participants received at least 1 dose of Prevenar 20 and 2323 participants received Prevenar 13 (control vaccine).

Participants 6 weeks to less than 15 months of age.

Clinical trials were conducted in healthy infants 6 weeks to less than 15 months of age using a 3 dose schedule (Phase 3 trial B7471012 [study 1012]) or a 4-dose schedule (Phase 3 trials B7471011 and B7471013 [study 1011 and 1013,] and the Phase 2 trial B7471003 [study 1003]). In these four infant trials, 5,156 participants received at least 1 dose of vaccine: 2,833 received Prevenar 20 and 2,323 received Prevenar 13. Overall, approximately 90% of participants in each group received all doses through the study-specified toddler dose. In all studies, local reactions and systemic events were collected after each dose and adverse events (AEs) were collected from the first dose through 1 month after the last infant vaccination and from the toddler dose through 1 month after the toddler dose in all studies. Serious adverse events were evaluated through 1 month after the last dose in Study 1012 and 6 months after the last dose in studies 1011, 1013 and 1003.
Prevenar 20 was well tolerated when administered in a 3-dose and a 4-dose series, in the infant study populations with low rates of severe local reactions and systemic events, and most reactions resolving within 1 to 3 days. The percentages of participants with local reactions and systemic events after Prevenar 20 were generally similar to those after Prevenar 13. Based on the infant data, the most frequently reported local reactions and systemic events after any dose of Prevener 20 were irritability, drowsiness, and pain at injection site. In these studies, Prevenar 20 was co-administered or permitted to be administered with certain routine paediatric vaccines (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Study 1012 was a pivotal, double-blind, randomised, active-controlled Phase 3 trial, in which 601 healthy infants, 2 months (≥ 42 to ≤ 112 days) of age and born at > 36 weeks of gestation received Prevenar 20 in a 3 dose series. The most frequently reported adverse reactions (> 10%) after any dose of Prevenar 20 were irritability (71.0% to 71.9%), drowsiness/increased sleep (50.9% to 61.2%), pain at injection site (22.8% to 42.4%), decreased appetite (24.7% to 39.3%), redness at the injection site (25.3% to 36.9%), swelling at the injection site (21.4% to 29.8%), and fever ≥ 38.0℃ (8.9% to 24.3%). Most adverse reactions occurred within 1 to 2 days following vaccination and were mild or moderate in severity and of short duration (1 to 2 days).
Studies 1011, 1013 and 1003, were double-blind, randomised, active controlled trials that included 2,232 healthy infants, vaccinated with Prevenar 20 in a 4-dose series. The most frequently reported adverse reactions (> 10%) observed after any dose of Prevenar 20 in infants were irritability (58.5% to 70.6%), drowsiness/increased sleep (37.7% to 66.2%), pain at injection site (32.8% to 45.5%), decreased appetite (23.0% to 26.4%), redness at the injection site (22.6% to 24.5%) and swelling at the injection site (15.1% to 17.6%). Most adverse reactions were mild or moderate following vaccination and severe reactions were reported infrequently. In study 1013, the local reactions and systemic events in the preterm subgroup (111 infants born at 34 to less than 37 weeks of gestation) were similar to or lower than the term infants in the study. In the preterm subgroup the frequency of any reported local reaction (31.7% to 55.3% in the Prevenar 20 group and 37.9% to 47.1% in the Prevenar 13 group) and systemic event (65.0% to 85.5% in the Prevenar 20 group and 59.4% to 77.4% in the Prevenar 13 group).
The frequency and severity of the adverse reactions in all infant clinical trials were generally similar in the Prevenar 20 and Prevenar 13 groups.

Participants aged 15 months to less than 18 years of age.

In the Phase 3 trial B7471014 (study 1014), 831 participants 15 months to less than 18 years of age received a single dose of Prevenar 20 in four age groups (209 participants 15 to less than 24 months of age; 216 participants 2 years to less than 5 years of age; 201 participants 5 years to less than 10 years age; and 205 participants 10 years to less than 18 years of age). The participants less than 5 years of age had received at least 3 prior doses of Prevenar 13.
The most frequently reported adverse reactions (> 10%) observed after any dose of Prevenar 20 in participants less than 2 years of age were irritability (61.8%), pain at the injection site (52.5%), drowsiness/increased sleep (41.7%), redness at the injection site (37.7%), decreased appetite (25.0%), swelling at the injection site (22.1%) and fever ≥ 38.0 C (11.8%). In participants aged 2 years and older, the most frequently reported adverse reactions were pain at the injection site (66.0% to 82.9%), muscle pain (26.5% to 48.3%), redness at the injection site (15.1% to 39.1%), fatigue (27.8% to 37.2%), headache (5.6% to 29.3%), and swelling at the injection site (15.6% to 27.1%).
Adults 18 years of age and older. The safety of Prevenar 20 was evaluated in 4,552 participants 18 years of age and older in six clinical trials (two Phase 1, one Phase 2, and three Phase 3), and 2,496 participants in the control groups.
In the Phase 3 trials, 4,263 participants received Prevenar 20, which included 1,798 adults 18 through 49 years of age, 334 adults 50 through 59 years of age, and 2,131 adults 60 years of age and older (1,138 were 65 years of age and older). Of the Phase 3 Prevenar 20 recipients, 3,639 adults were naïve to pneumococcal vaccines, 253 had received Pneumovax 23 (pneumococcal polysaccharide vaccine [23 valent]; 23vPPV) (≥ 1 to ≤ 5 years prior to enrolment), 246 had received Prevenar 13 only (≥ 6 months prior to enrolment), and 125 had received both Prevenar 13 followed by 23vPPV (the dose of 23vPPV ≥ 1 year prior to enrolment).
Participants in the Phase 3 trial B7471007 (Pivotal Study 1007), were evaluated for adverse events for 1 month after vaccination, and serious adverse events through 6 months after vaccination. This study included 447 participants 18 to 49 years of age, 445 participants 50 to 59 years of age, 1,985 participants 60 to 64 years of age, 624 participants 65 to 69 years of age, 319 participants 70 to 79 years of age, and 69 participants ≥ 80 years of age.
The most frequent adverse reactions (> 10%) after vaccination with Prevenar 20 in Phase 3 trials in adults ≥ 18 years of age were pain at the injection site (> 40%), muscle pain (> 30%), fatigue (> 20%) and headache (> 10%). A slightly lower frequency of reactogenicity events was associated with greater age.
In Study 1007 participants 18 to 59 years of age, the most commonly reported adverse reactions were pain at the injection site (> 70%), muscle pain (> 50%), fatigue (> 40%), headache (> 30%), and joint pain and injection site swelling (> 10%), while the most frequent in participants older than 60 years of age were pain at the injection site (> 50%), muscle pain and fatigue (> 30%), headache (> 20%), and joint pain (> 10%). These were usually mild or moderate in intensity and resolved within a few days after vaccination.

Tabulated list of adverse reactions.

Tabulated lists of adverse reactions from the infant Phase 2, Phase 3 clinical trials in paediatric and adult populations, and postmarketing experience are presented below.

Adverse reactions from clinical trials.

As Prevenar 20 contains the same 13 serotype-specific capsular polysaccharide conjugates and the same vaccine excipients as Prevenar 13, the adverse reactions already identified for Prevenar 13 have been adopted for Prevenar 20.
Table 2 presents adverse reactions reported in the Phase 2 infant trial, and Phase 3 trials in paediatric and adult populations, based on the highest frequency among adverse events, local reactions, or systemic events, after vaccination in a Prevenar 20 group or integrated dataset. The data from clinical trials in infants reflect Prevenar 20 administered simultaneously with other routine childhood vaccines. In the case of adverse reactions reported in clinical trials of Prevenar 13, but not reported in Prevenar 20 trials, the frequency is not known.
In clinical trials, the safety profile of Prevenar 20 was similar to that of Prevenar 13. No new adverse reactions were identified as compared to Prevenar 13, and none of the reported serious adverse events were considered related to Prevenar 20.
Adverse reactions are listed by system organ class, in decreasing order of frequency and seriousness. The frequency is defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from available data).

Safety with concomitant vaccine administration in adults.

When Prevenar 20 was administered to adults aged ≥ 65 years together with the third (booster) dose of a COVID-19 mRNA vaccine (nucleoside modified), the tolerability profile generally resembled that of the COVID-19 mRNA vaccine (nucleoside modified) administered alone. There were a few differences in the safety profile when compared to administration of Prevenar 20 alone. In the phase 3 trial B7471026 (Study 1026), pyrexia (13.0%) and chills (26.5%) were reported as ''very common'' with co-administration. There was also one report of dizziness (0.5%) in the co-administration group.

Adverse reactions from post-marketing experience.

Table 3 includes adverse experiences that have been spontaneously reported during Prevenar 13 postmarketing use in paediatric and adult populations, and may also be seen with Prevenar 20. The postmarketing safety experience with Prevenar 13 is relevant to Prevenar 20, as Prevenar 20 contains all components (polysaccharide conjugates and excipients) of Prevenar 13. Because these events were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or to establish, for all events, a causal relationship to vaccine exposure.

Additional information in special populations in studies with Prevenar 13.

Participants 6 to < 18 years of age with HIV infection have similar frequencies of adverse reactions in Table 2, except fever (11% to 19%), joint pain (24% to 42%), vomiting (8% to 18%) which were very common. Adults (≥ 18 years of age) with HIV infection have similar frequencies of adverse reactions in Table 2, except that fever (5% to 18%) and vomiting (8% to 12%) were very common and nausea (< 1% to 3%) common.
Participants 2 to < 18 years of age with HSCT have similar frequencies of adverse reactions in Table 2, except vaccination-site pain causing limitation of limb movement (5% to 15%), vomiting (6% to 21%), diarrhoea (15% to 32%), and joint pain (25% to 32%) which were very common. Adults (≥ 18 years of age) with an HSCT have similar frequencies of adverse reactions in Table 2, except that fever (4% to 15%), vomiting (6% to 21%), and diarrhoea (25% to 36%) were very common.
Participants 6 to < 18 years of age with SCD have similar frequencies of adverse reactions in Table 2, except vaccination-site pain causing limitation of limb movement (11% to 16%), fever (21% to 22%), vomiting (13% to 15%), diarrhoea (13% to 25%), and joint pain (40% to 45%) which were very common.

Safety with concomitant vaccine administration in adults.

The safety profile was similar when Prevenar 20 was administered with or without influenza vaccine, adjuvanted (Fluad Quadrivalent [QIV]).
Prevenar 20 administered together with COVID-19 mRNA vaccine (Comirnaty [tozinameran]) was observed to have a tolerability profile similar to COVID-19 mRNA vaccine (Comirnaty [tozinameran]) administered alone, and an overall safety profile consistent with Prevenar 20 or COVID-19 mRNA vaccine (Comirnaty [tozinameran]) given alone.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdose with Prevenar 20 is unlikely due to its presentation as a single dose pre-filled syringe. In the event of overdose, monitoring of vital functions and possible symptomatic treatment is recommended.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: vaccines, pneumococcal vaccines; ATC code: J07AL02.

Mechanism of action.

Prevenar 20 contains 20 pneumococcal capsular polysaccharides all conjugated to a CRM197 carrier protein, which modifies the immune response to the polysaccharide from a T-cell independent response to a T-cell dependent response. The T-cell dependent response leads to both an enhanced antibody response and generation of memory B-cells, allowing for an anamnestic (booster) response on re-exposure to the bacteria.
Vaccination with Prevenar 20 induces serum antibody production and immunologic memory against the serotypes contained within the vaccine. In adults, the levels of circulating antibodies, and in paediatric populations the serotype-specific levels, that correlate with protection against pneumococcal disease have not been clearly defined.
Protection against pneumococcal disease is conferred mainly by opsonophagocytic killing of S. pneumoniae. Prevenar 20 generates functional antibodies as measured by opsonophagocytic activity (OPA). An opsonic antibody titre that is predictive of protection against invasive pneumococcal disease or pneumococcal pneumonia has not been established.

Disease burden for adults.

S. pneumoniae (pneumococcus) is the most frequent bacterial cause of community-acquired pneumonia (CAP) and has been estimated to be responsible for approximately 30% of all CAP cases requiring hospitalisation in adults in developed countries, with the majority of cases considered nonbacteraemic. In addition, bacteraemic pneumonia is the most common manifestation of invasive pneumococcal disease (IPD) (approximately 80% of cases) in adults. Based on surveillance data, the pneumococcal serotypes in Prevenar 20 may be responsible for at least 63% to 76% (depending on country) of IPD in older adults in Europe.

Prevenar 20 effectiveness.

No efficacy studies have been performed for Prevenar 20, however the efficacy and effectiveness of Prevenar 13 are relevant to Prevenar 20, since the vaccines are manufactured similarly and contain 13 of the same polysaccharide conjugates.
Approval of Prevenar 20 for the paediatric population is based on comparing the totality of the immune responses in infants after receiving Prevenar 20 to the immune responses after receiving Prevenar 13. The comparison, following the World Health Organization (WHO) guideline, included the percentage of participants with predefined IgG (immunoglobulin G) concentrations and IgG geometric mean concentrations (GMCs). This approach is largely based upon the observed relationship between immunogenicity and invasive pneumococcal disease (IPD) efficacy from 3 placebo controlled trials with either Prevenar (7-valent pneumococcal conjugate vaccine) or the investigational 9-valent CRM197 conjugate polysaccharide vaccine conducted in Navajo and White Mountain Apache Indian infants (cluster randomised trial), infants in Soweto, South Africa, and infants in the Northern California Kaiser Permanente (NCKP) health organization in the United States (see Prevenar efficacy and Prevenar 13 effectiveness in children below). The predefined IgG concentration corresponding to 0.35 microgram/mL in the WHO enzyme-linked immunosorbent assay (ELISA) is only applicable at the population level and cannot be used to predict individual or serotype-specific protection against IPD.

Immunogenicity data.

Prevenar 20 clinical trials in infants, children and adolescents.

Two Phase 3 clinical trials (study 1012, study 1011) and one Phase 2 clinical trial (study 1003) evaluated the immunogenicity of Prevenar 20 in a 3 dose and 4 dose series in infants. One Phase 3 trial (study 1014) of children 15 months to less than 18 years of age evaluated a single dose of Prevenar 20.

Pneumococcal IgG immune responses following 3 doses of 3-dose vaccination series.

In study 1012, the immunogenicity of Prevenar 20 was evaluated in infants when administered in a series of 2 infant doses and 1 toddler dose in infants enrolled from Europe and Australia. The study enrolled infants 2 months (≥ 42 to ≤ 112 days) of age and born at > 36 weeks of gestation. Participants were randomised (1:1) to receive either Prevenar 20 or Prevenar 13 with the first dose given at 42 to 112 days of age, a second dose given approximately 2 months later, and the third dose given at approximately 11 to 12 months of age. Participants received concomitant vaccines at these visits.
Prevenar 20 elicited immune responses, as assessed by the percentage of participants with predefined IgG concentrations, IgG GMCs and OPA GMTs for all 20 serotypes contained in the vaccine. The observed IgG GMCs and percentage of participants with predefined IgG concentrations 1 month after the third (last) dose of Prevenar 20 were generally comparable to the Prevenar 13 group for the 13 matched serotypes and higher for the 7 additional serotypes (see Table 4).
One month after the 2 infant doses the observed IgG GMCs were generally comparable for most serotypes to the Prevenar 13 group and the percentages of participants with predefined IgG concentrations for the 13 matched serotypes were generally lower in the Prevenar 20 group than the Prevenar 13 group (see Table 5). The immune responses to the additional 7 serotypes were higher in the Prevenar 20 group than the Prevenar 13 group after the second dose.

OPA responses after 2 and 3 doses in a 3-dose vaccination series of Prevenar 20.

The OPA geometric mean titres (GMTs) for the 13 matched serotypes at 1 month after Dose 2 and 1 month after Dose 3 in the Prevenar 20 group were generally similar to the observed OPA GMTs in the Prevenar 13 group for most serotypes. The observed OPA GMTs were lower for serotype 6B after Dose 2 and serotype 1 after Dose 3 in the Prevenar 20 group. OPA GMTs were higher after Dose 3 than after Dose 2 for all serotypes. The observed OPA GMTs for the 7 additional serotypes, including serotypes 10A and 12F, both 1 month after the second dose and 1 month after the third dose were substantially higher in the Prevenar 20 group than those in the Prevenar 13 group (Table 6).

Booster responses after the last dose in a 3-dose infant vaccination series.

Prevenar 20 immune responses show boosting in IgG GMCs and percentage of participants with a predefined IgG concentrations after Dose 3, that are higher than concentrations before Dose 3, and also increased relative to the levels after Dose 2, indicating that a memory response was elicited by the 2 infant doses. (see Table 4 and Table 5). For all serotypes, the OPA responses also show a generally similar pattern of boosting as observed with the IgG responses, with priming evidenced by the robust OPA responses (geometric mean fold rise (GMFRs) and the percentages of participants with a ≥ 4-fold rise in OPA titres) from before to one month after Dose 3. In summary, Prevenar 20 elicits immune responses that are comparable to Prevenar 13 for the 13 matched serotypes and the 7 additional serotypes after the third (toddler) dose.
The totality of data show that a 3-dose series of Prevenar 20 elicited immune responses expected to provide children protection against pneumococcal disease similar to that of Prevenar 13 for all 20 vaccine serotypes.

Immune responses following 3 and 4 doses in a 4-dose infant vaccination series.

Clinical studies evaluating the immunogenicity of Prevenar 20 in infants with a 4-dose series (3 infant doses and a toddler dose) at 2, 4, 6, and 12 to 15 months of age have been conducted in 2 randomised Phase 2 (study 1003) and Phase 3 studies (study 1011) in United States/Puerto Rico.
In Study 1011, healthy infants 2 months (≥ 42 to ≤ 98 days) of age at the time of consent and born at > 36 weeks of gestation, were enrolled. Participants were randomised (1:1) to receive either Prevenar 20 or Prevenar 13 at approximately 2, 4, 6, and 12 to 15 months of age. At one month after the fourth dose, the IgG GMCs for Prevenar 20 were noninferior to Prevenar 13 for all 13 matched serotypes, and 7 additional serotypes to the lowest IgG GMC among the vaccine serotypes (excluding serotype 3) in the Prevenar 13 group based on a 2-fold noninferiority criterion. This was also the case for the IgG GMCs for Prevenar 13, 1 month after the third dose. The percentages of participants with predefined serotype-specific IgG concentrations one month after the third dose was met for 8 of the 13 serotypes and missed by small margins for 4 serotypes (serotypes 1, 4, 9V, and 23F) with a 10% noninferiority criterion. Six of the 7 additional serotypes met the noninferiority criterion; serotype 12F missed the statistical noninferiority criterion. The IgG GMCs at both time points and percentages of participants with predefined IgG concentrations for all 7 additional serotypes, including serotype 12F, were much higher than the corresponding serotype responses in the Prevenar 13 group, consistent with statistically greater antibody levels based on the lower bounds of the nominal 2-sided 95% confidence limits (not adjusted for multiplicity).
OPA GMTs for the 13 matched serotypes 1 month after Dose 3 and Dose 4 in the Prevenar 20 group were generally numerically similar to the OPA GMTs in the Prevenar 13 group, and have similar distributions. The observed OPA GMTs were substantially higher for the 7 additional serotypes in the Prevenar 20 group than the Prevenar 13 group.
Prevenar 20 elicits IgG immune responses that are comparable to Prevenar 13 for the 13 matched serotypes and the 7 additional serotypes after 3 doses in infants and a fourth dose in toddlers. Prevenar 20 also elicits functional antibody to all 20 serotypes that was observed 1 month after Dose 3 and 1 month after Dose 4. Prevenar 20 immune responses also show boosting after Dose 4, indicating that a memory response was elicited by the 3 infant doses.

Children 15 months to less than 18 years of age (study 1014).

In a multicenter, single-arm trial (study 1014), participants were enrolled into the study by age group (approximately 200 participants per group) to receive a single dose Prevenar 20 as described below.

Children 15 months to less than 5 years of age previously vaccinated with Prevenar 13.

In 15 to less than 24 months and 2 years to less than 5 years age groups, participants had been previously vaccinated with 3 or 4 doses of Prevenar 13. Increases in IgG concentrations from before to 1 month after Prevenar 20 were observed for all 20 vaccine serotypes in participants 15 months to less than 5 years of age with prior vaccination with Prevenar 13. The observed IgG GMFRs to the 7 additional serotypes ranged from 27.9 to 1847.7 and increases in IgG GMCs were observed in all 20 vaccine serotypes from before to 1 month after Prevenar 20 (see Table 7). In children 15 months to less than 24 months of age 83.2% - 100.0% had predefined IgG concentrations to 6 of the 7 additional serotypes, serotype 12F was 40.0%.

Children and adolescents 5 years to less than 18 years of age previously unvaccinated or vaccinated with Prevenar 13 or Prevenar.

In the study, age groups 5 to less than 10 years and 10 to less than 18 years, participants could be unvaccinated or previously vaccinated with Prevenar 13 or Prevenar. Prevenar 20 elicited robust IgG and OPA immune responses to the 20 vaccine serotypes after a single dose in participants 5 to less than 18 years of age. OPA GMFRs ranged from 11.5 to 499.0 to the 7 additional serotypes and increases in OPA GMTs were observed for all 20 vaccine serotypes (see Table 8).
In summary, a single dose of Prevenar 20 administered to children and adolescents 15 months to less than 18 years of age is expected to generate protective responses against pneumococcal disease due to the 7 additional serotypes, and to the 13 matched serotypes.

Preterm infants.

The safety and tolerability of Prevenar 20 were evaluated in study 1013, which included 111 late preterm infants (born at 34 to less than 37 weeks of gestational age) among the total study population. Participants were randomised to receive a 4-dose series of either Prevenar 20 (N=77) or Prevenar 13 (N=34). Studies have not been specifically conducted to describe the immunogenicity of Prevenar 20 in preterm infants. Based on experience with Prevenar and Prevenar 13, immune responses are elicited in preterm infants, although they may be lower than in term infants.

Prevenar 13 efficacy study in adults 65 years of age and older.

The efficacy of Prevenar 13 against vaccine-type (VT) pneumococcal community-acquired pneumonia (CAP) and IPD was assessed in a randomised, double-blind, placebo controlled study (CAPiTA) conducted over approximately 4 years in the Netherlands. A total of 84,496 subjects, 65 years and older, received a single dose of either Prevenar 13 or placebo in a 1:1 randomisation; 42,240 subjects were vaccinated with Prevenar 13 and 42,256 subjects were vaccinated with placebo.
The primary objective was to demonstrate the efficacy of Prevenar 13 in the prevention of a first episode of confirmed VT-CAP (defined as presence of ≥ 2 specified clinical criteria; chest X ray consistent with CAP as determined by a central committee of radiologists; and positive VT-specific Urinary Antigen Detection assay (UAD) or isolation of VT S. pneumoniae from blood or other sterile site). The secondary objectives were to demonstrate the efficacy of Prevenar 13 in the prevention of a first episode of 1) confirmed non-bacteraemic/non-invasive (NB/NI) VT-CAP (an episode of VT-CAP for which the blood culture result and any other sterile site culture results were negative for S. pneumoniae) and 2) VT-IPD (the presence of S. pneumoniae in a sterile site).
Surveillance for suspected pneumonia and IPD began immediately after vaccination and continued through identification of a pre-specified number of cases. Subjects who had a CAP or IPD episode with symptom onset less than 14 days after vaccination were excluded from all analyses.
The median duration of follow up per subject was 3.93 years (0-4.95 years). Prevenar 13 demonstrated statistically significant vaccine efficacy (VE) in preventing first episodes of VT pneumococcal CAP, non-bacteraemic/non-invasive (NB/NI) VT pneumococcal CAP, and VT-IPD (see Table 9).
A post hoc analysis was used to estimate the following public health outcomes against clinical CAP (as defined in the CAPiTA study, and based on clinical findings regardless of radiologic infiltrate or etiologic confirmation): vaccine efficacy, incidence rate reduction and number needed to vaccinate (see Table 10).
Although CAPiTA was not powered to demonstrate serotype specific VE, an evaluation of clinical CAP data (as defined in the CAPiTA study and based on clinical findings regardless of radiologic infiltrate or etiologic confirmation) was performed in a post-hoc analysis for serotypes with at least 10 outcomes in the placebo group. VE (95% CI) for the five evaluated serotypes against first clinical CAP episodes were: serotype 1, 20.0% (-83.1% to 65.8%); serotype 3, 61.5% (17.6% to 83.4%); serotype 6A, 33.3% (-58.6% to 73.2%); serotype 7F, 73.3% (40.5% to 89.4%); and serotype 19A, 45.2% (-2.2% to 71.5%).

Prevenar 20 clinical trials in adults.

Three Phase 3 clinical trials, B7471006, B7471007 and B7471008 (Study 1006, Study 1007 and Study 1008, respectively), were conducted in the United States and Sweden evaluating the immunogenicity of Prevenar 20 in different adult age groups and in individuals who were either pneumococcal vaccine naïve or who were previously vaccinated with Prevenar 13, 23vPPV, or both.
Each study included healthy adults and immunocompetent adults with stable underlying conditions including chronic cardiovascular disease, chronic pulmonary disease, renal disorders, diabetes mellitus, chronic liver disease, and medical risk conditions and behaviours (e.g. smoking) that are known to increase the risk of serious pneumococcal pneumonia and IPD. In the pivotal study (Study 1007), these risk factors were identified in 34%, 32%, and 26% of participants 60 years of age and over, 50 to 59 years of age, and 18 to 49 years of age, respectively. A stable medical condition was defined as a medical condition not requiring significant change in therapy in the previous 6 weeks (i.e. change to new therapy category due to worsening disease) or any hospitalisation for worsening disease within 12 weeks before receipt of the study vaccine.
In each study, immune responses elicited by Prevenar 20 and the control pneumococcal vaccines were measured by an opsonophagocytic activity (OPA) assay. OPA assays measure functional antibodies to S. pneumoniae. See Table 11.

Comparison of immune responses of Prevenar 20 to Prevenar 13 and 23vPPV in pneumococcal vaccine naive adults.

In a randomised, active-controlled, double-blind non-inferiority clinical trial (Pivotal Study 1007) of Prevenar 20 in the United States and Sweden, pneumococcal vaccine-naive adults 18 years of age and older were enrolled into 1 of 3 cohorts based on their age at enrolment (18 to 49, 50 to 59, and ≥ 60 years of age) enrolment and randomised to receive either Prevenar 20 or control. Participants 60 years of age and older were randomised (1:1 ratio) and received Prevenar 20 (n = 1,507) followed 1 month later with saline placebo or Prevenar 13 (n = 1,490) followed 1 month later with 23vPPV. Participants 18 to 49 years of age and 50 to 59 years of age were randomly assigned (3:1 ratio) and received a dose of Prevenar 20 (18 to 49 years of age: n = 335, 50 to 59 years of age: n = 334) or Prevenar 13 (18 to 49 years of age: n = 112, 50 to 59 years of age: n = 111).
Serotype-specific OPA geometric mean titres (GMTs) were measured before the first vaccination and 1 month after each vaccination. Non-inferiority of immune responses, OPA GMTs 1 month after vaccination, with Prevenar 20 to a control vaccine for a serotype was declared if the lower bound of the 2 sided 95% confidence interval (CI) for the GMT ratio (Prevenar 20/Prevenar 13; Prevenar 20/23vPPV) for that serotype was greater than 0.5.
In adults 60 years of age and older, immune responses to all 13 matched serotypes elicited by Prevenar 20 were non-inferior to the immune responses to the serotypes elicited by Prevenar 13 1 month after vaccination. Immune responses to 6 out of the 7 additional serotypes induced by Prevenar 20 were non-inferior to the immune responses to these same serotypes induced by 23vPPV one month after vaccination.
The response to serotype 8 missed the pre-specified statistical non-inferiority criterion (the lower bound of the 2 sided 95% CI for the GMT ratio being 0.49 versus > 0.50) (see Table 12). The clinical relevance of this single data point is unknown, particularly since supportive analyses for other serotype 8 endpoints showed favourable outcomes. These include 22.1 geometric mean fold rise (GMFR) from before vaccination to 1 month post-vaccination, for serotype 8 in the Prevenar 20 group, 77.8% of participants achieved a ≥ 4-fold rise in OPA titres from before vaccination to 1 month after vaccination, and 92.9% of participants achieved OPA titres ≥ LLOQ 1 month after vaccination; these were within the corresponding ranges observed for the 13 serotypes in the Prevenar 13 control group.

Immunogenicity in pneumococcal vaccine naive adults 18 through 59 years of age.

In Study 1007, described above, participants 50 through 59 years of age and participants 18 through 49 years of age were randomly assigned (3:1 ratio) to receive 1 vaccination with Prevenar 20 or Prevenar 13. Serotype-specific OPA GMTs were measured before vaccination and 1 month after vaccination. Higher immune responses were observed in younger adults compared with older adults. A non-inferiority analysis of Prevenar 20 in the younger age group versus Prevenar 20 in adults 60 through 64 years of age for a serotype was performed to support the indication in adults 18 through 49 years of age and 50 through 59 years of age. Non-inferiority was to be declared if the lower bound of the 2 sided 95% CI for the GMT ratio (Prevenar 20 in participants 18 through 49 years of age/ 60 through 64 years of age and in 50 through 59 years of age/ 60 through 64 years of age) for the 20 serotypes was > 0.5. Prevenar 20 elicited immune responses to all 20 vaccine serotypes in both of the younger age groups that were non-inferior to responses in adults 60 through 64 years of age 1 month after vaccination (Table 13).

Immunogenicity of Prevenar 20 in adults previously vaccinated with pneumococcal vaccine.

A Phase 3 randomised, open-label clinical trial (Study 1006) described immune responses to Prevenar 20 in adults 65 years of age and older previously vaccinated with 23vPPV, with Prevenar 13, or previously vaccinated with Prevenar 13 followed by 23vPPV. Participants in this study previously vaccinated with Prevenar 13 (Prevenar 13 only or followed by 23vPPV) were enrolled at sites in the United States and participants previously vaccinated with 23vPPV only were also enrolled from Swedish sites (35.5% in that category).
Prevenar 20 elicited immune responses to all 20 vaccine serotypes in adults 65 years of age and older with prior pneumococcal vaccination. (Table 14). Immune responses were lower in subjects in both groups who received prior 23vPPV vaccinations.

Concomitant vaccine administration.

Paediatric population. In study 1012, the concomitant administration of Infanrix hexa (containing DTaP, HBV, IPV, and Hib antigens) with all 3 doses of Prevenar 20 or Prevenar 13 and single doses of a vaccine containing MMR antigens and Varilrix (varicella antigens) were also administered with the third dose and evaluated 1 month after the third (toddler) dose of Prevenar 20 or Prevenar 13. Noninferiority was demonstrated for immune responses to diphtheria, tetanus, acellular pertussis, hepatitis B, poliovirus, Hib, MMR, and varicella vaccine antigens co-administered with Prevenar 20 compared with Prevenar 13. The results from study 1012 support co-administration of Prevenar 20 with routine paediatric vaccines. No safety concerns were identified in this study.
In study 1011, the concomitant administration of a vaccine containing DTaP, HBV, IPV antigens and Hiberix (Hib antigen) with each of the 3 infant doses of either Prevenar 20 or Prevenar 13 were evaluated 1 month after the third dose. Concomitant administration of single doses of M-M-R II (MMR antigens) and Varivax (varicella antigens) with the fourth dose of either Prevenar 20 or Prevenar 13 were evaluated 1 month following vaccination. Noninferiority was demonstrated for immune responses to the co-administered diphtheria, tetanus, acellular pertussis, hepatitis B virus, poliovirus, and Hib vaccine antigens 1 month after 3 infant doses and co-administered MMR, and varicella virus vaccine antigens after the fourth (toddler) dose of Prevenar 20 compared with Prevenar 13. The results from Study 1011 support co-administration of Prevenar 20 with routine paediatric vaccines. No safety concerns were identified in this study.
Influenza and rotavirus vaccines were permitted to be administered concomitantly at any time during these studies according to local or national recommendations.
Adults.

Clinical trial in adults to assess Prevenar 20 given with influenza vaccine, adjuvanted (Fluad Quadrivalent, [QIV]).

In a double-blind, randomised study B7471004 (Study 1004), adults 65 years of age and older were randomised in a 1:1 ratio to receive Prevenar 20 concomitantly administered with an influenza vaccine, adjuvanted (Fluad Quadrivalent, [QIV]) (Group 1, N = 898) or Prevenar 20 administered 1 month after receiving QIV (Group 2, N = 898). Pneumococcal serotype-specific OPA GMTs were evaluated 1 month after Prevenar 20 and influenza vaccine strain hemagglutinin inhibition assay (HAI) GMTs were evaluated 1 month after QIV. The noninferiority criteria for the comparisons of OPA GMTs (lower limit of the 2-sided 95% CI of the GMT ratio [Group 1/Group 2] > 0.5, 2-fold noninferiority criterion) were met for all 20 pneumococcal serotypes in Prevenar 20. OPA GMTs were slightly lower for some serotypes when Prevenar 20 was administered concomitantly with QIV compared to Prevenar 20 administered alone. The noninferiority criteria for the comparisons of HAI GMTs (lower limit of the 2-sided 95% CI for the GMT ratio [Group 1/Group 2] > 0.67, 1.5-fold noninferiority criterion) were also met for all 4 influenza vaccine strains.

Clinical trial in adults to assess Prevenar 20 given with a third (booster) dose of COVID-19 mRNA vaccine (Comirnaty [tozinameran]).

In a double-blind, randomised descriptive study B7471026 (Study 1026), adults 65 years of age and older who had received 2 doses of COVID-19 mRNA vaccine (Comirnaty [tozinameran]) at least 6 months earlier, were randomised in a 1:1:1 ratio to receive Prevenar 20 concomitantly administered with a third (booster) dose of COVID-19 mRNA vaccine (Comirnaty [tozinameran]) (N = 190), Prevenar 20 administered alone (N = 191), or a third (booster) dose of COVID-19 mRNA vaccine (Comirnaty [tozinameran]) administered alone (N = 189).
Immune responses to both vaccines were observed after co-administration of Prevenar 20 and COVID-19 mRNA vaccine (Comirnaty [tozinameran]). OPA GMTs for the 20 pneumococcal serotypes were similar to Prevenar 20 administered alone and IgG GMCs for the full-length S-binding protein were similar to COVID-19 mRNA vaccine (Comirnaty [tozinameran]) administered alone. A post hoc analysis found the immune responses to all 20 serotypes elicited by Prevenar 20 when co-administered with COVID-19 mRNA vaccine (Comirnaty [tozinameran]) would have met conventional 2-fold noninferiority criteria compared to Prevenar 20 alone, and the full-length S-binding IgG GMC elicited by COVID-19 mRNA vaccine (Comirnaty [tozinameran]) would have met conventional 1.5-fold noninferiority compared to COVID-19 mRNA vaccine (Comirnaty [tozinameran]) alone.

Prevenar 13 immune responses in special populations.

Individuals with the conditions described below have an increased risk of pneumococcal disease. Studies in SCD, HIV and haematopoietic stem cell transplant (HSCT) participants have not been conducted with Prevenar 20; however, safety and immunogenicity of Prevenar 13 are relevant to Prevenar 20, since the vaccines are manufactured similarly and contain 13 of the same polysaccharide conjugates.
Sickle cell disease (SCD). An open label single arm study with 2 doses of Prevenar 13 given 6 months apart was conducted in 158 children and adolescents ≥ 6 to < 18 years of age with sickle cell disease who were previously vaccinated with one or more doses of 23vPPV at least 6 months prior to enrolment. After the first vaccination, Prevenar 13 elicited antibody levels measured by both IgG GMCs and OPA GMTs that were statistically significant higher when compared to levels prior to vaccination. After the second dose, immune responses were comparable to the ones after the first dose.
OPA GMTs in subjects with SCD, before and after each dose are presented in Table 15 for the evaluable immunogenicity population. In general, antibodies increased in response to dose 1, declined over the 6 months between doses 1 and 2, but remained higher than before dose 1 levels for all serotypes. OPA GMTs then increased in response to dose 2. The OPA GMTs after dose 2 were similar to or higher than those after dose 1 for subjects in the evaluable immunogenicity population for all serotypes.
One year after the second dose, antibody levels measured by both IgG GMCs and OPA GMTs were higher than levels prior to the first dose of Prevenar 13, except the IgG GMC for serotype 3 that was similar.

Additional Prevenar (7-valent) immunogenicity data: children with sickle cell disease.

The immunogenicity of Prevenar has been investigated in an open-label, multicentre study in 49 infants with sickle cell disease. Children were vaccinated with Prevenar (3 doses one month apart from the age of 2 months), and 46 of these children also received a 23vPPV at the age of 15-18 months. After primary immunisation, 95.6% of the subjects had antibody levels of at least 0.35 microgram/mL for all seven serotypes found in Prevenar (7-valent). A significant increase was seen in the concentrations of antibodies against the seven serotypes after the polysaccharide vaccination, suggesting that immunological memory was well established.
HIV infection.

Children and adults not previously vaccinated with a pneumococcal vaccine.

In Study 6115A1-3002 (B1851021), 151 HIV-infected participants 6 to < 18 years of age and 152 participants ≥ 18 years of age (CD4 ≥ 200 cells/microL, viral load < 50,000 copies/mL and free of active acquired immunodeficiency syndrome [AIDS]-related illness) not previously vaccinated with a pneumococcal vaccine received 3 doses of Prevenar 13. As per general recommendations, a single dose of 23vPPV was subsequently administered. Vaccines were administered at 1 month intervals. Immune responses were assessed in 128 to 133 evaluable participants 6 to < 18 years of age and in 131 to 137 evaluable participants ≥ 18 years of age approximately 1 month after each dose of vaccine. After the first dose, Prevenar 13 elicited antibody levels, measured by both IgG GMCs and OPA GMTs that were statistically significantly higher when compared to levels prior to vaccination. After the second and third dose of Prevenar 13, immune responses were similar to or higher than those after the first dose.

Adults previously vaccinated with 23vPPV.

In Study 6115A1-3017 (B1851028), immune responses were assessed in 329 HIV-infected adults ≥ 18 years of age (CD4+ T cell count ≥ 200 cells/microL and viral load < 50,000 copies/mL) previously vaccinated with 23vPPV administered at least 6 months prior to enrolment. Participants received 3 doses of Prevenar 13: at enrolment, 6 months, and 12 months after the first dose of Prevenar 13. After the first vaccination, Prevenar 13 elicited antibody levels measured by both IgG GMCs and OPA GMTs that were statistically significantly higher when compared to levels prior to vaccination. After the second and third dose of Prevenar 13, immune responses were comparable to or higher than those after the first dose. Participants who received 2 or more previous doses of 23vPPV showed a similar immune response compared with participants who received a single previous dose. The immune responses to Prevenar 13 observed in HIV infected adults were lower than the immune responses reported for healthy adults.
Haematopoietic stem cell transplant (HSCT). In Study 6115A1-3003 (B1851022), 61 participants 2 to < 18 years of age and 190 participants ≥ 18 years of age with an allogeneic HSCT received 3 doses of Prevenar 13 with an interval of at least 1 month between doses. The first dose was administered at 3 to 6 months after HSCT. A fourth (booster) dose of Prevenar 13 was administered 6 months after the third dose. As per general recommendations, a single dose of 23vPPV was administered 1 month after the fourth dose of Prevenar 13. Immune responses as measured by IgG GMCs, were assessed in 41 to 52 evaluable participants 2 to < 18 years of age and in 130 to 159 evaluable participants ≥ 18 years of age approximately 1 month after vaccination. Prevenar 13 elicited increased antibody levels after each dose. Immune responses after the fourth dose of Prevenar 13 were significantly increased for all serotypes compared with after the third dose with the exception of serotype 3 in the 2 to < 18 years age group. Overall, participants 2 to < 18 years of age had generally higher serotype-specific immune responses compared with those ≥ 18 years of age.
This study demonstrated that 4 doses of Prevenar 13 elicited serum IgG concentrations similar to those induced by a single dose in healthy participants of the same age group.

Paediatric population.

Prevenar efficacy and Prevenar 13 effectiveness in children.

Invasive pneumococcal disease (IPD).

The information captured in this section comes from published literature.
The impact of Prevenar 13 on the rates of IPD in the United States was measured using an active population-based and laboratory-based surveillance system: the Active Bacterial Core surveillance (ABCs). In 2000, Prevenar (7-valent) was introduced into the routine infant immunisation programme in the USA, with a 3 dose primary series and a booster dose in the second year of life. In 2010, Prevenar 13 replaced Prevenar.
For the 2012-2013 period, there were statistically significant declines in the incidence of IPD for the Prevenar-13 unique serotypes (i.e. “Prevenar 13 minus Prevenar” serotypes. The disease reductions were calculated using a model of observed versus expected (if Prevenar 13 had not replaced Prevenar) IPD cases with 95% Interval Estimates (IEs) see Table 16.
In all age groups, these reductions were driven principally by declines in IPD caused by serotypes 19A and 7F. There was no significant increase in disease caused by non-Prevenar 13 serotypes among children younger than 5 years and most adult age groups, except for adults 50-64 years old where a 26% increase (95% IE 13-44) was detected in non-Prevenar 13 type IPD during 2012-13 compared to expected incidence, although no non-Prevenar 13 serotype predominated. However, serotype replacement may not be expected within 2 years after introduction of Prevenar 13.
The prevalence of at least one risk factor increased among children and adults with IPD after the introduction of Prevenar 13. The proportions of cases resulting in hospital admission were also higher in the period after the introduction of Prevenar 13 in both children and adults, but case-fatality rates did not change.
After the introduction of Prevenar 13, a reduction in the incidence of antibiotic-resistant IPD (vaccine serotype or non-vaccine serotype IPD) was also identified. Penicillin-non-susceptible IPD, erythromycin-non-susceptible IPD and multiply-non-susceptible IPD decreased by 78-96% among children younger than 5 years. Among adults, reductions in the incidence of penicillin-non-susceptible IPD and multiply-non-susceptible IPD were also seen. The reductions in antibiotic non-susceptible IPD were largely attributable to reductions in IPD caused by serotype 19A, the serotype associated with increased antibiotic non-susceptibility before the introduction of Prevenar 13.
In England and Wales, 23vPPV was in use for risk subjects > 2 years of age from 1992. This vaccine was also recommended for adults ≥ 80 years, ≥ 75 years and ≥ 65years of age from 2003, 2004 and 2005, respectively. Prevenar (7-valent) was first recommended for risk children < 2 years of age in 2002 and from 2005 for “risk children” < 5 years. From 2006, Prevenar (7-valent) was introduced into the Routine Childhood Immunisation Programme with a catch-up campaign for children up to two years of age. As of April 2010 the Prevenar (7-valent) was replaced by Prevenar 13 and it simply replaced Prevenar (7-valent) at the point in the schedule that any child had reached. There was no catch up program.
Four years after the introduction of Prevenar (7-valent) as a two dose primary series plus booster dose in the second year of life and with a 94% vaccine uptake, a 98% (95% CI 95; 99) reduction of disease caused by the Prevenar (7-valent) vaccine serotypes was reported in children under 2 years, in England and Wales. However, reductions were accompanied by an increase in IPD from non-vaccine serotypes, such as 7F, 19A and 22F, thus diminishing the effect of Prevenar (7-valent) on overall IPD incidence.
Subsequently, four years following the switch to Prevenar 13, the additional reduction in incidence of IPD due to the 7 serotypes in Prevenar ranged from 76% (95% CI 7; 94) in children less than 2 years of age to 91% (95% CI 33; 99) in children 5 14 years of age. The serotype specific reductions for each of the 5 additional serotypes in Prevenar 13 (no cases of serotype 5 IPD were observed) by age group (see Table 17) and ranged from 68% (95% CI 6; 89) (serotype 3) to 100% (95% CI 62; 100) (serotype 6A) for children less than 5 years of age. Significant incidence reductions were also observed in older age groups who had not been vaccinated with Prevenar 13 (indirect effect). Overall, the reductions observed were attenuated by the increase in non-PCV13 IPD, both in adults ≥ 65 years and in children younger < 5 years - the two groups with the highest incidence of pneumococcal-attributable disease.

Otitis media (OM).

Information captured in this section has been taken from published literature.
A study was conducted one year following the introduction of Prevenar 13 in the USA. It utilised an insurance claims database of a large, nationwide managed health care plan. Enrolled children aged 6 years or younger and those with OM visits were identified (5.51 million child-years). There was a significant drop in OM visit rates that coincided with the introduction of Prevenar 13 in 2010 and the observed OM visit rates in 2010 and 2011 were lower than the projected rates based on the 2005-2009 trend (p < 0.001).
In a multicentre surveillance study of Streptococcus pneumoniae isolates from spontaneous drainage, PE tube placement, myringotomy or mastoid surgical cultures from 8 children's hospitals in the USA were obtained. In 2011, 74 of 149 (50%) isolates were Prevenar 13 plus a related serotype; in 2012 and 2013, these serotypes accounted for 47 of 116 (40.5%) and 34 of 118 (29%) of isolates, respectively. Overall, there was a reduction in the proportion of isolates included in Prevenar 13 over the 3 years following the introduction of that vaccine, including antibiotic resistant strains. Serotype 19A was the most common serotype isolated in each year. The number of serotype 19A isolates in 2013 (n = 12, 10.2% of total) decreased 76% compared with 2011 (n = 50, 33.6% of total).
In a published study performed prospectively in Israel between 2004 and 2013, the impact on OM of introduction of a 2-dose primary series of Prevenar 13 plus booster dose in the second year of life was recorded in a population-based active-surveillance system including culture results of middle ear fluid obtained by tympanocentesis. The decision to perform tympanocentesis in the presence of OM was independent of the study protocol. Overall, 6,122 OM episodes with middle ear fluid cultures were recorded in children less than 2 years of age. Declines in incidence were recorded from 2.1 to 0.1 cases per 1000 children (96%) for the Prevenar serotypes plus serotype 6A and a decline in incidence from 0.9 to 0.1 cases per 1000 children (85%) for the additional serotypes 1, 3, 5, 7F, and 19A in Prevenar 13. The annual overall pneumococcal incidence of OM declined from 9.6 to 2.1 cases per 1000 children (77%) between July 2004 (prior to the introduction of Prevenar) and June 2013 (post Prevenar 13 introduction). However, the true reduction of overall OM incidences could not be studied, as simple OM can be subclinical, subject to over- and under diagnosis and, above all, not subjected to middle ear fluid culture.
In a prospective, population-based, long-term surveillance study conducted in Israel between 2004 and 2015 following the introduction of pneumococcal 7-valent conjugate vaccine and subsequently Prevenar 13, reductions of non-pneumococcal bacteria isolated from children < 3 years of age with OM were 75% for all NTHi cases, and 81% and 62% for cases of OM due to M. catarrhalis and S. pyogenes, respectively.

Pneumonia.

Information captured in this section has been taken from published literature.
The effect of Prevenar 13 on admissions to hospital in the USA 2 years after its introduction in 2010 was assessed using data from a private inpatient discharge record database covering approximately 20% of inpatients in the USA. A multiple regression model was used to estimate change in admissions to hospital for all-cause pneumonia, invasive pneumococcal disease, non-invasive pneumococcal pneumonia, and empyema, and for negative controls, urinary tract infection and hospital admission for any reason. Direct cause and effect cannot be inferred from analyses of this type.
Reduction in hospital admission for all-cause pneumonia of 21% [95% CI 14-28] was reported for children aged less than 2 years and 17% [95% CI 7-27]. For those aged 2 - 4 years: For empyema the reduction was 50% [95% CI 22-68] for children age < 2 years, 46% [95% CI 21-64] for children 2-4 years, and 37% [95% CI 13-54] for those aged 5-17 years. All cause pneumonia was reduced in adults 18-39 years (12% (95% CI 6-17) but not for other adult age groups. Non-invasive pneumococcal or lobar pneumonia fell for all age groups except toddlers aged 2-4 years.
In a multicentre observational study in France between June 2009 and May 2012 comparing the periods before and after the switch from Prevenar (7-valent) to Prevenar 13, there was 16% reduction in all community acquired pneumonia (CAP) cases in emergency departments in children 1 month to 15 years of age. Reductions were 53% (p < 0.001) for CAP cases with pleural effusion and 63% (p < 0.002) for microbiologically confirmed pneumococcal CAP cases. In the second year after the introduction of Prevenar 13 the total number of CAP cases due to the 6 additional vaccine serotypes in Prevenar 13 was reduced by 74% (27 to 7 isolates).
In an ongoing surveillance system (2002 to 2013) to document the impact of Prevenar (7-valent) and subsequently Prevenar 13 on CAP in children less than 5 years in Southern Israel using a 2 dose primary series with a booster dose in the second year of life, there was a reduction of 68% (95% CI 61; 73) in outpatient visits and 32% (95% CI 22; 39) in hospitalisations for alveolar CAP (a dense opacity that may be a fluffy consolidation of a portion, whole of a lobe or of the entire lung, often containing air bronchogram and sometimes associated with pleural effusion) following the introduction of Prevenar 13 when compared to the period before the introduction of Prevenar (7-valent) was introduced.

Carriage.

The information captured in this section has been taken from published literature.
A study of nasopharyngeal carriage of Streptococcus pneumoniae in predominantly black children 6-59 months of age presenting to a children's hospital emergency department in Atlanta, USA between 1 July 2010 and 30 June 2013 showed a significant reduction in carriage of Prevenar 13 serotypes and antibiotic resistant strains after the introduction of Prevenar 13. The overall proportion of children with Streptococcus pneumoniae carriage ranged from 28% to 35.4% and did not significantly change through the study period. Carriage of Prevenar 13 serotypes decreased significantly from 29% (36/124) to 3% (3/99; p < 0.0001), primarily due to a significant decrease in serotype 19A carriage from 25.8% (32/124) to 3% (3/99; P < 0.0001). The proportion of carriage isolates with nonsusceptibility to ceftriaxone declined from 22.6% to 3% and nonsusceptibility to penicillin also declined from 24% to 3%.
The proportion of pneumococcal carriage accounted for by non-PCV13 serotypes (excluding 6C) increased from 68.4% (78/114) to 96.9% (95/98; P < 0.0001). Non-PCV13 serotypes 35B, 15B/C, 11A, 21, 23B and 15A were the most commonly carried serotypes during the last 2 study periods. Carriage of serotype 35B increased during the 6 study periods from 8.9% (11/124) to 25.3% (25/99). Serotype 35B demonstrated moderate non-susceptibility to selected antibiotics.

Reduction of antimicrobial resistance (AMR).

The information captured in this section has been taken from published literature.
Following the introduction of Prevenar (7-valent) and subsequently Prevenar 13, a reduction in AMR has been shown as a result of direct reduction of serotypes and clones associated with AMR from the population (including 19A), reduction of transmission (herd effects), and reduction in the use of antimicrobial agents.
A post-hoc analysis of a double blind, randomised, controlled study enrolling 1866 subjects in Israel conducted between February 2008 and September 2009, compared Prevenar (7-valent) and Prevenar 13. The reported reduction of new acquisitions of S. pneumoniae, serotypes 19A, 19F, and 6A not susceptible to either penicillin, erythromycin, clindamycin, penicillin plus erythromycin, or multiple drugs (≥ 3 antibiotics) ranged between 34% and 62% depending on serotype and antibiotic.
Data from 10 surveillance sites of the United States Centers for Disease Control and Prevention covering 31 million individuals show that from 2009 to 2013, rates of antibiotic-nonsusceptible IPD caused by serotypes included in Prevenar 13 but not in Prevenar (7-valent) decreased from 6.5 to 0.5 per 100,000 in children aged < 5 years and from 4.4 to 1.4 per 100,000 in adults aged ≥ 65 years. Antibiotic-non-susceptible IPD caused by non- Prevenar 13 serotypes increased from 41.8% (n = 1995) to 65.0% (n = 2397) (P < 0.001). Among antibiotic-non-susceptible IPD caused by non-Prevenar 13 serotypes, increases from 2009 to 2013 among children aged < 5 years (from 2.5 to 3.1 per 100,000) and among adults aged ≥ 65 years (from 6.4 to 7.3 per 100,000) were observed. In 2013, the most frequent non-vaccine serotypes among cases with antibiotic-non-susceptible IPD were 35B (16.2%), 33F (15.5%), 22F (12.3%), and 15A (11.7%). Among multidrug-non-susceptible IPD, the most frequent non-vaccine serotypes were 35B (59.9%), 15A (17.8%), 6C (5.6%), and 15C (5.6%).

Prevenar (7-valent) protective efficacy in infants and children.

The efficacy of Prevenar (7-valent) was evaluated in two major trials - the Northern California Kaiser Permanente (NCKP) trial and the Finnish Otitis Media trial (FinOM). Both trials were randomised, double blind, active-control trials in which infants were randomised to receive either Prevenar (7-valent) or control vaccine (NCKP, meningococcal serogroup C CRM-conjugate [MnCC] vaccine; FinOM, hepatitis B vaccine) in a four-dose series at 2, 4, 6, and 12 - 15 months of age. The various efficacy results from these trials (for invasive pneumococcal disease, pneumonia, and acute otitis media) are presented below (see Table 18).

5.2 Pharmacokinetic Properties

Not applicable.

5.3 Preclinical Safety Data

Genotoxicity.

Prevenar 20 has not been tested for genotoxic potential.

Carcinogenicity.

Prevenar 20 has not been tested for carcinogenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

Aluminium phosphate, sodium chloride, succinic acid, polysorbate 80, water for injections.

6.2 Incompatibilities

In the absence of compatibility studies, this vaccine must not be mixed with other medicinal products.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store in a refrigerator (2°C to 8°C). Pre-filled syringes should be stored in the refrigerator horizontally to minimise the re-suspension time.
Do not freeze. Discard if the vaccine has been frozen.
From a microbiological point of view, once removed from the refrigerator, the vaccine should be used immediately.
Stability data indicate that the vaccine is stable for 96 hours when stored at temperatures from 8°C to 25°C or 72 hours when stored at temperatures from 0°C to 2°C. At the end of these time periods Prevenar 20 should be used or discarded. These data are intended to guide healthcare professionals in case of temporary temperature excursion only.

6.5 Nature and Contents of Container

0.5 mL suspension for injection in pre-filled syringe (Type I glass) with a tip cap (synthetic isoprene/bromobutyl blend rubber) and a plunger stopper (chlorobutyl rubber).
Pack sizes of 1 and 10 pre-filled syringes, with or without needle.
Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

During storage, a white deposit and clear supernatant may be observed in the pre-filled syringe containing the suspension.
In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

No data available.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes