Sanofi Pasteur MSD Limited

PNEUMOVAX^® II Vial

Pneumococcal Polysaccharide Vaccine

The 0.5 mL dose of vaccine contains 25 micrograms of each of the following 23 pneumococcal serotypes: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F.

For full list of excipients, see section 6.1.

Solution for injection in a vial.

The vaccine is a clear, colourless solution.

PNEUMOVAX^® II is recommended for active immunisation against disease caused by the pneumococcal serotypes included in the vaccine. The vaccine is recommended for individuals 2 years of age or older in whom there is an increased risk of morbidity and mortality from pneumococcal disease. The specific at risk categories of persons to be immunised are to be determined on the basis of official recommendations.

The vaccine is not effective for the prevention of acute otitis media, sinusitis and other common upper respiratory tract infections.

Posology

Primary vaccination: Adults and children of 2 years of age or older- one single dose of 0.5 millilitre by intramuscular or subcutaneous injection. PNEUMOVAX^® II is not recommended for use in children below 2 years of age as the safety and efficacy of the vaccine have not been established and the antibody response may be poor.

Special dosing:

It is recommended that pneumococcal vaccine should preferably be given at least two weeks before elective splenectomy or the initiation of chemotherapy or other immunosuppressive treatment. Vaccination during chemotherapy or radiation therapy should be avoided.

Following completion of chemotherapy and/or radiation therapy for neoplastic disease, immune responses to vaccination may remain diminished. The vaccine should not be administered any sooner than three months after completion of such therapy. A longer delay may be appropriate for patients who have received intensive or prolonged treatment (see section 4.4).

Persons with asymptomatic or symptomatic HIV infection should be vaccinated as soon as possible after their diagnosis is confirmed.

Re-vaccination

One single dose of 0.5 millilitre by intramuscular or subcutaneous injection.

The specific timing of, and need for, re-vaccination should be determined on the basis of available official recommendations.

See section 5.1 for information on immune responses following re-vaccination.

Re-vaccination at an interval of less than three years is not recommended because of an increased risk of adverse reactions. The rates of local and, in persons aged 65 years, some systemic reactions have been shown to be higher after re-vaccination than after primary vaccination when three to five years have elapsed between doses. See section 4.8.

There are very limited clinical data regarding administration of more than two doses of PNEUMOVAX^® II.

Adults

Healthy adults should not be re-vaccinated routinely.

Re-vaccination may be considered for persons at increased risk of serious pneumococcal infection who were given pneumococcal vaccine more than five years earlier or for those known to have a rapid decline in pneumococcal antibody levels. For selected populations (e.g. asplenics) who are known to be at high risk of fatal pneumococcal infections, re-vaccination at three years may be considered.

Children

Healthy children should not be re-vaccinated routinely.

Children of 10 years of age and over

May be considered for re-vaccination according to the adult recommendation (see above).

Children between the ages of 2 and 10 years

Should only be considered for re-vaccination after 3 years if they are at high risk of pneumococcal infection (e.g. those with nephrotic syndrome, asplenia or sickle cell disease).

Method of administration

The vaccine is to be injected intramuscularly (IM) or subcutaneously (SC).

Hypersensitivity to the active substance(s) or to any of the excipients.

Delay the use of the vaccine in any significant febrile illness, other active infection or when a systemic reaction would pose a significant risk except when this delay may involve even greater risk.

PNEUMOVAX^® II should never be injected intravascularly, and precautions should be taken to make sure the needle does not enter a blood vessel. Also, the vaccine should not be injected intradermally, as injection by that route is associated with increased local reactions.

If the vaccine is administered to patients who are immunosuppressed due to either an underlying condition or medical treatment (e.g., immunosuppressive therapy such as cancer chemotherapy or radiation therapy), the expected serum antibody response may not be obtained after a first or second dose. Accordingly, such patients may not be as well protected against pneumococcal disease as immunocompetent individuals.

As with any vaccine, vaccination with PNEUMOVAX^® II may not result in complete protection in all recipients.

For patients receiving immunosuppressive therapy, the time to recovery of the immune response varies with the illness and the therapy. Significant improvement in antibody response has been observed for some patients during the two years following the completion of chemotherapy or other immunosuppressive therapy (with or without radiation), particularly as the interval between the end of treatment and pneumococcal vaccination increased. (See 4.2 Posology and method of administration, Special dosing.)

As with any vaccine, adequate treatment provisions including epinephrine (adrenaline) should be available for immediate use should an acute anaphylactic reaction occur.

Required prophylactic antibiotic therapy against pneumococcal infection should not be stopped after pneumococcal vaccination.

Patients at especially increased risk of serious pneumococcal infection (e.g., asplenics and those who have received immunosuppressive therapy for any reason), should be advised regarding the possible need for early antimicrobial treatment in the event of severe, sudden febrile illness.

Pneumococcal vaccine may not be effective in preventing infection resulting from basilar skull fracture or from external communication with cerebrospinal fluid.

A clinical study of PNEUMOVAX^® II primary vaccination and revaccination was conducted in 629 adults 65 years of age and 379 adults 50 to 64 years of age. The data obtained suggested that the rates of injection site and systematic adverse reactions among subjects 65 years of age were not higher than the rates amongst subjects 50 to 64 years of age. It should be noted that, in general, elderly individuals may not tolerate medical interventions as well as younger individuals; a higher frequency and/or a greater severity of reactions in some older individuals cannot be ruled out (see section 4.2).

Pneumococcal vaccine can be administered simultaneously with influenza vaccine as long as different needles and injection sites are used.

PNEUMOVAX^® II and ZOSTAVAX should not be given concurrently because concomitant use in a clinical trial resulted in reduced immunogenicity of ZOSTAVAX.

Animal studies are insufficient with respect to effects on pregnancy. PNEUMOVAX^® II should not be used during pregnancy unless clearly necessary (the potential benefit must justify any potential risk to the fetus).

PNEUMOVAX^® II has not been evaluated in fertility studies

It is not known whether this vaccine is excreted in human milk. Caution should be exercised when PNEUMOVAX^® II is administered to a nursing mother.

No studies on the effects on the ability to drive and use machines have been performed.

a. Summary of the safety profile

A clinical study of PNEUMOVAX^®II primary vaccination and revaccination was conducted in 379 adults 50 to 64 years of age and 629 adults 65 years of age.

The rates of overall injection site adverse reactions in primary vaccinees and revaccinees were 72.8% and 79.6%, respectively, in participants aged 50 to 64 years of age, and were 52.9% and 79.3%, respectively, in participants aged 65 years of age. The rate of overall injection site adverse experiences reactions in the older revaccination group was comparable to the rate observed in the younger revaccination recipients. Injection site reactions occurred within 3 days of vaccination and typically resolved by day 5. The rates of overall systemic adverse events for primary vaccinees and revaccinees were 48.8% and 47.4%, respectively, in participants aged 50 to 64 years of age, and were 32.1% and 39.1%, respectively, in participants aged 65 years of age. The rates of investigator determined vaccine-related systemic adverse events for primary vaccinees and revaccinees were 35.5% and 37.5% respectively, in participants 50 to 64 years of age, and were 21.7% and 33.1% respectively, in participants 65 years of age. The rate of systemic and vaccine related systemic reactions in the older revaccination group was comparable to the rate observed in the younger revaccination recipients.

The most common systemic adverse experiences events overall were as follows: asthenia/fatigue, myalgia and headache. Symptomatic treatment resulted in complete recovery in most cases.

b. Tabulated summary of adverse reactions

The table below summarizes the frequencies of the adverse events that were reported with PNEUMOVAX^®II in clinical trials and/or post marketing surveillance, using the following convention: 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).

Adverse events following administration of PNEUMOVAX^® II from Clinical Trials and Post-Marketing Surveillance

^* in patients who have had other hematologic disorders

^** in patients with stabilized idiopathic thrombocytopenic purpura

^† with short onset time from vaccine administration

^†† in the injected extremity

Not applicable.

Pharmacotherapeutic group: pneumococcal vaccines, ATC code: J07 AL

The vaccine is prepared from purified pneumococcal capsular polysaccharide antigens derived from the 23 serotypes that account for approximately 90% of invasive pneumococcal disease types.

Immunogenicity

The presence of type-specific humoral antibodies is generally thought to be effective in preventing pneumococcal disease. A 2-fold increase in antibody level following vaccination was associated with efficacy in clinical trials of polyvalent pneumococcal polysaccharide vaccines. However, the concentration of anti-capsular antibody required to protect against pneumococcal infection caused by any specific capsular type has not been established. Most persons aged 2 years (85 to 95%) respond to vaccination by making antibody to most or all of the 23 pneumococcal polysaccharides in the vaccine. Bacterial capsular polysaccharides induce antibodies primarily by T-cell-independent mechanisms and elicit poor or inconsistent antibody responses in children aged < 2 years.

Antibodies can be detected by the third week following vaccination but may decline as soon as 3 to 5 years after vaccination and a more rapid decline may occur in some groups (e.g., children and the elderly).

Immune responses to eight of the polysaccharides in PNEUMOVAX^® II have been compared following administration of a single dose of vaccine or placebo. Four groups of subjects were entered as defined by age (50-64 years and 65 years) and by prior vaccination status (no prior vaccination or 1 vaccination 3-5 years previously).

• Prior to vaccination, antibody levels were higher in the revaccination group than in the primary vaccination group.

• In the primary and revaccination groups the geometric mean antibody levels for each serotype increased from pre- to post-vaccination.

• The ratios in geometric mean antibody concentrations by serotype at day 30 between those who were revaccinated and those who were given primary vaccination ranged from 0.60-0.94 in the 65 years group and from 0.62–0.97 for the group aged between 50-64 years.

The clinical relevance of the lower antibody responses observed on revaccination compared to primary vaccination is not known.

Efficacy

The efficacy of polyvalent pneumococcal polysaccharide vaccine was established for pneumococcal pneumonia and bacteremia in randomized controlled trials that were conducted among novice gold miners in South Africa. The protective efficacy against pneumococcal pneumonia, the primary endpoint in these studies, was 76.1% with a 6-valent vaccine and 91.7% with a 12-valent preparation. In trials conducted in populations for which the vaccine is indicated (see section 4.1), vaccine effectiveness was reported to be 50 to 70% (e.g., persons with diabetes mellitus, chronic cardiac or pulmonary disease, and anatomic asplenia).

One study found that vaccination was significantly protective against invasive pneumococcal disease caused by several individual serotypes (e.g., 1, 3, 4, 8, 9V, and 14). For other serotypes, the numbers of cases detected in this study were too small to draw conclusions about serotype specific protection.

The results from one epidemiologic study suggest that vaccination may provide protection for at least 9 years after receipt of the initial dose of vaccine. Decreasing estimates of effectiveness have been reported with increasing interval after vaccination, particularly among the very elderly (persons aged 85 years).

Since PNEUMOVAX^® II is a vaccine, pharmacokinetic studies were not performed.

No preclinical safety testing was performed using PNEUMOVAX^® II.

Phenol

Sodium chloride

Water for injections

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

28 months.

Store in a refrigerator (2°C – 8°C)

Do not freeze. If frozen, the vaccine should not be used.

0.5 mL of solution in vial (glass) with stopper (rubber) with a flip off cap (plastic), pack of 1, 10 or 20.

Not all pack sizes may be marketed.

The vaccine should be used directly as supplied; no dilution or reconstitution is necessary.

Any unused product or waste material should be disposed of in accordance with local requirements.

Sanofi Pasteur MSD Limited

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January 2000/May 2010

06/2011